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Drug overview for PROTECT IRON (multivitamins with min no.24/iron polysaccharides complex/fa):
Generic name: MULTIVITAMINS WITH MIN NO.24/IRON POLYSACCHARIDES COMPLEX/FA
Drug class: Iron
Therapeutic class: Electrolyte Balance-Nutritional Products
Ascorbic acid is the functional and principal in vivo form of vitamin C, an Calcium salts are used as a source of calcium, an essential nutrient Ferrous fumarate, ferrous gluconate, ferrous sulfate, carbonyl iron, and Folic acid is a water-soluble, B complex vitamin. cation. essential water-soluble vitamin. polysaccharide-iron complex are iron preparations that are commercially available in the US for oral administration in the prevention and treatment of iron deficiency.
Numerous multivitamin preparations are marketed, with little standardization of formulas. Useful multivitamin preparations should contain only essential vitamins (those for which there is a recommended daily dietary allowance (RDA)). (See Dosage and Administration.) Preparations containing iron and/or calcium supplements may be useful in some patients (e.g., pregnant or lactating women) but other essential minerals are usually obtained from the diet.
The addition of agents such as liver, yeast, and wheat germ to vitamin preparations offers no advantage over pure chemical ingredients, and inclusion of nonessential agents such as choline, bioflavonoids, inositol, betaine, lecithin, and methionine is unwarranted. Combinations of vitamins and other drugs such as hormones are irrational and should not be used. Calcium salts are used as a source of calcium cation for the treatment or Folic acid is used for the treatment of megaloblastic and macrocytic anemias resulting from folate deficiency.
The drug is usually indicated in prevention of calcium depletion in patients in whom dietary measures are inadequate. Conditions that may be associated with calcium deficiency the treatment of nutritional macrocytic anemia; megaloblastic anemias of include hypoparathyroidism, achlorhydria, chronic diarrhea, vitamin D pregnancy, infancy, and childhood; and megaloblastic anemia associated with deficiency, steatorrhea, sprue, pregnancy and lactation, menopause, primary liver disease, alcoholism and alcoholic cirrhosis, intestinal pancreatitis, renal failure, alkalosis, and hyperphosphatemia. strictures, anastomoses, or sprue.
Folate deficiency may also result from Administration of certain drugs (e.g., some diuretics, anticonvulsants) may increased loss of folate secondary to renal dialysis or the administration of some drugs such as phenytoin, primidone, barbiturates, methotrexate, sometimes result in hypocalcemia which may warrant calcium replacement nitrofurantoin, or sulfasalazine. therapy. Calcium should be administered in long-term electrolyte replacement regimens and is also recommended for the routine prophylaxis of Folic acid is not effective in the treatment of normocytic, refractory, or hypocalcemia during transfusions with citrated blood.
Administration of aplastic anemias or, when used alone, in the treatment of pernicious calcium salts should not preclude the use of other measures intended to anemia. Folic acid antagonists (e.g., methotrexate, pyrimethamine, correct the underlying cause of calcium depletion. trimethoprim) inhibit folic acid reductases and prevent the formation of tetrahydrofolic acid. Therefore, folic acid is not effective as an antidote following overdosage of these drugs, and leucovorin calcium must be used.
In large doses, folic acid is used in the treatment of tropical sprue. In patients with this disease, the drug appears to exert a beneficial effect on the underlying mucosal abnormality as well as to correct folate deficiency. Although prophylactic administration of folic acid is not required in most individuals, supplemental folic acid may be required to prevent deficiency of the vitamin in patients with conditions that increase folic acid requirements such as pregnancy, nursing, or chronic hemolytic anemia.
In some patients, such as those with nutritional megaloblastic anemia associated with vitamin B12 deficiency or tropical or nontropical sprue, a simultaneous deficiency of folic acid and cyanocobalamin may exist, and combined therapy may be warranted. Likewise, combined folic acid and iron therapy may be indicated for prevention or treatment of megaloblastic anemia associated with iron deficiency as may occur in conditions such as sprue, megaloblastic anemia of pregnancy, and megaloblastic anemia of infants.
Generic name: MULTIVITAMINS WITH MIN NO.24/IRON POLYSACCHARIDES COMPLEX/FA
Drug class: Iron
Therapeutic class: Electrolyte Balance-Nutritional Products
Ascorbic acid is the functional and principal in vivo form of vitamin C, an Calcium salts are used as a source of calcium, an essential nutrient Ferrous fumarate, ferrous gluconate, ferrous sulfate, carbonyl iron, and Folic acid is a water-soluble, B complex vitamin. cation. essential water-soluble vitamin. polysaccharide-iron complex are iron preparations that are commercially available in the US for oral administration in the prevention and treatment of iron deficiency.
Numerous multivitamin preparations are marketed, with little standardization of formulas. Useful multivitamin preparations should contain only essential vitamins (those for which there is a recommended daily dietary allowance (RDA)). (See Dosage and Administration.) Preparations containing iron and/or calcium supplements may be useful in some patients (e.g., pregnant or lactating women) but other essential minerals are usually obtained from the diet.
The addition of agents such as liver, yeast, and wheat germ to vitamin preparations offers no advantage over pure chemical ingredients, and inclusion of nonessential agents such as choline, bioflavonoids, inositol, betaine, lecithin, and methionine is unwarranted. Combinations of vitamins and other drugs such as hormones are irrational and should not be used. Calcium salts are used as a source of calcium cation for the treatment or Folic acid is used for the treatment of megaloblastic and macrocytic anemias resulting from folate deficiency.
The drug is usually indicated in prevention of calcium depletion in patients in whom dietary measures are inadequate. Conditions that may be associated with calcium deficiency the treatment of nutritional macrocytic anemia; megaloblastic anemias of include hypoparathyroidism, achlorhydria, chronic diarrhea, vitamin D pregnancy, infancy, and childhood; and megaloblastic anemia associated with deficiency, steatorrhea, sprue, pregnancy and lactation, menopause, primary liver disease, alcoholism and alcoholic cirrhosis, intestinal pancreatitis, renal failure, alkalosis, and hyperphosphatemia. strictures, anastomoses, or sprue.
Folate deficiency may also result from Administration of certain drugs (e.g., some diuretics, anticonvulsants) may increased loss of folate secondary to renal dialysis or the administration of some drugs such as phenytoin, primidone, barbiturates, methotrexate, sometimes result in hypocalcemia which may warrant calcium replacement nitrofurantoin, or sulfasalazine. therapy. Calcium should be administered in long-term electrolyte replacement regimens and is also recommended for the routine prophylaxis of Folic acid is not effective in the treatment of normocytic, refractory, or hypocalcemia during transfusions with citrated blood.
Administration of aplastic anemias or, when used alone, in the treatment of pernicious calcium salts should not preclude the use of other measures intended to anemia. Folic acid antagonists (e.g., methotrexate, pyrimethamine, correct the underlying cause of calcium depletion. trimethoprim) inhibit folic acid reductases and prevent the formation of tetrahydrofolic acid. Therefore, folic acid is not effective as an antidote following overdosage of these drugs, and leucovorin calcium must be used.
In large doses, folic acid is used in the treatment of tropical sprue. In patients with this disease, the drug appears to exert a beneficial effect on the underlying mucosal abnormality as well as to correct folate deficiency. Although prophylactic administration of folic acid is not required in most individuals, supplemental folic acid may be required to prevent deficiency of the vitamin in patients with conditions that increase folic acid requirements such as pregnancy, nursing, or chronic hemolytic anemia.
In some patients, such as those with nutritional megaloblastic anemia associated with vitamin B12 deficiency or tropical or nontropical sprue, a simultaneous deficiency of folic acid and cyanocobalamin may exist, and combined therapy may be warranted. Likewise, combined folic acid and iron therapy may be indicated for prevention or treatment of megaloblastic anemia associated with iron deficiency as may occur in conditions such as sprue, megaloblastic anemia of pregnancy, and megaloblastic anemia of infants.
DRUG IMAGES
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The following indications for PROTECT IRON (multivitamins with min no.24/iron polysaccharides complex/fa) have been approved by the FDA:
Indications:
Iron deficiency anemia
Mineral deficiency prevention
Mineral deficiency
Vitamin deficiency prevention
Vitamin deficiency
Professional Synonyms:
Hypochromic microcytic anemia
Vitamin deficiency prophylaxis
Indications:
Iron deficiency anemia
Mineral deficiency prevention
Mineral deficiency
Vitamin deficiency prevention
Vitamin deficiency
Professional Synonyms:
Hypochromic microcytic anemia
Vitamin deficiency prophylaxis
The following dosing information is available for PROTECT IRON (multivitamins with min no.24/iron polysaccharides complex/fa):
Dosage of folic acid injection (sodium folate) is expressed in terms of folic acid. In general, although patient response to folic acid therapy depends on the degree and nature of the deficiency, once proper corrective measures are undertaken, folate-deficient patients generally respond rapidly. During the first 24 hours of treatment, the patient experiences an improved sense of well-being, and within 48 hours, the bone marrow begins to become normoblastic.
Reticulocytosis generally begins within 2-5 days following initiation of folic acid therapy.
Dosage of the oral calcium supplements is usually expressed in grams or mg of elemental calcium and depends on the requirements of the individual patient. Dosage of parenteral calcium replacements is usually expressed as mEq of calcium and depends on individual patient requirements. One mEq of elemental calcium is equivalent to 20 mg.
See Table 1 for the approximate calcium content of the various calcium salts.
Table 1.
Calcium Salt Calcium Content calcium acetate 253 mg (12.7 mEq) per g calcium carbonate 400 mg (20 mEq) per g calcium chloride 270 mg (13.5 mEq) per g calcium citrate 211 mg (10.6 mEq) per g calcium gluceptate 82 mg (4.1 mEq) per g calcium gluconate 90 mg (4.5 mEq) per g calcium glycerophosphate 191 mg (9.6 mEq) per g calcium lactate 130 mg (6.5 mEq) per g calcium phosphate dibasic anhydrous 290 mg (14.5 mEq) per g calcium phosphate dibasic dihydrate 230 mg (11.5 mEq) per g calcium phosphate tribasic 400 mg (20 mEq) per g
Oral calcium supplements usually are administered in 3 or 4 divided doses daily. Optimum calcium absorption may require supplemental vitamin D in individuals with inadequate vitamin D intake, those with impaired renal activation of the vitamin, or those not receiving adequate exposure to sunlight.
If calcium administration is necessary during cardiac arrest, an IV dose of 0.109-0.218 mEq/kg (repeated as necessary) using calcium chloride has been recommended.
Alternatively, adults have been given IV calcium doses of 7-14 mEq using calcium chloride. However, routine administration of calcium in patients with cardiac arrest is not recommended. (See Advanced Cardiovascular Life Support under Uses: Parenteral Preparations.)
If administration of calcium is indicated for the treatment of hypocalcemia, calcium-channel blocker overdosage, hypermagnesemia, or hyperkalemia during pediatric resuscitation, experts recommend a pediatric IV or IO+ calcium dose of 0.272 mEq/kg using calcium chloride. In critically ill children, calcium chloride may provide a greater increase in ionized calcium than calcium gluconate.
The appropriate dose should be administered by slow IV or IO+ injection.
When calcium acetate is used orally to control hyperphosphatemia in adults with chronic renal failure, the recommended initial dosage is 1.334 g of calcium acetate (338 mg of calcium) with each meal. Dosage may be increased gradually according to serum phosphate concentrations, provided hypercalcemia does not occur.
The manufacturer states that most patients require about 2-2.67 g (about 500-680 mg of calcium) with each meal. However, some experts state that the dosage of calcium provided by calcium-containing phosphate binders should not exceed 1.5
g daily and that the total calcium intake (including dietary calcium) should not exceed 2 g daily. These experts state that dialysis patients who remain hyperphosphatemic despite such therapy should receive a calcium-containing phosphate binder in combination with a non-calcium-, non-aluminum-, non-magnesium-containing phosphate binder. The manufacturer recommends that serum calcium concentrations be monitored twice weekly during initiation of calcium acetate therapy and subsequent dosage adjustment; serum phosphorus concentrations also should be monitored periodically.
If hypercalcemia occurs, dosage should be reduced or the salt should be withheld. If severe hypercalcemia occurs, specific measures (e.g., hemodialysis) for the management of overdosage may be necessary. Patients should be advised of the importance of dosage compliance, adherence to instructions about diet, and avoidance of concomitant use of antacids or other preparations containing clinically important concentrations of calcium.
Patients also should be advised of potential manifestations of hypercalcemia.
For the treatment of hyperkalemia with secondary cardiac toxicity, 2.25-14 mEq of calcium may be administered IV while monitoring the ECG. Doses may be repeated after 1-2 minutes if necessary.
Magnesium intoxication in adults is treated initially with 7 mEq of IV calcium; subsequent doses should be adjusted according to patient response. Alternatively, for the treatment of hypermagnesemia in adults, an IV calcium dose of 6.8-13.6
mEq using 10% calcium chloride (5-10 mL) has been administered, and repeated as necessary.
For the treatment of drug-induced cardiovascular emergencies associated with calcium-channel blocking agent toxicity in pediatric patients, an IV calcium dose of 0.272 mEq/kg using 10% calcium chloride (0.2 mL/kg) has been administered over 5-10 minutes; if a beneficial effect was observed, an IV calcium infusion of 0.27-0.68
mEq/kg per hour using calcium chloride has been administered. Ionized calcium concentrations should be monitored to prevent hypercalcemia.
Calcium is also administered IV during exchange transfusions in neonates in a dosage of 0.45 mEq of calcium after every 100 mL of citrated blood exchanged. In adults receiving transfusions of citrated blood, about 1.35
mEq of calcium should be administered IV concurrently with each 100 mL of citrated blood.
In the calcium infusion test+, calcium is given IV in a dosage of 0.25 mEq/kg per hour for a 3-hour period; serum gastrin concentrations are determined 30 minutes before the infusion, at the start of the infusion, and at 30-minute intervals thereafter for 4 hours. In most patients with Zollinger-Ellison syndrome, preinfusion serum gastrin concentrations increase by more than 50% or by greater than 500 pg/mL during the infusion.
In the diagnosis of medullary thyroid carcinoma+, about 7 mEq of calcium is given IV over 5-10 minutes. In patients with medullary thyroid carcinoma, plasma calcitonin concentrations are elevated above normal basal concentrations.
Dosage of oral iron preparations should be expressed in terms of elemental iron. The elemental iron content of the various preparations is approximately:
Table 1.
Drug Elemental Iron ferric pyrophosphate 120 mg/g ferrous gluconate 120 mg/g ferrous sulfate 200 mg/g ferrous sulfate, dried 300 mg/g ferrous fumarate 330 mg/g ferrous carbonate, anhydrous 480 mg/g carbonyl iron 1000 mg/g
carbonyl iron is elemental iron, not an iron salt.
Reticulocytosis generally begins within 2-5 days following initiation of folic acid therapy.
Dosage of the oral calcium supplements is usually expressed in grams or mg of elemental calcium and depends on the requirements of the individual patient. Dosage of parenteral calcium replacements is usually expressed as mEq of calcium and depends on individual patient requirements. One mEq of elemental calcium is equivalent to 20 mg.
See Table 1 for the approximate calcium content of the various calcium salts.
Table 1.
Calcium Salt Calcium Content calcium acetate 253 mg (12.7 mEq) per g calcium carbonate 400 mg (20 mEq) per g calcium chloride 270 mg (13.5 mEq) per g calcium citrate 211 mg (10.6 mEq) per g calcium gluceptate 82 mg (4.1 mEq) per g calcium gluconate 90 mg (4.5 mEq) per g calcium glycerophosphate 191 mg (9.6 mEq) per g calcium lactate 130 mg (6.5 mEq) per g calcium phosphate dibasic anhydrous 290 mg (14.5 mEq) per g calcium phosphate dibasic dihydrate 230 mg (11.5 mEq) per g calcium phosphate tribasic 400 mg (20 mEq) per g
Oral calcium supplements usually are administered in 3 or 4 divided doses daily. Optimum calcium absorption may require supplemental vitamin D in individuals with inadequate vitamin D intake, those with impaired renal activation of the vitamin, or those not receiving adequate exposure to sunlight.
If calcium administration is necessary during cardiac arrest, an IV dose of 0.109-0.218 mEq/kg (repeated as necessary) using calcium chloride has been recommended.
Alternatively, adults have been given IV calcium doses of 7-14 mEq using calcium chloride. However, routine administration of calcium in patients with cardiac arrest is not recommended. (See Advanced Cardiovascular Life Support under Uses: Parenteral Preparations.)
If administration of calcium is indicated for the treatment of hypocalcemia, calcium-channel blocker overdosage, hypermagnesemia, or hyperkalemia during pediatric resuscitation, experts recommend a pediatric IV or IO+ calcium dose of 0.272 mEq/kg using calcium chloride. In critically ill children, calcium chloride may provide a greater increase in ionized calcium than calcium gluconate.
The appropriate dose should be administered by slow IV or IO+ injection.
When calcium acetate is used orally to control hyperphosphatemia in adults with chronic renal failure, the recommended initial dosage is 1.334 g of calcium acetate (338 mg of calcium) with each meal. Dosage may be increased gradually according to serum phosphate concentrations, provided hypercalcemia does not occur.
The manufacturer states that most patients require about 2-2.67 g (about 500-680 mg of calcium) with each meal. However, some experts state that the dosage of calcium provided by calcium-containing phosphate binders should not exceed 1.5
g daily and that the total calcium intake (including dietary calcium) should not exceed 2 g daily. These experts state that dialysis patients who remain hyperphosphatemic despite such therapy should receive a calcium-containing phosphate binder in combination with a non-calcium-, non-aluminum-, non-magnesium-containing phosphate binder. The manufacturer recommends that serum calcium concentrations be monitored twice weekly during initiation of calcium acetate therapy and subsequent dosage adjustment; serum phosphorus concentrations also should be monitored periodically.
If hypercalcemia occurs, dosage should be reduced or the salt should be withheld. If severe hypercalcemia occurs, specific measures (e.g., hemodialysis) for the management of overdosage may be necessary. Patients should be advised of the importance of dosage compliance, adherence to instructions about diet, and avoidance of concomitant use of antacids or other preparations containing clinically important concentrations of calcium.
Patients also should be advised of potential manifestations of hypercalcemia.
For the treatment of hyperkalemia with secondary cardiac toxicity, 2.25-14 mEq of calcium may be administered IV while monitoring the ECG. Doses may be repeated after 1-2 minutes if necessary.
Magnesium intoxication in adults is treated initially with 7 mEq of IV calcium; subsequent doses should be adjusted according to patient response. Alternatively, for the treatment of hypermagnesemia in adults, an IV calcium dose of 6.8-13.6
mEq using 10% calcium chloride (5-10 mL) has been administered, and repeated as necessary.
For the treatment of drug-induced cardiovascular emergencies associated with calcium-channel blocking agent toxicity in pediatric patients, an IV calcium dose of 0.272 mEq/kg using 10% calcium chloride (0.2 mL/kg) has been administered over 5-10 minutes; if a beneficial effect was observed, an IV calcium infusion of 0.27-0.68
mEq/kg per hour using calcium chloride has been administered. Ionized calcium concentrations should be monitored to prevent hypercalcemia.
Calcium is also administered IV during exchange transfusions in neonates in a dosage of 0.45 mEq of calcium after every 100 mL of citrated blood exchanged. In adults receiving transfusions of citrated blood, about 1.35
mEq of calcium should be administered IV concurrently with each 100 mL of citrated blood.
In the calcium infusion test+, calcium is given IV in a dosage of 0.25 mEq/kg per hour for a 3-hour period; serum gastrin concentrations are determined 30 minutes before the infusion, at the start of the infusion, and at 30-minute intervals thereafter for 4 hours. In most patients with Zollinger-Ellison syndrome, preinfusion serum gastrin concentrations increase by more than 50% or by greater than 500 pg/mL during the infusion.
In the diagnosis of medullary thyroid carcinoma+, about 7 mEq of calcium is given IV over 5-10 minutes. In patients with medullary thyroid carcinoma, plasma calcitonin concentrations are elevated above normal basal concentrations.
Dosage of oral iron preparations should be expressed in terms of elemental iron. The elemental iron content of the various preparations is approximately:
Table 1.
Drug Elemental Iron ferric pyrophosphate 120 mg/g ferrous gluconate 120 mg/g ferrous sulfate 200 mg/g ferrous sulfate, dried 300 mg/g ferrous fumarate 330 mg/g ferrous carbonate, anhydrous 480 mg/g carbonyl iron 1000 mg/g
carbonyl iron is elemental iron, not an iron salt.
Vitamins are usually administered orally; however, the drugs may be given parenterally in patients in whom oral administration is not feasible, including those receiving total parenteral nutrition. For IV administration, vitamins should be diluted according to the manufacturers' recommendations. Multivitamin injections are reportedly incompatible with IV solutions containing various drugs.
Published data are too varied and/or limited to permit generalizations, and specialized references should be consulted for specific compatibility information. Folic acid is usually administered orally. When oral administration is not feasible or when malabsorption is suspected, the drug may be administered by deep IM, subcutaneous, or IV injection.
However, most patients with malabsorption are able to absorb oral folic acid. Ascorbic acid is usually administered orally. When oral administration is The acetate, carbonate, citrate, gluconate, lactate, and phosphate salts of calcium are administered orally.
It has been recommended that most oral not feasible or when malabsorption is suspected, the drug may be administered IM, IV, or subcutaneously. When given parenterally, calcium supplements be administered 1-1.5 hours after meals or with a demulcent (e.g., milk).
However, calcium carbonate powder (i.e., CAL utilization of the vitamin reportedly is best after IM administration and CARB-HD(R)) should generally be administered with meals, since the that is the preferred parenteral route. manufacturer recommends mixing the powder with food for administration. Calcium salts used to bind dietary phosphate in patients with end-stage renal disease should be administered with meals (e.g., 10-15 minutes before, or during, the meal).
