Calcium carbonate; famotidine; magnesium hydroxide is an oral combination of antacids and an H2-receptor antagonist indicated for the treatment of heartburn associated with acid indigestion and sour stomach. Central nervous system adverse reactions, including confusion, delirium, hallucinations, disorientation, agitation, seizures, and lethargy, have been reported in elderly patients and patients with moderate and severe renal impairment treated with famotidine. Calcium carbonate; famotidine; magnesium hydroxide can reduce the absorption of other drugs, due to chelation and/or its effect on reducing intragastric acidity, leading to loss of efficacy of the concomitant drug.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
Oral Solid Formulations
-Chewable tablets: Chew tablets completely. Do not swallow whole.
Administration of calcium carbonate; magnesium hydroxide can cause gastric hypersecretion and acid rebound. Other common GI adverse reactions to calcium carbonate therapy include flatulence, gastric distension, constipation, and eructation. Constipation was reported in more than 1% of famotidine-treated patients during clinical trials. Other gastrointestinal adverse events reported in less than 1% of famotidine-treated patients include elevated hepatic enzymes, vomiting, nausea, abdominal discomfort, anorexia, xerostomia, and taste disorder. Cholestasis with jaundice and hepatitis have been reported during postmarketing experience with famotidine. If magnesium hydroxide is used in patients with impaired renal function or at high doses for extended periods of time, hypermagnesemia may occur. Hypermagnesemia results in a depressant effect on the central nervous system (causing anorexia and nausea) and neuromuscular system (causing decreased deep tendon reflexes and skeletal muscle weakness). Hypotension, muscle weakness, and electrocardiographic changes may be indicative of magnesium toxicity.
Large doses of calcium carbonate; magnesium hydroxide can lead to the development of hypercalcemia or nephrolithiasis (kidney stones or renal calculi) in susceptible patients. Clinical manifestations of hypercalcemia may include anorexia, thirst, nausea, vomiting, constipation, abdominal pain, muscle weakness (myasthenia), tiredness, mental disturbances, polydipsia, polyuria, bone pain, nephrocalcinosis, renal calculi (nephrolithiasis), and in severe cases, cardiac arrhythmias. Milk-alkali syndrome, characterized by hypercalcemia and metabolic alkalosis and, if left untreated, renal failure can occur during prolonged therapy with oral calcium antacids.
Headache and dizziness were reported in more than 1% of famotidine-treated patients during clinical trials. Other central nervous system adverse events reported in less than 1% of famotidine-treated patients include seizures, hallucinations, depression, anxiety, libido decrease, insomnia, and drowsiness. Confusion, agitation, and paresthesias have been reported during postmarketing experience with famotidine. Confusion, delirium, hallucinations, disorientation, agitation, seizures, and lethargy have been reported in elderly patients and patients with moderate and severe renal impairment treated with famotidine; famotidine dosage reduction is recommended in patients with moderate to severe renal impairment. A review of central nervous system reactions to H2-antagonists revealed that the incidence varies widely depending on the specific report and that no single H2-antagonist is more likely to induce CNS reactions than another.
Hypersensitivity or skin-related adverse reactions reported in less than 1% of famotidine-treated patients during clinical trials include orbital edema, rash, conjunctival injection, bronchospasm, pruritus, xerosis, and flushing. Anaphylactoid reactions, angioedema, facial edema, urticaria, Stevens-Johnson syndrome, and toxic epidermal necrolysis have been reported during postmarketing experience with famotidine.
Increasing evidence suggests a link between acid-suppression therapy and respiratory infection, specifically pneumonia (community- and hospital-acquired). Several mechanisms have been proposed to account for this association. One such mechanism states that gastric pH serves as a barrier against pathogenic colonization of the gastrointestinal tract. An increase in gastric pH allows for bacterial and viral invasion which, in theory, can precipitate respiratory infections. Another proposed mechanism accounts for the role that gastric acid may have on stimulating the cough reflex that allows for the clearing of infectious agents from the respiratory tract. Finally, the fact that acid-suppressive therapy may impair white blood cell function, which in turn may lead to a depressed immune response to an infection, is listed among possible mechanisms. Regardless of the mechanism, the use of H2-blockers has been associated with the development of pneumonia. Data from a large epidemiological trial, including 364,683 individuals who developed 5,551 first occurrences of community-acquired pneumonia (CAP), suggest an increased risk of developing CAP among users of acid-suppressive therapy compared to those who stopped therapy. Users of H2-blockers had an adjusted RR of 1.63 (95% CI, 1.07 to 2.48) compared to those who stopped therapy. In a second large cohort trial, including 63,878 hospital admissions, acid-suppressive therapy was ordered in 52% (83% PPI and 23% H2-blocker, with some patients exposed to both) of new admissions. Hospital-acquired pneumonia occurred in 2,219 admissions (3.5%) with a higher incidence recorded among acid-suppressive therapy exposed patients compared to non-exposed patients. A non-significant association with pneumonia was found with H2-blockers (OR, 1.2; 95% CI, 0.98 to 1.4); however, the lack of significance was attributed to the studies lack of power to detect significance for an OR of less than 1.3. Interstitial pneumonia has been reported during postmarketing experience with famotidine.
Atrophic gastritis, a precursor for gastric cancer, has been associated with prolonged acid suppression with high dose H2-blockers like famotidine in patients who are H. pylori positive. A 'test and treat' approach for baseline H. pylori infections is recommended for patients with reflux esophagitis on long term acid suppression therapy. Treatment of baseline infection decreases inflammation and may reverse corpus gastritis.
Palpitations were reported in less than 1% of famotidine-treated patients during clinical trials. Arrhythmia, AV block, and QT prolongation have been reported during postmarketing experience with famotidine. Prolonged QT intervals have been reported in patients receiving famotidine with moderate to severe renal impairment; famotidine dosage reduction is recommended in patients with moderate to severe renal impairment.
Thrombocytopenia was reported in less than 1% of famotidine-treated patients during clinical trials. Agranulocytosis, pancytopenia, and leukopenia have been reported during postmarketing experience with famotidine.
Fever, asthenia, fatigue, musculoskeletal pain, and arthralgia were reported in less than 1% of famotidine-treated patients during clinical trials. Rhabdomyolysis and muscle cramps have been reported during postmarketing experience with famotidine.
Tinnitus was reported in less than 1% of famotidine-treated patients during clinical trials.
Impotence (erectile dysfunction) was reported in less than 1% of famotidine-treated patients during clinical trials.
Long-term (e.g., generally more than 3 years) treatment with acid-suppressing agents can lead to malabsorption of vitamin B12 (cyanocobalamin). One large case-controlled study compared patients with and without an incident diagnosis of vitamin B12 deficiency (n = 25,956 and 184,199, respectively). A correlation was demonstrated between vitamin B12 deficiency and gastric acid-suppression therapy. Patients receiving 2 years or more of a H2-receptor antagonist (OR, 1.25 [95% CI, 1.17 to 1.34]) were associated with having an increased risk for vitamin B12 deficiency.
Famotidine is contraindicated in patients with a history of famotidine or other H2-blocker hypersensitivity.
Symptomatic response to therapy with famotidine does not preclude the presence of gastric cancer. Consider evaluation for gastric malignancy in adults who have suboptimal response or an early symptomatic relapse after completing treatment with famotidine. Do not use calcium carbonate; famotidine; magnesium hydroxide in a patient with GI bleeding.
Symptomatic response to therapy with famotidine does not preclude the presence of H. pylori infection. Famotidine therapy does not appear to interfere with the sensitivity of gastric urease biopsy. It is controversial whether H2-blockers interfere with urea breath-tests for the detection of H. pylori; many laboratories recommend holding these drugs for 24 to 48 hours prior to testing. H2-blockers, as single agents, will not eradicate H. pylori infection.
Famotidine should be used cautiously in patients with hepatic disease, renal impairment or renal failure (renal disease), because the drug can accumulate, causing toxicity. There is a close relationship between the drug's elimination half-life and creatinine clearance. Dosages of famotidine should be adjusted in patients with moderate or severe renal impairment. Confusion, delirium, hallucinations, disorientation, agitation, seizures, and lethargy have been reported in patients treated with famotidine with moderate and severe renal impairment. Rarely, QT prolongation or central nervous system (CNS) reactions have been reported in patients with impaired renal function whose dose/dosing interval of famotidine may not have been adjusted appropriately. Use famotidine with caution in patients with renal impairment and other conditions that may increase the risk of QT prolongation.
According to the Beers Criteria, H2-receptor antagonists such as famotidine are considered potentially inappropriate medications (PIMs) in geriatric adults with delirium/high risk of delirium (potential for new-onset or worsening delirium). The Beers panel also recommends dosage reduction of H2-antagonists in geriatric adults with a creatinine clearance less than 50 mL/minute due to the potential for mental status changes.
There is no specific information on the use of calcium carbonate; famotidine; magnesium hydroxide products during pregnancy. Adverse effects have not been reported with calcium carbonate use within the recommended dietary daily intakes for a pregnant female. Calcium carbonate and magnesium hydroxide antacids are considered to be safe for use during pregnancy. Animal studies and epidemiologic data during pregnancy suggest famotidine use when necessary is not harmful, even though there are no adequate and well-controlled studies evaluating famotidine use in pregnant patients. In one such study of human data, exposure to H2-blockers, including famotidine, was not associated with an increased risk for congenital malformations (adjusted OR 1.03, 95% CI: 0.80, 1.32); also, no such association was found when therapeutic pregnancy terminations were included in the analysis (adjusted OR 1.17, 95% CI: 0.93, 1.46). Exposure to H2-blockers was not associated with perinatal mortality, premature delivery, low birth weight, or low Apgar scores. In animal reproduction studies, no adverse development effects were observed with oral famotidine at doses up to approximately 243 and 122 times, respectively, the recommended human dose of 80 mg/day for the treatment of erosive esophagitis. Guidelines recommend a trial of lifestyle modifications as first-line therapy for heartburn and gastroesophageal reflux disease (GERD) during pregnancy, followed by antacids if lifestyle adjustments are ineffective. For ongoing symptoms, H2-blockers such as famotidine can be used. Other medications should be reserved for pregnant patients who fail H2-blocker therapy. Self-medication with H2-blockers (OTC formulations) during pregnancy is not recommended. Pregnant patients should see their health care professional for a proper diagnosis and for treatment recommendations.
There is no information on the use of calcium carbonate; famotidine; magnesium hydroxide combination products during lactation. However, based on expert guidelines regarding the use of famotidine and calcium and magnesium based antacids during lactation, use of this combination product can be considered compatible with breast-feeding. There are limited data suggesting the presence of famotidine in human breast milk; however, there were no effects on the breastfed infant. There are no data on famotidine effects on milk production. Famotidine is present in the milk of lactating rats. Famotidine is indicated for use in infants and is used in newborns at doses that are higher than those excreted in breast milk. According to guidelines, if heartburn/gastroesophageal reflux (GERD) symptoms persist after delivery, antacids and sucralfate are safe to use during lactation because they are not concentrated in breast milk. H2-blockers are excreted in breast milk, but cimetidine and famotidine are considered safe for use during lactation and may be used if symptoms persist despite antacid use. Famotidine is preferred in lactation due to the low concentration in breast milk.
For the treatment of pyrosis (heartburn) associated with acid indigestion or sour stomach:
Oral dosage (tablets containing calcium carbonate 800 mg, famotidine 10 mg, magnesium hydroxide 165 mg):
Adults: 1 tablet PO as needed. Max: 2 tablets/day.
Children and Adolescents 12 years and older: 1 tablet PO as needed. Max: 2 tablets/day.
Maximum Dosage Limits:
-Adults
2 tablets/day (calcium carbonate 1,600 mg/day, famotidine 20 mg/day, magnesium hydroxide 330 mg/day) PO.
-Geriatric
2 tablets/day (calcium carbonate 1,600 mg/day, famotidine 20 mg/day, magnesium hydroxide 330 mg/day) PO.
-Adolescents
2 tablets/day (calcium carbonate 1,600 mg/day, famotidine 20 mg/day, magnesium hydroxide 330 mg/day) PO.
-Children
Children 12 years: 2 tablets/day (calcium carbonate 1,600 mg/day, famotidine 20 mg/day, magnesium hydroxide 330 mg/day) PO.
Children 1 to 11 years: Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
Abacavir; Dolutegravir; Lamivudine: (Moderate) Administer dolutegravir 2 hours before or 6 hours after taking supplements containing calcium if given under fasting conditions. When taken with food, dolutegravir and supplements containing calcium can be taken at the same time. Simultaneous administration under fasted conditions may result in reduced bioavailability of dolutegravir.
