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Drug overview for COMPLETE FORMULATION PEDIATRIC (pediatric multivitamin no.77/cholecalciferol/phytonadione):
Generic name: PEDIATRIC MULTIVITAMIN NO.77/CHOLECALCIFEROL/PHYTONADIONE
Drug class: Vitamin D
Therapeutic class: Electrolyte Balance-Nutritional Products
Phytonadione is a fat-soluble naphthoquinone derivative that is identical to naturally occurring vitamin K1.
Numerous multivitamin preparations are marketed, with little Vitamin D analogs are used to prevent or treat rickets or osteomalacia and standardization of formulas. Useful multivitamin preparations should to manage hypocalcemia associated with hypoparathyroidism or contain only essential vitamins (those for which there is a recommended pseudohypoparathyroidism. Since calcitriol is more expensive than daily dietary allowance (RDA)). (See Dosage and Administration.) ergocalciferol, use of the former drug is generally reserved for patients Preparations containing iron and/or calcium supplements may be useful in with inadequate metabolism of ergocalciferol.
The initial treatment of severe hypocalcemia is immediate IV administration of a calcium salt such some patients (e.g., pregnant or lactating women) but other essential as calcium gluconate. Vitamin D analogs are then used to maintain minerals are usually obtained from the diet. The addition of agents such as liver, yeast, and wheat germ to vitamin preparations offers no advantage normocalcemia.
Because of its shorter onset of action, calcitriol may be over pure chemical ingredients, and inclusion of nonessential agents such preferable to ergocalciferol in the acute treatment of hypocalcemia. as choline, bioflavonoids, inositol, betaine, lecithin, and methionine is Oral calcitriol also is used in the management of secondary unwarranted. Combinations of vitamins and other drugs such as hormones are hyperparathyroidism and resultant metabolic bone disease in patients with irrational and should not be used.
moderate to severe chronic kidney disease (CKD) who do not yet require maintenance dialysis therapy (predialysis patients) and in the management of hypocalcemia and resultant metabolic bone disease in patients with CKD undergoing dialysis. IV calcitriol is used in the management of hypocalcemia in patients with chronic renal failure undergoing dialysis. IV or oral doxercalciferol is used for the treatment of secondary hyperparathyroidism in patients with CKD undergoing dialysis.
Oral doxercalciferol also is used for the treatment of secondary hyperparathyroidism in patients with stage 3 or 4 CKD who do not yet require maintenance dialysis (predialysis patients). IV paricalcitol is used in the prevention and treatment of secondary hyperparathyroidism in patients with stage 5 CKD, while oral paricalcitol is used in the prevention and treatment of secondary hyperparathyroidism in patients with stage 3 or 4 CKD as well as in those with stage 5 CKD requiring hemodialysis or peritoneal dialysis. Calcifediol is used in the treatment of secondary hyperparathyroidism in patients with stage 3 or 4 CKD and vitamin D insufficiency.
Because of the risk of toxicity, therapy with vitamin D analogs should be closely monitored, and indiscriminate use of these drugs should be avoided. Phytonadione is used in the prophylaxis and/or treatment of coagulation disorders due to faulty formation of factors II, VII, IX, and X caused by vitamin K deficiency or interference with vitamin K activity. Phytonadione is more effective than, and is preferred to, other vitamin K preparations in the presence of impending or actual hemorrhage.
However, because phytonadione may require 3 hours or longer to stop active bleeding, administration of clotting factors (e.g., prothrombin complex concentrate (human)), fresh whole blood, or plasma may be necessary for more rapid control of severe bleeding.
Generic name: PEDIATRIC MULTIVITAMIN NO.77/CHOLECALCIFEROL/PHYTONADIONE
Drug class: Vitamin D
Therapeutic class: Electrolyte Balance-Nutritional Products
Phytonadione is a fat-soluble naphthoquinone derivative that is identical to naturally occurring vitamin K1.
Numerous multivitamin preparations are marketed, with little Vitamin D analogs are used to prevent or treat rickets or osteomalacia and standardization of formulas. Useful multivitamin preparations should to manage hypocalcemia associated with hypoparathyroidism or contain only essential vitamins (those for which there is a recommended pseudohypoparathyroidism. Since calcitriol is more expensive than daily dietary allowance (RDA)). (See Dosage and Administration.) ergocalciferol, use of the former drug is generally reserved for patients Preparations containing iron and/or calcium supplements may be useful in with inadequate metabolism of ergocalciferol.
