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Drug overview for VITAFOL-OB+DHA (prenatal vitamins comb 10/ferrous fumarate/folic acid/dha):
Generic name: PRENATAL VITAMINS COMB 10/FERROUS FUMARATE/FOLIC ACID/DHA
Drug class: Folic Acid
Therapeutic class: Electrolyte Balance-Nutritional Products
No enhanced Introduction information available for this drug.
No enhanced Uses information available for this drug.
Generic name: PRENATAL VITAMINS COMB 10/FERROUS FUMARATE/FOLIC ACID/DHA
Drug class: Folic Acid
Therapeutic class: Electrolyte Balance-Nutritional Products
No enhanced Introduction information available for this drug.
No enhanced Uses information available for this drug.
DRUG IMAGES
VITAFOL-OB+DHA COMBO PACK
The following indications for VITAFOL-OB+DHA (prenatal vitamins comb 10/ferrous fumarate/folic acid/dha) have been approved by the FDA:
Indications:
Lactation
Pregnancy
Professional Synonyms:
Fetation
Gestation
Gravidism
Graviditas
Lactating patient
Nursing patient
Pregnant
Indications:
Lactation
Pregnancy
Professional Synonyms:
Fetation
Gestation
Gravidism
Graviditas
Lactating patient
Nursing patient
Pregnant
The following dosing information is available for VITAFOL-OB+DHA (prenatal vitamins comb 10/ferrous fumarate/folic acid/dha):
No enhanced Dosing information available for this drug.
No enhanced Administration information available for this drug.
No dosing information available.
No generic dosing information available.
The following drug interaction information is available for VITAFOL-OB+DHA (prenatal vitamins comb 10/ferrous fumarate/folic acid/dha):
There are 1 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 |
|---|---|
| Vitamin A/Selected Retinoids 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: 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 |
There are 7 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) If concurrent use cannot be avoided, separate the administration of phosphate containing products by as much time as possible from medications containing aluminum, calcium, or magnesium. 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 |
| Raltegravir (600 mg HD)/Calcium Carbonate SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Calcium carbonate may alter raltegravir absorption by altering gastric pH and binding to raltegravir in the GI tract, preventing its absorption.(1) CLINICAL EFFECTS: Calcium carbonate may reduce levels and clinical effectiveness of raltegravir.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Calcium carbonate is not recommended for patients receiving one daily raltegravir (600 mg HD tablets).(1) DISCUSSION: Simultaneous administration of calcium carbonate (3000 mg) with raltegravir (1200 mg singe dose given as two 600 mg HD tablets) decreased raltegravir maximum concentration (Cmax), area-under-curve (AUC), and minimum concentration (Cmin) by 74%, 72%, and 48%, respectively.(1,2) Administration of calcium carbonate (3000 mg) 12 hours after raltegravir (1200 mg singe dose given as two 600 mg HD tablets) decreased raltegravir Cmax, AUC, and Cmin by 2%, 10%, and 57%, respectively.(1,2) Data from in vitro(3) and in vivo simulations(4) suggest that magnesium's effect on raltegravir may involve chelation as well as changes in pH. Calcium may have a similar effect. |
ISENTRESS HD |
| 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 |
| Fluorouracil & Fluorouracil Prodrugs/Folic Acid SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Folic acid has been shown to enhance both the therapeutic and toxic effects of fluoropyrimidines, such as 5-fluorouracil (5-FU) and fluorouracil prodrugs.(1-3) Fluorouracil prodrugs include capecitabine and tegafur. CLINICAL EFFECTS: Folic acid, when used concurrently with 5-FU or fluorouracil prodrugs, has been shown to increase side effects of 5-FU.(1-3) PREDISPOSING FACTORS: Patients who are intermediate or poor dihydropyrimidine dehydrogenase (DPYD) metabolizers have diminished or no DPYD function. Since DPYD is the rate-limiting enzyme involved in fluoropyrimidine metabolism, these patients may be more susceptible to the effects of this interaction.(3) PATIENT MANAGEMENT: Folic acid or folate analog-containing products should not be used concurrently with fluorouracil or fluorouracil prodrugs unless directed by the healthcare provider.