Calcium chloride and calcium gluconate may be administered IV. Calcium chloride also may be administered by intraosseous (IO) injection+ in the setting of pediatric resuscitation; onset of action and systemic concentrations are comparable to those achieved with venous administration. Parenteral calcium salts may be administered in large volume IV infusion fluids.
IV calcium injections must be administered slowly at a rate not exceeding 0.7-1.8 mEq/minute, and the injection should be stopped if the patient complains of discomfort.
Following IV injection, the patient should remain recumbent for a short time. Close monitoring of serum calcium concentrations is essential during IV administration of calcium. Calcium chloride should not be injected IM or into subcutaneous or perivascular tissue, since severe necrosis and sloughing may occur.
Although other calcium salts may cause mild to severe local reactions, they are generally less irritating than calcium chloride. (See Cautions.) The fixed combination of calcium glycerophosphate and calcium lactate is injected IM. Although some manufacturers previously stated that calcium gluconate could be injected IM when IV administration was not possible, manufacturers of calcium gluconate currently state that the drug should not be injected IM or into subcutaneous tissue because of the potential for severe local reactions.
In children, calcium salts should not be administered through scalp veins. Oral administration of calcium supplements or calcium-rich foods should replace parenteral calcium therapy as soon as possible. The interaction of calcium and phosphate in parenteral nutrition solutions is a complex phenomenon; various factors have been identified as playing a role in the solubility or precipitation of a given combination.
Calcium salts are conditionally compatible with phosphate in parenteral nutrition solutions; incompatibility is dependent on a solubility and concentration phenomenon and is not entirely predictable. Precipitation may occur during compounding or at some time after compounding is completed. Specialized references should be consulted for specific compatibility information.
Oral iron preparations generally should be taken between meals (e.g., 1 hour before or 2 hours after a meal) for maximum absorption but may be taken with or after meals, if necessary, to minimize adverse GI effects. Patients who have difficulty tolerating oral iron supplements also may benefit from smaller, more frequent doses, starting with a lower dose and increasing slowly to the target dose, trying a different form or preparation, or taking the supplement at bedtime.
Published data are too varied and/or limited to permit generalizations, and specialized references should be consulted for specific compatibility information. Folic acid is usually administered orally. When oral administration is not feasible or when malabsorption is suspected, the drug may be administered by deep IM, subcutaneous, or IV injection.
However, most patients with malabsorption are able to absorb oral folic acid. Ascorbic acid is usually administered orally. When oral administration is The acetate, carbonate, citrate, gluconate, lactate, and phosphate salts of calcium are administered orally.
It has been recommended that most oral not feasible or when malabsorption is suspected, the drug may be administered IM, IV, or subcutaneously. When given parenterally, calcium supplements be administered 1-1.5 hours after meals or with a demulcent (e.g., milk).
However, calcium carbonate powder (i.e., CAL utilization of the vitamin reportedly is best after IM administration and CARB-HD(R)) should generally be administered with meals, since the that is the preferred parenteral route. manufacturer recommends mixing the powder with food for administration. Calcium salts used to bind dietary phosphate in patients with end-stage renal disease should be administered with meals (e.g., 10-15 minutes before, or during, the meal).
Calcium chloride and calcium gluconate may be administered IV. Calcium chloride also may be administered by intraosseous (IO) injection+ in the setting of pediatric resuscitation; onset of action and systemic concentrations are comparable to those achieved with venous administration. Parenteral calcium salts may be administered in large volume IV infusion fluids.
IV calcium injections must be administered slowly at a rate not exceeding 0.7-1.8 mEq/minute, and the injection should be stopped if the patient complains of discomfort.
Following IV injection, the patient should remain recumbent for a short time. Close monitoring of serum calcium concentrations is essential during IV administration of calcium. Calcium chloride should not be injected IM or into subcutaneous or perivascular tissue, since severe necrosis and sloughing may occur.
Although other calcium salts may cause mild to severe local reactions, they are generally less irritating than calcium chloride. (See Cautions.) The fixed combination of calcium glycerophosphate and calcium lactate is injected IM. Although some manufacturers previously stated that calcium gluconate could be injected IM when IV administration was not possible, manufacturers of calcium gluconate currently state that the drug should not be injected IM or into subcutaneous tissue because of the potential for severe local reactions.
In children, calcium salts should not be administered through scalp veins. Oral administration of calcium supplements or calcium-rich foods should replace parenteral calcium therapy as soon as possible. The interaction of calcium and phosphate in parenteral nutrition solutions is a complex phenomenon; various factors have been identified as playing a role in the solubility or precipitation of a given combination.
Calcium salts are conditionally compatible with phosphate in parenteral nutrition solutions; incompatibility is dependent on a solubility and concentration phenomenon and is not entirely predictable. Precipitation may occur during compounding or at some time after compounding is completed. Specialized references should be consulted for specific compatibility information.
Oral iron preparations generally should be taken between meals (e.g., 1 hour before or 2 hours after a meal) for maximum absorption but may be taken with or after meals, if necessary, to minimize adverse GI effects. Patients who have difficulty tolerating oral iron supplements also may benefit from smaller, more frequent doses, starting with a lower dose and increasing slowly to the target dose, trying a different form or preparation, or taking the supplement at bedtime.
| DRUG LABEL | DOSING TYPE | DOSING INSTRUCTIONS |
|---|---|---|
| PROTECT IRON TABLET | Maintenance | Adults take 1 tablet by oral route once daily |
No generic dosing information available.
The following drug interaction information is available for PROTECT IRON (multivitamins with min no.24/iron polysaccharides complex/fa):
There are 2 contraindications.
These drug combinations generally should not be dispensed or administered to the same patient. A manufacturer label warning that indicates the contraindication warrants inclusion of a drug combination in this category, regardless of clinical evidence or lack of clinical evidence to support the contraindication.
| Drug Interaction | Drug Names |
|---|---|
| Lemborexant (Greater Than 5 mg)/Weak CYP3A4 Inhibitors SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Inhibitors of CYP3A4 may inhibit the metabolism of lemborexant.(1) CLINICAL EFFECTS: Concurrent use of an inhibitor of CYP3A4 may result in increased levels of and effects from lemborexant, including somnolence, fatigue, CNS depressant effects, daytime impairment, headache, and nightmare or abnormal dreams.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The maximum recommended dose of lemborexant with concurrent use of a weak CYP3A4 inhibitors should not exceed 5 mg per dose.(1) DISCUSSION: Lemborexant is a CYP3A4 substrate. In a PKPB model, concurrent use of lemborexant with itraconazole increased area-under-curve (AUC) and concentration maximum (Cmax) by 3.75-fold and 1.5-fold, respectively. Concurrent use of lemborexant with fluconazole increased AUC and Cmax by 4.25-fold and 1.75-fold, respectively.(1) Weak inhibitors of CYP3A4 include: alprazolam, amiodarone, amlodipine, asciminib, azithromycin, Baikal skullcap, belumosudil, berberine, bicalutamide, blueberry, brodalumab, cannabidiol, capivasertib, chlorzoxazone, cilostazol, cimetidine, ciprofloxacin, clotrimazole, cranberry, cyclosporine, daclatasvir, daridorexant, delavirdine, dihydroberberine, diosmin, everolimus, flibanserin, fosaprepitant, fostamatinib, gepotidacin, ginkgo, givinostat, glecaprevir/pibrentasvir, goldenseal, grazoprevir, isoniazid, istradefylline, ivacaftor, lacidipine, lapatinib, larotrectinib, lazertinib, leflunomide, levamlodipine, linagliptin, lomitapide, lurasidone, mavorixafor, olaparib, osilodrostat, palbociclib, pazopanib, peppermint oil, piperine, propiverine, propofol, ranitidine, ranolazine, remdesivir, resveratrol, roxithromycin, rucaparib, selpercatinib, simeprevir, sitaxsentan, skullcap, suvorexant, teriflunomide, ticagrelor, tolvaptan, trofinetide, viloxazine, and vonoprazan.(1,2) |
DAYVIGO |
| Fezolinetant/CYP1A2 Inhibitors SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Inhibitors of CYP1A2 may inhibit the metabolism of fezolinetant.(1) CLINICAL EFFECTS: Concurrent use of a CYP1A2 inhibitor may increase levels of and adverse effects from fezolinetant.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of fezolinetant states that concurrent use with CYP1A2 inhibitors is contraindicated.(1) DISCUSSION: In a study, fluvoxamine, a strong CYP1A2 inhibitor, increased fezolinetant maximum concentration (Cmax) and area-under-curve (AUC) by 80% and 840%, respectively. Mexiletine (400 mg every 8 hours), a moderate CYP1A2 inhibitor, increased fezolinetant Cmax and AUC by 40% and 360%, respectively. Cimetidine (300 mg every 6 hours), a weak CYP1A2 inhibitor, increased fezolinetant Cmax and AUC by 30% and 100%, respectively.(1) Strong CYP1A2 inhibitors linked to this monograph include angelica root, ciprofloxacin, enasidenib, enoxacin, fluvoxamine, and rofecoxib. Moderate CYP1A2 inhibitors linked to this monograph include capmatinib, dipyrone, fexinidazole, genistein, hormonal contraceptives, methoxsalen, mexiletine, osilodrostat, phenylpropanolamine, pipemidic acid, rucaparib, troleandomycin, vemurafenib, and viloxazine. Weak CYP1A2 inhibitors linked to this monograph include allopurinol, artemisinin, caffeine, cannabidiol, cimetidine, curcumin, dan-shen, deferasirox, disulfiram, Echinacea, famotidine, ginseng, norfloxacin, obeticholic acid, parsley, piperine, propafenone, propranolol, ribociclib, simeprevir, thiabendazole, ticlopidine, triclabendazole, verapamil, zileuton.(2-4) |
VEOZAH |
There are 11 severe interactions.
These drug interactions can produce serious consequences in most patients. Actions required for severe interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration scheduling, and providing additional patient monitoring. Review the full interaction monograph for more information.
| Drug Interaction | Drug Names |
|---|---|
| Levodopa/Iron Salts, Oral SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Iron salts appear to decrease the absorption of levodopa by chelate formation. CLINICAL EFFECTS: The therapeutic effect of levodopa may be decreased. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Separate the administration times of levodopa and iron by as much as possible. Observe the patient for a decrease in clinical response and adjust the dose of levodopa as necessary. DISCUSSION: Ferrous sulfate administration produced decreases in the serum concentration of levodopa and area-under-curve (AUC). Patients receiving levodopa plus carbidopa also experienced a reduction in the serum concentration and AUC for carbidopa during concurrent administration of ferrous sulfate. In addition, a loss in therapeutic response was demonstrated. |
CARBIDOPA-LEVODOPA, CARBIDOPA-LEVODOPA ER, CREXONT, DHIVY, DUOPA, INBRIJA, LEVODOPA, RYTARY, SINEMET |
| Oral Phosphate Supplements; Urinary pH Modifiers/Aluminum; Calcium; Magnesium SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Medications containing significant amounts of aluminum, calcium, or magnesium may bind to the phosphate and prevent its absorption.(1) CLINICAL EFFECTS: Concurrent use of medications containing significant amounts of aluminum, calcium, or magnesium may result in decreased effectiveness of phosphate supplements and urinary pH modifiers high in phosphate.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Patients receiving phosphate supplements or urinary pH modifiers high in phosphate should be instructed to avoid medications containing aluminum, calcium, or magnesium.(1) Some phosphate laxative products used as phosphate supplements may contain sufficient quantities of phosphate to interact as well. DISCUSSION: The manufacturer of K-Phos states that products containing aluminum, calcium, or magnesium may bind to the phosphate and prevent its absorption. Therefore, patients receiving phosphate supplements and urinary pH modifiers high in phosphate should be instructed to avoid products containing aluminum, calcium, or magnesium.(1) |
K-PHOS NO.2, K-PHOS ORIGINAL, POTASSIUM PHOSPHATE, SODIUM PHOSPHATE DIBASIC, UROQID-ACID NO.2 |
| Citalopram (Greater Than 20 mg)/Select CYP2C19 Inhibitors SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Citalopram is primarily metabolized by the CYP2C19 isoenzyme.(1) CLINICAL EFFECTS: Concurrent use of an agent that inhibits CYP2C19 may result in elevated levels of and toxicity from citalopram, including including risks for serotonin syndrome or prolongation of the QTc interval.(1-5) Prolongation of the QT interval may result in life-threatening arrhythmias, including torsades de pointes.(2) Symptoms of serotonin syndrome may include tremor, agitation, diaphoresis, hyperreflexia, clonus, tachycardia, hyperthermia, and muscle rigidity.(5) PREDISPOSING FACTORS: The risk of QT prolongation or torsades de pointes may be increased in patients with cardiovascular disease (e.g. heart failure, myocardial infarction, history of torsades de pointes, congenital long QT syndrome), hypokalemia, hypomagnesemia, hypocalcemia, bradycardia, female gender, advanced age, poor metabolizer status at CYP2C19, or higher blood concentrations of citalopram.(2) Concurrent use of more than one drug known to cause QT prolongation or higher systemic concentrations of either QT prolonging drug are additional risk factors for torsades de pointes. Factors which may increase systemic drug concentrations include rapid infusion of an intravenous dose or impaired metabolism or elimination of the drug (e.g. coadministration with an agent which inhibits its metabolism or elimination, genetic impairment in drug metabolism or elimination, and/or renal/hepatic dysfunction).(2) Predisposing factors for serotonin-related adverse effects include use in the elderly, in patients with hepatic impairment, and in patients receiving multiple agents which increase central serotonin levels.(1,5) If concurrent therapy is warranted, consider obtaining serum calcium, magnesium, and potassium levels and monitoring ECG at baseline and at regular intervals. Correct any electrolyte abnormalities. Instruct patients to report any irregular heartbeat, dizziness, or fainting. PATIENT MANAGEMENT: The dose of citalopram should be limited to 20 mg in patients receiving concurrent therapy with an inhibitor of CYP2C19.(1,4) Evaluate the patient for other drugs, diseases and conditions which increase risk for QT prolongation and correct risk factors (e.g. correct hypokalemia, discontinue other QT prolonging drugs) when possible.(1,2) Weigh the specific benefits versus risks for each patient. The US manufacturer recommends ECG monitoring for citalopram patients with congestive heart failure, bradyarrhythmias, taking concomitant QT prolonging medications or receiving concurrent therapy.(4) Citalopram should be discontinued in patients with persistent QTc measurements greater than 500 ms.(2) If concurrent therapy is warranted, consider obtaining serum calcium, magnesium, and potassium levels and monitoring ECG at baseline and at regular intervals. Correct any electrolyte abnormalities. Instruct patients to report any irregular heartbeat, dizziness, or fainting. If concurrent therapy is warranted, patients should be monitored for signs and symptoms of serotonin syndrome. Instruct patients to report muscle twitching, tremors, shivering and stiffness, fever, heavy sweating, heart palpitations, restlessness, confusion, agitation, trouble with coordination, or severe diarrhea. DISCUSSION: Concurrent use of citalopram (40 mg daily) and cimetidine (400 mg twice daily) for 8 days increased the maximum concentration (Cmax) and area-under-curve (AUC) of citalopram by 39% and 43%, respectively.(1) Inhibitors of CYP2C19 include: abrocitinib, allicin (garlic derivative), berotralstat, cannabidiol (CBD), cenobamate, cimetidine strengths > or = 200 mg, enasidenib, eslicarbazepine, esomeprazole, etravirine, fedratinib, felbamate, fluoxetine, fluvoxamine, givosiran, isoniazid, moclobemide, modafinil, obeticholic acid, omeprazole, piperine, rolapitant, stiripentol, and tecovirimat.(7,8) |
CELEXA, CITALOPRAM HBR |
| Clopidogrel/Selected CYP2C19 Inhibitors SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Clopidogrel is a prodrug and is converted to its active metabolite via a 2 step process. The first conversion step is mediated by CYP2C19, CYP1A2 and CYP2B6, while the second step is mediated by CYP3A4, CYP2B6 and CYP2C19.(1,2) CYP2C19 contributes to both steps and is thought to be the more important enzyme involved in formation of the pharmacologically active metabolite.(1) Inhibitors of CYP2C19 may decrease the conversion of clopidogrel to its active metabolite.(1) CLINICAL EFFECTS: Concurrent use of CYP2C19 inhibitors may result in decreased clopidogrel effectiveness, resulting in increased risk of adverse cardiac events. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Evaluate medication list or interaction alerts to determine if patient is receiving additional drugs which may also inhibit clopidogrel active metabolite formation. The US manufacturer of clopidogrel states that alternatives to clopidogrel should be considered in patients who are poor metabolizers of CYP2C19.(1) It would be prudent to assume that patients taking strong inhibitors of CYP2C19 are poor metabolizers of this isoenzyme. Moderate or weak inhibitors of CYP2C19 may have less of an effect on this interaction. Consider alternatives to CYP2C19 inhibitors in patients stabilized on clopidogrel and alternatives to clopidogrel in patients stabilized on CYP2C19 inhibitors. If concurrent therapy is warranted, consider appropriate testing to assure adequate inhibition of platelet reactivity. DISCUSSION: Clopidogrel is a prodrug and requires conversion to the active metabolite by CYP2C19. Clopidogrel is not a sensitive substrate for CYP2C19 as CYP3A4, CYP2B6 and CYP1A2 also participate in active metabolite formation. Studies have not evaluated this specific drug combination; the actual magnitude of this interaction is not known. Given the possible consequences of clopidogrel treatment failure, it would be prudent to avoid concomitant use of clopidogrel and CYP2C19 inhibitors when possible. Selected CYP2C19 inhibitors include: armodafinil, asciminib, berotralstat, cenobamate, elagolix, enasidenib, eslicarbazepine, fedratinib, fexinidazole, givosiran, lonafarnib, moclobemide, modafinil, obeticholic acid, osilodrostat, piperine, pirtobrutinib, rolapitant, rucaparib, tecovirimat, treosulfan, and triclabendazole.(4,5) |
CLOPIDOGREL, CLOPIDOGREL BISULFATE, PLAVIX |
| Lomitapide (Less Than or Equal To 30 mg)/Weak CYP3A4 Inhibitors SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Weak inhibitors of CYP3A4 may inhibit the metabolism of lomitapide.(1) Lomitapide is very susceptible to CYP3A4 inhibition. For example, in an interaction study with a strong CYP3A4 inhibitor (ketoconazole) lomitapide exposure was increased 27-fold.(2) Thus even weak CYP3A4 inhibitors may affect lomitapide exposure (AUC, area-under-curve). CLINICAL EFFECTS: Concurrent use of a weak inhibitor of CYP3A4 may result in 2-fold increases in lomitapide levels and toxicity from lomitapide.(1) PREDISPOSING FACTORS: This interaction may be more severe in patients with hepatic impairment or with end-stage renal disease.(1) PATIENT MANAGEMENT: The maximum lomitapide dose should be 30 mg daily for patients taking concomitant weak CYP3A4 inhibitors. Due to lomitapide's long half-life, it may take 1 to 2 weeks to see the full effect of this interaction. When initiating a weak CYP3A4 inhibitor in patients taking lomitapide 10 mg daily or more, decrease the dose of lomitapide by 50%. In patients taking lomitapide 5 mg daily, continue current dose. DISCUSSION: Lomitapide is very susceptible to CYP3A4 inhibition. For example, in an interaction study with a strong CYP3A4 inhibitor (ketoconazole) lomitapide exposure was increased 27-fold.(2) Based upon interactions with stronger inhibitors, weak inhibitors of CYP3A4 are predicted to increase lomitapide area-under-curve(AUC) 2-fold.(1) Weak CYP3A4 inhibitors linked to this interaction include alprazolam, amiodarone, amlodipine, asciminib, atorvastatin, azithromycin, Baikal skullcap, belumosudil, bicalutamide, blueberry juice, brodalumab, cannabidiol, capivasertib, cilostazol, cimetidine, ciprofloxacin, chlorzoxazone, clotrimazole, cranberry juice, cyclosporine, daridorexant, delavirdine, diosmin, everolimus, flibanserin, fosaprepitant, fostamatinib, gepotidacin, ginkgo, givinostat, glecaprevir/pibrentasvir, goldenseal, grazoprevir, isoniazid, istradefylline, ivacaftor, larotrectinib, lacidipine, lapatinib, lazertinib, leflunomide, levamlodipine, linagliptin, lurasidone, maribavir, mavorixafor, olaparib, osilodrostat, palbociclib, pazopanib, peppermint oil, piperine, propiverine, propofol, ranitidine, ranolazine, remdesivir, resveratrol, roxithromycin, rucaparib, selpercatinib, sitaxsentan, skullcap, teriflunomide, ticagrelor, tolvaptan, trofinetide, viloxazine, vonoprazan, and zileuton.(1-3) |
JUXTAPID |