Acalabrutinib: (Moderate) Separate the administration of acalabrutinib capsules and calcium carbonate by at least 2 hours if these agents are used together; decreased acalabrutinib exposure occurred when acalabrutinib capsules and calcium carbonate were coadministered in a drug interaction study. Acalabrutinib capsule solubility decreases with increasing pH values. In healthy subjects, the AUC of acalabrutinib was decreased by 53% when acalabrutinib capsules were coadministered with calcium carbonate 1 gram. (Moderate) Separate the administration of acalabrutinib capsules and H2-blockers if these agents are used together; administer acalabrutinib capusles 2 hours before the H2-blocker. Acalabrutinib capsule solubility decreases with increasing pH values; therefore, coadministration may result in decreased acalabrutinib exposure and effectiveness.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Minor) It appears that antacids increase pseudoephedrine plasma concentrations. This interaction can be avoided by separating the administration of pseudoephedrine and antacids by 1 to 2 hours. If antacids are used on a regular basis, an alternative to pseudoephedrine may be considered.
Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Minor) It appears that antacids increase pseudoephedrine plasma concentrations. This interaction can be avoided by separating the administration of pseudoephedrine and antacids by 1 to 2 hours. If antacids are used on a regular basis, an alternative to pseudoephedrine may be considered.
Acetaminophen; Dextromethorphan; Pseudoephedrine: (Minor) It appears that antacids increase pseudoephedrine plasma concentrations. This interaction can be avoided by separating the administration of pseudoephedrine and antacids by 1 to 2 hours. If antacids are used on a regular basis, an alternative to pseudoephedrine may be considered.
Acetaminophen; Pseudoephedrine: (Minor) It appears that antacids increase pseudoephedrine plasma concentrations. This interaction can be avoided by separating the administration of pseudoephedrine and antacids by 1 to 2 hours. If antacids are used on a regular basis, an alternative to pseudoephedrine may be considered.
Acrivastine; Pseudoephedrine: (Minor) It appears that antacids increase pseudoephedrine plasma concentrations. This interaction can be avoided by separating the administration of pseudoephedrine and antacids by 1 to 2 hours. If antacids are used on a regular basis, an alternative to pseudoephedrine may be considered.
Albuterol; Budesonide: (Moderate) Enteric-coated budesonide granules dissolve at a pH > 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and antacids, milk, or other drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. In general, it may be prudent to avoid drugs such as antacids in combination with enteric-coated budesonide. In addition, calcium absorption is reduced when calcium carbonate is taken concomitantly with systemic corticosteroids. Systemic corticosteroids induce a negative calcium balance by inhibiting intestinal calcium absorption as well as by increasing renal calcium losses. The mechanism by which these drugs inhibit calcium absorption in the intestine is likely to involve a direct inhibition of absorptive cell function. (Moderate) Monitor for loss of oral, enteric-coated budesonide efficacy during concomitant famotidine use. Since the dissolution of oral, enteric-coated budesonide is pH dependent, the release properties and uptake of the drug may be altered when used after H2-blockers.
Alendronate: (Moderate) Separate administration of alendronate and calcium-containing supplements by at least 30 minutes. Calcium will interfere with the absorption of alendronate.
Alendronate; Cholecalciferol: (Moderate) Separate administration of alendronate and calcium-containing supplements by at least 30 minutes. Calcium will interfere with the absorption of alendronate.
Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium.
Alogliptin; Metformin: (Minor) Famotidine may decrease the renal clearance of metformin secondary to competition for renal tubular transport systems. Such an interaction has been observed when cimetidine was administered with metformin. The decrease in renal excretion led to a 40% increase in metformin AUC. Although interactions with cationic drugs remain theoretical (except for cimetidine), caution is warranted when famotidine and metformin are prescribed concurrently. Famotidine may be less likely to interact with metformin versus cimetidine or ranitidine because of less tubular excretion.
Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium.
Amlodipine: (Minor) Monitor blood pressure during concurrent use of calcium and calcium-channel blockers. Concomitant use may reduce the response to calcium-channel blockers.
Amlodipine; Atorvastatin: (Minor) Monitor blood pressure during concurrent use of calcium and calcium-channel blockers. Concomitant use may reduce the response to calcium-channel blockers.
Amlodipine; Benazepril: (Minor) Monitor blood pressure during concurrent use of calcium and calcium-channel blockers. Concomitant use may reduce the response to calcium-channel blockers.
Amlodipine; Celecoxib: (Minor) Monitor blood pressure during concurrent use of calcium and calcium-channel blockers. Concomitant use may reduce the response to calcium-channel blockers.
Amlodipine; Olmesartan: (Minor) Monitor blood pressure during concurrent use of calcium and calcium-channel blockers. Concomitant use may reduce the response to calcium-channel blockers.
Amlodipine; Valsartan: (Minor) Monitor blood pressure during concurrent use of calcium and calcium-channel blockers. Concomitant use may reduce the response to calcium-channel blockers.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium. (Minor) Monitor blood pressure during concurrent use of calcium and calcium-channel blockers. Concomitant use may reduce the response to calcium-channel blockers.
Amphetamine: (Moderate) Use amphetamine; dextroamphetamine and H2-blockers concomitantly with caution. Gastrointestinal alkalinizing agents may increase exposure to amphetamine; dextroamphetamine and exacerbate its actions. (Minor) Monitor for an increase in amphetamine-related adverse effects during concomitant antacid use. Increasing gastric or urine pH may increase amphetamine exposure and the risk for side effects in some patients. As antacids have rarely been observed to increase gastric or urinary pH above 6.5, antacid-related pH changes may be insufficient to warrant clinical concern in most patients.
Amphetamine; Dextroamphetamine Salts: (Moderate) Use amphetamine; dextroamphetamine and H2-blockers concomitantly with caution. Gastrointestinal alkalinizing agents may increase exposure to amphetamine; dextroamphetamine and exacerbate its actions.
Amphetamine; Dextroamphetamine: (Moderate) Use amphetamine; dextroamphetamine and H2-blockers concomitantly with caution. Gastrointestinal alkalinizing agents may increase exposure to amphetamine; dextroamphetamine and exacerbate its actions. (Minor) Monitor for an increase in amphetamine-related adverse effects during concomitant antacid use. Increasing gastric or urine pH may increase amphetamine exposure and the risk for side effects in some patients. As antacids have rarely been observed to increase gastric or urinary pH above 6.5, antacid-related pH changes may be insufficient to warrant clinical concern in most patients.
Amphetamines: (Minor) Monitor for an increase in amphetamine-related adverse effects during concomitant antacid use. Increasing gastric or urine pH may increase amphetamine exposure and the risk for side effects in some patients. As antacids have rarely been observed to increase gastric or urinary pH above 6.5, antacid-related pH changes may be insufficient to warrant clinical concern in most patients.
Anticholinergics: (Major) Avoid concomitant use of calcium carbonate and anticholinergics. Antacids may interfere with the absorption of anticholinergics.
Aripiprazole: (Minor) Coadministration of aripiprazole with famotidine decreases aripiprazole's solubility and rate of absorption. The Cmax of aripiprazole and the metabolite dehydroaripiprazole are decreased by 37% and 21%, respectively, and the AUC of aripiprazole and the dehydroaripiprazole metabolite are decreased by 13% and 15%, respectively. This interaction does not appear to cause clinically relevant effects and therefore no dosage adjustments are required.
Atazanavir: (Major) Atazanavir solubility decreases as gastric pH increases. Although drug interactions between atazanavir and antacids have not been specifically studied, based on data with other protease inhibitors, it is recommended that antacids not be given at the same time as atazanavir because of potential interference with absorption of atazanavir. Separate the administration of atazanavir and antacids to avoid the potential for interaction; give atazanavir 2 hours before or 1 hour after the antacid. (Major) Coadministration of H2-blockers with atazanavir reduces serum atazanavir concentrations; however, H2-blockers can be used under specific administration restrictions. Although data are insufficient to recommend atazanavir dosing in children < 40 kg receiving concomitant H2-blockers, the same recommendations regarding timing and maximum doses of concomitant H2-blockers should be followed. In treatment-naive patients >= 40 kg, do not exceed an H2- blocker dose equivalent to famotidine 40 mg twice daily, and give atazanavir 300 mg with ritonavir 100 mg once daily with food. Give atazanavir simultaneously with and/or at least 10 hours after the H2- blocker. If a treatment-naive adult or adolescent (>= 40 kg) cannot tolerate ritonavir, do not exceed an H2- blocker dose equivalent to famotidine 20 mg twice daily, and the atazanavir dose should be increased to 400 mg once daily with food given at least 2 hours before or 10 hours after the H2- blocker. Data are insufficent to recommend atazanavir dosing in children or adolescents < 40 kg not receiving ritonavir boosting. In treatment-naive patients on a cobicistat-boosted regimen, cobicistat and atazanavir may be administered without dosage adjustment if given at the same time or a minimum of 10 hours after dosing of the H2-blocker. The H2-blocker dose should not exceed a dose that is comparable to 40 mg/day of famotidine in treatment-naive patients. In treatment-experienced patients >= 40 kg, do not exceed an H2- blocker dose equivalent to famotidine 20 mg twice daily, and give atazanavir 300 mg with ritonavir 100 mg once daily with food. Give atazanavir simultaneously with and/or at least 10 hours after the H2- blocker. In treatment-experienced patients >= 40 kg receiving H2-antagonists and tenofovir, atazanavir should be dosed 400 mg with ritonavir 100 mg once daily with food. In antiretroviral-experienced patients on a cobicistat-boosted regimen, the dosage of cobicistat with atazanavir needs to be increased if administered with H2-blockers; the recommended dose is cobicistat 150 mg/day with atazanavir 400 mg/day and 20 mg/day or less of famotidine or other comparably dosed H2-blocker. Significant reductions in atazanavir serum concentrations may lead to therapeutic failure and the development of HIV resistance. Closely monitor patients for antiretroviral therapeutic failure and resistance development during treatment with an H2- blocker.
Atazanavir; Cobicistat: (Major) Atazanavir solubility decreases as gastric pH increases. Although drug interactions between atazanavir and antacids have not been specifically studied, based on data with other protease inhibitors, it is recommended that antacids not be given at the same time as atazanavir because of potential interference with absorption of atazanavir. Separate the administration of atazanavir and antacids to avoid the potential for interaction; give atazanavir 2 hours before or 1 hour after the antacid. (Major) Coadministration of H2-blockers with atazanavir reduces serum atazanavir concentrations; however, H2-blockers can be used under specific administration restrictions. Although data are insufficient to recommend atazanavir dosing in children < 40 kg receiving concomitant H2-blockers, the same recommendations regarding timing and maximum doses of concomitant H2-blockers should be followed. In treatment-naive patients >= 40 kg, do not exceed an H2- blocker dose equivalent to famotidine 40 mg twice daily, and give atazanavir 300 mg with ritonavir 100 mg once daily with food. Give atazanavir simultaneously with and/or at least 10 hours after the H2- blocker. If a treatment-naive adult or adolescent (>= 40 kg) cannot tolerate ritonavir, do not exceed an H2- blocker dose equivalent to famotidine 20 mg twice daily, and the atazanavir dose should be increased to 400 mg once daily with food given at least 2 hours before or 10 hours after the H2- blocker. Data are insufficent to recommend atazanavir dosing in children or adolescents < 40 kg not receiving ritonavir boosting. In treatment-naive patients on a cobicistat-boosted regimen, cobicistat and atazanavir may be administered without dosage adjustment if given at the same time or a minimum of 10 hours after dosing of the H2-blocker. The H2-blocker dose should not exceed a dose that is comparable to 40 mg/day of famotidine in treatment-naive patients. In treatment-experienced patients >= 40 kg, do not exceed an H2- blocker dose equivalent to famotidine 20 mg twice daily, and give atazanavir 300 mg with ritonavir 100 mg once daily with food. Give atazanavir simultaneously with and/or at least 10 hours after the H2- blocker. In treatment-experienced patients >= 40 kg receiving H2-antagonists and tenofovir, atazanavir should be dosed 400 mg with ritonavir 100 mg once daily with food. In antiretroviral-experienced patients on a cobicistat-boosted regimen, the dosage of cobicistat with atazanavir needs to be increased if administered with H2-blockers; the recommended dose is cobicistat 150 mg/day with atazanavir 400 mg/day and 20 mg/day or less of famotidine or other comparably dosed H2-blocker. Significant reductions in atazanavir serum concentrations may lead to therapeutic failure and the development of HIV resistance. Closely monitor patients for antiretroviral therapeutic failure and resistance development during treatment with an H2- blocker.
Atenolol: (Minor) Calcium antacids (e.g., calcium carbonate) and supplements (e.g., other oral calcium salts) have been reported to reduce the mean peak concentrations by 51% and the AUC of atenolol by 32%. In another study, antacids reduced the AUC of atenolol by 33%. Separate doses of atenolol and calcium-containing antacids or supplements by at least 2 hours to minimize this potential interaction,. However, most clinicians consider the interaction of atenolol with antacids to be of minor clinical significance, since clinical efficacy (heart rate and blood pressure parameters) appear to be unchanged under usual intermittent clinical use.