(1-3) Fluorouracil prodrugs include capecitabine and tegafur. DISCUSSION: Due to increased toxic effects, stomatitis and diarrhea are observed more commonly, may be more severe, and may occur for a prolonged duration when compared to therapy with 5-FU alone. It is postulated that the lower standard dose of 5-FU in the US versus other regions may be due to increased folic acid supplementation within the US food supply.(2) In a cohort study in 290 patients, the use of dietary supplements with folic acid during treatment compared to nonuse increased the risk of capecitabine toxicities (HR 1.81, 95%CI: 1.15,2.85). The detection of folic acid in plasma also increased the risk of capecitabine toxicities (HR 2.09, 95%CI: 1.24,3.52 and HR 2.31, 95%CI: 1.29,4.13 at diagnosis and during treatment, respectively).(4) In a cohort study of 9 patients, patients taking folate-containing supplements and higher serum folate levels had an increased risk of grade >=2 toxicity. The risk of grade >=2 toxicity increased by 9% for every increase in serum folate level by 10 nmol/L. Patients with grade >=2 toxicity had higher serum folate levels than patients with grade <= 1 toxicity (28 nmol/L [range, 13.2-45.4] vs. 20 nmol/L [range, 12.8-45.4]; p=0.001).(5) In two case reports, patients developed capecitabine toxicity while taking supplements containing folic acid 400-500 mcg.(6) In a case report, a woman developed grade 4 diarrhea, grade 3 vomiting, and grade 3 hand-foot syndrome 8 days after the addition of capecitabine (2500 mg/m2/day) to high-dose folic acid supplementation. She developed necrotic colitis and died, despite the discontinuation of folic acid and capecitabine.(7) There are two other reports of excessive fluorouracil toxicity in patients treated with folic acid.(8) |
ADRUCIL, CAPECITABINE, FLUOROURACIL |
| Selected Mesalamine/Antacids SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Certain mesalamine formulations (namely Apriso) contain granules with an enteric coating that dissolves at pH 6 and above. Antacids may raise the intragastric pH, resulting in premature release of the drug in the stomach.(1) CLINICAL EFFECTS: Simultaneous administration of certain mesalamine formulations (namely Apriso) with an antacid may result in premature release of mesalamine in the stomach and decreased effectiveness in the intestines and colon.(1-2) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of Apriso states that coadministration with antacids should be avoided.(1) Some vitamin preparations may contain sufficient quantities of calcium and/or magnesium salts with antacid properties to interact as well. DISCUSSION: Dissolution of the enteric coating of mesalamine is pH-dependent. Coadministration of certain mesalamine formulations (namely Apriso) with antacids should be avoided.(1) |
APRISO, MESALAMINE ER |
| Ziftomenib/Antacids SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: The aqueous solubility of ziftomenib is pH dependent. Higher gastric pH leads to lower solubility which may reduce ziftomenib absorption.(1) CLINICAL EFFECTS: Coadministration with antacids may reduce the bioavailability of ziftomenib, leading to decreased systemic levels and effectiveness.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of ziftomenib states that concurrent use with antacids should be avoided.(1) If concurrent use cannot be avoided, administer ziftomenib 2 hours before or 2 hours after the administration of an antacid.(1) Some vitamin preparations may contain sufficient quantities of calcium and/or magnesium salts with antacid properties to interact as well. DISCUSSION: The impact of antacids on the pharmacokinetics of ziftomenib has not been investigated in clinical studies. In an interaction study, coadministration of proton pump inhibitors (PPIs) decreased ziftomenib area-under-the-curve (AUC) by 53% and maximum concentration (Cmax) by 70%.(1) |
KOMZIFTI |
There are 50 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) The US manufacturer of ferric maltose recommends separation of ferric maltose by at least 4 hours.(22) 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, DEPEN, PENICILLAMINE, PENICILLAMINE(D-) |