| Bortezomib/Ascorbic Acid (Vitamin C) SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Vitamin C can form a complex with the boronic acid moiety of the bortezomib molecule, preventing its absorption into cells.(1-4) This may protect normal tissue in the body, which may have higher levels of Vitamin C.(5) CLINICAL EFFECTS: Concurrent administration of Vitamin C may result in decreased bortezomib activity.(1-4) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Instruct patients receiving bortezomib therapy not to begin taking vitamin C supplements without consulting their oncologist first. Patients who are instructed to take vitamin C should follow their oncologist's instructions on how to separate dosages and should be carefully monitored for bortezomib efficacy. DISCUSSION: An in vitro study with human plasma and multiple myeloma cells found that high levels of vitamin C (following 1 gram/day of ascorbic acid for 4 days) decreased bortezomib effectiveness by 26%. An in vivo study in mice found that vitamin C administration with bortezomib completely blocked the response of bortezomib.(6) An in vitro study in rat Schwann cells and myeloma cells(4) and an in vivo study in mice(7) found that delayed administration of vitamin C had no effect on bortezomib effects. In an in vivo study in multiple myeloma patients, concurrent ascorbic acid, arsenic trioxide, bortezomib, and high-dose melphalan in which ascorbic acid was administered close to bortezomib, the combination was safe and well tolerated, but produced no changes in response rates.(8) In another in vivo study in multiple myeloma patients, a regimen of ascorbic acid, bortezomib, and melphalan in which bortezomib was administered in the morning and ascorbic acid in the evening was found to be safe and efficacious, with 74% of patients responding to therapy.(9) |
BORTEZOMIB, BORUZU, VELCADE |
| Bosentan/Strong and Moderate CYP2C9 Inhibitors SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Bosentan is metabolized by CYP2C9 and CYP3A4. It is also an inducer of these enzymes. With regular dosing bosentan auto-induces its own metabolism.(1) Strong and moderate CYP2C9 inhibitors may inhibit the CYP2C9 mediated metabolism of bosentan.(2) CLINICAL EFFECTS: Concurrent use of bosentan with an inhibitor of CYP2C9 may result in elevated levels of and toxicity from bosentan.(3) PREDISPOSING FACTORS: Concurrent use of bosentan, a CYP2C9 inhibitor and a CYP3A4 inhibitor (e.g. aprepitant, boceprevir, ceritinib, ciprofloxacin, clarithromycin, conivaptan, crizotinib, cyclosporine, darunavir, diltiazem, dronedarone, erythromycin, fluconazole, fosaprepitant, idelalisib, imatinib, isavuconazole, itraconazole, ketoconazole, letermovir, mibefradil, nefazodone, netupitant, nilotinib, posaconazole, ribociclib, telaprevir, telithromycin, troleandomycin, verapamil, and voriconazole)(3) could lead to blockade of both major metabolic pathways for bosentan, resulting in large increases in bosentan plasma concentrations.(3) PATIENT MANAGEMENT: Review medication list to see if patient is also receiving a CYP3A4 inhibitor (e.g. aprepitant, boceprevir, ceritinib, ciprofloxacin, clarithromycin, conivaptan, crizotinib, cyclosporine, darunavir, diltiazem, dronedarone, erythromycin, fluconazole, fosaprepitant, idelalisib, imatinib, isavuconazole, itraconazole, ketoconazole, letermovir, mibefradil, nefazodone, netupitant, nilotinib, posaconazole, ribociclib, telaprevir, telithromycin, troleandomycin, verapamil, and voriconazole). Concomitant use of both a CYP2C9 and CYP3A4 inhibitor is not recommended by the manufacturer as the combination may lead to large increases in bosentan plasma concentrations.(1) For patients stabilized on bosentan when a CYP2C9 inhibitor is initiated, monitor tolerance to concomitant therapy and adjust bosentan dose if needed. DISCUSSION: Concurrent use with CYP2C9 inhibitors has not been studied. In a study in healthy subjects, concurrent bosentan and ketoconazole, a strong CYP3A4 inhibitor, administration increased bosentan steady-state maximum concentrations (Cmax) and area-under-curve (AUC) by 2.1-fold and 2.3-fold, respectively.(2) Strong CYP2C9 inhibitors linked to this monograph include: miconazole.(3) Moderate CYP2C9 inhibitors linked to this monograph include: amiodarone, apazone, asciminib, benzbromarone, cannabidiol, nitisinone, oxandrolone, piperine, sulfaphenazole, and phenylbutazone.(3) |
BOSENTAN, TRACLEER |
| Eliglustat/Weak CYP3A4 Inhibitors SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Weak inhibitors of CYP3A4 may inhibit the metabolism of eliglustat. If the patient is also taking an inhibitor of CYP2D6, eliglustat metabolism can be further inhibited.(1) CLINICAL EFFECTS: Concurrent use of an agent that is a weak inhibitor of CYP3A4 may result in elevated levels of and clinical effects of eliglustat, including prolongation of the PR, QTc, and/or QRS intervals, which may result in life-threatening cardiac arrhythmias.(1) PREDISPOSING FACTORS: If the patient is also taking an inhibitor of CYP2D6, is a poor metabolizer of CYP2D6, and/or has hepatic impairment, eliglustat metabolism can be further inhibited.(1) The risk of QT prolongation or torsades de pointes may be increased in patients with cardiovascular disease (e.g. heart failure, myocardial infarction, history of torsades de pointes, congenital long QT syndrome), hypokalemia, hypomagnesemia, hypocalcemia, bradycardia, female gender, or advanced age.(2) Concurrent use of more than one drug known to cause QT prolongation or higher systemic concentrations of either QT prolonging drug are additional risk factors for torsades de pointes. Factors which may increase systemic drug concentrations include rapid infusion of an intravenous dose or impaired metabolism or elimination of the drug (e.g. coadministration with an agent which inhibits its metabolism or elimination, genetic impairment in drug metabolism or elimination, and/or renal/hepatic dysfunction).(2) PATIENT MANAGEMENT: The concurrent use of eliglustat with weak inhibitors of CYP3A4 in poor metabolizers of CYP2D6 should be avoided.(1) The dosage of eliglustat with weak inhibitors of CYP3A4 in extensive metabolizers of CYP2D6 with mild (Child-Pugh Class A) hepatic impairment should be limited to 84 mg daily.(1) If concurrent therapy is warranted, consider obtaining serum calcium, magnesium, and potassium levels and monitoring ECG at baseline and at regular intervals. Correct any electrolyte abnormalities. Instruct patients to report any irregular heartbeat, dizziness, or fainting. DISCUSSION: Ketoconazole (400 mg daily), a strong inhibitor of CYP3A4, increased eliglustat (84 mg BID) maximum concentration (Cmax) and area-under-curve (AUC) by 4-fold and 4.4-fold, respectively, in extensive metabolizers. Physiologically-based pharmacokinetic (PKPB) models suggested ketoconazole would increase eliglustat Cmax and AUC by 4.4-fold and 5.4-fold, respectively, in intermediate metabolizers. PKPB models suggested ketoconazole may increase the Cmax and AUC of eliglustat (84 mg daily) by 4.3-fold and 6.2-fold, respectively, in poor metabolizers.(1) PKPB models suggested fluconazole, a moderate inhibitor of CYP3A4, would increase eliglustat Cmax and AUC by 2.8-fold and 3.2-fold, respectively, in extensive metabolizers and by 2.5-fold and 2.9-fold, respectively in intermediate metabolizers. PKPB models suggest that concurrent eliglustat (84 mg BID), paroxetine (a strong inhibitor of CYP2D6), and ketoconazole would increase eliglustat Cmax and AUC by 16.7-fold and 24.2-fold, respectively, in extensive metabolizers. In intermediate metabolizers, eliglustat Cmax and AUC would be expected to increase 7.5-fold and 9.8-fold, respectively.(1) PKPB models suggest that concurrent eliglustat (84 mg BID), terbinafine (a moderate inhibitor of CYP2D6), and ketoconazole would increase eliglustat Cmax and AUC by 10.2-fold and 13.6-fold, respectively, in extensive metabolizers. In intermediate metabolizers, eliglustat Cmax and AUC would be expected to increase 4.2-fold and 5-fold, respectively.(1) Weak inhibitors of CYP3A4 include: alprazolam, amlodipine, asciminib, azithromycin, Baikal skullcap, belumosudil, berberine, bicalutamide, blueberry, brodalumab, cannabidiol, chlorzoxazone, cilostazol, cimetidine, ciprofloxacin, clotrimazole, cranberry, cyclosporine, daclatasvir, daridorexant, delavirdine, dihydroberberine, diosmin, everolimus, flibanserin, fosaprepitant, fostamatinib, gepotidacin, ginkgo, givinostat, glecaprevir/pibrentasvir, goldenseal, grazoprevir, isoniazid, istradefylline, ivacaftor, lacidipine, lapatinib, larotrectinib, lazertinib, leflunomide, levamlodipine, linagliptin, lomitapide, lurasidone, olaparib, osilodrostat, palbociclib, pazopanib, peppermint oil, piperine, propiverine, propofol, ranolazine, remdesivir, resveratrol, roxithromycin, rucaparib, selpercatinib, simeprevir, sitaxsentan, skullcap, suvorexant, teriflunomide, ticagrelor, tolvaptan, trofinetide, and vonoprazan.(3,4) |
CERDELGA |
| Siponimod/Selected Moderate CYP2C9 Inhibitors SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Inhibitors of CYP2C9 may inhibit the metabolism of siponimod.(1) CLINICAL EFFECTS: Concurrent use of an inhibitor of CYP2C9 may result in elevated levels of and clinical effects of siponimod, including immunosuppression and increased risk of infection.(1) Concurrent use of siponimod with immunosuppressive or immune-modulating agents, such as asciminib, may result in an additive risk and increased risk of serious infections. PREDISPOSING FACTORS: Concurrent use of a strong or moderate inhibitor of CYP3A4 may increase the effects of the interaction. PATIENT MANAGEMENT: Concurrent use of an inhibitor of CYP2C9 with siponimod is not recommended in patients also taking a strong or moderate inhibitor of CYP3A4.(1) Review the patient's therapy for concurrent use of strong or moderate inhibitors of CYP3A4 prior to initiating siponimod. DISCUSSION: Siponimod is metabolized by CYP2C9 (79.3%) and CYP3A4 (18.5%). Concurrent use of fluconazole (a dual moderate inhibitor of CYP2C9 and CYP3A4, 200 mg at steady state) in healthy subjects with the CYP2C9*1/*1 genotype increased the area-under-curve (AUC) of siponimod (4 mg single dose) by 2-fold. Siponimod half-life increased by 50%. Fluconazole increased siponimod AUC by 2-fold to 4-fold across all CYP2C9 genotypes.(1) Selected moderate CYP2C9 inhibitors linked to this monograph include: apazone, asciminib, benzbromarone, cannabidiol, felbamate, miconazole, milk thistle, nitisinone, oxandrolone, phenylbutazone, piperine, silibinin, and sulfaphenazole.(2) |
MAYZENT |
| Tizanidine/Selected Moderate and Weak CYP1A2 Inhibitors SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Moderate and weak CYP1A2 inhibitors may inhibit the metabolism of tizanidine by CYP1A2.(1) CLINICAL EFFECTS: Concurrent use of moderate and weak CYP1A2 inhibitors may result in elevated levels of and effects from tizanidine, including hypotension, bradycardia, drowsiness, sedation, and decreased psychomotor function. PREDISPOSING FACTORS: The risk of anticholinergic toxicities including cognitive decline, delirium, falls and fractures is increased in geriatric patients using more than one medicine with anticholinergic properties.(2) PATIENT MANAGEMENT: The US manufacturer of tizanidine states that concurrent use of tizanidine with inhibitors of CYP1A2 should be avoided. If concurrent use is warranted, tizanidine should be initiated with 2 mg dose and increased in 2-4 mg steps daily based on patient response to therapy.(3) If adverse reactions such as hypotension, bradycardia or excessive drowsiness occur, reduce or discontinue tizanidine therapy.(3) DISCUSSION: In a study, cannabidiol 750 mg twice daily (a weak CYP1A2 inhibitor) increased the maximum concentration (Cmax) and area-under-curve (AUC) of a 200 mg single dose of caffeine (a sensitive CYP1A2 substrate) by 15% and 95%, respectively.(1) In a study in 10 healthy subjects, concurrent fluvoxamine, a strong inhibitor of CYP1A2, increased tizanidine Cmax, AUC, and half-life (T1/2) by 12-fold, 33-fold, and 3-fold, respectively. Significant decreases in blood pressure and increases in drowsiness and psychomotor impairment occurred.(3) In a study in 10 healthy subjects, concurrent ciprofloxacin, a strong inhibitor of CYP1A2, increased tizanidine Cmax and AUC by 7-fold and 10-fold, respectively. Significant decreases in blood pressure and increases in drowsiness and psychomotor impairment occurred.(3) Moderate CYP1A2 inhibitors linked to this monograph include: dipyrone, fexinidazole, genistein, methoxsalen, phenylpropanolamine, pipemidic acid, propranolol, rucaparib, and troleandomycin. Weak CYP1A2 inhibitors linked to this monograph include: allopurinol, artemisinin, caffeine, cannabidiol, curcumin, dan-shen, disulfiram, Echinacea, ginseng, parsley, piperine, ribociclib, simeprevir, thiabendazole, and triclabendazole.(4) |
TIZANIDINE HCL, ZANAFLEX |
| Mavacamten/Weak CYP2C19 Inhibitors SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Weak CYP2C19 inhibitors may inhibit the metabolism of mavacamten.(1-3) CLINICAL EFFECTS: Concurrent use of weak CYP2C19 inhibitors increases plasma exposure of mavacamten which may increase the incidence and severity of adverse reactions of mavacamten.(1-3) PREDISPOSING FACTORS: CYP2C19 rapid and ultrarapid metabolizers may experience an increased incidence or severity of adverse effects.(1-3) PATIENT MANAGEMENT: The US manufacturer of mavacamten recommends to initiate mavacamten at the recommended starting dosage of 5 mg orally once daily in patients who are on stable therapy with a weak CYP2C19 inhibitor. Reduce dose by one level (i.e., 15 to 10 mg, 10 to 5 mg, or 5 to 2.5 mg) in patients who are on mavacamten treatment and intend to initiate a weak CYP2C19 inhibitor. Schedule clinical and an echocardiographic assessment 4 weeks after inhibitor initiation, and do not up-titrate mavacamten until 12 weeks after inhibitor initiation.(1) Avoid initiation of concomitant weak CYP2C19 inhibitors in patients who are on stable treatment with 2.5 mg of mavacamten because a lower dose is not available.(1) For short-term use (e.g. 1 week), interrupt mavacamten therapy for the duration of the weak CYP2C19 inhibitor. After therapy with the weak CYP2C19 inhibitor is discontinued, mavacamten may be reinitiated at the previous dose immediately upon discontinuation.(1) The Canadian manufacturer of mavacamten recommends additional monitoring when concurrent use of weak CYP2C19 inhibitors is warranted. Adjust the dose of mavacamten based on clinical assessment.(2) The UK manufacturer of mavacamten states no dose adjustment is necessary with weak CYP2C19 inhibitors. Monitor left ventricular ejection fraction (LVEF) in 4 weeks then resume usual monitoring schedule.(3) DISCUSSION: Concomitant use of mavacamten (15 mg) with omeprazole (20 mg), a weak CYP2C19 inhibitor, once daily increased mavacamten area-under-curve (AUC) by 48% with no effect on maximum concentration (Cmax) in healthy CYP2C19 normal metabolizers and rapid metabolizers.(1) Weak CYP2C19 inhibitors include: armodafinil, cimetidine, enasidenib, eslicarbazepine, felbamate, givosiran, isoniazid, obeticholic acid, osilodrostat, piperine, rucaparib, tecovirimat.(4,5) |
CAMZYOS |
There are 55 moderate interactions.
The clinician should assess the patient’s characteristics and take action as needed. Actions required for moderate interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration.
| Drug Interaction | Drug Names |
|---|---|
| Hydantoins/Folic Acid; Pyrimethamine SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Unknown, but probably involves altered metabolism of the hydantoin. CLINICAL EFFECTS: May observe decreased effectiveness of hydantoin, resulting in loss of seizure control. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: If both drugs are administered, monitor both the hydantoin plasma levels as well as the seizure control of the patient. Adjust the dose of hydantoin accordingly. DISCUSSION: The effects of an interaction are not expected to occur in the majority of patients. Discontinuation of folic acid has caused phenytoin levels to increase in patients who experienced a decrease in phenytoin levels when folic acid was started. Monitor these patients for hydantoin toxicity. Signs and symptoms of hydantoin toxicity include ataxia, nystagmus and involuntary movements. |
CEREBYX, DILANTIN, DILANTIN-125, FOSPHENYTOIN SODIUM, PHENYTEK, PHENYTOIN, PHENYTOIN SODIUM, PHENYTOIN SODIUM EXTENDED |
| Tetracyclines/Divalent & Trivalent Cations SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Di- and trivalent cations may form chelation complexes with tetracyclines, preventing their absorption.(1,2) CLINICAL EFFECTS: Simultaneous administration of di- or trivalent cations may result in decreased levels of and therapeutics effects from tetracyclines. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Administer tetracyclines at least two hours before or after the di- or trivalent cations. When used for the treatment of H. pylori infection, tetracyclines and bismuth should be given simultaneously. The US manufacturer of omadacycline states to fast for at least four hours, administer omadacycline, and then wait four hours before taking di- or trivalent cations.(21) DISCUSSION: Concurrent administration of aluminum hydroxide or divalent cations (such as calcium, magnesium, or zinc) has been shown to significantly decrease the gastrointestinal absorption of tetracycline.(3-5) Concurrent administration of tetracycline and magnesium-aluminum hydroxide gel has been shown to decrease the tetracycline area-under-curve (AUC) by 90%.(6) Magnesium-aluminum silicate has been shown to decrease the AUC of tetracycline by 27%.(7) Demeclocycline(8,9) methacycline,(10) chlortetracycline,(11) and oxytetracycline(10,12) have been shown to interact with aluminum hydroxide and/or dairy products. Doxycycline has been reported to interact with aluminum hydroxide gel.(13) Aluminum magnesium hydroxide has been shown to decrease doxycycline absorption by 84%.(14) Minocycline absorption has been shown to be impaired by aluminum, calcium, and magnesium.(15) Bismuth subsalicylate has been shown to decrease absorption of doxycycline and tetracycline by 37%(16) and 34%,(17) respectively. Since sucralfate is an aluminum salt of a sulfated disaccharide, it may also prevent absorption of tetracyclines. This complex has been used to provide site-specific delivery of tetracycline to gastric ulcers in the treatment of Helicobacter pylori gastric ulcer disease and may be useful in some indications.(18) Quinapril tablets contain a high percentage of magnesium and have been shown to decrease the absorption of tetracycline by 28-37%.(19) Lanthanum is expected to interact with tetracyclines as well.(20) |
AVIDOXY, AVIDOXY DK, BENZODOX 30, BENZODOX 60, BISMUTH-METRONIDAZOLE-TETRACYC, DEMECLOCYCLINE HCL, DORYX, DORYX MPC, DOXYCYCLINE HYCLATE, DOXYCYCLINE IR-DR, DOXYCYCLINE MONOHYDRATE, EMROSI, MINOCYCLINE ER, MINOCYCLINE HCL, MINOCYCLINE HCL ER, MONDOXYNE NL, MORGIDOX, NUZYRA, ORACEA, OXYTETRACYCLINE HCL, PYLERA, SEYSARA, TARGADOX, TETRACYCLINE HCL, XIMINO |
| Penicillamine, Oral/Polyvalent Cations SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Penicillamine chelates with polyvalent cations such as aluminum, calcium, iron, magnesium, and zinc in the GI tract reducing the absorption of the penicillamine. CLINICAL EFFECTS: Reduced (to 30% of fasting) bioavailability of penicillamine with decreased pharmacologic response. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: In order to assure systemic absorption and maximal effectiveness from penicillamine, counsel patient to separate penicillamine by at least 1 hour before or 1 hours after any medications or products containing polyvalent cations such as antacids or mineral supplements. Monitor clinical status for decreased effectiveness and adjust the penicillamine dose if necessary. DISCUSSION: Clinical studies with polyvalent cations have not been conducted. Multivitamins with low doses of cations including iron and zinc may decrease penicillamine absorption so insure patient is aware of the risks. |
CUPRIMINE, D-PENAMINE, DEPEN, PENICILLAMINE, PENICILLAMINE(D-) |
| Levodopa/Pyridoxine SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Pyridoxine increases levodopa metabolism, decreasing the amount of levodopa available to the central nervous system. CLINICAL EFFECTS: The pharmacologic effects of levodopa may be decreased. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Avoid pyridoxine in patients receiving levodopa alone; however, the interaction can be minimized by giving levodopa with a peripheral decarboxylase inhibitor (e.g. carbidopa, benserazide). DISCUSSION: In patients with Parkinson's disease, as little as 10 mg of pyridoxine may reverse the clinical benefits as well as the adverse effects of levodopa. Coadministration of levodopa with either carbidopa or benserazide has minimized the effects of this interaction. |
INBRIJA, LEVODOPA |
| Mycophenolate/Aluminum & Magnesium Antacids; Lanthanum; Sevelamer SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Aluminum or magnesium antacids and non-calcium containing phosphate binders such as lanthanum and sevelamer decrease the absorption of mycophenolate.(1-3) CLINICAL EFFECTS: The simultaneous administration of mycophenolate with aluminum or magnesium antacids and non-calcium containing phosphate binders such as lanthanum and sevelamer may decrease the levels of mycophenolate and its clinical effects. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of mycophenolate mofetil states that calcium free phosphate binders, such as sevelamer, should not be administered simultaneously with mycophenolate mofetil. Administer sevelamer at least 2 hours after administration of mycophenolate mofetil to decrease the extent of the interaction.(1) The US manufacturer of mycophenolate sodium states that mycophenolate sodium should not be administered simultaneously with antacids. Administer aluminum or magnesium containing antacids at least 2 hours after mycophenolate.(2) Close monitoring of mycophenolic acid levels may be warranted in patients on mycophenolate mofetil therapy that are initiating or discontinuing concurrent therapy with these agents. Patients on concurrent therapies may also require higher doses of mycophenolate mofetil in order to achieve desired blood levels. DISCUSSION: In a study in 10 rheumatoid arthritis patients, the simultaneous administration of mycophenolate and Maalox TC (an antacid containing magnesium and aluminum hydroxide) resulted in decreases in the maximum concentration (Cmax) and area-under-curve (AUC) of mycophenolate by 33% and 17%, respectively.(1,2) In a study of 3 adult patients and 6 pediatric patients with stable renal graft function receiving mycophenolate mofetil, sevelamer (3-4 capsules of 403 mg twice daily) decreased the AUC and Cmax of mycophenolic acid by 26% and 36%, respectively.(1,3) In a study in 12 stable renal transplant patients, administration of magnesium-aluminum-containing antacids (30 ml) increased the Cmax and AUC of a single dose of mycophenolate sodium by 25% and 37%, respectively.(2) |
CELLCEPT, MYCOPHENOLATE MOFETIL, MYCOPHENOLIC ACID, MYFORTIC, MYHIBBIN |