Atenolol; Chlorthalidone: (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium. (Minor) Calcium antacids (e.g., calcium carbonate) and supplements (e.g., other oral calcium salts) have been reported to reduce the mean peak concentrations by 51% and the AUC of atenolol by 32%. In another study, antacids reduced the AUC of atenolol by 33%. Separate doses of atenolol and calcium-containing antacids or supplements by at least 2 hours to minimize this potential interaction,. However, most clinicians consider the interaction of atenolol with antacids to be of minor clinical significance, since clinical efficacy (heart rate and blood pressure parameters) appear to be unchanged under usual intermittent clinical use.
Atracurium: (Moderate) Concomitant use of neuromuscular blockers and calcium may result in resistance to neuromuscular blockade. Calcium antagonizes the potentiating effect of magnesium on neuromuscular blockade. Also, calcium triggers acetylcholine release, and therefore, may both reduce the sensitivity to neuromuscular blockers and decrease the duration of neuromuscular blockade.
Atropine: (Major) Avoid concomitant use of calcium carbonate and anticholinergics. Antacids may interfere with the absorption of anticholinergics.
Atropine; Difenoxin: (Major) Avoid concomitant use of calcium carbonate and anticholinergics. Antacids may interfere with the absorption of anticholinergics.
Azilsartan; Chlorthalidone: (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium.
Baloxavir Marboxil: (Major) Do not administer baloxavir with products that contain calcium. Polyvalent cations, such as calcium, can chelate with baloxavir, reducing its absorption.
Beclomethasone: (Moderate) Calcium absorption is reduced when calcium carbonate is taken concomitantly with systemic corticosteroids.
Belladonna; Opium: (Major) Avoid concomitant use of calcium carbonate and anticholinergics. Antacids may interfere with the absorption of anticholinergics.
Bempedoic Acid; Ezetimibe: (Minor) Antacids (e.g., 20 ml aluminum hydroxide; magnesium hydroxide) have no significant effect on the oral bioavailability of total ezetimibe (ezetimibe plus ezetimibe-glucuronide), ezetimibe-glucuronide, or ezetimibe based on AUC values. However, the peak plasma concentration (Cmax) of total ezetimibe is decreased by 30%. The effect of the antacids in this regard is not expected to have a significant effect on the ability of ezetimibe to lower cholesterol. However, to limit any potential interaction, it would be prudent to administer ezetimibe at least 1 hour before or 2 hours after administering antacids.
Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Major) Avoid concomitant use of calcium carbonate and anticholinergics. Antacids may interfere with the absorption of anticholinergics. (Major) Avoid the concomitant use of calcium carbonate and methenamine. Calcium carbonate may cause the urine to become alkaline. This may reduce the effectiveness of methenamine by inhibiting its conversion to formaldehyde.
Benzphetamine: (Minor) Monitor for an increase in amphetamine-related adverse effects during concomitant antacid use. Increasing gastric or urine pH may increase amphetamine exposure and the risk for side effects in some patients. As antacids have rarely been observed to increase gastric or urinary pH above 6.5, antacid-related pH changes may be insufficient to warrant clinical concern in most patients.
Benztropine: (Major) Avoid concomitant use of calcium carbonate and anticholinergics. Antacids may interfere with the absorption of anticholinergics.
Betamethasone: (Moderate) Calcium absorption is reduced when calcium carbonate is taken concomitantly with systemic corticosteroids. Systemic corticosteroids induce a negative calcium balance by inhibiting intestinal calcium absorption as well as by increasing renal calcium losses. The mechanism by which these drugs inhibit calcium absorption in the intestine is likely to involve a direct inhibition of absorptive cell function.
Bictegravir; Emtricitabine; Tenofovir Alafenamide: (Moderate) Administer bictegravir with food at the same time as oral calcium supplements. Routine administration of bictegravir under fasting conditions simultaneously with, or 2 hours after, calcium supplements is not recommended. Calcium is a polyvalent cation that can bind bictegravir in the GI tract. Taking these drugs simultaneously without food results in reduced bioavailability of bictegravir. In drug interaction studies, simultaneous administration of bictegravir with another calcium supplement under fasted conditions decreased the mean AUC of bictegravir by approximately 33%.
Bisacodyl: (Moderate) By increasing intragastric pH, calcium carbonate can affect the dissolution of oral bisacodyl tablets; administration should be separated by 1 hour. (Minor) The concomitant use of bisacodyl tablets with H2-blockers can cause the enteric coating of the bisacody tablet to dissolve prematurely, leading to possible gastric irritation or dyspepsia. Avoid H2-blockers within 1 hour before or after the bisacodyl dosage.
Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of these antibiotics will be significantly reduced by other orally administered compounds that contain calcium salts, particularly if the time of administration is within 60 minutes of each other. Calcium salts and tetracyclines should not be administered within 1 to 2 hours of each other, although doxycycline chelates less with calcium than other tetracyclines.
Bismuth Subsalicylate: (Minor) H2-blockers may increase the systemic absorption of bismuth from bismuth-containing compounds like bismuth subsalicylate.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of these antibiotics will be significantly reduced by other orally administered compounds that contain calcium salts, particularly if the time of administration is within 60 minutes of each other. Calcium salts and tetracyclines should not be administered within 1 to 2 hours of each other, although doxycycline chelates less with calcium than other tetracyclines. (Minor) H2-blockers may increase the systemic absorption of bismuth from bismuth-containing compounds like bismuth subsalicylate.
Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium.
Bosutinib: (Major) Bosutinib displays pH-dependent aqueous solubility; therefore, concomitant use of bosutinib and antacids may result in decreased plasma exposure of bosutinib. Separate the administration of bosutinib and antacids by more than 2 hours. (Moderate) Bosutinib displays pH-dependent aqueous solubility; therefore, concomitant use of bosutinib and H2-blockers may result in decreased plasma exposure of bosutinib. Separate the administration of bosutinib and H2-blockers by more than 2 hours.
Brompheniramine; Pseudoephedrine: (Minor) It appears that antacids increase pseudoephedrine plasma concentrations. This interaction can be avoided by separating the administration of pseudoephedrine and antacids by 1 to 2 hours. If antacids are used on a regular basis, an alternative to pseudoephedrine may be considered.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Minor) It appears that antacids increase pseudoephedrine plasma concentrations. This interaction can be avoided by separating the administration of pseudoephedrine and antacids by 1 to 2 hours. If antacids are used on a regular basis, an alternative to pseudoephedrine may be considered.
Budesonide: (Moderate) Enteric-coated budesonide granules dissolve at a pH > 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and antacids, milk, or other drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. In general, it may be prudent to avoid drugs such as antacids in combination with enteric-coated budesonide. In addition, calcium absorption is reduced when calcium carbonate is taken concomitantly with systemic corticosteroids. Systemic corticosteroids induce a negative calcium balance by inhibiting intestinal calcium absorption as well as by increasing renal calcium losses. The mechanism by which these drugs inhibit calcium absorption in the intestine is likely to involve a direct inhibition of absorptive cell function. (Moderate) Monitor for loss of oral, enteric-coated budesonide efficacy during concomitant famotidine use. Since the dissolution of oral, enteric-coated budesonide is pH dependent, the release properties and uptake of the drug may be altered when used after H2-blockers.
Budesonide; Formoterol: (Moderate) Enteric-coated budesonide granules dissolve at a pH > 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and antacids, milk, or other drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. In general, it may be prudent to avoid drugs such as antacids in combination with enteric-coated budesonide. In addition, calcium absorption is reduced when calcium carbonate is taken concomitantly with systemic corticosteroids. Systemic corticosteroids induce a negative calcium balance by inhibiting intestinal calcium absorption as well as by increasing renal calcium losses. The mechanism by which these drugs inhibit calcium absorption in the intestine is likely to involve a direct inhibition of absorptive cell function. (Moderate) Monitor for loss of oral, enteric-coated budesonide efficacy during concomitant famotidine use. Since the dissolution of oral, enteric-coated budesonide is pH dependent, the release properties and uptake of the drug may be altered when used after H2-blockers.
Budesonide; Glycopyrrolate; Formoterol: (Major) Avoid concomitant use of calcium carbonate and anticholinergics. Antacids may interfere with the absorption of anticholinergics. (Moderate) Enteric-coated budesonide granules dissolve at a pH > 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and antacids, milk, or other drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. In general, it may be prudent to avoid drugs such as antacids in combination with enteric-coated budesonide. In addition, calcium absorption is reduced when calcium carbonate is taken concomitantly with systemic corticosteroids. Systemic corticosteroids induce a negative calcium balance by inhibiting intestinal calcium absorption as well as by increasing renal calcium losses. The mechanism by which these drugs inhibit calcium absorption in the intestine is likely to involve a direct inhibition of absorptive cell function. (Moderate) Monitor for loss of oral, enteric-coated budesonide efficacy during concomitant famotidine use. Since the dissolution of oral, enteric-coated budesonide is pH dependent, the release properties and uptake of the drug may be altered when used after H2-blockers.
Bupivacaine; Lidocaine: (Moderate) Concomitant use of systemic lidocaine and famotidine may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; famotidine inhibits CYP1A2.
Cabotegravir: (Moderate) Administer oral calcium at least two hours before or four hours after taking oral cabotegravir. Calcium is a polyvalent cation that can bind cabotegravir in the GI tract. Taking these drugs simultaneously may result in reduced oral bioavailability of cabotegravir.
Cabotegravir; Rilpivirine: (Moderate) Administer oral calcium at least two hours before or four hours after taking oral cabotegravir. Calcium is a polyvalent cation that can bind cabotegravir in the GI tract. Taking these drugs simultaneously may result in reduced oral bioavailability of cabotegravir. (Moderate) Coadministration with famotidine may significantly decrease rilpivirine plasma concentrations, potentially resulting in treatment failure. To decrease the risk of virologic failure, avoid use of famotidine for at least 12 hours before and at least 4 hours after administering rilpivirine. (Moderate) Concurrent administration of rilpivirine and antacids may significantly decrease rilpivirine plasma concentrations, potentially resulting in treatment failure. To decrease the risk of virologic failure, avoid use of antacids for at least 2 hours before and at least 4 hours after administering rilpivirine.
Calcifediol: (Moderate) Monitor serum calcium concentrations during concomitant use of high doses of calcium and vitamin D analogs; a dosage adjustment of the vitamin D analog may be needed. Hypercalcemia may be exacerbated by concomitant administration.
Calcipotriene: (Minor) There is evidence that calcipotriene can be absorbed in amounts that are sufficient to produce systemic effects, including elevated serum calcium; hypercalcemia has been observed in normal prescription use. Use calcipotriene cautiously with other agents that can produce hypercalcemia (e.g., calcium salts or supplements including calcium carbonate).
Calcipotriene; Betamethasone: (Minor) There is evidence that calcipotriene can be absorbed in amounts that are sufficient to produce systemic effects, including elevated serum calcium; hypercalcemia has been observed in normal prescription use. Use calcipotriene cautiously with other agents that can produce hypercalcemia (e.g., calcium salts or supplements including calcium carbonate).
Calcitonin: (Moderate) Calcitonin is given to hypercalcemic patients to reduce serum calcium concentrations. For the treatment of hypercalcemia, calcium supplements should be avoided. Calcium salts, including calcium carbonate, can elevate serum calcium concentrations and antagonize the effects of the calcitonin for this condition. For the treatment of osteoporosis adequate intake of calcium salts are necessary in conjunction with calcitonin. An increase in serum calcium concentrations helps to reduce bone resorption and loss of bone mass, and offsets the effect of calcitonin in lowering serum calcium levels.
Calcitriol: (Moderate) Monitor serum calcium concentrations during concomitant use of high doses of calcium and vitamin D analogs; a dosage adjustment of the vitamin D analog may be needed. Hypercalcemia may be exacerbated by concomitant administration.
Calcium Phosphate, Supersaturated: (Moderate) The concomitant use of oral sodium phosphate monobasic monohydrate; sodium phosphate dibasic anhydrous preparations in conjunction with antacids containing calcium (e.g., calcium carbonate, calcium salts) may bind the phosphate in the stomach and reduce its absorption. If the patient requires multiple mineral supplements or concurrent use of antacids, it is prudent to separate the administration of sodium phosphate salts from calcium containing products by at least one hour.
Calcium-channel blockers: (Minor) Monitor blood pressure during concurrent use of calcium and calcium-channel blockers. Concomitant use may reduce the response to calcium-channel blockers.
Canagliflozin; Metformin: (Minor) Famotidine may decrease the renal clearance of metformin secondary to competition for renal tubular transport systems. Such an interaction has been observed when cimetidine was administered with metformin. The decrease in renal excretion led to a 40% increase in metformin AUC. Although interactions with cationic drugs remain theoretical (except for cimetidine), caution is warranted when famotidine and metformin are prescribed concurrently. Famotidine may be less likely to interact with metformin versus cimetidine or ranitidine because of less tubular excretion.
Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium.
Captopril: (Major) Antacids can decrease the GI absorption of captopril if administered simultaneously.