| Slt Cation-Donating Antacids/Polystyrene Sulfonate SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Polystyrene sulfonate may bind the cation from the antacid, resulting in increased intestinal absorption of non-neutralized bicarbonate, which may result in systemic alkalosis and decreased potassium binding by polystyrene sulfonate. Intestinal obstruction has occurred with aluminum hydroxide because of concretion. CLINICAL EFFECTS: Simultaneous oral use may result in metabolic alkalosis and a decrease in the potassium lowering effect of polystyrene sulfonate. Intestinal obstruction has been reported with aluminum hydroxide. PREDISPOSING FACTORS: Patients with renal failure may be at a higher risk of systemic alkalosis. PATIENT MANAGEMENT: Consider the use of alternative agents to cation-donating antacids in patients receiving oral polystyrene sulfonate when possible. If concurrent use is required, separate the dosing by several hours.(1) Some vitamin preparations may contain sufficient quantities of calcium and/or magnesium salts with antacid properties to interact as well. DISCUSSION: In a study in 11 patients with decreased renal function, the administration of magnesium hydroxide and sodium polystyrene sulfonate produced moderate to moderately severe metabolic alkalosis.(2) There are case reports documenting this affect as well.(3-7) Intestinal obstruction has been reported with aluminum hydroxide and sodium polystyrene sulfonate.(8) If the polystyrene sulfonate is administered rectally, a clinically significant interaction is not likely to occur. |
KIONEX, SODIUM POLYSTYRENE SULFONATE, SPS |
| Itraconazole; Ketoconazole/Agents Affecting Gastric pH SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Antacids, buffers in didanosine products, H2 antagonists, and proton-pump inhibitors increase the stomach pH. Quinapril tablets may contain a high percentage of magnesium. Since some orally administered azole antifungal agents require an acidic medium for optimal absorption, agents may decrease the absorption of azole antifungal agents. CLINICAL EFFECTS: Simultaneous administration of an antacid, buffered didanosine, a H2 antagonist, or a proton-pump inhibitor may result in decreased therapeutic effects of the azole antifungal. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: If the concurrent administration of these two agents cannot be avoided, consider administering two capsules of glutamic acid hydrochloride 15 minutes before administering the antifungal and separate the administration times of the antifungal and the agent affecting gastric pH by at least two hours. DISCUSSION: Itraconazole, ketoconazole, and posaconazole require an acidic medium for predictable dissolution and absorption decreases as pH increases and proton pump inhibitors are expected to decrease their absorption.(1-4) In a study in 11 healthy subjects, omeprazole (40 mg daily) decreased the maximum concentration (Cmax) and area-under-curve (AUC) of itraconazole (200 mg single dose) by 66% and 64%, respectively.(5) In a study in 15 healthy subjects, omeprazole (40 mg daily) had no effect on the pharmacokinetics of itraconazole solution.(6) In a study in 9 healthy subjects, omeprazole (60 mg) decreased the AUC of ketoconazole (200 mg single dose) by 83.4% compared to control (ketoconazole alone). Administration of Coca-Cola (240 ml) with ketoconazole and omeprazole raised ketoconazole AUC to 65% of control values.(7) Omeprazole has been shown to have no significant effect on the absorption of fluconazole(8) or voriconazole.(9) Case reports and in-vivo studies have documented significant decreases in ketoconazole levels during concurrent therapy with H-2 antagonists, including cimetidine and ranitidine. Concurrent administration of itraconazole and famotidine resulted in a significant decrease in itraconazole levels, but no significant changes in famotidine levels. An interaction should be expected to occur between both ketoconazole or itraconazole and the other H-2 antagonists.(10-14) In randomized, open-labeled, cross-over study in 12 healthy subjects, simultaneous administration of an antacid decreased the area-under-curve (AUC) and maximum concentration (Cmax) of a single dose of itraconazole (200 mg) by 66% and 70%, respectively. Time to Cmax (Tmax) increased by 70%.(15) This interaction has also been reported in a case report.(16) In a study in 3 subjects, simultaneous administration of a combination aluminum hydroxide/magnesium hydroxide (30 ml) decreased the AUC of a single dose of ketoconazole (200 mg) by 41%.(172) In a case report, a patient receiving concurrent ketoconazole with aluminum hydroxide, cimetidine, and sodium bicarbonate did not respond to therapy until cimetidine was discontinued and the administration time of aluminum hydroxide and cimetidine was changed to 2 hours after ketoconazole. In a follow-up study in 2 subjects, concurrent cimetidine and sodium hydroxide lowered ketoconazole levels.