The initial treatment of severe hypocalcemia is immediate IV administration of a calcium salt such some patients (e.g., pregnant or lactating women) but other essential as calcium gluconate. Vitamin D analogs are then used to maintain minerals are usually obtained from the diet. The addition of agents such as liver, yeast, and wheat germ to vitamin preparations offers no advantage normocalcemia.
Because of its shorter onset of action, calcitriol may be over pure chemical ingredients, and inclusion of nonessential agents such preferable to ergocalciferol in the acute treatment of hypocalcemia. as choline, bioflavonoids, inositol, betaine, lecithin, and methionine is Oral calcitriol also is used in the management of secondary unwarranted. Combinations of vitamins and other drugs such as hormones are hyperparathyroidism and resultant metabolic bone disease in patients with irrational and should not be used.
moderate to severe chronic kidney disease (CKD) who do not yet require maintenance dialysis therapy (predialysis patients) and in the management of hypocalcemia and resultant metabolic bone disease in patients with CKD undergoing dialysis. IV calcitriol is used in the management of hypocalcemia in patients with chronic renal failure undergoing dialysis. IV or oral doxercalciferol is used for the treatment of secondary hyperparathyroidism in patients with CKD undergoing dialysis.
Oral doxercalciferol also is used for the treatment of secondary hyperparathyroidism in patients with stage 3 or 4 CKD who do not yet require maintenance dialysis (predialysis patients). IV paricalcitol is used in the prevention and treatment of secondary hyperparathyroidism in patients with stage 5 CKD, while oral paricalcitol is used in the prevention and treatment of secondary hyperparathyroidism in patients with stage 3 or 4 CKD as well as in those with stage 5 CKD requiring hemodialysis or peritoneal dialysis. Calcifediol is used in the treatment of secondary hyperparathyroidism in patients with stage 3 or 4 CKD and vitamin D insufficiency.
Because of the risk of toxicity, therapy with vitamin D analogs should be closely monitored, and indiscriminate use of these drugs should be avoided. Phytonadione is used in the prophylaxis and/or treatment of coagulation disorders due to faulty formation of factors II, VII, IX, and X caused by vitamin K deficiency or interference with vitamin K activity. Phytonadione is more effective than, and is preferred to, other vitamin K preparations in the presence of impending or actual hemorrhage.
However, because phytonadione may require 3 hours or longer to stop active bleeding, administration of clotting factors (e.g., prothrombin complex concentrate (human)), fresh whole blood, or plasma may be necessary for more rapid control of severe bleeding.
DRUG IMAGES
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The following indications for COMPLETE FORMULATION PEDIATRIC (pediatric multivitamin no.77/cholecalciferol/phytonadione) have been approved by the FDA:
Indications:
Vitamin deficiency prevention
Vitamin deficiency
Professional Synonyms:
Vitamin deficiency prophylaxis
Indications:
Vitamin deficiency prevention
Vitamin deficiency
Professional Synonyms:
Vitamin deficiency prophylaxis
The following dosing information is available for COMPLETE FORMULATION PEDIATRIC (pediatric multivitamin no.77/cholecalciferol/phytonadione):
Dose, frequency of administration, and duration of treatment with phytonadione depend on the severity of the prothrombin deficiency and the response of the patient; the lowest effective dose of phytonadione should be used.
Dietary intake of ergocalciferol and cholecalciferol varies among individual patients, and dietary intake should always be considered when calculating the appropriate dosage of vitamin D analogs. During therapy with vitamin D analogs, dosage depends on the nature and severity of the patient's hypocalcemia and must be individualized to maintain serum calcium concentrations of 9-10 mg/dL. In the management of hypoparathyroidism, pseudohypoparathyroidism, and familial hypophosphatemia, the range between therapeutic and toxic effects is narrow; however, hypercalcemia may occur at any time when therapeutic doses of vitamin D analogs are used, and careful monitoring is imperative.
In the management of secondary hyperparathyroidism, dosage of vitamin D analogs should be individualized according to serum or plasma intact parathyroid hormone (iPTH) concentrations and serum calcium and phosphorus concentrations.
During therapy with vitamin D analogs, patients should receive adequate amounts of calcium through management of diet or administration of calcium supplements; however, overdosage of calcium may lead to hypercalcemia. Dosage of vitamin D analogs should be decreased when symptoms improve and before biochemical normality or complete bone healing has occurred because requirements for vitamin D analogs often decrease after bone healing occurs. In patients who become bedridden (especially children), dosage reduction may occasionally be needed to avoid hypercalcemia.