Captopril; Hydrochlorothiazide, HCTZ: (Major) Antacids can decrease the GI absorption of captopril if administered simultaneously. (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium.
Cardiac glycosides: (Moderate) Monitor for signs and symptoms of digoxin toxicity during concomitant calcium use. Hypercalcemia may predispose persons to digoxin toxicity. If IV calcium is administered rapidly in a person receiving digoxin, serious arrhythmias may occur. Monitor ECG and calcium concentrations closely during IV calcium and digoxin administration.
Cefpodoxime: (Moderate) Because cefpodoxime proxetil requires a low gastric pH for dissolution, drugs which increase gastric pH, such as antacids, can decrease the bioavailability of cefpodoxime. (Moderate) H2-blockers should be avoided during treatment with cefpodoxime. Coadministration could result in antibiotic failure. H2-blockers increase gastric pH. Cefpodoxime proxetil requires low gastric pH for dissolution. While the rate of absorption is not affected, coadministration reduces cefpodoxime AUC, peak plasma concentration (by 42%), and extent of absorption (by 32%).
Cefuroxime: (Major) Avoid the concomitant use of H2-blockers and cefuroxime. Drugs that reduce gastric acidity, such as H2-blockers, can interfere with the oral absorption of cefuroxime axetil and may result in reduced antibiotic efficacy. (Moderate) Antacids can interfere with the oral absorption of cefuroxime axetil and may result in reduced antibiotic efficacy. If an antacid must be used while a patient is taking cefuroxime, administer the oral dosage of cefuroxime at least 1 hour before or 2 hours after the antacid.
Cetirizine; Pseudoephedrine: (Minor) It appears that antacids increase pseudoephedrine plasma concentrations. This interaction can be avoided by separating the administration of pseudoephedrine and antacids by 1 to 2 hours. If antacids are used on a regular basis, an alternative to pseudoephedrine may be considered.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Minor) It appears that antacids increase pseudoephedrine plasma concentrations. This interaction can be avoided by separating the administration of pseudoephedrine and antacids by 1 to 2 hours. If antacids are used on a regular basis, an alternative to pseudoephedrine may be considered.
Chlordiazepoxide; Clidinium: (Major) Avoid concomitant use of calcium carbonate and anticholinergics. Antacids may interfere with the absorption of anticholinergics.
Chloroquine: (Major) Chloroquine absorption may be reduced by antacids. Administer chloroquine and antacids at least 4 hours apart.
Chlorothiazide: (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Minor) It appears that antacids increase pseudoephedrine plasma concentrations. This interaction can be avoided by separating the administration of pseudoephedrine and antacids by 1 to 2 hours. If antacids are used on a regular basis, an alternative to pseudoephedrine may be considered.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Minor) It appears that antacids increase pseudoephedrine plasma concentrations. This interaction can be avoided by separating the administration of pseudoephedrine and antacids by 1 to 2 hours. If antacids are used on a regular basis, an alternative to pseudoephedrine may be considered.
Chlorpheniramine; Pseudoephedrine: (Minor) It appears that antacids increase pseudoephedrine plasma concentrations. This interaction can be avoided by separating the administration of pseudoephedrine and antacids by 1 to 2 hours. If antacids are used on a regular basis, an alternative to pseudoephedrine may be considered.
Chlorthalidone: (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium.
Ciprofloxacin: (Moderate) Administer oral ciprofloxacin at least 2 hours before or 6 hours after oral products that contain calcium. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids and multivitamins that contain calcium.
Cisatracurium: (Moderate) Concomitant use of neuromuscular blockers and calcium may result in resistance to neuromuscular blockade. Calcium antagonizes the potentiating effect of magnesium on neuromuscular blockade. Also, calcium triggers acetylcholine release, and therefore, may both reduce the sensitivity to neuromuscular blockers and decrease the duration of neuromuscular blockade.
Clevidipine: (Minor) Monitor blood pressure during concurrent use of calcium and calcium-channel blockers. Concomitant use may reduce the response to calcium-channel blockers.
Cod Liver Oil: (Minor) Doses in excess of 1,500 to 2,000 mcg per day of Vitamin A may lead to bone loss and will counteract the effects of supplementation with calcium salts.
Codeine; Guaifenesin; Pseudoephedrine: (Minor) It appears that antacids increase pseudoephedrine plasma concentrations. This interaction can be avoided by separating the administration of pseudoephedrine and antacids by 1 to 2 hours. If antacids are used on a regular basis, an alternative to pseudoephedrine may be considered.
Conjugated Estrogens: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Conjugated Estrogens; Bazedoxifene: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Conjugated Estrogens; Medroxyprogesterone: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Corticotropin, ACTH: (Moderate) Calcium absorption is reduced when calcium carbonate is taken concomitantly with systemic corticosteroids. Systemic corticosteroids induce a negative calcium balance by inhibiting intestinal calcium absorption as well as by increasing renal calcium losses. The mechanism by which these drugs inhibit calcium absorption in the intestine is likely to involve a direct inhibition of absorptive cell function. Patients taking systemic corticosteroids should ensure proper intake of calcium as directed by their health care provider.
Cortisone: (Moderate) Calcium absorption is reduced when calcium carbonate is taken concomitantly with systemic corticosteroids. Systemic corticosteroids induce a negative calcium balance by inhibiting intestinal calcium absorption as well as by increasing renal calcium losses. The mechanism by which these drugs inhibit calcium absorption in the intestine is likely to involve a direct inhibition of absorptive cell function.
Cysteamine: (Major) In general, cysteamine may be administered with electrolyte and mineral replacements necessary for managing Fanconi syndrome, as well as with vitamin D and thyroid hormone. However, delayed-release cysteamine (Procysbi) should be administered at least 1 hour before or 1 after medications that increase gastric pH, including those containing bicarbonate or carbonate (i.e.calcium carbonate). Drugs that increase the gastric pH, such as bicarbonate and carbonate, may cause the premature release of cysteamine from delayed-release capsules, leading to an increase in WBC cystine concentration. (Major) Monitor white blood cell (WBC) cystine concentration closely when administering delayed-release cysteamine (Procysbi) with H2-blockers. Drugs that increase the gastric pH may cause the premature release of cysteamine from delayed-release capsules, leading to an increase in WBC cystine concentration.
Dacomitinib: (Moderate) Administer dacomitinib at least 6 hours before or 10 hours after famotidine. Taking these medications at the same time may reduce dacomitinib absorption and decrease its efficacy.
Dapagliflozin; Metformin: (Minor) Famotidine may decrease the renal clearance of metformin secondary to competition for renal tubular transport systems. Such an interaction has been observed when cimetidine was administered with metformin. The decrease in renal excretion led to a 40% increase in metformin AUC. Although interactions with cationic drugs remain theoretical (except for cimetidine), caution is warranted when famotidine and metformin are prescribed concurrently. Famotidine may be less likely to interact with metformin versus cimetidine or ranitidine because of less tubular excretion.
Dasatinib: (Major) Do not administer H2-blockers with dasatinib due to the potential for decreased dasatinib exposure and reduced efficacy. Consider using an antacid if acid suppression therapy is needed. Administer the antacid at least 2 hours prior to or 2 hours after the dose of dasatinib. Concurrent use of an H2-blocker reduced the mean Cmax and AUC of dasatinib by 63% and 61%, respectively. (Moderate) Separate the administration of dasatinib and calcium carbonate by at least 2 hours if these agents are used together. The simultaneous administration of an antacid with dasatinib decreased the Cmax and AUC of dasatinib by 58% and 55%, respectively.
Delafloxacin: (Major) Administer oral delafloxacin at least 2 hours before or 6 hours after oral products that contain calcium. Delafloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with fluoroquinolone bioavailability include antacids and multivitamins that contain calcium.
Delavirdine: (Major) Coadministration of delavirdine with antacids results in decreased absorption of delavirdine. Administration of delavirdine and antacids should be separated by at least 1 hour. (Major) Coadministration of delavirdine with H2-blockers results in decreased absorption of delavirdine. Administration of delavirdine and H2-blockers should be separated by at least 1 hour. Chronic use of H2-blockers with delavirdine is not recommended.
Demeclocycline: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of these antibiotics will be significantly reduced by other orally administered compounds that contain calcium salts, particularly if the time of administration is within 60 minutes of each other. Calcium salts and tetracyclines should not be administered within 1 to 2 hours of each other, although doxycycline chelates less with calcium than other tetracyclines.
Desloratadine; Pseudoephedrine: (Minor) It appears that antacids increase pseudoephedrine plasma concentrations. This interaction can be avoided by separating the administration of pseudoephedrine and antacids by 1 to 2 hours. If antacids are used on a regular basis, an alternative to pseudoephedrine may be considered.
Desogestrel; Ethinyl Estradiol: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Dexbrompheniramine; Pseudoephedrine: (Minor) It appears that antacids increase pseudoephedrine plasma concentrations. This interaction can be avoided by separating the administration of pseudoephedrine and antacids by 1 to 2 hours. If antacids are used on a regular basis, an alternative to pseudoephedrine may be considered.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Minor) It appears that antacids increase pseudoephedrine plasma concentrations. This interaction can be avoided by separating the administration of pseudoephedrine and antacids by 1 to 2 hours. If antacids are used on a regular basis, an alternative to pseudoephedrine may be considered.
Dextroamphetamine: (Moderate) Use amphetamine; dextroamphetamine and H2-blockers concomitantly with caution. Gastrointestinal alkalinizing agents may increase exposure to amphetamine; dextroamphetamine and exacerbate its actions. (Minor) Monitor for an increase in amphetamine-related adverse effects during concomitant antacid use. Increasing gastric or urine pH may increase amphetamine exposure and the risk for side effects in some patients. As antacids have rarely been observed to increase gastric or urinary pH above 6.5, antacid-related pH changes may be insufficient to warrant clinical concern in most patients.
Dextromethorphan; Guaifenesin; Pseudoephedrine: (Minor) It appears that antacids increase pseudoephedrine plasma concentrations. This interaction can be avoided by separating the administration of pseudoephedrine and antacids by 1 to 2 hours. If antacids are used on a regular basis, an alternative to pseudoephedrine may be considered.
Dextromethorphan; Quinidine: (Major) By increasing urinary pH, calcium carbonate can decrease the urinary excretion of quinidine.
Diazepam: (Moderate) The coadministration of diazepam with antacids results in delayed diazepam absorption due to the fact that antacids delay gastric emptying. It may be prudent to separate dosing by 2 hours to limit any potential interaction.
Dichlorphenamide: (Major) Concomitant use of dichlorphenamide and famotidine is not recommended because of an increased risk of famotidine-related adverse effects. Monitor closely for signs of famotidine-related drug toxicity if coadministration cannot be avoided. Increased famotidine exposure is possible. Dichlorphenamide inhibits OAT1. Famotidine is a sensitive OAT1 substrate. Consider if an alternative to famotidine would be appropriate for the patient.
Dicyclomine: (Major) Avoid concomitant use of calcium carbonate and anticholinergics. Antacids may interfere with the absorption of anticholinergics.
Dienogest; Estradiol valerate: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Diflunisal: (Moderate) Concurrent use of diflunisal with antacids, such as calcium carbonate, may reduce plasma diflunisal concentrations. The effect may be clinically significant if antacids are used on a continuous schedule.
Digoxin: (Moderate) Monitor for signs and symptoms of digoxin toxicity during concomitant calcium use. Hypercalcemia may predispose persons to digoxin toxicity. If IV calcium is administered rapidly in a person receiving digoxin, serious arrhythmias may occur. Monitor ECG and calcium concentrations closely during IV calcium and digoxin administration.
Diltiazem: (Minor) Monitor blood pressure during concurrent use of calcium and calcium-channel blockers. Concomitant use may reduce the response to calcium-channel blockers.
Diphenhydramine; Naproxen: (Moderate) Avoid concomitant use of enteric-coated, delayed-release naproxen and H2-blockers due to the gastric pH elevating effects of H2-blockers. Enteric-coated, delayed-release naproxen tablets are designed to dissolve at a pH of 6 or more.
Diphenoxylate; Atropine: (Major) Avoid concomitant use of calcium carbonate and anticholinergics. Antacids may interfere with the absorption of anticholinergics.
Dolutegravir: (Moderate) Administer dolutegravir 2 hours before or 6 hours after taking supplements containing calcium if given under fasting conditions. When taken with food, dolutegravir and supplements containing calcium can be taken at the same time. Simultaneous administration under fasted conditions may result in reduced bioavailability of dolutegravir.
Dolutegravir; Lamivudine: (Moderate) Administer dolutegravir 2 hours before or 6 hours after taking supplements containing calcium if given under fasting conditions. When taken with food, dolutegravir and supplements containing calcium can be taken at the same time. Simultaneous administration under fasted conditions may result in reduced bioavailability of dolutegravir.