| Thyroid Preparations/Calcium; Iron; Sucralfate SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: The mechanism by which malabsorption of thyroid preparations occurs from calcium-containing products is presumed to be a binding of the medication to the thyroid hormone, forming an insoluble or nonabsorbable complex.(1-3) Iron may form a ferric-thyroxine complex with thyroid agents, preventing their absorption from the gastrointestinal tract.(1,4) Sucralfate binds to other agents in the gastrointestinal tract and alters absorption of other drugs, including thyroid agents.(1,5) CLINICAL EFFECTS: The simultaneous administration of thyroid preparations with calcium, iron, or sucralfate may result in decreased levels and clinical effects of thyroid preparations.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Instruct patients to separate the administration time of thyroid preparations from calcium or iron by as much time as possible, preferably by at least four hours.(1) Administer thyroid preparations at least 2 hours before sucralfate.(5) Patients taking thyroid preparations and calcium- or iron-containing products or sucralfate should be monitored for changes in thyroid function. The dosage of the thyroid preparation may need to be increased. Separating the administration times of the thyroid preparation and the calcium- or iron-containing products or sucralfate may decrease the effects of the interaction.(1-5) DISCUSSION: In a pharmacokinetic study 8 healthy, euthyroid adults were given levothyroxine alone and levothyroxine coadministered with calcium carbonate, calcium citrate, or calcium acetate in doses containing 500 mg elemental calcium. The coadministration of each of the three calcium preparations significantly reduced levothyroxine absorption by about 20%-25% compared with levothyroxine given alone.(3) In a study in 14 subjects, the simultaneous administration of thyroxine with ferrous sulfate for 12 weeks resulted in an increase in the mean level of thyroid stimulating hormone (TSH) from 1.6+/-0.4 mU/L to 5.4+/-2.8 mU/L. Mixing thyroxine with ferrous sulfate in vitro resulted in a poorly soluble complex.(4) In a study in 20 hypothyroid patients, the simultaneous administration of levothyroxine and calcium carbonate (1200 mg) daily for three months resulted in reductions in the mean free T4 and total T4 levels. These values increased in most patients following the discontinuation of calcium carbonate. A concurrent in-vitro study found that calcium carbonate adsorbed levothyroxine in solution at a pH of 2, gastric pH, but not at a pH of 7.4.(6) One author reported three cases of decreased levothyroxine efficacy following the addition of calcium carbonate to therapy.(7) In a study in 5 healthy subjects, levothyroxine (five 200 mcg tablets) was administered in 3 different dosing regimens: after an overnight fast, with the fifth and final dose of sucralfate (1 gram every 6 hours) and 8 hours after the second and final dose of sucralfate (2 grams every 12 hours). When administered alone, 80% of levothyroxine was absorbed within 6 hours of administration, compared to 23% when administered concurrently with sucralfate. There was no difference in levothyroxine absorption when administered alone or 8 hours after sucralfate.(8) There are several case reports documenting decreased effects of thyroid supplementation as the result of simultaneous administration of sucralfate.(9,10) One or more of the drug pairs linked to this monograph have been included in a list of interactions that could be considered for classification as "non-interruptive" in EHR systems. This DDI subset was vetted by an expert panel commissioned by the U.S. Office of the National Coordinator (ONC) for Health Information Technology. |
ADTHYZA, ARMOUR THYROID, CYTOMEL, ERMEZA, EUTHYROX, LEVO-T, LEVOTHYROXINE SODIUM, LEVOTHYROXINE SODIUM DILUTION, LEVOXYL, LIOTHYRONINE SODIUM, NIVA THYROID, NP THYROID, PCCA T3 SODIUM DILUTION, PCCA T4 SODIUM DILUTION, RENTHYROID, SYNTHROID, THYQUIDITY, THYROID, TIROSINT, TIROSINT-SOL, UNITHROID |
| Selected NSAIDs/Selected CYP2C9 Inhibitors SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: The major metabolic pathway for many non-steroidal anti-inflammatory agents (NSAIDs) is CYP2C9. Inhibitors of CYP2C9 include: amiodarone, asciminib, cannabidiol, diosmin, fluconazole, ketoconazole, miconazole, nitisinone, oxandrolone, piperine, voriconazole, and zafirlukast.(1,2) CLINICAL EFFECTS: Concurrent use of NSAIDs with inhibitors of CYP2C9 may result in increased levels of and adverse effects from NSAIDs, including increased risk for bleeding. NSAIDs linked to this monograph are celecoxib, diclofenac, flurbiprofen, ibuprofen, meloxicam, naproxen, parecoxib, piroxicam and valdecoxib. PREDISPOSING FACTORS: Higher doses of either agent would be expected to increase the risk for serious adverse effects such as gastrointestinal bleeding (GIB) or renal failure. Patients who smoke, are elderly, debilitated, dehydrated, have renal impairment, or who have a history of GIB due to NSAIDs are also at increased risk for serious adverse events.(3-7) The risk for bleeding episodes may be greater in patients with disease-associated factors (e.g. thrombocytopenia). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g. NSAIDs). PATIENT MANAGEMENT: Patients on routine NSAID therapy when an inhibitor of CYP2C9 is started should be evaluated for patient-specific risk factors for NSAID toxicity. Based upon this risk assessment, consider dose reduction of the NSAID or close monitoring for adverse effects. For a patient already receiving a CYP2C9 inhibitor when an NSAID is started, consider initiating the NSAID at a lower than usual dose, particularly when predisposing risk factors for harm are present. The manufacturer of celecoxib recommends that celecoxib be introduced at the lowest recommended dose in patients receiving fluconazole therapy.(3) The manufacturer of fluconazole states that half the dose of celecoxib may be necessary when fluconazole is added.(4) It would be prudent to follow this recommendation with other CYP2C9 inhibitors and to decrease the dose of celecoxib in patients in whom CYP2C9 inhibitors are added to celecoxib therapy. The manufacturer of diclofenac-misoprostol states that the total daily dose of diclofenac should not exceed the lowest recommended dose of 50 mg twice daily in patients taking CYP2C9 inhibitors.(5) It would be prudent to use the lowest recommended dose of other diclofenac formulations in patients taking CYP2C9 inhibitors. The manufacturer of parecoxib states that the dose of parecoxib should be reduced in those patients who are receiving fluconazole therapy.(6) It would be prudent to follow this recommendation with other CYP2C9 inhibitors. If concurrent therapy is warranted, monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin, hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. When applicable, perform agent-specific laboratory test (e.g. INR, aPTT) to monitor efficacy and safety of anticoagulation. Discontinue anticoagulation in patients with active pathologic bleeding. Instruct patients to report any signs and symptoms of bleeding, such as unusual bleeding from the gums or nose; unusual bruising; red or black, tarry stools; red, pink or dark brown urine; acute abdominal or joint pain and/or swelling. DISCUSSION: The concomitant administration of celecoxib and fluconazole (200 mg daily) resulted in a 2-fold increase in celecoxib plasma concentration.(3) In vitro studies in human hepatocytes found that amiodarone inhibited diclofenac metabolism.(7) In two separate studies, single doses of diclofenac (50 mg) or ibuprofen (400 mg) were coadministered with the last dose of voriconazole (400 mg q12h on Day 1, followed by 200 mg q12h on Day 2). Voriconazole increased the mean AUC of diclofenac by 78% and increased the AUC of the active isomer of ibuprofen by 100%.(8-10) Coadministration of diosmin increased diclofenac levels by 63%.(2) Coadministration of flurbiprofen or ibuprofen with fluconazole increased the AUC of flurbiprofen by 81% and of the active ibuprofen by 82% compared with either agent alone.(4) Concurrent voriconazole increased meloxicam AUC by 47%.(11,12) The concurrent administration of fluconazole and parecoxib resulted in increases in the area-under-curve (AUC) and maximum concentration (Cmax) of valdecoxib (the active metabolite of parecoxib) by 62% and 19%, respectively.(6) In a study, single dose diclofenac (50mg) given concurrently with the last dose of voriconazole (400 mg every 12 hours on Day 1, 200 mg every 12 hours on Day 2) increased Cmax and AUC by 2.1-fold and 1.8-fold, respectively. (5) Inhibitors of CYP2C9 include: amiodarone, asciminib, cannabidiol, diosmin, fluconazole, ketoconazole, miconazole, nitisinone, oxandrolone, piperine, voriconazole, and zafirlukast.(1,2) |
ANAPROX DS, ANJESO, ARTHROTEC 50, ARTHROTEC 75, CALDOLOR, CAMBIA, CELEBREX, CELECOXIB, COMBOGESIC, COMBOGESIC IV, CONSENSI, DICLOFENAC, DICLOFENAC POTASSIUM, DICLOFENAC SODIUM, DICLOFENAC SODIUM ER, DICLOFENAC SODIUM MICRONIZED, DICLOFENAC SODIUM-MISOPROSTOL, EC-NAPROSYN, ELYXYB, FELDENE, FLURBIPROFEN, HYDROCODONE-IBUPROFEN, IBU, IBUPAK, IBUPROFEN, IBUPROFEN LYSINE, IBUPROFEN-FAMOTIDINE, INFLAMMACIN, INFLATHERM(DICLOFENAC-MENTHOL), LOFENA, LURBIPR, MELOXICAM, NAPRELAN, NAPROSYN, NAPROTIN, NAPROXEN, NAPROXEN SODIUM, NAPROXEN SODIUM CR, NAPROXEN SODIUM ER, NAPROXEN-ESOMEPRAZOLE MAG, NEOPROFEN, PIROXICAM, SUMATRIPTAN SUCC-NAPROXEN SOD, SYMBRAVO, TOXICOLOGY SALIVA COLLECTION, TRESNI, TREXIMET, VIMOVO, VIVLODEX, ZIPSOR, ZORVOLEX, ZYNRELEF |
| Gabapentin/Aluminum; Magnesium-Containing Compounds SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Aluminum or magnesium containing products may reduce the bioavailability of gabapentin.(1) CLINICAL EFFECTS: Simultaneous administration of aluminum or magnesium containing products and gabapentin may result in decreased absorption of gabapentin by 20% and reduce its clinical effectiveness.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: If the use of both medications is unavoidable, it is recommended that gabapentin be taken at least 2 hours following the administration of aluminum or magnesium containing products.(1) DISCUSSION: In 16 subjects, Maalox reduced the bioavailability of gabapentin by about 20%. The reduction was only 5% when gabapentin was administered 2 hours after the Maalox dose. It is for this reason that the manufacturer of gabapentin recommends that it be taken at least 2 hours after the administration of aluminum or magnesium containing products.(1) |
GABAPENTIN, GABAPENTIN ER, GABARONE, GRALISE, HORIZANT, NEURONTIN |
| Cefdinir/Oral Iron SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Iron may form a chelation complex with cefdinir, preventing its absorption.(1,2) CLINICAL EFFECTS: Simultaneous administration of cefdinir with iron may result in decreased levels and clinical effectiveness of cefdinir.(1,2) Concurrent use may also result in a reddish color of stools.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Cefdinir should be taken at least 2 hours before or after iron supplements, including multivitamins containing iron.(1) Patients should be counseled that their stool may turn reddish during treatment with cefdinir. Cefdinir may be administered simultaneously with iron-fortified infant formula.(1) DISCUSSION: Simultaneous administration of cefdinir with a therapeutic iron supplement containing 60 mg of elemental iron as ferrous sulfate or vitamins containing 10 mg of elemental iron decreased cefdinir absorption by 80% and 31%, respectively.(1) Simultaneous administration of iron with cefdinir (200 mg) decreased cefdinir area-under-curve (AUC) by 93%.(2) There have been reports of reddish stools in patients taking cefdinir, most of these patients were taking iron-containing products.(1) |
CEFDINIR |
| Selected Cephalosporins/Aluminum; Magnesium Compounds SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Aluminum and magnesium containing antacids may form chelation complexes with some cephalosporins, preventing their absorption.(1,2) CLINICAL EFFECTS: Simultaneous administration of an aluminum and/or magnesium containing antacid with some cephalosporins may result in decreased levels and effectiveness of the cephalosporin.(1,2) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of cefdinir recommends that cefdinir be taken at least 2 hours before or after an aluminum and/or magnesium containing antacid.(1) It would be prudent to separate the administration of cefaclor by at least this amount of time as well.(2) DISCUSSION: Simultaneous administration of cefdinir (300 mg) with Maalox TC (30 ml) decreased cefdinir area-under-curve (AUC) and maximum concentration (Cmax) by 40%.(1) In a study in 15 healthy subjects, simultaneous administration of cefaclor advanced formulation (500 mg) with Maalox TC decreased the extent of cefaclor absorption.(2) |
CEFACLOR, CEFACLOR ER, CEFDINIR |
| Orlistat/Fat Soluble Vitamins SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: The acetate ester forms of vitamin A and vitamin E must undergo hydrolysis for absorption from the gastrointestinal tract.(1) The enzyme responsible for this hydrolysis is inhibited by orlistat.(2) CLINICAL EFFECTS: Orlistat may reduce absorption of fat soluble vitamins, leading to a deficiency state. PREDISPOSING FACTORS: A pre-existing deficiency of fat soluble vitamins (A,D,E and K) or chronic malabsorption syndrome. PATIENT MANAGEMENT: The inhibition of fat soluble vitamin absorption by orlistat should be borne in mind during implementation of a vitamin supplementation strategy. Patients should be strongly encouraged to take a multivitamin supplement which contains fat soluble vitamins, particularly Vitamin D as it appears most susceptible to this interaction.(4,5) Multivitamin supplements should be taken at least two hours before or after the dose of orlistat, or at bedtime.(4) Patients with chronic malabsorption syndromes should not receive orlistat.(4) DISCUSSION: Adult patients taking orlistat without supplementation showed a greater reduction in vitamin A,D,E and beta-carotene levels compared to placebo during two or more consecutive visits in studies of 1-2 years duration; these patients had normal baseline values prior to orlistat therapy. Low vitamin values in orlistat patients were as follows: low Vitamin D 12%, low beta-carotene 6.1%, low Vitamin E 5.8%, low Vitamin A 2.2%.(4) A pharmacokinetic interaction study showed a 30% reduction in beta-carotene supplement absorption and a 60% decreased in vitamin E acetate absorption with concomitant orlistat.(4) In a study, orlistat produced the vitamin net concentration by approximately 43%.(1) In a study, no statistically significant decrease in vitamin A absorption was observed with concurrent orlistat.(2) In a study, mean vitamin D levels were significantly reduced compared with baseline after one month of orlistat therapy despite multivitamin supplementation.(5) |
ORLISTAT, XENICAL |
| Oral Bisphosphonates/Oral Multivalent Cations SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Multivalent cations may bind to and inhibit the absorption of oral bisphosphonates.(1-6) CLINICAL EFFECTS: Simultaneous administration of products containing multivalent cations may result in decreased levels of and clinical effects from oral bisphosphonates.(1-6) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Instruct patients to separate the administration times of products containing multivalent cations and oral bisphosphonates. Manufacturer recommendations regarding the separation of administration times of oral bisphosphonates and multivalent cations vary. Do NOT give multivalent cation-containing products: - until at least 30 minutes after taking alendronate(1) - within 2 hours of etidronate(2) - until at least 1 hour after taking ibandronate(3) - until at least 30 minutes after taking risedronate(4) - within 2 hours of tiludronate(5) DISCUSSION: Multivalent cations may bind to and inhibit the absorption of oral bisphosphonates, resulting in decreased levels of and clinical effects from these agents.(1-6) Administration of aluminum- or magnesium-containing antacids 1 hour before tiludronate decreased the bioavailability of tiludronate by 60%.(5) |
ACTONEL, ALENDRONATE SODIUM, ATELVIA, BINOSTO, FOSAMAX, FOSAMAX PLUS D, IBANDRONATE SODIUM, RISEDRONATE SODIUM, RISEDRONATE SODIUM DR |
| Chloroquine; Hydroxychloroquine/Di-; Trivalent Cations SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Di- and trivalent cations such as aluminum, calcium, lanthanum, and magnesium may adsorb chloroquine and hydroxychloroquine; preventing their absorption.(1-5) The adsorption may also limit the effectiveness of the di- or trivalent cation.(1) CLINICAL EFFECTS: Simultaneous administration of di- or trivalent cations may result in decreased levels and effectiveness of chloroquine and hydroxychloroquine(2-5) and decreased effectiveness of the di- or trivalent cation.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Instruct patients to separate the administration times of these medicines by 2 to 4 hours.(2,3) DISCUSSION: Adsorption of chloroquine by magnesium trisilicate was found to decrease hydrochloric acid uptake and decrease the amount of magnesium released in an acidic environment.(1) In a study, calcium carbonate, kaolin, and magnesium trisilicate were found to decrease the absorption of chloroquine by 52.8%, 46.5%, and 31.3%, respectively.(3) Magnesium trisilicate and magnesium oxide have been shown to decrease the release of chloroquine from tablets and to adsorb chloroquine after its release.(4) In a study in 6 subjects, magnesium trisilicate and kaolin decreased the area-under-curve (AUC) of chloroquine by 18.2% and 28.6%, respectively.(5) |
CHLOROQUINE PHOSPHATE, HYDROXYCHLOROQUINE SULFATE, PLAQUENIL, SOVUNA |
| Phenytoin/Aluminum-Magnesium Hydroxide; Oral Calcium SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Aluminum hydroxide; magnesium hydroxide, and oral calcium may bind to phenytoin, preventing its absorption.(1-4) CLINICAL EFFECTS: Simultaneous ingestion of aluminum-magnesium hydroxide and/or calcium-containing products may result in decreased levels and effectiveness of phenytoin.(1-4) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of phenytoin recommends that administration times of phenytoin and antacids being staggered.(1) DISCUSSION: In a study in 8 healthy subjects, simultaneous administration of phenytoin (600 mg) with calcium carbonate significantly decreased the area-under-curve (AUC) of phenytoin.(2) In a study in 8 healthy subjects, simultaneous administration of aluminum-magnesium hydroxide or calcium carbonate significantly decreased the AUC of phenytoin.(3) In a study in 6 patients with epilepsy, concurrent administration of an aluminum-magnesium hydroxide antacid resulted in a small but statistically significant decrease in phenytoin AUC.(4) |
DILANTIN, DILANTIN-125, PHENYTEK, PHENYTOIN, PHENYTOIN SODIUM, PHENYTOIN SODIUM EXTENDED |
| Eltrombopag/Polyvalent Cations SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Eltrombopag chelates polyvalent cations such as aluminum, calcium, iron, magnesium, selenium, and zinc.(1) CLINICAL EFFECTS: Simultaneous administration of eltrombopag and polyvalent cations may decrease the absorption and clinical effects of eltrombopag. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of eltrombopag states that it should be administered at least 2 hours before or 4 hours after any medications or products containing polyvalent cations such as antacids or mineral supplements.(1) DISCUSSION: In a crossover study in 25 healthy subjects, administration of eltrombopag with an antacid (1524 mg aluminum hydroxide/1425 mg magnesium carbonate/sodium alginate) decreased eltrombopag levels by 70%.(1,2) |
ALVAIZ, PROMACTA |