Dietary intake of ergocalciferol and cholecalciferol varies among individual patients, and dietary intake should always be considered when calculating the appropriate dosage of vitamin D analogs. During therapy with vitamin D analogs, dosage depends on the nature and severity of the patient's hypocalcemia and must be individualized to maintain serum calcium concentrations of 9-10 mg/dL. In the management of hypoparathyroidism, pseudohypoparathyroidism, and familial hypophosphatemia, the range between therapeutic and toxic effects is narrow; however, hypercalcemia may occur at any time when therapeutic doses of vitamin D analogs are used, and careful monitoring is imperative.
In the management of secondary hyperparathyroidism, dosage of vitamin D analogs should be individualized according to serum or plasma intact parathyroid hormone (iPTH) concentrations and serum calcium and phosphorus concentrations.
During therapy with vitamin D analogs, patients should receive adequate amounts of calcium through management of diet or administration of calcium supplements; however, overdosage of calcium may lead to hypercalcemia. Dosage of vitamin D analogs should be decreased when symptoms improve and before biochemical normality or complete bone healing has occurred because requirements for vitamin D analogs often decrease after bone healing occurs. In patients who become bedridden (especially children), dosage reduction may occasionally be needed to avoid hypercalcemia.
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. Phytonadione may be administered orally or parenterally (IV, IM, or subcutaneously). The parenteral preparation also has been administered orally+ in neonates.
The route of administration of phytonadione depends on the severity of the prothrombin deficiency and the risks associated with administration by each route. The manufacturers state that because of the possibility of severe adverse reactions (see Cautions: Adverse Effects), IV or IM administration is indicated only when other routes of administration are not feasible and the serious risk is justified. However, the effects of phytonadione have been reported to be delayed and/or unpredictable following subcutaneous injection, and subcutaneous administration may be less effective for reversal of excessive anticoagulation than IV or oral administration.
The American College of Chest Physicians (ACCP) and other clinicians recommend IV administration of phytonadione in emergency situations for major bleeding due to vitamin K-antagonist anticoagulants because of its more rapid onset; these clinicians recommend that subcutaneous administration be avoided. Oral administration of phytonadione usually reduces international normalized ratio (INR) levels in 24-48 hours and generally is recommended over parenteral administration in selected asymptomatic (nonbleeding) patients with hypoprothrombinemia due to vitamin K-antagonist anticoagulants. In patients with decreased bile secretion, bile salts (e.g., ox bile extract 300 mg or dehydrocholic acid 500 mg) should be given with each oral dose of phytonadione to ensure absorption.
Parenteral administration is indicated in patients who are unable to retain or absorb the drug from the GI tract. When phytonadione injection is administered IV, it should be injected at a rate not exceeding 1 mg/minute. The drug may be diluted for infusion with 0.9%
sodium chloride, 5% dextrose, or 5% dextrose in 0.9% sodium chloride injection; other diluents that may contain benzyl alcohol should not be used. (See Cautions: Pediatric Precautions.) The drug should be administered immediately after dilution, and any unused portion of the dilution and the unused contents of the ampul or vial should be discarded.
The infusion container must be protected from light at all times. (See Chemistry and Stability: Stability.) Vitamin D analogs are usually administered orally; however, calcitriol, doxercalciferol, and paricalcitol may be given by IV injection. Ergocalciferol may be given by IM injection; however, a suitable formulation of the drug for IM injection no longer is commercially available in the US.
Published data are too varied and/or limited to permit generalizations, and specialized references should be consulted for specific compatibility information. Phytonadione may be administered orally or parenterally (IV, IM, or subcutaneously). The parenteral preparation also has been administered orally+ in neonates.
The route of administration of phytonadione depends on the severity of the prothrombin deficiency and the risks associated with administration by each route. The manufacturers state that because of the possibility of severe adverse reactions (see Cautions: Adverse Effects), IV or IM administration is indicated only when other routes of administration are not feasible and the serious risk is justified. However, the effects of phytonadione have been reported to be delayed and/or unpredictable following subcutaneous injection, and subcutaneous administration may be less effective for reversal of excessive anticoagulation than IV or oral administration.