(18) In a study in 14 subjects, simultaneous administration of aluminum hydroxide/magnesium hydroxide (20 ml, 1800 mg/1200 mg) had no significant effects on fluconazole pharmacokinetics.(3) In a randomized, open-label, cross-over study in 6 subjects, simultaneous administration of itraconazole with buffered didanosine tablets resulted in undetectable levels of itraconazole.(19) In a randomized cross-over study in 12 HIV-positive subjects, administration of buffered didanosine tablets 2 hours after ketoconazole had no effects on ketoconazole levels.(20) In a randomized, cross-over, open-label study in 24 healthy subjects, simultaneous administration of enteric-coated didanosine had no effect on ketoconazole pharmacokinetics.(21) 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. |
ITRACONAZOLE, ITRACONAZOLE MICRONIZED, KETOCONAZOLE, SPORANOX, TOLSURA |
| Quinine/Aluminum and Magnesium Antacids; Lanthanum SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Aluminum and magnesium antacids may delay or decrease the absorption of quinine. CLINICAL EFFECTS: Concurrent use of antacids may result in decreased levels and effectiveness of quinine. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of quinine states that concurrent use with aluminum or magnesium containing antacids should be avoided. Some vitamin preparations may contain sufficient quantities of magnesium salts with antacid properties to interact as well. DISCUSSION: Aluminum and magnesium antacids have been shown to decrease quinine absorption in rats. |
QUALAQUIN, QUININE HCL, QUININE SULFATE |
| 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, EVEXITHROID, LEVO-T, LEVOTHYROXINE SODIUM, LEVOTHYROXINE SODIUM DILUTION, LEVOXYL, LIOMNY, LIOTHYRONINE SODIUM, NIVA THYROID, NP THYROID, PCCA T3 SODIUM DILUTION, PCCA T4 SODIUM DILUTION, RENTHYROID, SYNTHROID, THYQUIDITY, THYROID, TIROSINT, TIROSINT-SOL, UNITHROID |
| 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, RELGAABI |
| Amprenavir; Atazanavir/Antacids; Buffered Formulations SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Antacids increase gastric pH. As gastric pH increases, the solubility of atazanavir decreases.(1,2) The exact mechanism behind the interaction between amprenavir and antacids is unknown.(3) CLINICAL EFFECTS: Simultaneous administration of amprenavir or atazanavir with antacids or buffered formulations may result in decreased levels and effectiveness of amprenavir(3) and atazanavir.(1,2) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of amprenavir states that amprenavir should be administered 1 hour before or after antacids or buffered formulations such as didanosine.(3) The manufacturer of atazanavir states that atazanavir should be administered 2 hours before or 1 hour after antacids or buffered formulations.(1,2) Some vitamin preparations may contain sufficient quantities of calcium and/or magnesium salts with antacid properties to interact as well. DISCUSSION: Simultaneous administration of atazanavir with didanosine buffered tablets decreased atazanavir area-under-curve (AUC), maximum concentration (Cmax) and minimum concentration (Cmin) by 87%, 89% and 84%, respectively. Administration of atazanavir 1 hour after didanosine buffered tablets had no significant effect on atazanavir pharmacokinetics.(1) Other buffered formulations and antacids are expected to substantially decrease atazanavir concentrations and therapeutic effectiveness as well.(1,2) |
ATAZANAVIR SULFATE, EVOTAZ, REYATAZ |
| 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 |
| Selected Kinase Inhibitors/Antacids SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: The solubility of bosutinib,(1) dasatinib,(2) erlotinib,(3) gefitinib,(4) neratinib,(5) nilotinib(6), pazopanib,(7) and pexidartinib(8) is pH dependent. Antacid-induced changes in gastric pH may decrease the absorption of these agents.(1-8) CLINICAL EFFECTS: Simultaneous administration of antacids may result in decreased levels and effectiveness of bosutinib,(1) dasatinib,(2) erlotinib,(3) gefitinib,(4) neratinib,(5) nilotinib(6), pazopanib,(7) and pexidartinib.