| Selected Oral Quinolones/Selected Oral Cations SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Aluminum, calcium, iron, lanthanum, magnesium, and zinc may form chelation compounds with the quinolones.(1-39) CLINICAL EFFECTS: Simultaneous administration or administration of products containing aluminum, calcium, iron, lanthanum, magnesium, and/or zinc close to the administration time of an oral quinolone may result in decreased absorption and clinical effectiveness of the quinolone. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: If possible, avoid concurrent therapy with quinolones and cation-containing products. If it is necessary to administer these agents concurrently, follow the manufacturers' recommendations regarding timing of administration of the quinolone and cation-containing products. Manufacturer recommendations regarding the separation of administration times of quinolones and products containing aluminum, calcium, iron, lanthanum, magnesium, and/or zinc vary: ---Do not give ciprofloxacin for at least 2 hours before or 6 hours after oral cations.(1) ---Do not give delafloxacin for at least 2 hours before or 6 hours after oral cations.(2) ---Do not give enoxacin for at least 2 hours before or 8 hours after oral cations.(3) ---Do not give levofloxacin for at least 2 hours before or 2 hours after oral cations.(4) ---Do not give nalidixic acid for at least 2 hours before or 2 hours after oral cations.(5) ---Do not give norfloxacin for at least 2 hours before or 2 hours after oral cations.(6) ---Do not give ofloxacin for at least 2 hours before or 2 hours after oral cations.(7) ---Do not give sparfloxacin for at least 4 hours before oral cations.(8) The US manufacturer of lanthanum recommends that quinolones be taken at least 1 hour before or 4 hours after lanthanum;(9) however, it would be prudent to follow the specific quinolone manufacturers' recommendations regarding concurrent administration of cations. For quinolones not listed above, separate their administration from oral cations by as much time as feasible. DISCUSSION: Aluminum, calcium, iron, magnesium, and zinc products have been shown to form chelation compounds with quinolone antibiotics, resulting in decreased absorption of the quinolone.(1-38) Treatment failures have been reported.(10-12) In a study in 12 healthy subjects, simultaneous administration of didanosine chewable tablets, which contain aluminum and magnesium, decreased ciprofloxacin area-under-curve (AUC) and maximum concentration (Cmax) by 92% and 98%, respectively.(13) The administration of ciprofloxacin 2 hours prior to Videx chewable/dispersible tablets decreased ciprofloxacin concentrations by 26%.(14,15) In a study in healthy subjects, pretreatment with an antacid containing aluminum-magnesium hydroxide at 5-10 minutes, 2 hours, and 4 hours before a single dose of ciprofloxacin decreased ciprofloxacin AUC by 84.9%, 76.8%, and 30%, respectively. There was no effect when the antacid was administered 6 hours before or 2 hours after.(16) In a study in 12 healthy subjects, aluminum hydroxide decreased ciprofloxacin AUC by 85%.(17) In a study in patients on continuous ambulatory peritoneal dialysis, peak levels of ciprofloxacin were decreased by 67% to 92% in patients receiving aluminum-containing antacids.(18) In a study in 15 healthy subjects, simultaneous administration of calcium acetate decreased the bioavailability of ciprofloxacin by 51%.(19) In a study in 6 healthy males, simultaneous administration of calcium carbonate decreased ciprofloxacin Cmax and AUC by 40% and 43%, respectively.(20) In a study in 12 healthy subjects, calcium carbonate decreased ciprofloxacin AUC by 40%.(17) In a study in 13 healthy males, calcium carbonate had no effect on ciprofloxacin bioavailability when administered 2 hours prior to the antibiotic.(21,22) In a study in healthy males, simultaneous administration of calcium polycarbophil decreased ciprofloxacin AUC by 50%.(23) In a study in 8 healthy males, simultaneous administration of ferrous fumarate (200 mg) decreased ciprofloxacin AUC by 70%.(24) In a study in healthy subjects, ferrous gluconate decreased ciprofloxacin bioavailability by 50%; however, no significant effects were seen with iron-ovotransferrin.(25) In a study in 8 healthy subjects, ferrous sulfate decreased the Cmax and AUC of simultaneously administered ciprofloxacin by 54% and 57%, respectively.(26) In a study in 8 healthy subjects, administration of ferrous sulfate decreased the Cmax and AUC of ciprofloxacin by 33% and 46%, respectively. Administration of ferrous gluconate decreased the Cmax and AUC of ciprofloxacin by 57% and 67%, respectively. Administration of a multivitamin product containing calcium, copper, iron, magnesium, manganese, and zinc decreased the Cmax and AUC of ciprofloxacin by 53% and 56%, respectively.(27) In a study in 12 healthy males, ferrous sulfate decreased ciprofloxacin AUC by 63%.(28) In a study in 12 healthy subjects, lanthanum carbonate decreased the area-under-curve (AUC) and maximum concentration (Cmax) of concurrently administered ciprofloxacin by 54% and 56%, respectively.(29) In a study in 12 healthy males, a multivitamin containing zinc decreased ciprofloxacin AUC by 22%.(28) In a study in 12 healthy subjects, an antacid containing aluminum-magnesium hydroxide had no effect on the pharmacokinetics of intravenous enoxacin.(30) In a study in 10 healthy subjects, administration of an aluminum-magnesium hydroxide antacid 0.5 hours or 2 hours before oral enoxacin (400 mg single dose) decreased the AUC of enoxacin by 73% and 43%, respectively. There were no significant effects on enoxacin AUC when the antacid was administered 8 hours before or 2 hours after enoxacin.(31) In a study in 9 healthy subjects, colloidal aluminum phosphate had no effect on the amount of enoxacin absorbed; however, ferrous sulfate (1050 mg) decreased the amount of enoxacin absorption by 10%.(32) In a study in 5 healthy subjects and 5 patients with cystic fibrosis, separation of levofloxacin (750 mg) and calcium carbonate (500 mg 3 times daily with meals) by 2 hours resulted in no interaction in healthy subjects; however, levofloxacin levels were not bioequivalent in patients with cystic fibrosis.(33) Concurrent magnesium-aluminum hydroxide or calcium have been shown to decrease the bioavailability of norfloxacin by 91.0% and 63.5%, respectively.(34) Concurrent zinc has been shown to decrease the bioavailability of norfloxacin.(35) In a study in 8 healthy subjects, ferrous sulfate decreased the Cmax and AUC of simultaneously administered norfloxacin by 75% and 73%, respectively.(26) Simultaneous aluminum phosphate was found to decrease the rate, but not the extent, of absorption of ofloxacin.(36) In a study in 8 healthy subjects, ferrous sulfate decreased the Cmax and AUC of simultaneously administered norfloxacin by 36% and 25%, respectively.(26) In an in vitro study, ferrous sulfate, aluminum hydroxide, and calcium carbonate decreased ofloxacin availability by 32.6%, 30.7%, and 26.2%, respectively. However, in vivo tests showed a significant effect with only aluminum hydroxide.(37) In a study in 9 healthy subjects, simultaneous administration colloidal aluminum phosphate had no effect on ofloxacin (200 mg) absorption; however, ferrous sulfate (1050 mg) decreased the ofloxacin fraction of dose absorbed by 10.85%.(32) In a study in 16 subjects, administration of either aluminum-magnesium hydroxide or calcium carbonate at least 2 hours before or after ofloxacin administration had no significant effects on ofloxacin levels.(38) The administration of an antacid containing aluminum hydroxide and magnesium hydroxide 2 hours before, 2 hours after, and 4 hours after sparfloxacin decreased sparfloxacin levels by 23%, 17%, and 5%, respectively.(39) One or more of the drug pairs linked to this monograph have been included in a list of interactions that could be considered for classification as "non-interruptive" in EHR systems. This DDI subset was vetted by an expert panel commissioned by the U.S. Office of the National Coordinator (ONC) for Health Information Technology. |
BAXDELA, CIPRO, CIPROFLOXACIN, CIPROFLOXACIN HCL, LEVOFLOXACIN, LEVOFLOXACIN HEMIHYDRATE, NALIDIXIC ACID, OFLOXACIN |
| Deferoxamine/Ascorbic Acid (Vitamin C) SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: It is believed that ascorbic acid increases the iron available for chelation from an labile intracellular iron pool. Ascorbic acid may then facilitate iron-induced oxidative tissue damage.(1) CLINICAL EFFECTS: Dietary ascorbic acid may increase the absorption of dietary iron. Supplemental ascorbic acid therapy given during chelation therapy may improve iron output;(1-9) however, excessive dosages may result in cardiac toxicity from iron-induced oxidative tissue damage.(1,2,11-13) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Ascorbic acid intake is often restricted in patients with iron overload; however, it has been used in conjunction with deferoxamine to increase iron excretion.(2) Supplemental ascorbic acid therapy should only be initiated after one month of deferoxamine therapy. Ascorbic acid therapy should only be given in patients receiving deferoxamine regularly and the dose should be given after the infusion has started. The dosage of ascorbic acid should be limited to 50 mg daily in children under 10 years of age; 100 mg daily in older children; and 200 mg daily, in divided doses, in adults.(2) Cardiac function should be monitored in patients receiving concurrent therapy. Discontinue ascorbic acid therapy in patients who develop cardiac dysfunction.(2) DISCUSSION: Supplemental ascorbic acid therapy given during chelation therapy has been shown to improve iron output,(1-9) possibly by increasing iron available for chelation from an labile intracellular iron pool.(1) However, dosages in excess of 500 mg daily have been associated with cardiac dysfunction.(1,2,11-13) |
DEFEROXAMINE MESYLATE, DESFERAL MESYLATE |
| Rivaroxaban/Selected P-gp and Weak CYP3A4 Inhibitors SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Amiodarone, azithromycin, brodalumab, chloramphenicol, cimetidine, cyclosporine, felodipine, fluvoxamine, fostamatinib, glecaprevir/pibrentasvir, hydroquinidine, ivacaftor, nilotinib, piperine, pirtobrutinib, quinidine, ranolazine, simeprevir, ticagrelor and tolvaptan may inhibit the metabolism of rivaroxaban by CYP3A4 and by P-glycoprotein.(1,2) CLINICAL EFFECTS: Concurrent use of an agent that is both an inhibitor of P-gp and a weak inhibitor of CYP3A4 may result in elevated levels of and clinical effects of rivaroxaban, including an increased risk of bleeding, in patients with decreased renal function.(1,2) PREDISPOSING FACTORS: Patients with decreased renal function (CrCL of 15 ml/min to 80 ml/min) may be predisposed to this interaction.(1) The risk for bleeding episodes may be greater in patients with disease-associated factors (e.g. thrombocytopenia). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g. NSAIDs). PATIENT MANAGEMENT: The US manufacturer states no precautions are necessary with the concurrent use of these agents and rivaroxaban in patients with normal renal function.(1) It would be prudent to closely monitor concurrent use in patients with reduced renal function (CrCL of 15 ml/min to 80 ml/min). If concurrent therapy is warranted, monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin, hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. When applicable, perform agent-specific laboratory test (e.g. INR, aPTT) to monitor efficacy and safety of anticoagulation. Discontinue anticoagulation in patients with active pathologic bleeding. Instruct patients to report any signs and symptoms of bleeding, such as unusual bleeding from the gums or nose; unusual bruising; red or black, tarry stools; red, pink or dark brown urine; acute abdominal or joint pain and/or swelling. DISCUSSION: Clarithromycin (500 mg twice daily) increased the area-under-curve (AUC) and maximum concentration (Cmax) of a single dose of rivaroxaban by 50% and 40%, respectively.(1,2) Erythromycin (500 mg three times daily) increased the AUC and Cmax of a single dose of rivaroxaban by 30% and 30%, respectively.(1-3) In patients with mild renal impairment (CrCl of 50 ml/min to 79 ml/min) who were receiving erythromycin, rivaroxaban levels were increased 76% when compared to administration of rivaroxaban in patients with normal renal function receiving rivaroxaban alone. In patients with moderate renal impairment (CrCl of 30 ml/min to 49 ml/min) who were receiving erythromycin, rivaroxaban levels were increased 99% when compared to administration of rivaroxaban in patients with normal renal function receiving rivaroxaban alone.(1) Fluconazole increased the AUC and Cmax of a single dose of rivaroxaban by 40%% and 30%, respectively.(1) These changes are not expected to be clinically significant in patients with normal renal function.(1,2) In a case report, an 88-year-old woman with renal impairment on rivaroxaban presented with an elevated INR of 2.5 and a rivaroxaban peak plasma concentration above the upper limit of detection at >800 mcg/L (therapeutic range 58-211 mcg/L). Nothing in her medical history suggested a reason for supratherapeutic rivaroxaban levels except for a 7-week amiodarone regimen that was discontinued 3 weeks prior. This suggests the potential for amiodarone to persist in the body weeks after its use and precipitate drug-drug interactions.(4) A retrospective cohort study examined 24,943 patients aged 66 years and older with concurrent therapy of an anticoagulant, either rivaroxaban (40.0%), apixaban (31.9%), or dabigatran (28.1%), with either azithromycin or clarithromycin. The primary outcome of hospital admission with major hemorrhage within 30 days on concurrent therapy was higher in patients on clarithromycin (0.77%) compared to azithromycin (0.43%) with an adjusted hazard ratio of 1.71 (95% CI, 1.20-2.45). In a self-controlled case series, 744 major hemorrhage events were identified among 647 unique individuals taking anticoagulants who were exposed to clarithromycin. The rate of events that occurred during clarithromycin use had a significant rate ratio of 1.44 (95% CI, 1.08-1.92).(5) A propensity matched cohort evaluated the concurrent use of combined P-gp and moderate CYP3A4 inhibitors with apixaban or rivaroxaban. Combined inhibitors included amiodarone, diltiazem, erythromycin, dronedarone, and verapamil. Bleeding occurred in 26.4% of patients in the inhibitor group compared to 18.4% in the control group (hazard ratio 1.8; 95% CI 1.19-2.73; p=0.006). Although not statistically significant, patients in the inhibitor group also had a higher rate of major bleeding (15% vs 10.3%) and minor bleeding (8.9% vs 5.2%), respectively.(6) A summary of pharmacokinetic interactions with rivaroxaban and amiodarone concluded that concurrent use should be avoided if CrCl < 80 ml/min.(7) A prospective cohort study of 174 patients evaluated the concurrent use of rivaroxaban and amiodarone. The combination of rivaroxaban and amiodarone was associated with a higher incidence of bleeding events (p=0.041; HR=2.83, 95% CI 1.05-7.66) and clinically relevant non-major bleeding (p=0.021; HR=3.65, 95% CI 1.21-10.94). Concurrent use of amiodarone and rivaroxaban in non-valvular atrial fibrillation patients was an independent risk factor for increased risk of bleeding (p=0.044; OR 2.871, 95% CI 1.028-8.023).(8) P-gp and weak CYP3A4 inhibitors linked to this monograph are: amiodarone, azithromycin, belumosudil, brodalumab, chloramphenicol, cimetidine, cyclosporine, daridorexant, diosmin, flibanserin, fostamatinib, glecaprevir/pibrentasvir, hydroquinidine, istradefylline, ivacaftor, mavorixafor, nilotinib, piperine, pirtobrutinib, quinidine, ranolazine, simeprevir and tolvaptan.(9,10) |
RIVAROXABAN, XARELTO |
| Citalopram (Less than or Equal To 20 mg)/Selected CYP2C19 Inhibitors SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Citalopram is primarily metabolized by the CYP2C19 isoenzyme.(1) CLINICAL EFFECTS: Concurrent use of an agent that inhibits CYP2C19 may result in elevated levels of and toxicity from citalopram, including including risks for serotonin syndrome or prolongation of the QTc interval.(1-5) Prolongation of the QT interval may result in life-threatening arrhythmias, including torsades de pointes.(2) Symptoms of serotonin syndrome may include tremor, agitation, diaphoresis, hyperreflexia, clonus, tachycardia, hyperthermia, and muscle rigidity.(5) PREDISPOSING FACTORS: The risk of QT prolongation or torsades de pointes may be increased in patients with cardiovascular disease (e.g. heart failure, myocardial infarction, history of torsades de pointes, congenital long QT syndrome), hypokalemia, hypomagnesemia, hypocalcemia, bradycardia, female gender, advanced age, poor metabolizer status at CYP2C19, or higher blood concentrations of citalopram.(2) Concurrent use of more than one drug known to cause QT prolongation or higher systemic concentrations of either QT prolonging drug are additional risk factors for torsades de pointes. Factors which may increase systemic drug concentrations include rapid infusion of an intravenous dose or impaired metabolism or elimination of the drug (e.g. coadministration with an agent which inhibits its metabolism or elimination, genetic impairment in drug metabolism or elimination, and/or renal/hepatic dysfunction).(2) Predisposing factors for serotonin-related adverse effects include use in the elderly, in patients with hepatic impairment, and in patients receiving multiple agents which increase central serotonin levels.(1,5) If concurrent therapy is warranted, consider obtaining serum calcium, magnesium, and potassium levels and monitoring ECG at baseline and at regular intervals. Correct any electrolyte abnormalities. Instruct patients to report any irregular heartbeat, dizziness, or fainting. PATIENT MANAGEMENT: The dose of citalopram should be limited to 20 mg in patients receiving concurrent therapy with an inhibitor of CYP2C19.(1,4) Evaluate the patient for other drugs, diseases and conditions which increase risk for QT prolongation and correct risk factors (e.g. correct hypokalemia, hypocalcemia, hypomagnesemia, discontinue other QT prolonging drugs) when possible.(1,2) Weigh the specific benefits versus risks for each patient. The US manufacturer recommends ECG monitoring for citalopram patients with congestive heart failure, bradyarrhythmias, taking concomitant QT prolonging medications or receiving concurrent therapy.(4) Citalopram should be discontinued in patients with persistent QTc measurements greater than 500 ms.(2) If concurrent therapy is warranted, consider obtaining serum calcium, magnesium, and potassium levels and monitoring ECG at baseline and at regular intervals. Correct any electrolyte abnormalities. Instruct patients to report any irregular heartbeat, dizziness, or fainting. If concurrent therapy is warranted, patients should be monitored for signs and symptoms of serotonin syndrome. Instruct patients to report muscle twitching, tremors, shivering and stiffness, fever, heavy sweating, heart palpitations, restlessness, confusion, agitation, trouble with coordination, or severe diarrhea. DISCUSSION: Concurrent use of citalopram (40 mg daily) and cimetidine (400 mg twice daily) for 8 days increased the maximum concentration (Cmax) and area-under-curve (AUC) of citalopram by 39% and 43%, respectively.(1) Inhibitors of CYP2C19 include: abrocitinib, allicin (garlic derivative), berotralstat, cannabidiol (CBD), cenobamate, cimetidine strengths > or = 200 mg, enasidenib, eslicarbazepine, esomeprazole, etravirine, fedratinib, felbamate, fluoxetine, fluvoxamine, givosiran, isoniazid, moclobemide, modafinil, obeticholic acid, omeprazole, piperine, rolapitant, stiripentol, and tecovirimat.(7,8) |
CELEXA, CITALOPRAM HBR |
| Deferiprone/Aluminum, Iron, Zinc SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Deferiprone chelates polyvalent cations such as aluminum, iron, and zinc.(1) CLINICAL EFFECTS: Deferiprone chelation with oral aluminum, iron or zinc containing products in the gastrointestinal tract may decrease the amount of free deferiprone available for systemic iron chelation. Zinc supplements prescribed to counteract deferiprone-induced zinc deficiency may not be effective if taken near time of deferiprone administration. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer recommends at least a four hour interval between deferiprone dose and administration of aluminum, iron or zinc containing medications or supplements.(1) Avoid use of iron-containing vitamins or nutritional supplements in patients who require chelation therapy for iron overload. DISCUSSION: The US manufacturer has not studied this interaction. The recommendation to separate deferiprone and polyvalent cation doses by at least four hours is based upon the deferiprone mechanism of action.(1) |
DEFERIPRONE, DEFERIPRONE (3 TIMES A DAY), FERRIPROX, FERRIPROX (2 TIMES A DAY), FERRIPROX (3 TIMES A DAY) |
| Selected Oral Quinolones/Selected Oral Cations SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Aluminum, iron, lanthanum, magnesium, and zinc may form chelation compounds with the quinolones.(1-23) CLINICAL EFFECTS: Simultaneous administration or administration of products containing aluminum, iron, lanthanum, magnesium, and/or zinc close to the administration time of an oral quinolone may result in decreased absorption and clinical effectiveness of the quinolone PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: If possible, avoid concurrent therapy with quinolones and cation-containing products. If it is necessary to administer these agents concurrently, follow the manufacturers' recommendations regarding timing of administration of the quinolone and cation-containing products. Manufacturer recommendations regarding the separation of administration times of quinolones and products containing aluminum, iron, lanthanum, magnesium, and/or zinc vary: ---Do not give gatifloxacin for at least 4 hours before oral cations(1) ---Do not give gemifloxacin for at least 2 hours before or 3 hours after oral cations.(2) ---Do not give lomefloxacin for at least 2 hours before or 4 hours after oral cations.(3) ---Do not give moxifloxacin for at least 4 hours before or 8 hours after oral cations.(4) ---Do not give trovafloxacin for at least 2 hours before or after oral cations.(5) ---Do not give prulifloxacin for at least 2 hours before or 4 hours after oral cations.(23) The US manufacturer of lanthanum recommends that quinolones be taken at least 1 hour before or 4 hours after lanthanum;(6) however, it would be prudent to follow the specific quinolone manufacturers' recommendations regarding concurrent administration of cations. For quinolones not listed above, separate their administration from oral cations by as much time as feasible. DISCUSSION: Magnesium and aluminum compounds have been shown to form chelation compounds with quinolone antibiotics, resulting in decreased absorption of the quinolone.(1-22) Treatment failures during concurrent use of cations and gatifloxacin(7) and pefloxacin(8) have been reported. In a study in 24 healthy subjects, administration of an aluminum-magnesium hydroxide antacid simultaneously, 2 hours before, or 2 hours after decreased the area-under-curve (AUC) of a single dose of gatifloxacin (400 mg) by 42%, 64%, or 18%, respectively. There were no affects on gatifloxacin AUC when the antacid was administered 4 hours after gatifloxacin.(9) In a study in 16 healthy males, administration of an aluminum-magnesium hydroxide antacid 10 minutes before or 3 hours after a single dose of gemifloxacin (320 mg) decreased the gemifloxacin AUC by 85% and 15%, respectively. There was no affect when the antacid was administered 2 hours after gemifloxacin.(10) In a study in 16 subjects, simultaneous administration of calcium carbonate decreased the maximum concentration (Cmax) and AUC of a single dose of gemifloxacin (320 mg) by 17% and 21%, respectively. There was no effect of calcium carbonate when administered either 2 hours before or after gemifloxacin.(11) In a study in 27 healthy males, the administration of ferrous sulfate (325 mg) 3 hours before a single dose of gemifloxacin (320 mg) decreased the Cmax and AUC of gemifloxacin by 20% and 11%, respectively. There were no effects when ferrous sulfate was administered 2 hours after gemifloxacin.(12) In a study in 8 healthy subjects, ferrous sulfate (100 mg elemental iron) decreased the Cmax and AUC of a single dose of lomefloxacin by 26% and 13%, respectively. There were no effects with concurrent calcium carbonate (500 mg calcium).(13) Magnesium- and aluminum-containing antacids have been shown to decrease the bioavailability of lomefloxacin by 40%.(14) Administration of moxifloxacin 2 hours before, simultaneously, or 4 hours after a magnesium- and aluminum-containing antacid decreased moxifloxacin AUC by 26%, 60%, and 23%, respectively.(15) Simultaneous administration of moxifloxacin and ferrous sulfate (100 mg) decreased the area-under-curve (AUC) and maximum concentration (Cmax) of moxifloxacin by 39% and 59%, respectively.(16) Concurrent administration of calcium had no affect on moxifloxacin pharmacokinetics.(17) In a study in 10 healthy subjects, an aluminum-magnesium hydroxide antacid decreased the bioavailability of pefloxacin (400 mg) by 44.4%.(18) The administration of an antacid containing aluminum hydroxide and magnesium hydroxide 5 minutes before rufloxacin decreased rufloxacin levels by 36%. Administration of the antacid 4 hours after rufloxacin decreased rufloxacin levels by 13%.(19) Magnesium- and aluminum-containing antacids have been shown to decrease the bioavailability of temafloxacin by 40%.(20) Aluminum hydroxide has been shown to decrease the bioavailability of tosufloxacin by 31.6%.(21) Administration of an antacid containing aluminum hydroxide and magnesium hydroxide 30 minutes before trovafloxacin decreased trovafloxacin levels by 66%.(22) One or more of the drug pairs linked to this monograph have been included in a list of interactions that could be considered for classification as "non-interruptive" in EHR systems. This DDI subset was vetted by an expert panel commissioned by the U.S. Office of the National Coordinator (ONC) for Health Information Technology. |