Dolutegravir; Rilpivirine: (Moderate) Administer dolutegravir 2 hours before or 6 hours after taking supplements containing calcium if given under fasting conditions. When taken with food, dolutegravir and supplements containing calcium can be taken at the same time. Simultaneous administration under fasted conditions may result in reduced bioavailability of dolutegravir. (Moderate) Coadministration with famotidine may significantly decrease rilpivirine plasma concentrations, potentially resulting in treatment failure. To decrease the risk of virologic failure, avoid use of famotidine for at least 12 hours before and at least 4 hours after administering rilpivirine. (Moderate) Concurrent administration of rilpivirine and antacids may significantly decrease rilpivirine plasma concentrations, potentially resulting in treatment failure. To decrease the risk of virologic failure, avoid use of antacids for at least 2 hours before and at least 4 hours after administering rilpivirine.
Doxercalciferol: (Moderate) Monitor serum calcium concentrations during concomitant use of high doses of calcium and vitamin D analogs; a dosage adjustment of the vitamin D analog may be needed. Hypercalcemia may be exacerbated by concomitant administration.
Doxycycline: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of these antibiotics will be significantly reduced by other orally administered compounds that contain calcium salts, particularly if the time of administration is within 60 minutes of each other. Calcium salts and tetracyclines should not be administered within 1 to 2 hours of each other, although doxycycline chelates less with calcium than other tetracyclines.
Drospirenone; Estetrol: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Drospirenone; Estradiol: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Drospirenone; Ethinyl Estradiol: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Drospirenone; Ethinyl Estradiol; Levomefolate: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Edetate Calcium Disodium, Calcium EDTA: (Major) Because edetate disodium chelates and lowers serum calcium, oral or parenteral calcium salts should not be administered concomitantly.
Elagolix; Estradiol; Norethindrone acetate: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Eltrombopag: (Major) Eltrombopag chelates polyvalent cations (e.g., calcium, aluminum, and magnesium) in food, mineral supplements, and antacids. In a clinical study, systemic exposure to eltrombopag was decreased by 70% when it was administered with a polyvalent cation-containing antacid. Administer eltrombopag at least 2 hours before or 4 hours after any oral products containing polyvalent cations, such as aluminum salts, (like aluminum hydroxide), calcium salts, (including calcium carbonate), and magnesium salts.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Separate administration of elvitegravir and calcium by at least 2 hours. Due to the formation of ionic complexes in the gastrointestinal tract, simultaneous administration results in lower elvitegravir plasma concentrations.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Separate administration of elvitegravir and calcium by at least 2 hours. Due to the formation of ionic complexes in the gastrointestinal tract, simultaneous administration results in lower elvitegravir plasma concentrations.
Empagliflozin; Linagliptin; Metformin: (Minor) Famotidine may decrease the renal clearance of metformin secondary to competition for renal tubular transport systems. Such an interaction has been observed when cimetidine was administered with metformin. The decrease in renal excretion led to a 40% increase in metformin AUC. Although interactions with cationic drugs remain theoretical (except for cimetidine), caution is warranted when famotidine and metformin are prescribed concurrently. Famotidine may be less likely to interact with metformin versus cimetidine or ranitidine because of less tubular excretion.
Empagliflozin; Metformin: (Minor) Famotidine may decrease the renal clearance of metformin secondary to competition for renal tubular transport systems. Such an interaction has been observed when cimetidine was administered with metformin. The decrease in renal excretion led to a 40% increase in metformin AUC. Although interactions with cationic drugs remain theoretical (except for cimetidine), caution is warranted when famotidine and metformin are prescribed concurrently. Famotidine may be less likely to interact with metformin versus cimetidine or ranitidine because of less tubular excretion.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Coadministration with famotidine may significantly decrease rilpivirine plasma concentrations, potentially resulting in treatment failure. To decrease the risk of virologic failure, avoid use of famotidine for at least 12 hours before and at least 4 hours after administering rilpivirine. (Moderate) Concurrent administration of rilpivirine and antacids may significantly decrease rilpivirine plasma concentrations, potentially resulting in treatment failure. To decrease the risk of virologic failure, avoid use of antacids for at least 2 hours before and at least 4 hours after administering rilpivirine.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Moderate) Coadministration with famotidine may significantly decrease rilpivirine plasma concentrations, potentially resulting in treatment failure. To decrease the risk of virologic failure, avoid use of famotidine for at least 12 hours before and at least 4 hours after administering rilpivirine. (Moderate) Concurrent administration of rilpivirine and antacids may significantly decrease rilpivirine plasma concentrations, potentially resulting in treatment failure. To decrease the risk of virologic failure, avoid use of antacids for at least 2 hours before and at least 4 hours after administering rilpivirine.
Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium.
Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium.
Erdafitinib: (Major) Avoid coadministration of calcium carbonate with erdafitinib before the initial dose increase period (days 14 to 21) which is based on serum phosphate levels. Calcium carbonate decreases serum phosphate levels. The initial dose increase of erdafitinib on days 14 to 21 is based on serum phosphate levels; changes in serum phosphate levels by calcium carbonate may interfere with the determination of this initial dose increase.
Erlotinib: (Major) If concomitant use of erlotinib with famotidine is necessary, erlotinib must be taken 10 hours after the last dose of famotidine and at least 2 hours before the next dose. Erlotinib displays pH-dependent solubility with decreased solubility at a higher pH; the increased gastric pH resulting from famotidine therapy may reduce the bioavailability of erlotinib. Increasing the dose of erlotinib without modifying the administration schedule is unlikely to compensate for loss of exposure. Erlotinib exposure was decreased by 33% and the Cmax by 54% when erlotinib was administered 2 hours after a single dose of an H2-antagonist. When administered at least 10 hours after an evening dose of an H2-antagonist and 2 hours before the morning dose, erlotinib exposure was decreased by 15% and Cmax by 17%. (Major) Separate administration by several hours if concomitant use of erlotinib with calcium carbonate is necessary. Erlotinib displays pH-dependent solubility with decreased solubility at a higher pH; the increased gastric pH resulting from calcium carbonate therapy may reduce the bioavailability of erlotinib. Increasing the dose of erlotinib without modifying the administration schedule is unlikely to compensate for loss of exposure. The effects of antacids on erlotinib pharmacokinetics has not been evaluated.
Ertugliflozin; Metformin: (Minor) Famotidine may decrease the renal clearance of metformin secondary to competition for renal tubular transport systems. Such an interaction has been observed when cimetidine was administered with metformin. The decrease in renal excretion led to a 40% increase in metformin AUC. Although interactions with cationic drugs remain theoretical (except for cimetidine), caution is warranted when famotidine and metformin are prescribed concurrently. Famotidine may be less likely to interact with metformin versus cimetidine or ranitidine because of less tubular excretion.
Esterified Estrogens: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Esterified Estrogens; Methyltestosterone: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Estradiol: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Estradiol; Levonorgestrel: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Estradiol; Norethindrone: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Estradiol; Norgestimate: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Estradiol; Progesterone: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Estramustine: (Major) Administration of estramustine with calcium impairs the oral absorption of estramustine significantly, due to formation of a calcium-phosphate complex. Calcium-containing drugs must not be taken simultaneously with estramustine. Patients should be instructed to take estramustine with water at least 1 hour before or 2 hours after calcium supplements.
Estrogens: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Estropipate: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Ethinyl Estradiol; Norelgestromin: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Ethinyl Estradiol; Norethindrone Acetate: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Ethinyl Estradiol; Norgestrel: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Ethotoin: (Major) Oral absorption of phenytoin can be reduced by calcium salts. Calcium salts can form complexes that are nonabsorbable. Separating the administration of phenytoin and calcium salts by at least 2 hours to help avoid this interaction. A similar interaction may occur with ethotoin.
Ethynodiol Diacetate; Ethinyl Estradiol: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Etidronate: (Moderate) Separate administration of oral etidronate and calcium-containing supplements by at least 2 hours. Calcium will interfere with the absorption of oral etidronate.
Etonogestrel; Ethinyl Estradiol: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Ezetimibe: (Minor) Antacids (e.g., 20 ml aluminum hydroxide; magnesium hydroxide) have no significant effect on the oral bioavailability of total ezetimibe (ezetimibe plus ezetimibe-glucuronide), ezetimibe-glucuronide, or ezetimibe based on AUC values. However, the peak plasma concentration (Cmax) of total ezetimibe is decreased by 30%. The effect of the antacids in this regard is not expected to have a significant effect on the ability of ezetimibe to lower cholesterol. However, to limit any potential interaction, it would be prudent to administer ezetimibe at least 1 hour before or 2 hours after administering antacids.
Ezetimibe; Simvastatin: (Minor) Antacids (e.g., 20 ml aluminum hydroxide; magnesium hydroxide) have no significant effect on the oral bioavailability of total ezetimibe (ezetimibe plus ezetimibe-glucuronide), ezetimibe-glucuronide, or ezetimibe based on AUC values. However, the peak plasma concentration (Cmax) of total ezetimibe is decreased by 30%. The effect of the antacids in this regard is not expected to have a significant effect on the ability of ezetimibe to lower cholesterol. However, to limit any potential interaction, it would be prudent to administer ezetimibe at least 1 hour before or 2 hours after administering antacids.
Felodipine: (Minor) Monitor blood pressure during concurrent use of calcium and calcium-channel blockers. Concomitant use may reduce the response to calcium-channel blockers.
Ferric Maltol: (Moderate) Antacids (e.g., calcium carbonate, aluminum hydroxide, or magnesium hydroxide) may decrease the absorption of oral iron preparations (e.g., iron salts or polysaccharide-iron complex). At higher pH values, iron is more readily ionized to its ferric state and is more poorly absorbed. Doses of antacids and iron should be taken as far apart as possible to minimize the potential for interaction. (Minor) The bioavailability of oral iron salts is influenced by gastric pH, and the concomitant administration of H2-blockers can decrease iron absorption. The non-heme ferric form of iron needs an acidic intragastric pH to be reduced to ferrous and to be absorbed. Iron salts and polysaccharide-iron complex provide non-heme iron. H2-blockers have long-lasting effects on the secretion of gastric acid and thus, increase the pH of the stomach. The increase in intragastric pH can interfere with the absorption of iron salts.
Fexofenadine: (Moderate) Co-administration with antacids within 15 minutes decreases the AUC and Cmax of fexofenadine. Separate administration is recommended.
Fexofenadine; Pseudoephedrine: (Moderate) Co-administration with antacids within 15 minutes decreases the AUC and Cmax of fexofenadine. Separate administration is recommended. (Minor) It appears that antacids increase pseudoephedrine plasma concentrations. This interaction can be avoided by separating the administration of pseudoephedrine and antacids by 1 to 2 hours. If antacids are used on a regular basis, an alternative to pseudoephedrine may be considered.
Flavoxate: (Major) Avoid concomitant use of calcium carbonate and anticholinergics. Antacids may interfere with the absorption of anticholinergics.
Fludrocortisone: (Moderate) Calcium absorption is reduced when calcium carbonate is taken concomitantly with systemic corticosteroids.
Flunisolide: (Moderate) Calcium absorption is reduced when calcium carbonate is taken concomitantly with systemic corticosteroids.
Fosamprenavir: (Moderate) Administer fosamprenavir at least 1 hour before or 1 hour after calcium carbonate. Coadministration of antacids, such as calcium carbonate, may decrease the exposure of fosamprenavir and impair its efficacy. (Moderate) Monitor for decreased fosamprenavir efficacy if coadministered with H2-blockers. Concurrent use may decrease the plasma concentrations of fosamprenavir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance.
Fosinopril: (Moderate) Coadministration of antacids with fosinopril may impair absorption of fosinopril. Therefore, if concomitant administration of these agents is indicated, dosing should be separated by 2 hours.
Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) Coadministration of antacids with fosinopril may impair absorption of fosinopril. Therefore, if concomitant administration of these agents is indicated, dosing should be separated by 2 hours. (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium.
Gastrointestinal Enzymes: (Major) The effectiveness of gastrointestinal enzymes can be diminished with concurrent administration of antacids. In-vitro studies suggest that calcium and magnesum cations exert their deleterious effect on replacement enzyme therapy by formation of poorly soluble calcium or magnesium soaps and precipitation of glycine conjugated bile salts.
Gefitinib: (Major) Avoid coadministration of calcium carbonate with gefitinib if possible due to decreased exposure to gefitinib, which may lead to reduced efficacy. If concomitant use is unavoidable, take gefitinib 6 hours after the last dose or 6 hours before the next dose of calcium carbonate. Gefitinib exposure is affected by gastric pH. Coadministration with another drug to maintain gastric pH above 5 decreased gefitinib exposure by 47%. (Major) Avoid coadministration of famotidine with gefitinib if possible due to decreased exposure to gefitinib, which may lead to reduced efficacy. If concomitant use is unavoidable, take gefitinib 6 hours after the last dose or 6 hours before the next dose of famotidine. Gefitinib exposure is affected by gastric pH. Coadministration with high doses of another H2-blocker to maintain gastric pH above 5 decreased gefitinib exposure by 47%.