(8) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Antacid use should be considered in place of H2 blockers or proton pump inhibitors in patients receiving bosutinib,(1) dasatinib,(2) erlotinib,(3) gefitinib,(4) neratinib,(5) nilotinib(6), pazopanib,(7) and pexidartinib;(8) however, separation of administration times is required. If antacids are used, separate the administration times by several hours(1-8) but at least 2 hours for bosutinib,(1) dasatinib,(2) nilotinib,(6) and pexidartinib(8), 6 hours for gefitinib,(4) and 3 hours for neratinib.(5) Some vitamin preparations may contain sufficient quantities of calcium and/or magnesium salts with antacid properties to interact as well. DISCUSSION: In a study in 24 healthy subjects, lansoprazole (60 mg) decreased bosutinib (400 mg single dose) area-under-curve (AUC) and maximum concentration (Cmax) by 26% and 46%, respectively.(1) In a study in 24 healthy subjects, simultaneous administration of dasatinib (50 mg) with aluminum hydroxide/magnesium hydroxide (30 ml) decreased dasatinib AUC and Cmax by 55% and 58%, respectively. In the same subjects, administration of the antacid 2 hours before dasatinib decreased dasatinib Cmax by 26%, but had no effect on dasatinib AUC.(2) In a study in 24 healthy subjects, administration of a single dose of dasatinib (50 mg) 10 hours after famotidine decreased dasatinib AUC and Cmax by 61% and 63%, respectively.(2) In a study, concurrent omeprazole decreased the AUC and Cmax of erlotinib by 46% and 61%, respectively.3) In a study, concurrent esomeprazole decreased the AUC of nilotinib by 34%.(6) In a study in 15 healthy subjects, lansoprazole (30 mg at steady state) decreased the Cmax and AUC of a single dose of neratinib (240 mg) by 71% and 65%, respectively.(5) There were no significant changes in nilotinib pharmacokinetics when famotidine was administered 10 hours before or 2 hours after nilotinib.(6) There were no significant changes in nilotinib pharmacokinetics when an antacid (aluminum hydroxide/magnesium hydroxide/simethicone) was administered 2 hours before or after nilotinib.(6) Coadministration of esomeprazole decreased pexidartinib Cmax and AUC by 55% and 50%, respectively.(8) |
BOSULIF, DANZITEN, DASATINIB, ERLOTINIB HCL, GEFITINIB, IRESSA, NERLYNX, NILOTINIB D-TARTRATE, NILOTINIB HCL, PAZOPANIB HCL, PHYRAGO, SPRYCEL, TASIGNA, TURALIO, VOTRIENT |
| 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, ELTROMBOPAG OLAMINE, 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.(1-40) 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) ---Do not give sitafloxacin for at least 2 hours before or 2 hours after oral cations.(9) The US manufacturer of lanthanum recommends that quinolones be taken at least 1 hour before or 4 hours after lanthanum;(10) however, it would be prudent to follow the specific quinolone manufacturers' recommendations regarding concurrent administration of cations. The US manufacturer of ferric maltose recommends separation of ferric maltose by at least 4 hours. 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.(1-40) Treatment failures have been reported.(11-12) 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.(14) The administration of ciprofloxacin 2 hours prior to Videx chewable/dispersible tablets decreased ciprofloxacin concentrations by 26%.(15,16) 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.(17) In a study in 12 healthy subjects, aluminum hydroxide decreased ciprofloxacin AUC by 85%.(18) 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.(19) In a study in 15 healthy subjects, simultaneous administration of calcium acetate decreased the bioavailability of ciprofloxacin by 51%.(20) In a study in 6 healthy males, simultaneous administration of calcium carbonate decreased ciprofloxacin Cmax and AUC by 40% and 43%, respectively.(21) In a study in 12 healthy subjects, calcium carbonate decreased ciprofloxacin AUC by 40%.(18) In a study in 13 healthy males, calcium carbonate had no effect on ciprofloxacin bioavailability when administered 2 hours prior to the antibiotic.(22,23) In a study in healthy males, simultaneous administration of calcium polycarbophil decreased ciprofloxacin AUC by 50%.(24) In a study in 8 healthy males, simultaneous administration of ferrous fumarate (200 mg) decreased ciprofloxacin AUC by 70%.(25) In a study in healthy subjects, ferrous gluconate decreased ciprofloxacin bioavailability by 50%; however, no significant effects were seen with iron-ovotransferrin.