GATIFLOXACIN SESQUIHYDRATE, MOXIFLOXACIN HCL |
| Selected Cephalosporins/Antacids SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Absorption of oral cefuroxime may be reduced in patients receiving concomitant treatment with acid reducing agents.(1,2) CLINICAL EFFECTS: Antibiotic efficacy against organisms with a high minimum inhibitory concentration (MIC) to cefuroxime could be decreased. PREDISPOSING FACTORS: Taking cefuroxime on an empty stomach magnifies this effect. PATIENT MANAGEMENT: Separate the administration of cefuroxime by at least 1-2 hours after administration of antacids. Some vitamin preparations may contain sufficient quantities of calcium and/or magnesium salts with antacid properties to interact as well. Since concurrent use of H2 antagonists and proton pump inhibitors (PPIs) in patients taking cefuroxime should be avoided, these would not be alternatives to antacids in these patients. DISCUSSION: In a study performed prior to the introduction of PPIs, administration of ranitidine 300 mg and sodium bicarbonate followed by cefuroxime taken on a empty stomach lowered both Cmax and AUC of cefuroxime by approximately 40 per cent compared with administration of cefuroxime alone on an empty stomach. Postprandial administration of cefuroxime in subjects taking ranitidine was similar to that of subjects taking cefuroxime on an empty stomach.(2) |
CEFUROXIME |
| Elvitegravir/Selected Oral Cations SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: The exact mechanism is unknown, but aluminum, calcium, iron, magnesium, sucralfate, and zinc may bind to elvitegravir in GI tract. CLINICAL EFFECTS: Simultaneous administration or administration of products containing aluminum, calcium, iron, magnesium, and/or sucralfate may result in decreased levels and effectiveness of elvitegravir, as well as the development of resistance.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Separate the administration of elvitegravir and products containing aluminum, calcium, iron, magnesium, and/or sucralfate by at least 2 hours.(1) Some vitamin preparations may contain sufficient quantities of calcium and/or magnesium salts with antacid properties to interact as well. DISCUSSION: Administration of an antacid (exact formulation not stated) 2 hours before elvitegravir (50 mg) decreased the maximum concentration (Cmax), area-under-curve (AUC), or minimum concentration (Cmin) of elvitegravir by 18%, 15%, and 10%, respectively.(1) Administration of an antacid 2 hours after elvitegravir (50 mg) decreased the Cmax, AUC, or Cmin of elvitegravir by 21%, 20%, and 20%, respectively.(1) Administration of an antacid 4 hours before elvitegravir (50 mg) decreased the Cmax and AUC of elvitegravir by 5%, and 4%, respectively.(1) Administration of an antacid 4 hours before elvitegravir (50 mg) decreased both the Cmax and AUC of elvitegravir by 2%.(1) |
GENVOYA, STRIBILD |
| Escitalopram (Greater Than 15 mg)/Selected CYP2C19 Inhibitors SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: At lower systemic concentrations, escitalopram is primarily metabolized by CYP2C19; at higher concentrations is also metabolized by CYP3A4.(1) CLINICAL EFFECTS: Concurrent use of an agent which significantly inhibits CYP2C19, or which inhibits both CYP2C19 and CYP3A4 may result in elevated concentrations and toxicity from escitalopram, including risks for serotonin syndrome or prolongation of the QTc interval.(1,5) Prolongation of the QT interval may result in life-threatening arrhythmias, including torsades de pointes.(2) Symptoms of serotonin syndrome may include tremor, agitation, diaphoresis, hyperreflexia, clonus, tachycardia, hyperthermia, and muscle rigidity.(3) PREDISPOSING FACTORS: The risk of QT prolongation may be increased in patients with congenital long QT syndrome, cardiovascular disease (e.g. heart failure, myocardial infarction), hypokalemia, hypomagnesemia, hypocalcemia, bradycardia, female sex, advanced age, poor metabolizer status at CYP2C19, concurrent use of more than one agent known to cause QT prolongation, or with higher blood concentrations of escitalopram.(2) Concurrent use of more than one drug known to cause QT prolongation or higher systemic concentrations of either QT prolonging drug are additional risk factors for torsades de pointes. Factors which may increase systemic drug concentrations include rapid infusion of an intravenous dose or impaired metabolism or elimination of the drug (e.g. coadministration with an agent which inhibits its metabolism or elimination, genetic impairment in drug metabolism or elimination, and/or renal/hepatic dysfunction).(2) Predisposing factors for serotonin-related adverse effects include use in the elderly, in patients with hepatic impairment, and in patients receiving multiple agents which increase central serotonin levels.(1,3) If concurrent therapy is warranted, consider obtaining serum calcium, magnesium, and potassium levels and monitoring ECG at baseline and at regular intervals. Correct any electrolyte abnormalities. Instruct patients to report any irregular heartbeat, dizziness, or fainting. PATIENT MANAGEMENT: Evaluate patient for other drugs, diseases and conditions which may further increase risk for QT prolongation and correct risk factors (e.g. correct hypokalemia, discontinue other QT prolonging drugs) when possible.(2,3) It would be prudent to limit the escitalopram dose to 10 mg daily in patients with QT prolonging risk factors who also receive concurrent therapy with selected CYP2C19 inhibitors.(5) Weigh the specific benefits versus risks for each patient. If concurrent therapy is warranted, patients should be monitored for signs and symptoms of serotonin syndrome. Instruct patients to report muscle twitching, tremors, shivering and stiffness, fever, heavy sweating, heart palpitations, restlessness, confusion, agitation, trouble with coordination, or severe diarrhea. DISCUSSION: A thorough QT study evaluating escitalopram 10 mg or 30 mg once daily was conducted; a change of 10 msec for upper bound of the 95% confidence level is the threshold for regulatory concern. In this study, changes to the upper bound of the 95% confidence interval were 6.4 msec and 12.6 msec for the 10 mg and supratherapeutic 30 mg dose respectively. The Cmax for 30 mg was 1.7-fold higher than the Cmax for the maximum recommended escitalopram dose of 20 mg. Systemic exposure at the 30 mg dose was similar to expected steady state concentrations in 2C19 poor metabolizers following a 20 mg escitalopram dose.(1) In an interaction study, 30 mg of omeprazole, an irreversible inhibitor of CYP2C19 was administered daily for 6 days. On day 5 a single dose of escitalopram 20 mg was also administered; the area-under-curve (AUC) of escitalopram was increased by 50%. Manufacturer prescribing information recommends a maximum citalopram dose of 20mg daily in patients receiving CYP2C19 inhibitors.(1) Inhibitors of CYP2C19 include: abrocitinib, allicin (garlic derivative), berotralstat, cannabidiol (CBD), cenobamate, cimetidine strengths > or = 200 mg, enasidenib, eslicarbazepine, esomeprazole, etravirine, fedratinib, felbamate, fluoxetine, fluvoxamine, givosiran, isoniazid, moclobemide, modafinil, obeticholic acid, omeprazole, piperine, rolapitant, stiripentol, tecovirimat, and tipranavir.(4) |
ESCITALOPRAM OXALATE, LEXAPRO |
| Dolutegravir/Selected Oral Cations SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Aluminum, calcium, iron, lanthanum, magnesium, sucralfate, and zinc may form chelation compounds with dolutegravir.(1) CLINICAL EFFECTS: Simultaneous administration or administration of products containing aluminum, calcium, iron, lanthanum, magnesium, and/or sucralfate close to the administration time of dolutegravir may result in decreased absorption and clinical effectiveness of dolutegravir.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: If possible, avoid concurrent therapy with dolutegravir and cation-containing products. If it is necessary to use these agents concurrently, dolutegravir should be administered 2 hours before or 6 hours after taking these medications.(1) Alternatively, dolutegravir and supplements containing calcium or iron can be taken together with food.(1) DISCUSSION: In a study in 16 subjects, the administration of an antacid (Maalox - aluminum and magnesium hydroxide) simultaneously with dolutegravir (50 mg single dose) decreased the maximum concentration (Cmax), area-under-curve (AUC), and minimum concentration (Cmin) of dolutegravir by 72%, 74%, and 74%, respectively.(1) In a study in 16 subjects, the administration of an antacid (Maalox - aluminum and magnesium hydroxide) 2 hours after dolutegravir (50 mg single dose) decreased dolutegravir Cmax, AUC, and Cmin by 18%, 26%, and 30%, respectively.(1) In a study in 16 subjects, the administration of a multiple vitamin (One-A-Day) simultaneously with dolutegravir (50 mg single dose) decreased dolutegravir Cmax, AUC, and Cmin by 35%, 33%, and 32%, respectively.(1) |
DOVATO, TIVICAY, TIVICAY PD, TRIUMEQ, TRIUMEQ PD |
| Riociguat/Antacids SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: The mechanism of interaction is not clear. Increased gastric pH is thought to decrease riociguat solubility and absorption.(1) CLINICAL EFFECTS: Simultaneous administration of riociguat with an antacid may result in decreased levels and effectiveness of riociguat.(1-2) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Separate the administration of antacids and riociguat by at least 1 hour.(1) Some vitamin preparations may contain sufficient quantities of calcium and/or magnesium salts with antacid properties to interact as well. DISCUSSION: Administration of 10 mL of an aluminum hydroxide-magnesium hydroxide containing antacid decreased the area-under-curve (AUC)and maximum concentration (Cmax)of riociguat by 34% and 56% respectively.(1) |
ADEMPAS |
| Oral Methyldopa/Oral Iron SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Iron, in several forms, binds strongly to methyldopa, producing iron complexes thereby reducing methyldopa absorption. CLINICAL EFFECTS: Concomitant use of methyldopa with iron supplementation may decrease the clinical efficacy of methyldopa. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Patients requiring iron supplementation should be advised to take methyldopa two hours prior to any iron products. DISCUSSION: In a randomized crossover trial with 12 subjects, concurrent use of methyldopa (500 mg daily) and ferrous sulfate (325 mg daily) showed a 28.4% decrease in the proportion of "free" methyldopa (p<0.01), a 28% increase in the proportion excreted as methyldopa sulfate (p<0.01), and a 21.2% decrease in total absorbed methyldopa (p<0.01). Similar results were found when administering ferrous gluconate (600 mg daily). Antihypertensive effects of methyldopa while taking ferrous sulfate were also assessed in five patients chronically taking methyldopa. All participants showed an increase in systolic blood pressure (p=0.03) after two weeks of ferrous sulfate administration. Diastolic blood pressure increased in four patients (p>0.05). After 14 days, three patients had an increase in systolic pressure greater than 15 mm Hg and two patients had an increase of greater than 10 mm Hg in diastolic blood pressures. Both systolic and diastolic pressures decreased after ferrous sulfate was discontinued.(2) |
METHYLDOPA, METHYLDOPA-HYDROCHLOROTHIAZIDE |
| Theophylline Derivatives/Selected CYP1A2 Inhibitors SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: CYP1A2 inhibitors may reduce the elimination rate of theophylline derivatives. CLINICAL EFFECTS: The concurrent administration of selected CYP1A2 inhibitors and theophylline or their derivatives may result in increased levels and toxicity of theophylline.(1-19) PREDISPOSING FACTORS: Concomitant therapy with inhibitors of CYP3A4 (e.g. clarithromycin, itraconazole, ritonavir) which block a secondary metabolic pathway for theophylline, may increase the magnitude of this interaction. PATIENT MANAGEMENT: Theophylline levels should be closely monitored in patients receiving concurrent therapy. The dosage of theophylline may need to be decreased after a CYP1A2 inhibitor is initiated. If the CYP1A2 inhibitor is discontinued in a patient stabilized on the combination, the theophylline level may fall. Monitor theophylline levels and adjust dose accordingly. DISCUSSION: A study in 5 patients with active hepatitis B and 4 healthy subjects examined the effects of a single dose of interferon alpha (9 million units in 8 subjects, 18 million units in 1 subject). There was no effect on theophylline in 1 subject. In the other 8 subjects, interferon increased theophylline half-life by 70% and decreased theophylline clearance by 49% (range 33% to 81%).(1) A study in 11 healthy subjects examined the effects of interferon alpha (3 million International Units daily for 3 days) on a single aminophylline (4 mg/kg) infusion. Interferon increased the half-life, area-under-curve (AUC), and mean residence time by 13.7%, 17.9%, and 16.3%, respectively. Theophylline clearance decreased by 9.1%.(2) In a study in healthy males, peginterferon alfa-2a (180 mcg once weekly for 4 weeks) increased theophylline AUC by 25%.(3,4) Concurrent interferon alfa has been shown to increase theophylline levels by 100%.(5) A study in 7 patients with chronic hepatitis C examined the effects of interferon beta (3 million to 9 million International Units daily for 8 weeks) on theophylline ethylenediamine (single 250 mg infusion). Interferon decreased theophylline clearance by 26.3% and increased theophylline half-life by 39.3%. There was no correlation between interferon dose and effect. The greatest effect was seen in a patient who received 3 million International Units daily, while no effect was seen in a patient who received 9 million International Units daily.(6) Increased serum theophylline levels with signs and symptoms of theophylline toxicity have been reported in patients following the addition of mexiletine to their treatment.(7-15) In a study evaluated the combination of disulfiram and theophylline in 20 recovering alcoholics. Patients received a single IV dose of theophylline while being given either 250 mg or 500 mg of disulfiram daily. Both dosages of disulfiram decreased the clearance of theophylline. However, the effect was greatest in patients receiving disulfiram 500 mg daily.(16) Increases in serum theophylline concentration and half-life have been reported during concurrent administration of theophylline and ticlopidine.(17) In healthy subjects, rofecoxib (12.5 mg/day, 25 mg/day, or 50 mg/day for seven days) increased the area-under-curve (AUC) of a single dose of theophylline (300 mg) by 38% to 60%. Therefore, the manufacturer of rofecoxib recommends that theophylline levels be monitored if rofecoxib is initiated or changed in patients receiving theophylline.(18) Selected CYP1A2 inhibitors linked to this monograph include: Angelica dahurica, artemisinin, cannabidiol, curcumin, danshen, dipyrone, disulfiram, echinacea, enasidenib, fexinidazole, genistein, ginseng, interferons, methoxsalen, mexiletine, parsley, phenylpropanolamine, pipemidic acid, piperine, propafenone, ribociclib, rofecoxib, rucaparib, simeprevir, ticlopidine, triclabendazole, verapamil.(19) |
AMINOPHYLLINE, DYPHYLLINE, ELIXOPHYLLIN, THEO-24, THEOPHYLLINE, THEOPHYLLINE ANHYDROUS, THEOPHYLLINE ER, THEOPHYLLINE ETHYLENEDIAMINE |
| Ledipasvir; Velpatasvir/Antacids; H2 Antagonists SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: The aqueous solubility of ledipasvir and velpatasvir is pH dependent. Higher gastric pH leads to lower solubility which may reduce ledipasvir and velpatasvir's absorption.(1-3) CLINICAL EFFECTS: Administration of antacids and H2 antagonists may reduce the bioavailability of ledipasvir and velpatasvir, leading to decreased systemic levels and effectiveness.(1-3) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: In order to assure systemic absorption and maximal effectiveness from use of this Hepatitis C treatment, counsel patient to separate products containing ledipasvir or velpatasvir from antacid administration by 4 hours.(1-3) H2 antagonists may be administered simultaneously or 12 hours apart from products containing ledipasvir or velpatasvir at a dose that does not exceed doses comparable to famotidine 40 mg twice daily (or a total daily dose comparable to famotidine 80 mg).(1-3) Some vitamin preparations may contain sufficient quantities of calcium and/or magnesium salts with antacid properties to interact as well. DISCUSSION: In an interaction study, famotidine 40 mg, given with or 12 hours after a ledipasvir-sofosbuvir dose did not have significant effects on ledipasvir-sofosbuvir exposure.(1) In an interaction study, famotidine 40 mg, given with or 12 hours prior to a velpatasvir-sofosbuvir dose did not have a significant effect on velpatasvir-sofosbuvir exposure.(2) In an interaction study, famotidine (dosage not stated) did not have a significant effect on the pharmacokinetic of sofosbuvir, velpatasvir, or voxilaprevir.(3) |
EPCLUSA, HARVONI, LEDIPASVIR-SOFOSBUVIR, SOFOSBUVIR-VELPATASVIR, VOSEVI |
| Lesinurad/Moderate CYP2C9 Inhibitors SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Moderate inhibitors of CYP2C9 may inhibit the metabolism of lesinurad.(1) CLINICAL EFFECTS: Concurrent use of moderate inhibitors of CYP2C9 may result in elevated levels and toxicity from lesinurad, include nephrotoxicity.(1) PREDISPOSING FACTORS: Patients with decreased renal function (CrCl less than 60 ml/min) and patients not receiving a xanthine oxidase inhibitor may be at increased risk of nephrotoxicity.(1) PATIENT MANAGEMENT: Approach the concurrent use of lesinurad and moderate inhibitors of CYP2C9 with caution.(1) Monitor renal function in patients receiving concurrent therapy closely. Interrupt therapy and measure serum creatinine promptly in patients who report flank pain and/or nausea/vomiting. DISCUSSION: Fluconazole (200 mg daily), a moderate inhibitor of CYP2C9, increased lesinurad levels by 50%.(1) |
DUZALLO |
| Dolutegravir-Rilpivirine/Selected Oral Cations; Antacids; H2 Antagonists SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Aluminum, calcium, iron, lanthanum, magnesium, sucralfate, and zinc may form chelation compounds with dolutegravir.(1) Rilpivirine requires an acidic medium for absorption. Antacid or H2 antagonist induced decrease in gastric pH may result in decrease in rilpivirine absorption.(1) CLINICAL EFFECTS: Simultaneous administration or administration of products containing aluminum, calcium, iron, lanthanum, magnesium, and/or sucralfate close to the administration time of dolutegravir may result in decreased absorption and clinical effectiveness of dolutegravir.(1) Simultaneous administration of an antacid or a H2 antagonist may result in decreased levels and effectiveness of rilpivirine, as well as the development of resistance.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: If possible, avoid concurrent therapy with dolutegravir-rilpivirine and cation-containing products. If it is necessary to use these agents concurrently, dolutegravir-rilpivirine should be administered 4 hours before or 6 hours after taking these medications.(1) Alternatively, dolutegravir-rilpivirine and supplements containing calcium or iron can be taken together with food.(1) In patients maintained on dolutegravir-rilpivirine, administer dolutegravir-rilpivirine at least 4 hours before or 6 hours after antacids .(1) In patients maintained on dolutegravir-rilpivirine, administer dolutegravir-rilpivirine at least 4 hours before or 12 hours after H2 antagonists.(1) Concurrent use of proton pump inhibitors will dolutegravir-rilpivirine is contraindicated.(1) DISCUSSION: In a study in 16 subjects, the administration of an antacid (Maalox - aluminum and magnesium hydroxide) simultaneously with dolutegravir (50 mg single dose) decreased the maximum concentration (Cmax), area-under-curve (AUC), and minimum concentration (Cmin) of dolutegravir by 72%, 74%, and 74%, respectively.(1) In a study in 16 subjects, the administration of an antacid (Maalox - aluminum and magnesium hydroxide) 2 hours after dolutegravir (50 mg single dose) decreased dolutegravir Cmax, AUC, and Cmin by 18%, 26%, and 30%, respectively.(1) In a study in 16 subjects, the administration of a multiple vitamin (One-A-Day) simultaneously with dolutegravir (50 mg single dose) decreased dolutegravir Cmax, AUC, and Cmin by 35%, 33%, and 32%, respectively.(1) In a study in 16 subjects, omeprazole (20 mg daily) decreased the Cmax, AUC, and Cmin of rilpivirine (150 mg daily) by 40%, 40%, and 33%, respectively. The Cmax and AUC of omeprazole decreased by 14% and 14%, respectively.(1) In a study in 24 subjects, famotidine (40 mg single dose) administered 12 hours before a single dose of rilpivirine (150 mg) had no significant effect on rilpivirine Cmax or AUC.(1) In a study in 23 subjects, famotidine (40 mg single dose) administered 2 hours before a single dose of rilpivirine (150 mg) decreased the rilpivirine Cmax and AUC by 85% and 76%, respectively.(1) In a study in 24 subjects, famotidine (40 mg single dose) administered 4 hours before a single dose of rilpivirine (150 mg) increased the rilpivirine Cmax and AUC by 21% and 13%, respectively.(1) |
JULUCA |