Glipizide: (Moderate) Antacids have been reported to increase the absorption of glipizide, enhancing their hypoglycemic effects. Although the exact mechanism is not known, theoretically it may be due to alterations in gastric pH. Consider closely monitoring blood glucose concentrations.
Glipizide; Metformin: (Moderate) Antacids have been reported to increase the absorption of glipizide, enhancing their hypoglycemic effects. Although the exact mechanism is not known, theoretically it may be due to alterations in gastric pH. Consider closely monitoring blood glucose concentrations. (Minor) Famotidine may decrease the renal clearance of metformin secondary to competition for renal tubular transport systems. Such an interaction has been observed when cimetidine was administered with metformin. The decrease in renal excretion led to a 40% increase in metformin AUC. Although interactions with cationic drugs remain theoretical (except for cimetidine), caution is warranted when famotidine and metformin are prescribed concurrently. Famotidine may be less likely to interact with metformin versus cimetidine or ranitidine because of less tubular excretion.
Glyburide: (Moderate) Antacids have been reported to increase the absorption of non-micronized glyburide, enhancing their hypoglycemic effects. Although the exact mechanism is not known, theoretically it may be due to alterations in gastric pH. Consider closely monitoring blood glucose concentrations.
Glyburide; Metformin: (Moderate) Antacids have been reported to increase the absorption of non-micronized glyburide, enhancing their hypoglycemic effects. Although the exact mechanism is not known, theoretically it may be due to alterations in gastric pH. Consider closely monitoring blood glucose concentrations. (Minor) Famotidine may decrease the renal clearance of metformin secondary to competition for renal tubular transport systems. Such an interaction has been observed when cimetidine was administered with metformin. The decrease in renal excretion led to a 40% increase in metformin AUC. Although interactions with cationic drugs remain theoretical (except for cimetidine), caution is warranted when famotidine and metformin are prescribed concurrently. Famotidine may be less likely to interact with metformin versus cimetidine or ranitidine because of less tubular excretion.
Glycopyrrolate: (Major) Avoid concomitant use of calcium carbonate and anticholinergics. Antacids may interfere with the absorption of anticholinergics.
Glycopyrrolate; Formoterol: (Major) Avoid concomitant use of calcium carbonate and anticholinergics. Antacids may interfere with the absorption of anticholinergics.
Guaifenesin; Pseudoephedrine: (Minor) It appears that antacids increase pseudoephedrine plasma concentrations. This interaction can be avoided by separating the administration of pseudoephedrine and antacids by 1 to 2 hours. If antacids are used on a regular basis, an alternative to pseudoephedrine may be considered.
Homatropine; Hydrocodone: (Major) Avoid concomitant use of calcium carbonate and anticholinergics. Antacids may interfere with the absorption of anticholinergics.
Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium.
Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium.
Hydroxychloroquine: (Moderate) Hydroxychloroquine absorption may be reduced by antacids as has been observed with the structurally similar chloroquine. Administer hydroxychloroquine and antacids at least 4 hours apart. Of note, a study demonstrated no significant difference in hydroxychloroquine serum concentration in patients taking concomitant antacids (n = 14) compared to those not taking antacids (n = 495).
Hyoscyamine: (Major) Avoid concomitant use of calcium carbonate and anticholinergics. Antacids may interfere with the absorption of anticholinergics.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Major) Avoid concomitant use of calcium carbonate and anticholinergics. Antacids may interfere with the absorption of anticholinergics. (Major) Avoid the concomitant use of calcium carbonate and methenamine. Calcium carbonate may cause the urine to become alkaline. This may reduce the effectiveness of methenamine by inhibiting its conversion to formaldehyde.
Ibandronate: (Moderate) Separate administration of oral ibandronate and calcium-containing supplements by at least 1 hour. Calcium will interfere with the absorption of oral ibandronate.
Ibritumomab Tiuxetan: (Moderate) The oral absorption of phosphorus is reduced by ingestion of pharmacologic doses of calcium carbonate or other phosphate-lowering calcium salts (e.g., calcium acetate). There is, however, no significant interference with phosphorus absorption by oral dietary calcium at intakes within the typical adult range. If the patient requires multiple calcium supplements or a calcium-containing antacid, it may be wise to separate the administration of phosphorus salts from calcium-containing products. In some instances the administration of calcium salts or calcium carbonate is used therapeutically (e.g., uremia) to decrease serum phosphorus levels, so the administration of phosphorus supplements would dynamically counteract the intended use of calcium in these settings, assuming hypophosphatemia is not present. Appropriate calcium-phosphorus ratios in vivo are important for proper calcium homeostasis in tissues and bone; if the serum ionized calcium concentration is elevated, the concomitant use of calcium salts and phosphorus salts may increase the risk of calcium deposition in soft tissue.
Ibuprofen; Pseudoephedrine: (Minor) It appears that antacids increase pseudoephedrine plasma concentrations. This interaction can be avoided by separating the administration of pseudoephedrine and antacids by 1 to 2 hours. If antacids are used on a regular basis, an alternative to pseudoephedrine may be considered.
Indacaterol; Glycopyrrolate: (Major) Avoid concomitant use of calcium carbonate and anticholinergics. Antacids may interfere with the absorption of anticholinergics.
Indomethacin: (Moderate) Antacids may inhibit the oral absorption of indomethacin. Simultaneous administration should be avoided; separate dosing by at least 2 hours to limit an interaction.
Infigratinib: (Moderate) Separate the administration of infigratinib and H2-receptor antagonists if concomitant use is necessary. Coadministration may decrease infigratinib exposure resulting in decreased efficacy. Administer infigratinib two hours before or ten hours after an H2-receptor antagonist. (Moderate) Separate the administration of infigratinib and locally acting antacids such as calcium carbonate if concomitant use is necessary. Coadministration may decrease infigratinib exposure resulting in decreased efficacy. Administer infigratinib two hours before or after calcium carbonate.
Irbesartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium.
Iron Salts: (Moderate) Antacids (e.g., calcium carbonate, aluminum hydroxide, or magnesium hydroxide) may decrease the absorption of oral iron preparations (e.g., iron salts or polysaccharide-iron complex). At higher pH values, iron is more readily ionized to its ferric state and is more poorly absorbed. Doses of antacids and iron should be taken as far apart as possible to minimize the potential for interaction. (Minor) The bioavailability of oral iron salts is influenced by gastric pH, and the concomitant administration of H2-blockers can decrease iron absorption. The non-heme ferric form of iron needs an acidic intragastric pH to be reduced to ferrous and to be absorbed. Iron salts and polysaccharide-iron complex provide non-heme iron. H2-blockers have long-lasting effects on the secretion of gastric acid and thus, increase the pH of the stomach. The increase in intragastric pH can interfere with the absorption of iron salts.
Iron: (Moderate) Antacids (e.g., calcium carbonate, aluminum hydroxide, or magnesium hydroxide) may decrease the absorption of oral iron preparations (e.g., iron salts or polysaccharide-iron complex). At higher pH values, iron is more readily ionized to its ferric state and is more poorly absorbed. Doses of antacids and iron should be taken as far apart as possible to minimize the potential for interaction. (Minor) The bioavailability of oral iron salts is influenced by gastric pH, and the concomitant administration of H2-blockers can decrease iron absorption. The non-heme ferric form of iron needs an acidic intragastric pH to be reduced to ferrous and to be absorbed. Iron salts and polysaccharide-iron complex provide non-heme iron. H2-blockers have long-lasting effects on the secretion of gastric acid and thus, increase the pH of the stomach. The increase in intragastric pH can interfere with the absorption of iron salts.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Moderate) Concomitant use of calcium carbonate and rifampin may decrease the absorption of rifampin. Daily doses of rifampin should be given at least 1 hour before the ingestion of calcium carbonate.
Isoniazid, INH; Rifampin: (Moderate) Concomitant use of calcium carbonate and rifampin may decrease the absorption of rifampin. Daily doses of rifampin should be given at least 1 hour before the ingestion of calcium carbonate.
Isradipine: (Minor) Monitor blood pressure during concurrent use of calcium and calcium-channel blockers. Concomitant use may reduce the response to calcium-channel blockers.
Itraconazole: (Moderate) When administering antacids with the 100 mg itraconazole capsule and 200 mg itraconazole tablet formulations, systemic exposure to itraconazole is decreased. Conversely, exposure to itraconazole is increased when antacids are administered with the 65 mg itraconazole capsule. Administer antacids at least 2 hours before or 2 hours after the 100 mg capsule or 200 mg tablet. Monitor for increased itraconazole-related adverse effects if antacids are administered with itraconazole 65 mg capsules. (Moderate) When administering H2-blockers with the 100 mg itraconazole capsule and 200 mg itraconazole tablet formulations, systemic exposure to itraconazole is decreased. Conversely, exposure to itraconazole is increased when H2-blockers are administered with the 65 mg itraconazole capsule. Administer H2-blockers at least 2 hours before or 2 hours after the 100 mg capsule or 200 mg tablet. Monitor for increased itraconazole-related adverse effects if H2-blockers are administered with itraconazole 65 mg capsules.
Ketoconazole: (Major) Avoid use of H2-blockers with ketoconazole. Medications that increase gastric pH may impair ketoconazole absorption. (Moderate) Administer calcium carbonate at least 1 hour before or 2 hours after taking ketoconazole. Antacids can impair the absorption of ketoconazole.
Lactulose: (Minor) Oral, nonabsorbable antacids may interfere with the decrease in colon pH necessary for lactulose's action.
Ledipasvir; Sofosbuvir: (Major) Solubility of ledipasvir decreases as gastric pH increases; thus, coadministration of ledipasvir; sofosbuvir with H2-blockers may result in lower ledipasvir plasma concentrations. Ledipasvir; sofosbuvir can be administered with H2-blockers if given simultaneously or separated by 12 hours. The H2-blocker dose should not exceed a dose that is comparable to famotidine 40 mg twice daily. (Moderate) Separate administration of ledipasvir and antacids by at least 4 hours. Solubility of ledipasvir decreases as gastric pH increases; thus, simultaneous administration of these drugs may result in lower ledipasvir plasma concentrations.
Levamlodipine: (Minor) Monitor blood pressure during concurrent use of calcium and calcium-channel blockers. Concomitant use may reduce the response to calcium-channel blockers.
Levofloxacin: (Moderate) Administer oral products that contain calcium at least 2 hours before or 2 hours after orally administered levofloxacin. Levofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Chelation of divalent cations with levofloxacin is less than with other quinolones. Examples of compounds that may interfere with quinolone bioavailability include antacids and multivitamins that contain calcium.
Levoketoconazole: (Major) Avoid use of H2-blockers with ketoconazole. Medications that increase gastric pH may impair ketoconazole absorption. (Moderate) Administer calcium carbonate at least 1 hour before or 2 hours after taking ketoconazole. Antacids can impair the absorption of ketoconazole.
Levonorgestrel; Ethinyl Estradiol: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Moderate) Antacids (e.g., calcium carbonate, aluminum hydroxide, or magnesium hydroxide) may decrease the absorption of oral iron preparations (e.g., iron salts or polysaccharide-iron complex). At higher pH values, iron is more readily ionized to its ferric state and is more poorly absorbed. Doses of antacids and iron should be taken as far apart as possible to minimize the potential for interaction. (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis. (Minor) The bioavailability of oral iron salts is influenced by gastric pH, and the concomitant administration of H2-blockers can decrease iron absorption. The non-heme ferric form of iron needs an acidic intragastric pH to be reduced to ferrous and to be absorbed. Iron salts and polysaccharide-iron complex provide non-heme iron. H2-blockers have long-lasting effects on the secretion of gastric acid and thus, increase the pH of the stomach. The increase in intragastric pH can interfere with the absorption of iron salts.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Moderate) Antacids (e.g., calcium carbonate, aluminum hydroxide, or magnesium hydroxide) may decrease the absorption of oral iron preparations (e.g., iron salts or polysaccharide-iron complex). At higher pH values, iron is more readily ionized to its ferric state and is more poorly absorbed. Doses of antacids and iron should be taken as far apart as possible to minimize the potential for interaction. (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis. (Minor) The bioavailability of oral iron salts is influenced by gastric pH, and the concomitant administration of H2-blockers can decrease iron absorption. The non-heme ferric form of iron needs an acidic intragastric pH to be reduced to ferrous and to be absorbed. Iron salts and polysaccharide-iron complex provide non-heme iron. H2-blockers have long-lasting effects on the secretion of gastric acid and thus, increase the pH of the stomach. The increase in intragastric pH can interfere with the absorption of iron salts.
Levothyroxine: (Moderate) Thyroid hormones should be administered at least 4 hours before or after the ingestion of oral calcium supplements. Calcium salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption. Some case reports have described clinical hypothyroidism resulting from coadministration of thyroid hormones with oral calcium supplements.