(26) In a study in 8 healthy subjects, ferrous sulfate decreased the Cmax and AUC of simultaneously administered ciprofloxacin by 54% and 57%, respectively.(27) 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.(28) In a study in 12 healthy males, ferrous sulfate decreased ciprofloxacin AUC by 63%.(29) 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.(30) In a study in 12 healthy males, a multivitamin containing zinc decreased ciprofloxacin AUC by 22%.(29) In a study in 12 healthy subjects, an antacid containing aluminum-magnesium hydroxide had no effect on the pharmacokinetics of intravenous enoxacin.(31) 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.(32) 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%.(33) 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.(34) Concurrent magnesium-aluminum hydroxide or calcium have been shown to decrease the bioavailability of norfloxacin by 91.0% and 63.5%, respectively.(35) Concurrent zinc has been shown to decrease the bioavailability of norfloxacin.(36) In a study in 8 healthy subjects, ferrous sulfate decreased the Cmax and AUC of simultaneously administered norfloxacin by 75% and 73%, respectively.(27) Simultaneous aluminum phosphate was found to decrease the rate, but not the extent, of absorption of ofloxacin.(37) In a study in 8 healthy subjects, ferrous sulfate decreased the Cmax and AUC of simultaneously administered norfloxacin by 36% and 25%, respectively.(27) 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.(38) 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%.(33) 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.(39) 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.(40) 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 |
| Rilpivirine/Antacids; H2 Antagonists SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Rilpivirine requires an acidic medium for absorption. Antacid or H2 antagonist induced decrease in gastric pH may result in a decrease in rilpivirine absorption.(1) CLINICAL EFFECTS: 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: In patients maintained on rilpivirine, administer antacids at least 2 hours before or 4 hours after rilpivirine.(1) In patients maintained on rilpivirine, administer H2 antagonists at least 12 hours before or 4 hours after rilpivirine.(1) Concurrent use of proton pump inhibitors with rilpivirine is contraindicated.(1) Some vitamin preparations may contain sufficient quantities of calcium and/or magnesium salts with antacid properties to interact as well. DISCUSSION: In a study in 16 subjects, omeprazole (20 mg daily) decreased the maximum concentration (Cmax), area-under-curve (AUC), and minimum concentration (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 after a single dose of rilpivirine (150 mg) increased the rilpivirine Cmax and AUC by 21% and 13%, respectively.(1) |
COMPLERA, EDURANT, EDURANT PED, EMTRICITABINE-RILPIVIRNE-TENOF, ODEFSEY, RILPIVIRINE |
| 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. The US manufacturer of ferric maltose recommends separation of ferric maltose by at least 4 hours. 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 |
| 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 |
| 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 |
| 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/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 |
| 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 |
| 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 |
| 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.(1-3) 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 ER 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 |
| Defactinib/Antacids SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: The aqueous solubility of defactinib is pH dependent. Higher gastric pH leads to lower solubility which may reduce defactinib absorption.(1) CLINICAL EFFECTS: Coadministration with antacids may reduce the bioavailability of defactinib, leading to decreased systemic levels and effectiveness.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of defactinib states that patients requiring acid-lowering therapy should separate defactinib from antacid administration by 2 hours.(1) Some vitamin preparations may contain sufficient quantities of calcium and/or magnesium salts with antacid properties to interact as well. DISCUSSION: The impact of antacids on the pharmacokinetics of defactinib has not been investigated in clinical studies. In an interaction study, defactinib area-under-the-curve (AUC) decreased by 79% and maximum concentration (Cmax) decreased by 85% following concomitant use of multiple doses of omeprazole 40 mg daily. The AUC and Cmax of N-desmethyl amide (M4), a major active metabolite of defactinib, decreased by 83% and 88%, respectively.(1) |