| Bictegravir/Polyvalent Cations; Sucralfate SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Polyvalent cations and sucralfate may bind to bictegravir in the GI tract, preventing its absorption.(1) CLINICAL EFFECTS: Polyvalent cations and sucralfate may reduce levels and clinical effectiveness of bictegravir.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Bictegravir must be taken 2 hours before or 6 hours after polyvalent cations or sucralfate. Medicines containing calcium can be taken together with bictegravir if taken with food.(1) Some vitamin preparations may contain sufficient quantities of polyvalent cations to interact as well. DISCUSSION: Simultaneous administration of aluminum and magnesium hydroxide (20 ml) in a fasted state with bictegravir (50 mg single dose) decreased bictegravir maximum concentration (Cmax) and area-under-curve (AUC) by 80% and 79%, respectively.(1) Administration of aluminum and magnesium hydroxide (20 ml) 2 hours after bictegravir (50 mg single dose) in a fasted state decreased bictegravir Cmax and AUC by 7% and 13%, respectively.(1) Administration of aluminum and magnesium hydroxide (20 ml) 2 hours before bictegravir (50 mg single dose) in a fasted state decreased bictegravir Cmax and AUC by 58% and 52%, respectively.(1) Simultaneous administration of aluminum and magnesium hydroxide (20 ml) in a fed state with bictegravir (50 mg single dose) decreased bictegravir Cmax and AUC by 49% and 47%, respectively.(1) Simultaneous administration of calcium carbonate (1200 mg single dose) in a fasted state with bictegravir (50 mg single dose) decreased bictegravir Cmax and AUC by 42% and 33%, respectively.(1) Simultaneous administration of calcium carbonate (1200 mg single dose) in a fed state with bictegravir (50 mg single dose) decreased bictegravir Cmax by 10% and increased AUC 3%, respectively.(1) Simultaneous administration of ferrous fumarate (324 mg single dose) in a fasted state with bictegravir (50 mg single dose) decreased bictegravir Cmax and AUC by 71% and 63%, respectively.(1) Simultaneous administration of ferrous fumarate (324 mg single dose) in a fed state with bictegravir (50 mg single dose) decreased bictegravir Cmax and AUC by 25% and 16%, respectively.(1) |
BIKTARVY |
| Bictegravir/Calcium & Iron Containing Supplements SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Calcium or iron containing supplements may bind to bictegravir in the GI tract, preventing its absorption.(1) CLINICAL EFFECTS: Calcium or iron containing supplements may reduce levels and clinical effectiveness of bictegravir.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Bictegravir and calcium or iron containing supplements may be taken together with food. Routine administration of bictegravir under fasting conditions simultaneously with, or within 2 hours after, calcium or iron containing supplements is not recommended.(1) In pregnant patients, if bictegravir is taken on an empty stomach, take bictegravir at least 2 hours before or 6 hours after calcium or iron containing supplements.(1) DISCUSSION: Simultaneous administration of aluminum and magnesium hydroxide (20 ml) in a fasted state with bictegravir (50 mg single dose) decreased bictegravir maximum concentration (Cmax) and area-under-curve (AUC) by 80% and 79%, respectively.(1) Administration of aluminum and magnesium hydroxide (20 ml) 2 hours after bictegravir (50 mg single dose) in a fasted state decreased bictegravir Cmax and AUC by 7% and 13%, respectively.(1) Administration of aluminum and magnesium hydroxide (20 ml) 2 hours before bictegravir (50 mg single dose) in a fasted state decreased bictegravir Cmax and AUC by 58% and 52%, respectively.(1) Simultaneous administration of aluminum and magnesium hydroxide (20 ml) in a fed state with bictegravir (50 mg single dose) decreased bictegravir Cmax and AUC by 49% and 47%, respectively.(1) Simultaneous administration of calcium carbonate (1200 mg single dose) in a fasted state with bictegravir (50 mg single dose) decreased bictegravir Cmax and AUC by 42% and 33%, respectively.(1) Simultaneous administration of calcium carbonate (1200 mg single dose) in a fed state with bictegravir (50 mg single dose) decreased bictegravir Cmax by 10% and increased AUC 3%, respectively.(1) Simultaneous administration of ferrous fumarate (324 mg single dose) in a fasted state with bictegravir (50 mg single dose) decreased bictegravir Cmax and AUC by 71% and 63%, respectively.(1) Simultaneous administration of ferrous fumarate (324 mg single dose) in a fed state with bictegravir (50 mg single dose) decreased bictegravir Cmax and AUC by 25% and 16%, respectively.(1) |
BIKTARVY |
| Escitalopram (Less Than or Equal To 15 mg)/Selected CYP2C19 Inhibitors SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: At lower systemic concentrations, escitalopram is primarily metabolized by CYP2C19; at higher concentrations is also metabolized by CYP3A4.(1) CLINICAL EFFECTS: Concurrent use of an agent which significantly inhibits CYP2C19, or which inhibits both CYP2C19 and CYP3A4 may result in elevated concentrations and toxicity from escitalopram, including risks for serotonin syndrome or prolongation of the QTc interval.(1,5) Prolongation of the QT interval may result in life-threatening arrhythmias, including torsades de pointes.(2) Symptoms of serotonin syndrome may include tremor, agitation, diaphoresis, hyperreflexia, clonus, tachycardia, hyperthermia, and muscle rigidity.(3) PREDISPOSING FACTORS: The risk of QT prolongation may be increased in patients with congenital long QT syndrome, cardiovascular disease (e.g. heart failure, myocardial infarction), hypokalemia, hypomagnesemia, hypocalcemia, bradycardia, female sex, advanced age, poor metabolizer status at CYP2C19, concurrent use of more than one agent known to cause QT prolongation, or with higher blood concentrations of escitalopram.(2) Concurrent use of more than one drug known to cause QT prolongation or higher systemic concentrations of either QT prolonging drug are additional risk factors for torsades de pointes. Factors which may increase systemic drug concentrations include rapid infusion of an intravenous dose or impaired metabolism or elimination of the drug (e.g. coadministration with an agent which inhibits its metabolism or elimination, genetic impairment in drug metabolism or elimination, and/or renal/hepatic dysfunction).(2) Predisposing factors for serotonin-related adverse effects include use in the elderly, in patients with hepatic impairment, and in patients receiving multiple agents which increase central serotonin levels.(1,3) If concurrent therapy is warranted, consider obtaining serum calcium, magnesium, and potassium levels and monitoring ECG at baseline and at regular intervals. Correct any electrolyte abnormalities. Instruct patients to report any irregular heartbeat, dizziness, or fainting. PATIENT MANAGEMENT: Evaluate patient for other drugs, diseases and conditions which may further increase risk for QT prolongation and correct risk factors (e.g. correct hypokalemia, discontinue other QT prolonging drugs) when possible.(2,3) It would be prudent to limit the escitalopram dose to 10 mg daily in patients with QT prolonging risk factors who also receive concurrent therapy with selected CYP2C19 inhibitors.(5) Weigh the specific benefits versus risks for each patient. If concurrent therapy is warranted, patients should be monitored for signs and symptoms of serotonin syndrome. Instruct patients to report muscle twitching, tremors, shivering and stiffness, fever, heavy sweating, heart palpitations, restlessness, confusion, agitation, trouble with coordination, or severe diarrhea. DISCUSSION: A thorough QT study evaluating escitalopram 10 mg or 30 mg once daily was conducted; a change of 10 msec for upper bound of the 95% confidence level is the threshold for regulatory concern. In this study, changes to the upper bound of the 95% confidence interval were 6.4 msec and 12.6 msec for the 10 mg and supratherapeutic 30 mg dose respectively. The Cmax for 30 mg was 1.7-fold higher than the Cmax for the maximum recommended escitalopram dose of 20 mg. Systemic exposure at the 30 mg dose was similar to expected steady state concentrations in 2C19 poor metabolizers following a 20 mg escitalopram dose.(1) In an interaction study, 30 mg of omeprazole, an irreversible inhibitor of CYP2C19 was administered daily for 6 days. On day 5 a single dose of escitalopram 20 mg was also administered; the area-under-curve (AUC) of escitalopram was increased by 50%. Manufacturer prescribing information recommends a maximum citalopram dose of 20mg daily in patients receiving CYP2C19 inhibitors.(1) Inhibitors of CYP2C19 include: abrocitinib, allicin (garlic derivative), berotralstat, cannabidiol (CBD), cenobamate, cimetidine strengths > or = 200 mg, enasidenib, eslicarbazepine, esomeprazole, etravirine, fedratinib, felbamate, fluoxetine, fluvoxamine, givosiran, isoniazid, moclobemide, modafinil, obeticholic acid, omeprazole, piperine, rolapitant, stiripentol, tecovirimat, and tipranavir.(4) |
ESCITALOPRAM OXALATE, LEXAPRO |
| Baloxavir/Polyvalent Cations SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Aluminum, calcium, iron, magnesium, selenium, and zinc may form chelation compounds with baloxavir.(1) CLINICAL EFFECTS: Simultaneous administration of products containing aluminum, calcium, iron, magnesium, selenium, and zinc may result in decreased levels of and clinical effects from baloxavir.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Avoid concurrent administration of baloxavir with cation-containing products.(1) DISCUSSION: A significant decrease in baloxavir exposure was observed when baloxavir was coadministered with calcium, aluminum, magnesium, or iron in monkeys. No studies have been conducted in humans.(1) |
XOFLUZA |
| Colesevelam/Fat Soluble Vitamins SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Colesevelam may decrease the absorption of fat-soluble vitamins A, D, E, and K.(1) CLINICAL EFFECTS: Colesevelam may reduce absorption of fat soluble vitamins, leading to a deficiency state. PREDISPOSING FACTORS: A pre-existing deficiency of fat soluble vitamins (A,D,E and K) or chronic malabsorption syndrome. PATIENT MANAGEMENT: The inhibition of fat soluble vitamin absorption by colesevelam should be borne in mind during implementation of a vitamin supplementation strategy. Oral multivitamin supplements should be taken at least four hours before the dose of colesevelam.(1) DISCUSSION: Colesevelam may decrease the absorption of fat-soluble vitamins A, D, E, and K.(1) |
COLESEVELAM HCL, WELCHOL |
| Trientine/Iron Salts, Oral SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Trientine is a chelating agent. Concurrent administration with iron may reduce the absorption of both trientine and iron. CLINICAL EFFECTS: Iron may decrease the levels and clinical effects of trientine, and trientine may reduce serum iron levels. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Avoid use of iron salts within 2 hours of trientine dose. Monitor clinical status for decreased effectiveness and adjust the trientine dose if necessary. DISCUSSION: Multivitamins with low doses of iron may decrease trientine absorption so ensure patient is aware of the risks. Also, as patients may be unaware which foods contain iron, instruct patients to take trientine on an empty stomach, at least one hour before meals or two hours after food or milk. |
CUVRIOR, SYPRINE, TRIENTINE HCL |
| Trientine/Selected Minerals, Oral SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Mineral supplements may bind to trientine and block its absorption. CLINICAL EFFECTS: The levels and clinical effects of trientine may be decreased. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of trientine states that mineral supplements should not be given with trientine. If concomitant therapy is necessary, take trientine on an empty stomach and separate administration at least one hour apart from any other drug. Monitor clinical status for decreased effectiveness and adjust the trientine dose if necessary. DISCUSSION: Multivitamins with minerals may decrease trientine absorption so ensure patient is aware of the risks. |
CUVRIOR, SYPRINE, TRIENTINE HCL |
| Tacrolimus/Moderate and Weak CYP3A4 Inhibitors SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Moderate and weak inhibitors of CYP3A4 may inhibit the metabolism of tacrolimus.(1) CLINICAL EFFECTS: Concurrent use of a CYP3A4 inhibitor may result in elevated levels of and toxicity from tacrolimus, including nephrotoxicity, neurotoxicity, and prolongation of the QTc interval and life-threatening cardiac arrhythmias, including torsades de pointes.(1) PREDISPOSING FACTORS: The risk of QT prolongation or torsade de pointes may be increased in patients with cardiovascular disease (e.g. heart failure, myocardial infarction, history of torsade de pointes, congenital long QT syndrome), hypokalemia, hypomagnesemia, hypocalcemia, bradycardia, female gender, or advanced age.(2) Concurrent use of more than one drug known to cause QT prolongation or higher systemic concentrations of either QT prolonging drug are additional risk factors for torsade de pointes. Factors which may increase systemic drug concentrations include rapid infusion of an intravenous dose or impaired metabolism or elimination of the drug (e.g. coadministration with an agent which inhibits its metabolism or elimination, and/or renal/hepatic dysfunction).(2) PATIENT MANAGEMENT: The US manufacturer of tacrolimus recommends monitoring tacrolimus whole blood trough concentrations and reducing tacrolimus dose if needed.(1) Consider obtaining serum calcium, magnesium, and potassium levels and monitoring ECG at baseline and at regular intervals. Correct any electrolyte abnormalities. Instruct patients to report any irregular heartbeat, dizziness, or fainting. DISCUSSION: In a study of 26 renal transplant recipients, conjugated estrogens 3.75 mg daily increased the tacrolimus dose-corrected concentration of tacrolimus by 85.6%. Discontinuation of the conjugated estrogens led to a decrease in tacrolimus concentration of 46.6%.(3) A case report describes a 65-year-old kidney transplant recipient who was stable on tacrolimus 9 mg per day with trough levels of 5 to 7.5 ng/mL. Ten days after starting on estradiol gel 0.5 mg per day, her tacrolimus level rose to 18.3 ng/mL and serum creatinine (Scr) rose from 1.1 mg/dL at baseline to 2 mg/dL. Tacrolimus dose was reduced by 60%, and trough levels and Scr normalized after two weeks.(4) A study of 16 healthy volunteers found that elbasvir 50 mg/grazoprevir 200 mg daily increased the area-under-curve (AUC) of tacrolimus by 43%, while the maximum concentration (Cmax) of tacrolimus was decreased by 40%.(5) An analysis of FAERS data from 2004-2017, found a significant assoc ation between transplant rejection and concurrent use of tacrolimus and clotrimazole (reporting odds ration 1.92, 95% CI). A retrospective study of 7 heart transplant patients on concurrent tacrolimus and clotrimazole troche showed a significant correlation between tacrolimus trough concentration and AUC after clotrimazole discontinuation. Tacrolimus clearance and bioavailability after clotrimazole discontinuation was 2.2-fold greater (0.27 vs. 0.59 L/h/kg) and the trough concentration decreased from 6.5 ng/mL at 1 day to 5.3 ng/mL at 2 days after clotrimazole discontinuation.(7) A retrospective study of 26 heart transplant patients found that discontinuation of concurrent clotrimazole with tacrolimus in the CYP3A5 expresser group had a 3.3-fold increase in apparent oral clearance and AUC of tacrolimus (0.27 vs. 0.89 L/h/kg) compared to the CYP3A5 non expresser group with a 2.2-fold mean increase (0.18 vs. 0.39 L/h/kg).(8) A study of 6 adult kidney transplant recipients found that clotrimazole (5-day course) increased the tacrolimus AUC 250% and the blood trough concentrations doubled (27.7 ng/ml versus 27.4 ng/ml). Tacrolimus clearance decreased 60% with coadministration of clotrimazole.(9) A case report describes a 23-year-old kidney transplant recipient who was stable on tacrolimus 5 mg twice daily, mycophenolate mofetil 30 mg daily, prednisone (30 mg daily tapered over time to 5 mg), and clotrimazole troche 10 mg four times daily. Discontinuation of clotrimazole resulted in a decrease in tacrolimus trough levels from 13.7 ng/ml to 5.4 ng/ml over a period of 6 days. Clotrimazole was restarted with tacrolimus 6 mg resulting in an increased tacrolimus level of 19.2 ng/ml.(10) A retrospective study in 95 heart transplant recipients on concurrent clotrimazole and tacrolimus found a median tacrolimus dose increase of 66.7% was required after clotrimazole discontinuation. Tacrolimus trough concentration was found to have decreased 42.5% after clotrimazole discontinuation.(11) A retrospective study in 65 pancreas transplant patients on concurrent tacrolimus, clotrimazole, cyclosporine, and prednisone found that clotrimazole discontinuation at 3 months after transplantation may cause significant tacrolimus trough level reductions.(12) Moderate CYP3A4 inhibitors linked to this monograph include: aprepitant, berotralstat, clofazimine, conivaptan, fluvoxamine, lenacapavir, letermovir, netupitant, nirogacestat, and tofisopam.(6) Weak CYP3A4 inhibitors linked to this monograph include: alprazolam, avacopan, baikal skullcap, berberine, bicalutamide, blueberry, brodalumab, chlorzoxazone, cimetidine, cranberry juice, daclatasvir, daridorexant, delavirdine, diosmin, estrogens, flibanserin, fosaprepitant, fostamatinib, ginkgo biloba, givinostat, glecaprevir/pibrentasvir, goldenseal, grazoprevir, isoniazid, istradefylline, ivacaftor, lacidipine, lazertinib, linagliptin, lomitapide, lumateperone, lurasidone, peppermint oil, piperine, propiverine, ranitidine, remdesivir, resveratrol, rimegepant, simeprevir, sitaxsentan, skullcap, suvorexant, ticagrelor, tolvaptan, trofinetide, viloxazine, and vonoprazan-amoxicillin.(6) |
ASTAGRAF XL, ENVARSUS XR, PROGRAF, TACROLIMUS, TACROLIMUS XL |
| Lemborexant (Less Than or Equal To 5 mg)/Weak CYP3A4 Inhibitors SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Inhibitors of CYP3A4 may inhibit the metabolism of lemborexant.(1) CLINICAL EFFECTS: Concurrent use of an inhibitor of CYP3A4 may result in increased levels of and effects from lemborexant, including somnolence, fatigue, CNS depressant effects, daytime impairment, headache, and nightmare or abnormal dreams.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The maximum recommended dose of lemborexant with concurrent use of a weak CYP3A4 inhibitors should not exceed 5 mg per dose.(1) DISCUSSION: Lemborexant is a CYP3A4 substrate. In a PKPB model, concurrent use of lemborexant with itraconazole increased area-under-curve (AUC) and concentration maximum (Cmax) by 3.75-fold and 1.5-fold, respectively. Concurrent use of lemborexant with fluconazole increased AUC and Cmax by 4.25-fold and 1.75-fold, respectively.(1) Weak inhibitors of CYP3A4 include: alprazolam, amiodarone, amlodipine, asciminib, azithromycin, Baikal skullcap, belumosudil, berberine, bicalutamide, blueberry, brodalumab, cannabidiol, capivasertib, chlorzoxazone, cilostazol, cimetidine, ciprofloxacin, clotrimazole, cranberry, cyclosporine, daclatasvir, daridorexant, delavirdine, dihydroberberine, diosmin, everolimus, flibanserin, fosaprepitant, fostamatinib, gepotidacin, ginkgo, givinostat, glecaprevir/pibrentasvir, goldenseal, grazoprevir, isoniazid, istradefylline, ivacaftor, lacidipine, lapatinib, larotrectinib, lazertinib, leflunomide, levamlodipine, linagliptin, lomitapide, lurasidone, mavorixafor, olaparib, osilodrostat, palbociclib, pazopanib, peppermint oil, piperine, propiverine, propofol, ranitidine, ranolazine, remdesivir, resveratrol, roxithromycin, rucaparib, selpercatinib, simeprevir, sitaxsentan, skullcap, suvorexant, teriflunomide, ticagrelor, tolvaptan, trofinetide, viloxazine, and vonoprazan.(1,2) |
DAYVIGO |
| Ubrogepant/Weak CYP3A4 Inhibitors SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Weak inhibitors of CYP3A4 may inhibit the metabolism of ubrogepant.(1) CLINICAL EFFECTS: Concurrent use of ubrogepant with weak CYP3A4 inhibitors may result in an increase in exposure of ubrogepant.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer recommends a dosage adjustment of ubrogepant when used concomitantly with weak CYP3A4 inhibitors. Initial dose of ubrogepant should not exceed 50 mg when used concomitantly with weak inhibitors of CYP3A4. A second dose may be given within 24 hours but should not exceed 50 mg when used concurrently with weak CYP3A4 inhibitors.(1) DISCUSSION: Coadministration of ubrogepant with verapamil, a moderate CYP3A4 inhibitor, resulted in a 3.5-fold and 2.8-fold increase in area-under-curve (AUC) and concentration maximum (Cmax), respectively. No dedicated drug interaction study was conducted to assess concomitant use with weak CYP3A4 inhibitors. The conservative prediction of the maximal potential increase in ubrogepant exposure with weak CYP3A4 inhibitors is not expected to be more than 2-fold.(1) Weak inhibitors of CYP3A4 include: alprazolam, amiodarone, amlodipine, asciminib, azithromycin, Baikal skullcap, berberine, bicalutamide, blueberry, brodalumab, cannabidiol, capivasertib, chlorzoxazone, cilostazol, cimetidine, ciprofloxacin, clotrimazole, cranberry, cyclosporine, daclatasvir, delavirdine, dihydroberberine, diosmin, elagolix, everolimus, flibanserin, fosaprepitant, fostamatinib, gepotidacin, givinostat, glecaprevir/pibrentasvir, goldenseal, grazoprevir, isoniazid, istradefylline, ivacaftor, lacidipine, lapatinib, larotrectinib, lazertinib, leflunomide, levamlodipine, linagliptin, lomitapide, lurasidone, maribavir, mavorixafor, osilodrostat, palbociclib, pazopanib, peppermint oil, piperine, propiverine, propofol, ranitidine, ranolazine, remdesivir, resveratrol, roxithromycin, simeprevir, sitaxsentan, skullcap, suvorexant, teriflunomide, ticagrelor, tolvaptan, trofinetide, viloxazine, and vonoprazan.(2,3) |
UBRELVY |
| Infigratinib; Selpercatinib/Antacids SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: The solubility of infigratinib and selpercatinib is pH dependent. Antacid-induced changes in gastric pH may decrease the absorption of infigratinib and selpercatinib.(1,2) CLINICAL EFFECTS: Simultaneous administration of antacids may result in decreased levels and effectiveness of infigratinib and selpercatinib.(1,2) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Avoid the use of antacids, proton pump inhibitors (PPIs), and H2 antagonists, in patients receiving treatment with infigratinib or selpercatinib. If coadministration with antacids cannot be avoided, take infigratinib or selpercatinib at least 2 hours before or 2 hours after the antacid.(1,2) If the antacid is replaced with a H2 antagonist, take infigratinib or selpercatinib 2 hours before or 10 hours after the H2 antagonist.(1,2) If the antacid is replaced with a PPI, take selpercatinib with food.(2) DISCUSSION: Infigratinib is practically insoluble at pH 6.8.(1) Selpercatinib solubility is pH dependent.(2) Antacids may decrease the solubility and absorption of infigratinib and selpercatinib and decrease their effectiveness. |
RETEVMO |
| Entacapone/Oral Iron Supplements SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Entacapone may chelate with iron within the gastrointestinal tract, reducing the absorption of both drugs. CLINICAL EFFECTS: Simultaneous administration of entacapone and orally administered iron may decrease the clinical effects of both medications. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Iron supplements should not be taken within 2-3 hours before or after entacapone to minimize the effects of this interaction.(1) Some multivitamin preparations that contain sufficient quantities of iron may interact and not be properly absorbed as well. DISCUSSION: Entacapone may form chelates with iron in the gastrointestinal tract, and preparations should be taken at least 2-3 hours apart.(1) Although the impact on the body's iron stores is unknown, clinical studies showed decreasing serum iron concentrations with coadministration of entacapone.(2) In repeated dose toxicity studies, anemia was observed most likely due to the iron chelating properties of entacapone.(1) Prescribing information of entacapone/levodopa/carbidopa states chelation of entacapone with iron may decrease bioavailability of entacapone/levodopa/carbidopa.(3) |