The American College of Chest Physicians (ACCP) and other clinicians recommend IV administration of phytonadione in emergency situations for major bleeding due to vitamin K-antagonist anticoagulants because of its more rapid onset; these clinicians recommend that subcutaneous administration be avoided. Oral administration of phytonadione usually reduces international normalized ratio (INR) levels in 24-48 hours and generally is recommended over parenteral administration in selected asymptomatic (nonbleeding) patients with hypoprothrombinemia due to vitamin K-antagonist anticoagulants. In patients with decreased bile secretion, bile salts (e.g., ox bile extract 300 mg or dehydrocholic acid 500 mg) should be given with each oral dose of phytonadione to ensure absorption.
Parenteral administration is indicated in patients who are unable to retain or absorb the drug from the GI tract. When phytonadione injection is administered IV, it should be injected at a rate not exceeding 1 mg/minute. The drug may be diluted for infusion with 0.9%
sodium chloride, 5% dextrose, or 5% dextrose in 0.9% sodium chloride injection; other diluents that may contain benzyl alcohol should not be used. (See Cautions: Pediatric Precautions.) The drug should be administered immediately after dilution, and any unused portion of the dilution and the unused contents of the ampul or vial should be discarded.
The infusion container must be protected from light at all times. (See Chemistry and Stability: Stability.) Vitamin D analogs are usually administered orally; however, calcitriol, doxercalciferol, and paricalcitol may be given by IV injection. Ergocalciferol may be given by IM injection; however, a suitable formulation of the drug for IM injection no longer is commercially available in the US.
No dosing information available.
No generic dosing information available.
The following drug interaction information is available for COMPLETE FORMULATION PEDIATRIC (pediatric multivitamin no.77/cholecalciferol/phytonadione):
There are 0 contraindications.
There are 4 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 |
|---|---|
| Selected Anticoagulants (Vitamin K antagonists)/Vitamin K SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Anticoagulants interfere with the activation of vitamin K-dependent clotting factors. Vitamin K administration may reverse this effect. CLINICAL EFFECTS: The pharmacological effect of anticoagulants may be reversed resulting in thrombus formation. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Patients receiving anticoagulants should avoid eating unusual increases in foods high in vitamin K content. The time of highest risk for a coumarin-type drug interaction is when the precipitant drug is initiated or discontinued. Contact the prescriber before initiating, altering the dose or discontinuing either drug. DISCUSSION: Numerous reports have demonstrated that vitamin K interferes with the hypoprothrombinemic effects of anticoagulants. However, reports of clinically important consequences are uncommon. A clearer understanding of the mechanism by which these drugs act has made it possible to use vitamin K to control bleeding side effects of warfarin therapy. One should be aware of the vitamin K content of enteral feeding products being administered to patients on anticoagulant therapy. Prothrombin time should be monitored when these products are given. |
ANISINDIONE, DICUMAROL, JANTOVEN, PHENINDIONE, WARFARIN SODIUM |
| Vitamin A/Selected Retinoids SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: The retinoids are structurally related to vitamin A. (1-6) CLINICAL EFFECTS: Concurrent use of retinoids with vitamin A supplements may result in signs of vitamin A toxicity.(1-6) Symptoms of vitamin A toxicity include nausea, vomiting, loss of appetite, weakness, dry or itchy skin or lips, irritability, and hair loss. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of acitretin states that concomitant use of vitamin A supplements should be avoided.(1) The manufacturer of bexarotene states that patients should be advised to limit vitamin A supplements. In clinical studies, patients were advised to limit their vitamin A intake to less than or equal to 15,000 International Units/day.(2) The manufacturer of isotretinoin states that patients should be advised against taking vitamin A supplements.(3) The manufacturer of palovarotene states that concomitant use of vitamin A must be avoided.(4) The manufacturer of tretinoin states that tretinoin must not be administered in combination with vitamin A.(5) The UK manufacturer of alitretinoin states that tretinoin must not be administered in combination with vitamin A.(6) DISCUSSION: The retinoids are structurally related to vitamin A. The concurrent use of retinoids with vitamin A may result in signs and symptoms of vitamin A toxicity.(1-6) |
ABSORICA, ABSORICA LD, ACCUTANE, ACITRETIN, AMNESTEEM, BEXAROTENE, CLARAVIS, ISOTRETINOIN, SOHONOS, TARGRETIN, ZENATANE |
| 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 |