AVMAPKI-FAKZYNJA, FAKZYNJA |
| Taletrectinib/Antacids SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: The aqueous solubility of taletrectinib is pH dependent. Higher gastric pH leads to lower solubility which may reduce taletrectinib absorption.(1) CLINICAL EFFECTS: Coadministration with antacids may reduce the bioavailability of taletrectinib, leading to decreased systemic levels and effectiveness.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of taletrectinib states that patients requiring acid-lowering therapy should separate taletrectinib from antacid administration by 2 hours.(1) Some vitamin preparations may contain sufficient quantities of calcium and/or magnesium salts with antacid properties to interact as well. DISCUSSION: The impact of antacids on the pharmacokinetics of taletrectinib has not been investigated in clinical studies. In an interaction study, taletrectinib area-under-the-curve (AUC) decreased by 40% and maximum concentration (Cmax) decreased by 65% following concomitant use of omeprazole 40 mg daily.(1) |
IBTROZI |
| Rilzabrutinib/Antacids SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Rilzabrutinib solubility decreases with increasing pH. Antacid induced increase in gastric pH may result in a decrease in rilzabrutinib absorption.(1) CLINICAL EFFECTS: Simultaneous administration of an antacid may result in decreased levels and effectiveness of rilzabrutinib.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Administer rilzabrutinib at least 2 hours before taking antacids.(1) Some vitamin preparations may contain sufficient quantities of calcium and/or magnesium salts with antacid properties to interact as well. DISCUSSION: The impact of antacids on the pharmacokinetics of rilzabrutinib has not been investigated in clinical studies. In an interaction study, administration of famotidine (H2 receptor antagonist) two hours after the evening dose of rilzabrutinib decreased the next morning dose of rilzabrutinib maximum concentration (Cmax) by 35% and area-under-curve (AUC) by 28%.(1) In another interaction study, coadministration of esomeprazole decreased rilzabrutinib Cmax by 55% and AUC by 51%.(1) |
WAYRILZ |
The following contraindication information is available for VITAFOL-OB+DHA (prenatal vitamins comb 10/ferrous fumarate/folic acid/dha):
Drug contraindication overview.
No enhanced Contraindications information available for this drug.
No enhanced Contraindications information available for this drug.
There are 1 contraindications.
Absolute contraindication.
| Contraindication List |
|---|
| Hemochromatosis |
There are 6 severe contraindications.
Adequate patient monitoring is recommended for safer drug use.
| Severe List |
|---|
| Chronic iron overload due to repeated blood transfusions |
| Diarrhea |
| Diverticular disease |
| Hemolytic anemia |
| Hemosiderosis |
| Ulcerative colitis |
There are 5 moderate contraindications.
Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.
| Moderate List |
|---|
| Gastritis |
| Increased risk of bleeding due to coagulation disorder |
| Kidney disease with reduction in glomerular filtration rate (GFr) |
| Peptic ulcer |
| Vitamin K deficiency induced hypoprothrombinemia |
The following adverse reaction information is available for VITAFOL-OB+DHA (prenatal vitamins comb 10/ferrous fumarate/folic acid/dha):
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 2 severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
| None. | None. |
| Rare/Very Rare |
|---|
|
Bronchospastic pulmonary disease Concentration difficulty |
There are 22 less severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
|
Black stools Constipation Diarrhea Flatulence Nausea |
Abdominal distension Acute abdominal pain 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 VITAFOL-OB+DHA (prenatal vitamins comb 10/ferrous fumarate/folic acid/dha):
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 |
No enhanced Pregnancy information available for this drug.
No enhanced Lactation information available for this drug.
No enhanced Geriatric Use information available for this drug.