Levothyroxine; Liothyronine (Porcine): (Moderate) Thyroid hormones should be administered at least 4 hours before or after the ingestion of oral calcium supplements. Calcium salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption. Some case reports have described clinical hypothyroidism resulting from coadministration of thyroid hormones with oral calcium supplements.
Levothyroxine; Liothyronine (Synthetic): (Moderate) Thyroid hormones should be administered at least 4 hours before or after the ingestion of oral calcium supplements. Calcium salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption. Some case reports have described clinical hypothyroidism resulting from coadministration of thyroid hormones with oral calcium supplements.
Lidocaine: (Moderate) Concomitant use of systemic lidocaine and famotidine may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; famotidine inhibits CYP1A2.
Lidocaine; Epinephrine: (Moderate) Concomitant use of systemic lidocaine and famotidine may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; famotidine inhibits CYP1A2.
Lidocaine; Prilocaine: (Moderate) Concomitant use of systemic lidocaine and famotidine may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; famotidine inhibits CYP1A2.
Linagliptin; Metformin: (Minor) Famotidine may decrease the renal clearance of metformin secondary to competition for renal tubular transport systems. Such an interaction has been observed when cimetidine was administered with metformin. The decrease in renal excretion led to a 40% increase in metformin AUC. Although interactions with cationic drugs remain theoretical (except for cimetidine), caution is warranted when famotidine and metformin are prescribed concurrently. Famotidine may be less likely to interact with metformin versus cimetidine or ranitidine because of less tubular excretion.
Liothyronine: (Moderate) Thyroid hormones should be administered at least 4 hours before or after the ingestion of oral calcium supplements. Calcium salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption. Some case reports have described clinical hypothyroidism resulting from coadministration of thyroid hormones with oral calcium supplements.
Lisdexamfetamine: (Minor) Monitor for an increase in amphetamine-related adverse effects during concomitant antacid use. Increasing gastric or urine pH may increase amphetamine exposure and the risk for side effects in some patients. As antacids have rarely been observed to increase gastric or urinary pH above 6.5, antacid-related pH changes may be insufficient to warrant clinical concern in most patients.
Lisinopril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium.
Lithium: (Moderate) Monitor serum calcium concentrations closely if concomitant use of calcium and lithium is necessary. Concomitant use may increase the risk of hypercalcemia.
Loratadine; Pseudoephedrine: (Minor) It appears that antacids increase pseudoephedrine plasma concentrations. This interaction can be avoided by separating the administration of pseudoephedrine and antacids by 1 to 2 hours. If antacids are used on a regular basis, an alternative to pseudoephedrine may be considered.
Losartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium.
Mefenamic Acid: (Moderate) Ingestion of mefenamic acid with antacids is not recommended. Administration with an antacid containing 1.7 grams of magnesium hydroxide resulted in a 36 percent increase in the area under the time versus concentration curve of mefenamic acid.
Mefloquine: (Moderate) Antacids, H2-blockers, and proton pump inhibitors (PPIs) may increase plasma concentrations of mefloquine. In a small study involving 6 healthy subjects and 6 peptic ulcer patients, cimetidine increased the Cmax and AUC of mefloquine. In the study, the pharmacokinetics of mefloquine were determined after receiving a single oral mefloquine 500 mg dose alone and after 3-days of cimetidine 400 mg PO bid. In both healthy subjects and peptic ulcer patients, mefloquine Cmax was increased 42.4% and 20.5%, respectively, and AUC was increased by 37.5% in both groups. Elimination half-life, total clearance, and volume of distribution were not significantly affected. An increase in adverse reactions was not noted. Patients on chronic mefloquine therapy might be at increased risk of adverse reactions, especially in patients with a neurological or psychiatric history. (Moderate) H2-blockers may increase plasma concentrations of mefloquine. Patients on chronic mefloquine therapy might be at increased risk of adverse reactions, especially patients with a neurological or psychiatric history. In a small study involving 6 healthy subjects and 6 peptic ulcer patients, cimetidine increased the Cmax and AUC of mefloquine. In the study, the pharmacokinetics of mefloquine were determined after receiving a single oral mefloquine 500 mg dose alone and after 3-days of cimetidine 400 mg PO twice daily. In both healthy subjects and peptic ulcer patients, Cmax was increased 42.4% and 20.5%, respectively. The AUC was increased by 37.5% in both groups. Elimination half-life, total clearance, and volume of distribution were not significantly affected. An increase in adverse reactions was not noted.
Mesalamine, 5-ASA: (Moderate) Do not coadminister mesalamine extended-release capsules (Apriso) with antacids. Apriso is a pH-dependent, delayed-release capsule product with an enteric coating that dissolves at a pH of at least 6. Other mesalamine products do not have an interaction with antacids.
Metformin: (Minor) Famotidine may decrease the renal clearance of metformin secondary to competition for renal tubular transport systems. Such an interaction has been observed when cimetidine was administered with metformin. The decrease in renal excretion led to a 40% increase in metformin AUC. Although interactions with cationic drugs remain theoretical (except for cimetidine), caution is warranted when famotidine and metformin are prescribed concurrently. Famotidine may be less likely to interact with metformin versus cimetidine or ranitidine because of less tubular excretion.
Metformin; Repaglinide: (Minor) Famotidine may decrease the renal clearance of metformin secondary to competition for renal tubular transport systems. Such an interaction has been observed when cimetidine was administered with metformin. The decrease in renal excretion led to a 40% increase in metformin AUC. Although interactions with cationic drugs remain theoretical (except for cimetidine), caution is warranted when famotidine and metformin are prescribed concurrently. Famotidine may be less likely to interact with metformin versus cimetidine or ranitidine because of less tubular excretion.
Metformin; Saxagliptin: (Minor) Famotidine may decrease the renal clearance of metformin secondary to competition for renal tubular transport systems. Such an interaction has been observed when cimetidine was administered with metformin. The decrease in renal excretion led to a 40% increase in metformin AUC. Although interactions with cationic drugs remain theoretical (except for cimetidine), caution is warranted when famotidine and metformin are prescribed concurrently. Famotidine may be less likely to interact with metformin versus cimetidine or ranitidine because of less tubular excretion.
Metformin; Sitagliptin: (Minor) Famotidine may decrease the renal clearance of metformin secondary to competition for renal tubular transport systems. Such an interaction has been observed when cimetidine was administered with metformin. The decrease in renal excretion led to a 40% increase in metformin AUC. Although interactions with cationic drugs remain theoretical (except for cimetidine), caution is warranted when famotidine and metformin are prescribed concurrently. Famotidine may be less likely to interact with metformin versus cimetidine or ranitidine because of less tubular excretion.
Methamphetamine: (Minor) Monitor for an increase in amphetamine-related adverse effects during concomitant antacid use. Increasing gastric or urine pH may increase amphetamine exposure and the risk for side effects in some patients. As antacids have rarely been observed to increase gastric or urinary pH above 6.5, antacid-related pH changes may be insufficient to warrant clinical concern in most patients.
Methenamine: (Major) Avoid the concomitant use of calcium carbonate and methenamine. Calcium carbonate may cause the urine to become alkaline. This may reduce the effectiveness of methenamine by inhibiting its conversion to formaldehyde.
Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Major) Avoid concomitant use of calcium carbonate and anticholinergics. Antacids may interfere with the absorption of anticholinergics. (Major) Avoid the concomitant use of calcium carbonate and methenamine. Calcium carbonate may cause the urine to become alkaline. This may reduce the effectiveness of methenamine by inhibiting its conversion to formaldehyde.
Methenamine; Sodium Salicylate: (Major) Avoid the concomitant use of calcium carbonate and methenamine. Calcium carbonate may cause the urine to become alkaline. This may reduce the effectiveness of methenamine by inhibiting its conversion to formaldehyde.
Methscopolamine: (Major) Avoid concomitant use of calcium carbonate and anticholinergics. Antacids may interfere with the absorption of anticholinergics.
Metolazone: (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium.
Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium.
Minocycline: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of these antibiotics will be significantly reduced by other orally administered compounds that contain calcium salts, particularly if the time of administration is within 60 minutes of each other. Calcium salts and tetracyclines should not be administered within 1 to 2 hours of each other, although doxycycline chelates less with calcium than other tetracyclines.
Moxifloxacin: (Major) Administer oral moxifloxacin at least 4 hours before or 8 hours after oral products that contain calcium. Moxifloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids and multivitamins that contain calcium.
Mycophenolate: (Major) Coadministration of mycophenolate mofetil with antacids decreases the bioavailability of mycophenolate mofetil. Aluminum or magnesium hydroxide antacids decrease AUC of mycophenolic acid by about 17%. Avoid administration of mycophenolate mofetil with agents that may decrease its absorption.
Naproxen: (Moderate) Avoid concomitant use of enteric-coated, delayed-release naproxen and H2-blockers due to the gastric pH elevating effects of H2-blockers. Enteric-coated, delayed-release naproxen tablets are designed to dissolve at a pH of 6 or more.
Naproxen; Esomeprazole: (Moderate) Avoid concomitant use of enteric-coated, delayed-release naproxen and H2-blockers due to the gastric pH elevating effects of H2-blockers. Enteric-coated, delayed-release naproxen tablets are designed to dissolve at a pH of 6 or more.
Naproxen; Pseudoephedrine: (Moderate) Avoid concomitant use of enteric-coated, delayed-release naproxen and H2-blockers due to the gastric pH elevating effects of H2-blockers. Enteric-coated, delayed-release naproxen tablets are designed to dissolve at a pH of 6 or more. (Minor) It appears that antacids increase pseudoephedrine plasma concentrations. This interaction can be avoided by separating the administration of pseudoephedrine and antacids by 1 to 2 hours. If antacids are used on a regular basis, an alternative to pseudoephedrine may be considered.
Neostigmine; Glycopyrrolate: (Major) Avoid concomitant use of calcium carbonate and anticholinergics. Antacids may interfere with the absorption of anticholinergics.
Neratinib: (Major) Administer neratinib at least 3 hours after administration of calcium carbonate if concomitant use is necessary due to decreased absorption and systemic exposure of neratinib; the solubility of neratinib decreases with increasing pH of the GI tract. (Major) Take neratinib at least 2 hours before the next dose of an H2-blocker or 10 hours after the last dose of an H2-blocker due to decreased absorption and systemic exposure of neratinib; the solubility of neratinib decreases with increasing pH of the GI tract. The Cmax and AUC of neratinib were reduced by 57% and 48%, respectively, when administered 2 hours after a daily dose of ranitidine 300 mg. The Cmax and AUC of neratinib were reduced by 44% and 32%, respectively, when administered 2 hours before ranitidine 150 mg twice daily (given approximately 12 hours apart).
Neuromuscular blockers: (Moderate) Concomitant use of neuromuscular blockers and calcium may result in resistance to neuromuscular blockade. Calcium antagonizes the potentiating effect of magnesium on neuromuscular blockade. Also, calcium triggers acetylcholine release, and therefore, may both reduce the sensitivity to neuromuscular blockers and decrease the duration of neuromuscular blockade.
Nicardipine: (Minor) Monitor blood pressure during concurrent use of calcium and calcium-channel blockers. Concomitant use may reduce the response to calcium-channel blockers.
NIFEdipine: (Minor) Monitor blood pressure during concurrent use of calcium and calcium-channel blockers. Concomitant use may reduce the response to calcium-channel blockers.
Nilotinib: (Moderate) If concomitant use of these agents is necessary, administer the antacid approximately 2 hours before or approximately 2 hours after the nilotinib dose. Nilotinib displays pH-dependent solubility with decreased solubility at a higher pH; therefore, concomitant use of nilotinib and antacids may result in decreased bioavailability of nilotinib. In a study in healthy subjects, there was no significant change in nilotinib pharmacokinetics when an antacid (aluminum hydroxide/magnesium hydroxide/simethicone) was administered approximately 2 hours before or approximately 2 hours after a single 400-mg nilotinib dose. (Moderate) If concomitant use of these agents is necessary, administer the H2-blocker approximately 10 hours before and approximately 2 hours after the nilotinib dose. Nilotinib displays pH-dependent solubility with decreased solubility at a higher pH. The concomitant use of nilotinib and H2-blockers that elevate the gastric pH may reduce the bioavailability of nilotinib. In a study in healthy subjects, there was no significant change in nilotinib pharmacokinetics when a single 400-mg nilotinib dose was given 10 hours after and 2 hours prior to famotidine.
Nimodipine: (Minor) Monitor blood pressure during concurrent use of calcium and calcium-channel blockers. Concomitant use may reduce the response to calcium-channel blockers.
Nirogacestat: (Major) Avoid concomitant use of nirogacestat and H2 receptor blockers. Concurrent use may impair nirogacestat absorption which may decrease nirogacestat exposure and reduce its efficacy. Antacids may be used with nirogacestat but administration should be separated by at least 2 hours. (Moderate) Separate the administration of nirogacestat and antacids by at least 2 hours. Simultaneous coadministration may impair nirogacestat absorption resulting in reduced exposure and efficacy.