CARBIDOPA-LEVODOPA-ENTACAPONE, ENTACAPONE |
| Cabotegravir/Polyvalent Cations SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Cabotegravir chelates polyvalent cations such as aluminum, calcium, iron, magnesium, selenium, and zinc.(1) CLINICAL EFFECTS: Simultaneous administration of cabotegravir and polyvalent cations may decrease the absorption and clinical effects of cabotegravir.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of cabotegravir states that it should be administered at least 2 hours before or 4 hours after any medications or products containing polyvalent cations such as antacids or mineral supplements.(1) DISCUSSION: Clinical studies have not been conducted. Prescribing information states cabotegravir levels may be decreased when coadministered with antacids containing polyvalent cations (examples include aluminum or magnesium hydroxide, calcium carbonate) suggesting cabotegravir is susceptible to chelation.(1) |
VOCABRIA |
| Sotorasib/Antacids SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: The aqueous solubility of sotorasib is pH dependent. Higher gastric pH leads to lower solubility which may reduce sotorasib absorption.(1) CLINICAL EFFECTS: Coadministration of antacids may reduce the bioavailability of sotorasib, leading to decreased systemic levels and effectiveness.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Coadministration of sotorasib with proton pump inhibitors, H2 antagonists, and antacids should be avoided. If coadministration with an acid-reducing agent is unavoidable, take sotorasib 4 hours before or 10 hours after a locally acting antacid.(1) DISCUSSION: The solubility of sotorasib in the aqueous media decreases over the range pH 1.2 to 6.8 from 1.3 mg/mL to 0.03 mg/mL. In an interaction study, coadministration of repeat doses of omeprazole with a single dose of sotorasib decreased sotorasib maximum concentration (Cmax) by 65% and area-under-curve (AUC) by 57% under fed conditions, and decreased sotorasib Cmax by 57% and AUC by 42% under fasted conditions. Coadministration of a single dose of famotidine given 10 hours prior to and 2 hours after a single dose of sotorasib under fed conditions decreased sotorasib Cmax by 35% and AUC by 38%.(1) |
LUMAKRAS |
| Sirolimus Protein-Bound/Slt Moderate and Weak CYP3A4 Inhibit SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Moderate and weak CYP3A4 inhibitors may inhibit the metabolism of sirolimus by CYP3A4.(1) CLINICAL EFFECTS: Concurrent use of moderate or weak CYP3A4 inhibitors may result in elevated levels of and side effects from sirolimus.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of sirolimus protein-bound injection (Fyarro) states a dose reduction to 56 mg/m2 is recommended when used concurrently with moderate or weak CYP3A4 inhibitors. Concurrent use with strong CYP3A4 inhibitors should be avoided.(1) DISCUSSION: In an open, randomized, cross-over trial in 18 healthy subjects, concurrent single doses of diltiazem (120 mg) and sirolimus (10 mg) increased sirolimus area-under-curve (AUC) and maximum concentration (Cmax) by 60% and by 43%, respectively. Sirolimus apparent oral clearance and volume of distribution decreased by 38% and 45%, respectively. There were no effects on diltiazem pharmacokinetics or pharmacodynamics.(2) In a study in 26 healthy subjects, concurrent sirolimus (2 mg daily) with verapamil (180 mg twice daily) increased sirolimus AUC and Cmax by 2.2-fold and 2.3-fold, respectively. The AUC and Cmax of the active S-enantiomer of verapamil each increased by 1.5-fold. Verapamil time to Cmax (Tmax) was increased by 1.2 hours.(2) Moderate and weak CYP3A4 inhibitors linked to this monograph include: alprazolam, amlodipine, aprepitant, avacopan, azithromycin, berberine, berotralstat, bicalutamide, blueberry, brodalumab, chlorzoxazone, cilostazol, cimetidine, ciprofloxacin, clofazimine, conivaptan, daclatasvir, daridorexant, delavirdine, diosmin, entrectinib, erythromycin, estrogen, flibanserin, fluvoxamine, fosaprepitant, fosnetupitant, fostamatinib, ginkgo, givinostat, glecaprevir/pibrentasvir, goldenseal, grazoprevir, isoniazid, istradefylline, ivacaftor, lacidipine, lazertinib, lenacapavir, levamlodipine, linagliptin, lomitapide, lumateperone, lurasidone, mavorixafor, netupitant, omeprazole, osilodrostat, peppermint oil, piperine, propiverine, propofol, ranitidine, ranolazine, remdesivir, resveratrol, rimegepant, roxithromycin, scutellarin, simeprevir, sitaxsentan, suvorexant, ticagrelor, tofisopam, tolvaptan, trofinetide and vonoprazan.(3,4) |
FYARRO |
| Pafolacianine/Folic Acid SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Folate, folic acid, and folate-containing supplements may reduce binding of pafolacianine to folate receptors expressed on ovarian cancer cells. CLINICAL EFFECTS: Folate, folic acid, and folate-containing supplements could reduce the detection of malignant lesions with pafolacianine. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Avoid administration of folate, folic acid, or folate-containing supplements within 48 hours before administration of pafolacianine. DISCUSSION: Folate, folic acid, and folate-containing supplements may reduce binding of pafolacianine to folate receptors expressed on cancer cells, which could result in reduced detection of malignant lesions with pafolacianine. |
CYTALUX |
| Levoketoconazole/Antacids SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: The aqueous solubility of levoketoconazole is pH dependent. Higher gastric pH leads to lower solubility. Antacids increase gastric pH and may decrease the absorption of levoketoconazole.(1) CLINICAL EFFECTS: Coadministration of antacids may reduce the bioavailability of levoketoconazole, leading to decreased systemic levels and effectiveness.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Coadministration of levoketoconazole with proton pump inhibitors and H2 antagonists should be avoided. If coadministration with an acid-reducing agent is unavoidable, take the antacid 2 hours before levoketoconazole.(1) DISCUSSION: Levoketoconazole is very slightly soluble in water but soluble below pH 2. Antacids raise gastric pH and may impair dissolution and absorption of levoketoconazole.(1) |
RECORLEV |
| Sparsentan/Antacids SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: The aqueous solubility of sparsentan is pH dependent. Higher gastric pH leads to lower solubility. Antacids increase gastric pH and may decrease the absorption of sparsentan.(1) CLINICAL EFFECTS: Coadministration of antacids may reduce the bioavailability of sparsentan, leading to decreased systemic levels and effectiveness.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: If coadministration with an acid-reducing agent is unavoidable, take an antacid 2 hours before or 2 hours after sparsentan. Coadministration of sparsentan with proton pump inhibitors and H2 antagonists should be avoided.(1) DISCUSSION: Sparsentan is practically insoluble in water but has intrinsic solubility of 1.48 mg/mL and 0.055 mg/mL below pH 1.2 and 6.8, respectively. Antacids raise gastric pH and may impair dissolution and absorption of sparsentan.(1) |
FILSPARI |
| Amphetamines/Antacids; Urinary Alkalinizers SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Antacids and urinary alkalinizers increase the absorption of amphetamines. CLINICAL EFFECTS: Concurrent use of amphetamines and antacids or urinary alkalinizers may result in increased amphetamine levels and side effects. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US and Canadian manufacturers state that coadministration of alkalinizing agents with amphetamines should be avoided.(1-3) The Canadian manufacturer states that concurrent use of proton pump inhibitors and amphetamines should be avoided.(3) The US manufacturer states that patients receiving concurrent therapy should be monitored for changes in clinical effects.(1) Monitor patients receiving concurrent therapy for changes in amphetamine effectiveness and side effects. If concurrent use cannot be avoided, separate the administration times of amphetamines and antacids. Some vitamin preparations may contain sufficient quantities of calcium and/or magnesium salts with antacid properties to interact as well. DISCUSSION: Concurrent use of alkalinizing agents with amphetamines increase the absorption of amphetamines. Co-administration of these should be avoided because of the potential of increased actions of the amphetamines.(1,2) |
ADDERALL, ADDERALL XR, ADZENYS XR-ODT, AMPHETAMINE SULFATE, DESOXYN, DEXEDRINE, DEXTROAMPHETAMINE SULFATE, DEXTROAMPHETAMINE SULFATE ER, DEXTROAMPHETAMINE-AMPHET ER, DEXTROAMPHETAMINE-AMPHETAMINE, DYANAVEL XR, EVEKEO, METHAMPHETAMINE HCL, MYDAYIS, PROCENTRA, ZENZEDI |
| Patiromer/Thiamine SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Patiromer may bind to thiamine.(1) CLINICAL EFFECTS: Concurrent use may result in decreased gastrointestinal absorption and loss of efficacy of thiamine.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of patiromer recommends administering patiromer at least 3 hours before or 3 hours after thiamine.(1) DISCUSSION: An in vitro binding study found potentially clinically significant binding of thiamine by patiromer. It is recommended to take these drugs 3 hours apart.(1) |
VELTASSA |
| Nirogacestat/Antacids SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: The aqueous solubility of nirogacestat is pH dependent. Higher gastric pH leads to lower solubility which may reduce nirogacestat absorption.(1) CLINICAL EFFECTS: Coadministration of antacids may reduce the bioavailability of nirogacestat, leading to decreased systemic levels and effectiveness.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Coadministration of nirogacestat with proton pump inhibitors, H2 antagonists, and antacids should be avoided. If coadministration with an acid-reducing agent is unavoidable, take nirogacestat 2 hours before or 2 hours after a locally acting antacid.(1) DISCUSSION: The solubility of nirogacestat is poor at a pH >= 6.(1) Concomitant use of proton pump inhibitors, H2 antagonists, or antacids are expected to reduce concentrations of nirogacestat.(1) |
OGSIVEO |
| Vadadustat/Polyvalent Cations and Phosphate Binders SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Vadadustat may form a chelate with iron supplements, phosphate binders, and other medicinal products whose primary component consists of polyvalent cations such as aluminum, calcium, magnesium, selenium, and zinc.(1) CLINICAL EFFECTS: Simultaneous administration of vadadustat and polyvalent cations and phosphate binders decreases the exposure and effectiveness of vadadustat.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of vadadustat states that it should be administered at least 1 hour before or 2 hours after any medications or products whose primary component consists of iron, phosphate binders and polyvalent cations.(1) DISCUSSION: Two studies evaluating the pharmacokinetics, safety, and tolerability of a single oral dose of vadadustat coadministered with a phosphate binder or iron supplement were conducted in healthy adult participants. Vadadustat exposure was reduced by coadministration with sevelamer carbonate, calcium acetate, ferric citrate, and ferrous sulfate. Geometric least squares mean ratios for area under the concentration-time curve (AUC) were reduced 37% to 55% by phosphate binders and 46% by ferrous sulfate. However, when vadadustat was administered 1 hour before phosphate binders, 90% confidence intervals for vadadustat exposure were within the no-effect boundaries of +50% to -33%, indicating that drug-drug interactions can be reduced by administering vadadustat 1 hour before phosphate binders.(2) |
VAFSEO |
| Cefpodoxime/Antacids SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Absorption of oral cefpodoxime may be reduced in patients receiving concomitant treatment with acid reducing agents.(1-3) CLINICAL EFFECTS: Antibiotic efficacy against organisms with a high minimum inhibitory concentration (MIC) to cefpodoxime could be decreased. PREDISPOSING FACTORS: Taking cefpodoxime on an empty stomach magnifies this effect. PATIENT MANAGEMENT: Separate the administration of cefpodoxime by at least 1-2 hours after administration of antacids. Some vitamin preparations may contain sufficient quantities of calcium and/or magnesium salts with antacid properties to interact as well. Since concurrent use of H2 antagonists and proton pump inhibitors (PPIs) in patients taking cefpodoxime should be avoided, these would not be alternatives to antacids in these patients. DISCUSSION: In a study of ten subjects, administration of cefpodoxime after single dose famotidine 40 mg decreased both maximum concentration (Cmax) and area-under-curve (AUC) by approximately 40% compared with administration of cefpodoxime on an empty stomach.(2) In a study of 17 subjects, administration of cefpodoxime after single dose ranitidine 150 mg decreased Cmax and AUC by approximately 40% compared with administration of cefpodoxime on an empty stomach.(3) |
CEFPODOXIME PROXETIL |
| Sotalol/Aluminium And Magnesium Antacids SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Aluminum- and magnesium-containing antacids may reduce the absorption of sotalol.(1) CLINICAL EFFECTS: Simultaneous administration of sotalol with antacids containing aluminum or magnesium may result in decreased levels and effectiveness of sotalol.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: If coadministration with an aluminum- or magnesium-containing antacid agent is unavoidable, take the antacid 2 hours before or 2 hours after sotalol.(1) DISCUSSION: In a study with 6 healthy volunteers, administration of oral sotalol simultaneously with antacids reduced the maximum concentration (Cmax) and area under the curve (AUC) of sotalol by 26% and 20%, respectively, compared to sotalol alone. There was a 25% reduction in the bradycardic effect at rest. Administration of the antacid two hours after oral sotalol had no effect on the pharmacokinetics or pharmacodynamics of sotalol.(1,2) |
BETAPACE, BETAPACE AF, SOTALOL, SOTALOL AF, SOTYLIZE |
The following contraindication information is available for PROTECT IRON (multivitamins with min no.24/iron polysaccharides complex/fa):
Drug contraindication overview.
No enhanced Contraindications information available for this drug.
No enhanced Contraindications information available for this drug.
There are 3 contraindications.
Absolute contraindication.
| Contraindication List |
|---|
| Hemochromatosis |
| Hemolytic anemia from pyruvate kinase and g6PD deficiencies |
| Leber's hereditary optic atrophy |
There are 9 severe contraindications.
Adequate patient monitoring is recommended for safer drug use.
| Severe List |
|---|
| Calcium oxalate renal calculi |
| Chronic iron overload due to repeated blood transfusions |
| Diarrhea |
| Diverticular disease |
| Glucose-6-phosphate dehydrogenase (g6Pd) deficiency |
| Hemolytic anemia |
| Hemosiderosis |
| Hyperoxaluria |
| Ulcerative colitis |
There are 10 moderate contraindications.
Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.
| Moderate List |
|---|
| Atrophic gastritis |
| Biliary obstruction |
| Disease of liver |
| Gastritis |
| Hemochromatosis |
| Hypokalemia |
| Hypotension |
| Kidney disease with reduction in glomerular filtration rate (GFr) |
| Peptic ulcer |
| Sickle cell disease |
The following adverse reaction information is available for PROTECT IRON (multivitamins with min no.24/iron polysaccharides complex/fa):
Adverse reaction overview.
No enhanced Common Adverse Effects information available for this drug.
No enhanced Common Adverse Effects information available for this drug.
There are 3 severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
|
Abdominal pain with cramps |
None. |
| Rare/Very Rare |
|---|
|
Bronchospastic pulmonary disease Concentration difficulty |
There are 24 less severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
|
Black stools Constipation Diarrhea Flatulence Nausea Vomiting |
Abdominal distension Acute abdominal pain Dental discoloration Vomiting |
| Rare/Very Rare |
|---|
|
Abdominal distension Acute cognitive impairment Anorexia Depression Dysgeusia Erythema Excitement Flatulence Irritability Malaise Nausea Pruritus of skin Skin rash Sleep disorder |
The following precautions are available for PROTECT IRON (multivitamins with min no.24/iron polysaccharides complex/fa):
No enhanced Pediatric Use information available for this drug.
Contraindicated
Severe Precaution
Management or Monitoring Precaution
Contraindicated
| None |
Severe Precaution
| None |
Management or Monitoring Precaution
| None |
During the first and second trimester of pregnancy, iron-deficiency anemia is associated with a twofold increased risk of premature delivery and a threefold increased risk of a low-birthweight delivery. Although iron supplementation during pregnancy has been shown to decrease the incidence of anemia, evidence on the effect of routine iron supplementation during pregnancy on adverse maternal and infant outcomes is inconclusive. Blood volume expands by about 35% during pregnancy, and growth of the fetus, placenta, and other maternal tissues increases the iron requirement threefold during the second and third trimesters of pregnancy to about 5 mg of iron daily.
Although menstruation ceases and iron absorption increases during pregnancy, most pregnant women who do not use iron supplements to meet increased iron requirements cannot maintain adequate iron stores, particularly during the last 2 trimesters. Following delivery, iron in the fetus and placenta are lost to the woman, although some of the iron in the expanded blood volume may return to blood stores. Among low-income pregnant women enrolled in health programs in the US, the prevalence of iron-deficiency anemia is 9, 14, and 37% during the first, second, and third trimesters, respectively.
While similar data currently are not available for all pregnant women in the US, the low dietary iron intake among US women of childbearing age, the high prevalence of iron deficiency and associated anemia among such women, and the increased iron requirements during pregnancy suggest that anemia during pregnancy may extend beyond low-income women. In addition, use of prenatal multivitamin and mineral supplements among African-Americans, native American and Alaskan Indians, women younger than 20 years of age, and those having less than a high school education is substantially lower than in the general US pregnant population. The principal reasons for the current lack of widespread adoption of a recommended iron supplementation regimen during pregnancy in US women may include lack of health-care provider and patient perceptions that iron supplements improve maternal and infant outcomes, complicated dose schedules, and adverse effects (e.g., constipation, nausea, vomiting).
However, adequate dietary iron intake and iron supplementation generally are recommended for primary prevention of iron deficiency during pregnancy. By employing low-dose (i.e., 30 mg of iron daily) regimens with simplified dose schedules (i.e., once-daily dosing), patient compliance may be improved; low-dose regimens have been shown to increase patient tolerance and are as effective as higher dosages (e.g., 60-120 mg iron daily) in preventing iron-deficiency anemia.
Although menstruation ceases and iron absorption increases during pregnancy, most pregnant women who do not use iron supplements to meet increased iron requirements cannot maintain adequate iron stores, particularly during the last 2 trimesters. Following delivery, iron in the fetus and placenta are lost to the woman, although some of the iron in the expanded blood volume may return to blood stores. Among low-income pregnant women enrolled in health programs in the US, the prevalence of iron-deficiency anemia is 9, 14, and 37% during the first, second, and third trimesters, respectively.
While similar data currently are not available for all pregnant women in the US, the low dietary iron intake among US women of childbearing age, the high prevalence of iron deficiency and associated anemia among such women, and the increased iron requirements during pregnancy suggest that anemia during pregnancy may extend beyond low-income women. In addition, use of prenatal multivitamin and mineral supplements among African-Americans, native American and Alaskan Indians, women younger than 20 years of age, and those having less than a high school education is substantially lower than in the general US pregnant population. The principal reasons for the current lack of widespread adoption of a recommended iron supplementation regimen during pregnancy in US women may include lack of health-care provider and patient perceptions that iron supplements improve maternal and infant outcomes, complicated dose schedules, and adverse effects (e.g., constipation, nausea, vomiting).
However, adequate dietary iron intake and iron supplementation generally are recommended for primary prevention of iron deficiency during pregnancy. By employing low-dose (i.e., 30 mg of iron daily) regimens with simplified dose schedules (i.e., once-daily dosing), patient compliance may be improved; low-dose regimens have been shown to increase patient tolerance and are as effective as higher dosages (e.g., 60-120 mg iron daily) in preventing iron-deficiency anemia.
No enhanced Lactation information available for this drug.
No enhanced Geriatric Use information available for this drug.
The following prioritized warning is available for PROTECT IRON (multivitamins with min no.24/iron polysaccharides complex/fa):
No warning message for this drug.
No warning message for this drug.
The following icd codes are available for PROTECT IRON (multivitamins with min no.24/iron polysaccharides complex/fa)'s list of indications:
| Iron deficiency anemia | |
| D50 | Iron deficiency anemia |
| D50.0 | Iron deficiency anemia secondary to blood loss (chronic) |
| D50.8 | Other iron deficiency anemias |
| D50.9 | Iron deficiency anemia, unspecified |
| Mineral deficiency | |
| E61.9 | Deficiency of nutrient element, unspecified |
| Vitamin deficiency | |
| E56.9 | Vitamin deficiency, unspecified |
Formulary Reference Tool