| Erdafitinib/Serum Phosphate Level-Altering Drugs SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Medications that alter serum phosphate may interfere with interpretation of phosphate levels that are needed to determine initial erdafitinib dose.(1) CLINICAL EFFECTS: Serum phosphate levels that are elevated by concomitant medications may result in an inappropriately low dose and decreased effectiveness of erdafitinib. Serum phosphate levels that are decreased by concomitant medications may result in an inappropriately high dose and increased toxicity from erdafitinib. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of erdafitinib states that agents that alter serum phosphate levels should be avoided before the initial dose increase period for erdafitinib based on serum phosphate levels (days 14 to 21).(1) DISCUSSION: Concomitant administration of serum phosphate level-altering agents during the initial dose increase period of erdafitinib based on serum phosphate levels (days 14 to 21) may interfere with serum phospate levels and lead to incorrect dosing of erdafitinib.(1) Agents that may alter serum phosphate levels linked to this monograph include: aluminum carbonate, aluminum hydroxide, calcium acetate, calcium carbonate, calcium citrate, cod liver oil, ferric citrate, lanthanum, magnesium carbonate, magnesium hydroxide, potassium phosphate, sevelamer, sodium phosphate, sucroferric oxyhydroxide, tenapanor, and vitamin D.(1) |
BALVERSA |
There are 20 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 |
|---|---|
| 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-) |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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/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 |
| 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 |
| 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 |
| 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 |
The following contraindication information is available for COMPLETE FORMULATION PEDIATRIC (pediatric multivitamin no.77/cholecalciferol/phytonadione):
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 |
|---|
| Hemolytic anemia from pyruvate kinase and g6PD deficiencies |
| Hypervitaminosis D |
| Leber's hereditary optic atrophy |
There are 3 severe contraindications.
Adequate patient monitoring is recommended for safer drug use.
| Severe List |
|---|
| Hypercalcemia |
| Hyperphosphatemia |
| Kidney stone |
There are 4 moderate contraindications.
Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.
| Moderate List |
|---|
| Atrophic gastritis |
| Hypokalemia |
| Kidney disease with reduction in glomerular filtration rate (GFr) |
| Sarcoidosis |
The following adverse reaction information is available for COMPLETE FORMULATION PEDIATRIC (pediatric multivitamin no.77/cholecalciferol/phytonadione):
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 0 severe adverse reactions.
There are 0 less severe adverse reactions.
The following precautions are available for COMPLETE FORMULATION PEDIATRIC (pediatric multivitamin no.77/cholecalciferol/phytonadione):
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 |
Reproduction studies have not been conducted in animals, and it is not known if phytonadione has teratogenic effects. A characteristic physiognomy, possibly with aortic valvular stenosis, retinopathy, and mental and/or physical retardation, has occurred following prolonged hypercalcemia in infants and in neonates of mothers with hypercalcemia during pregnancy. Hypercalcemia during pregnancy may also lead to suppression of PTH concentrations in the neonate resulting in hypocalcemia, tetany, and seizures. Safe use of calcifediol, calcitriol, dihydrotachysterol (no longer commercially available in the US), paricalcitol, or ergocalciferol during pregnancy has not been established; however, the risks to the mother and fetus from untreated hypoparathyroidism or hypophosphatemia may be greater than those resulting from administration of vitamin D analogs.
Safe use of calcifediol, calcitriol, dihydrotachysterol, doxercalciferol, paricalcitol, or ergocalciferol during lactation has not been established; however, the risks to the mother and fetus from untreated hypoparathyroidism or hypophosphatemia may be greater than those resulting from administration of vitamin D analogs. Large doses of vitamin D analogs should not be administered to nursing women.
No enhanced Geriatric Use information available for this drug.
The following prioritized warning is available for COMPLETE FORMULATION PEDIATRIC (pediatric multivitamin no.77/cholecalciferol/phytonadione):
WARNING: If your brand of multivitamin contains iron, it is important to keep this product out of reach of children. Accidental overdose of iron-containing products is a leading cause of fatal poisoning in children younger than 6 years. If overdose does occur, get medical help right away or call a poison control center.
WARNING: If your brand of multivitamin contains iron, it is important to keep this product out of reach of children. Accidental overdose of iron-containing products is a leading cause of fatal poisoning in children younger than 6 years. If overdose does occur, get medical help right away or call a poison control center.
The following icd codes are available for COMPLETE FORMULATION PEDIATRIC (pediatric multivitamin no.77/cholecalciferol/phytonadione)'s list of indications:
| Vitamin deficiency | |
| E56.9 | Vitamin deficiency, unspecified |
Formulary Reference Tool