The following prioritized warning is available for VITAFOL-OB+DHA (prenatal vitamins comb 10/ferrous fumarate/folic acid/dha):
WARNING: Accidental overdose of iron-containing products is a leading cause of fatal poisoning in children younger than 6 years. Keep this product out of reach of children. If overdose does occur, get medical help right away or call a poison control center.
WARNING: Accidental overdose of iron-containing products is a leading cause of fatal poisoning in children younger than 6 years. Keep this product out of reach of children. If overdose does occur, get medical help right away or call a poison control center.
The following icd codes are available for VITAFOL-OB+DHA (prenatal vitamins comb 10/ferrous fumarate/folic acid/dha)'s list of indications:
| Lactation | |
| Z39.1 | Encounter for care and examination of lactating mother |
| Pregnancy | |
| Z32.01 | Encounter for pregnancy test, result positive |
| Z33 | Pregnant state |
| Z33.1 | Pregnant state, incidental |
| Z33.3 | Pregnant state, gestational carrier |
| Z34.91 | Encounter for supervision of normal pregnancy, unspecified, first trimester |
| Z34.92 | Encounter for supervision of normal pregnancy, unspecified, second trimester |
| Z3A.0 | Weeks of gestation of pregnancy, unspecified or less than 10 weeks |
| Z3A.00 | Weeks of gestation of pregnancy not specified |
| Z3A.01 | Less than 8 weeks gestation of pregnancy |
| Z3A.08 | 8 weeks gestation of pregnancy |
| Z3A.09 | 9 weeks gestation of pregnancy |
| Z3A.1 | Weeks of gestation of pregnancy, weeks 10-19 |
| Z3A.10 | 10 weeks gestation of pregnancy |
| Z3A.11 | 11 weeks gestation of pregnancy |
| Z3A.12 | 12 weeks gestation of pregnancy |
| Z3A.13 | 13 weeks gestation of pregnancy |
| Z3A.14 | 14 weeks gestation of pregnancy |
| Z3A.15 | 15 weeks gestation of pregnancy |
| Z3A.16 | 16 weeks gestation of pregnancy |
| Z3A.17 | 17 weeks gestation of pregnancy |
| Z3A.18 | 18 weeks gestation of pregnancy |
| Z3A.19 | 19 weeks gestation of pregnancy |
| Z3A.2 | Weeks of gestation of pregnancy, weeks 20-29 |
| Z3A.20 | 20 weeks gestation of pregnancy |
| Z3A.21 | 21 weeks gestation of pregnancy |
| Z3A.22 | 22 weeks gestation of pregnancy |
| Z3A.23 | 23 weeks gestation of pregnancy |
| Z3A.24 | 24 weeks gestation of pregnancy |
| Z3A.25 | 25 weeks gestation of pregnancy |
| Z3A.26 | 26 weeks gestation of pregnancy |
| Z3A.27 | 27 weeks gestation of pregnancy |
| Z3A.28 | 28 weeks gestation of pregnancy |
| Z3A.29 | 29 weeks gestation of pregnancy |
| Z3A.3 | Weeks of gestation of pregnancy, weeks 30-39 |
| Z3A.30 | 30 weeks gestation of pregnancy |
| Z3A.31 | 31 weeks gestation of pregnancy |
| Z3A.32 | 32 weeks gestation of pregnancy |
| Z3A.33 | 33 weeks gestation of pregnancy |
| Z3A.34 | 34 weeks gestation of pregnancy |
| Z3A.35 | 35 weeks gestation of pregnancy |
| Z3A.36 | 36 weeks gestation of pregnancy |
| Z3A.37 | 37 weeks gestation of pregnancy |
| Z3A.38 | 38 weeks gestation of pregnancy |
| Z3A.39 | 39 weeks gestation of pregnancy |
| Z3A.4 | Weeks of gestation of pregnancy, weeks 40 or greater |
| Z3A.40 | 40 weeks gestation of pregnancy |
| Z3A.41 | 41 weeks gestation of pregnancy |
| Z3A.42 | 42 weeks gestation of pregnancy |
| Z3A.49 | Greater than 42 weeks gestation of pregnancy |
Formulary Reference Tool