Nisoldipine: (Minor) Monitor blood pressure during concurrent use of calcium and calcium-channel blockers. Concomitant use may reduce the response to calcium-channel blockers.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Moderate) Antacids (e.g., calcium carbonate, aluminum hydroxide, or magnesium hydroxide) may decrease the absorption of oral iron preparations (e.g., iron salts or polysaccharide-iron complex). At higher pH values, iron is more readily ionized to its ferric state and is more poorly absorbed. Doses of antacids and iron should be taken as far apart as possible to minimize the potential for interaction. (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis. (Minor) The bioavailability of oral iron salts is influenced by gastric pH, and the concomitant administration of H2-blockers can decrease iron absorption. The non-heme ferric form of iron needs an acidic intragastric pH to be reduced to ferrous and to be absorbed. Iron salts and polysaccharide-iron complex provide non-heme iron. H2-blockers have long-lasting effects on the secretion of gastric acid and thus, increase the pH of the stomach. The increase in intragastric pH can interfere with the absorption of iron salts.
Norethindrone; Ethinyl Estradiol: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Moderate) Antacids (e.g., calcium carbonate, aluminum hydroxide, or magnesium hydroxide) may decrease the absorption of oral iron preparations (e.g., iron salts or polysaccharide-iron complex). At higher pH values, iron is more readily ionized to its ferric state and is more poorly absorbed. Doses of antacids and iron should be taken as far apart as possible to minimize the potential for interaction. (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis. (Minor) The bioavailability of oral iron salts is influenced by gastric pH, and the concomitant administration of H2-blockers can decrease iron absorption. The non-heme ferric form of iron needs an acidic intragastric pH to be reduced to ferrous and to be absorbed. Iron salts and polysaccharide-iron complex provide non-heme iron. H2-blockers have long-lasting effects on the secretion of gastric acid and thus, increase the pH of the stomach. The increase in intragastric pH can interfere with the absorption of iron salts.
Norgestimate; Ethinyl Estradiol: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Octreotide: (Moderate) Coadministration of oral octreotide with antacids may require increased doses of octreotide. Coadministration of oral octreotide with drugs that alter the pH of the upper GI tract, including antacids, may alter the absorption of octreotide and lead to a reduction in bioavailability. (Moderate) Coadministration of oral octreotide with H2-blockers may require increased doses of octreotide. Coadministration of oral octreotide with drugs that alter the pH of the upper GI tract, including H2-blockers, may alter the absorption of octreotide and lead to a reduction in bioavailability.
Ofloxacin: (Moderate) Administer oral products that contain calcium at least 2 hours before or 2 hours after ofloxacin. Ofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids and multivitamins that contain calcium.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium. (Minor) Monitor blood pressure during concurrent use of calcium and calcium-channel blockers. Concomitant use may reduce the response to calcium-channel blockers.
Olmesartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium.
Omadacycline: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of these antibiotics will be significantly reduced by other orally administered compounds that contain calcium salts, particularly if the time of administration is within 60 minutes of each other. Calcium salts and tetracyclines should not be administered within 1 to 2 hours of each other, although doxycycline chelates less with calcium than other tetracyclines.
Oxybutynin: (Major) Avoid concomitant use of calcium carbonate and anticholinergics. Antacids may interfere with the absorption of anticholinergics.
Pancrelipase: (Major) The effectiveness of gastrointestinal enzymes can be diminished with concurrent administration of antacids. In-vitro studies suggest that calcium and magnesum cations exert their deleterious effect on replacement enzyme therapy by formation of poorly soluble calcium or magnesium soaps and precipitation of glycine conjugated bile salts.
Pancuronium: (Moderate) Concomitant use of neuromuscular blockers and calcium may result in resistance to neuromuscular blockade. Calcium antagonizes the potentiating effect of magnesium on neuromuscular blockade. Also, calcium triggers acetylcholine release, and therefore, may both reduce the sensitivity to neuromuscular blockers and decrease the duration of neuromuscular blockade.
Parathyroid Hormone: (Moderate) Monitor serum calcium concentrations closely if concomitant use of calcium and parathyroid hormone is necessary. Concomitant use may increase the risk of hypercalcemia.
Paricalcitol: (Moderate) Monitor serum calcium concentrations during concomitant use of high doses of calcium and vitamin D analogs; a dosage adjustment of the vitamin D analog may be needed. Hypercalcemia may be exacerbated by concomitant administration.
Pazopanib: (Major) Avoid coadministration of pazopanib with H2-blockers due to decreased absorption of pazopanib, which may decrease efficacy. If concomitant administration with a gastric acid-reducing agent is unavoidable, consider the use of a short-acting antacid in place of an H2-blocker; separate administration of the short-acting antacid and pazopanib by several hours to avoid a reduction in pazopanib exposure. Concomitant use of pazopanib with a proton pump inhibitor decreased pazopanib exposure (AUC and Cmax) by approximately 40%. (Moderate) Separate administration of pazopanib and antacids by several hours if coadministration is necessary in order to avoid a reduction in pazopanib exposure, which may decrease efficacy.
Penicillamine: (Moderate) Because penicillamine chelates heavy metals, it is possible that antacids could reduce penicillamine bioavailability, which can decrease the therapeutic effects of penicillamine. Simultaneous administration should be avoided; separate dosing by at least 2 hours to limit an interaction.
Perindopril; Amlodipine: (Minor) Monitor blood pressure during concurrent use of calcium and calcium-channel blockers. Concomitant use may reduce the response to calcium-channel blockers.
Pexidartinib: (Moderate) Administer pexidartinib 2 hours before or 10 hours after H2-blockers as concurrent administration may reduce pexidartinib exposure. Although the effects of H2-blockers on pexidartinib pharmacokinetics have not been studied, other acid-reducing agents have been shown to decrease pexidartinib exposure by 50%.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Avoid concomitant use of calcium carbonate and anticholinergics. Antacids may interfere with the absorption of anticholinergics.
Phenytoin: (Moderate) Calcium carbonate can significantly decrease the oral bioavailability of phenytoin. Calcium carbonate should not affect the pharmacokinetics of parenteral phenytoin. Separating the administration of phenytoin and calcium carbonate by at least 2 hours will help minimize the possibility of an interaction.
Phosphorated Carbohydrate Solution: (Moderate) The oral absorption of phosphorus is reduced by ingestion of pharmacologic doses of calcium carbonate or other phosphate-lowering calcium salts (e.g., calcium acetate). There is, however, no significant interference with phosphorus absorption by oral dietary calcium at intakes within the typical adult range. If the patient requires multiple calcium supplements or a calcium-containing antacid, it may be wise to separate the administration of phosphorus salts from calcium-containing products. In some instances the administration of calcium salts or calcium carbonate is used therapeutically (e.g., uremia) to decrease serum phosphorus levels, so the administration of phosphorus supplements would dynamically counteract the intended use of calcium in these settings, assuming hypophosphatemia is not present. Appropriate calcium-phosphorus ratios in vivo are important for proper calcium homeostasis in tissues and bone; if the serum ionized calcium concentration is elevated, the concomitant use of calcium salts and phosphorus salts may increase the risk of calcium deposition in soft tissue.
Phosphorus: (Moderate) The oral absorption of phosphorus is reduced by ingestion of pharmacologic doses of calcium carbonate or other phosphate-lowering calcium salts (e.g., calcium acetate). There is, however, no significant interference with phosphorus absorption by oral dietary calcium at intakes within the typical adult range. If the patient requires multiple calcium supplements or a calcium-containing antacid, it may be wise to separate the administration of phosphorus salts from calcium-containing products. In some instances the administration of calcium salts or calcium carbonate is used therapeutically (e.g., uremia) to decrease serum phosphorus levels, so the administration of phosphorus supplements would dynamically counteract the intended use of calcium in these settings, assuming hypophosphatemia is not present. Appropriate calcium-phosphorus ratios in vivo are important for proper calcium homeostasis in tissues and bone; if the serum ionized calcium concentration is elevated, the concomitant use of calcium salts and phosphorus salts may increase the risk of calcium deposition in soft tissue.
Pioglitazone; Metformin: (Minor) Famotidine may decrease the renal clearance of metformin secondary to competition for renal tubular transport systems. Such an interaction has been observed when cimetidine was administered with metformin. The decrease in renal excretion led to a 40% increase in metformin AUC. Although interactions with cationic drugs remain theoretical (except for cimetidine), caution is warranted when famotidine and metformin are prescribed concurrently. Famotidine may be less likely to interact with metformin versus cimetidine or ranitidine because of less tubular excretion.
Polyethylene Glycol; Electrolytes; Bisacodyl: (Moderate) By increasing intragastric pH, calcium carbonate can affect the dissolution of oral bisacodyl tablets; administration should be separated by 1 hour. (Minor) The concomitant use of bisacodyl tablets with H2-blockers can cause the enteric coating of the bisacody tablet to dissolve prematurely, leading to possible gastric irritation or dyspepsia. Avoid H2-blockers within 1 hour before or after the bisacodyl dosage.
Polysaccharide-Iron Complex: (Moderate) Antacids (e.g., calcium carbonate, aluminum hydroxide, or magnesium hydroxide) may decrease the absorption of oral iron preparations (e.g., iron salts or polysaccharide-iron complex). At higher pH values, iron is more readily ionized to its ferric state and is more poorly absorbed. Doses of antacids and iron should be taken as far apart as possible to minimize the potential for interaction. (Minor) The bioavailability of oral iron salts is influenced by gastric pH, and the concomitant administration of H2-blockers can decrease iron absorption. The non-heme ferric form of iron needs an acidic intragastric pH to be reduced to ferrous and to be absorbed. Iron salts and polysaccharide-iron complex provide non-heme iron. H2-blockers have long-lasting effects on the secretion of gastric acid and thus, increase the pH of the stomach. The increase in intragastric pH can interfere with the absorption of iron salts.
Potassium Phosphate: (Moderate) The oral absorption of phosphorus is reduced by ingestion of pharmacologic doses of calcium carbonate or other phosphate-lowering calcium salts (e.g., calcium acetate). There is, however, no significant interference with phosphorus absorption by oral dietary calcium at intakes within the typical adult range. If the patient requires multiple calcium supplements or a calcium-containing antacid, it may be wise to separate the administration of phosphorus salts from calcium-containing products. In some instances the administration of calcium salts or calcium carbonate is used therapeutically (e.g., uremia) to decrease serum phosphorus levels, so the administration of phosphorus supplements would dynamically counteract the intended use of calcium in these settings, assuming hypophosphatemia is not present. Appropriate calcium-phosphorus ratios in vivo are important for proper calcium homeostasis in tissues and bone; if the serum ionized calcium concentration is elevated, the concomitant use of calcium salts and phosphorus salts may increase the risk of calcium deposition in soft tissue.
Potassium Phosphate; Sodium Phosphate: (Moderate) The oral absorption of phosphorus is reduced by ingestion of pharmacologic doses of calcium carbonate or other phosphate-lowering calcium salts (e.g., calcium acetate). There is, however, no significant interference with phosphorus absorption by oral dietary calcium at intakes within the typical adult range. If the patient requires multiple calcium supplements or a calcium-containing antacid, it may be wise to separate the administration of phosphorus salts from calcium-containing products. In some instances the administration of calcium salts or calcium carbonate is used therapeutically (e.g., uremia) to decrease serum phosphorus levels, so the administration of phosphorus supplements would dynamically counteract the intended use of calcium in these settings, assuming hypophosphatemia is not present. Appropriate calcium-phosphorus ratios in vivo are important for proper calcium homeostasis in tissues and bone; if the serum ionized calcium concentration is elevated, the concomitant use of calcium salts and phosphorus salts may increase the risk of calcium deposition in soft tissue.
Propantheline: (Major) Avoid concomitant use of calcium carbonate and anticholinergics. Antacids may interfere with the absorption of anticholinergics.
Propranolol: (Moderate) Antacids may reduce the absorption of propranolol. The need to stagger doses of propranolol has not been established, but may be prudent. Monitor clinical response, and adjust propranolol dosage if needed to attain therapeutic goals.
Pseudoephedrine: (Minor) It appears that antacids increase pseudoephedrine plasma concentrations. This interaction can be avoided by separating the administration of pseudoephedrine and antacids by 1 to 2 hours. If antacids are used on a regular basis, an alternative to pseudoephedrine may be considered.
Pseudoephedrine; Triprolidine: (Minor) It appears that antacids increase pseudoephedrine plasma concentrations. This interaction can be avoided by separating the administration of pseudoephedrine and antacids by 1 to 2 hours. If antacids are used on a regular basis, an alternative to pseudoephedrine may be considered.
Quinapril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium.
Quinidine: (Major) By increasing urinary pH, calcium carbonate can decrease the urinary excretion of quinidine.
Quinine: (Major) Antacids may delay or decrease the absorption of quinine.
Raltegravir: (Major) Coadministration of calcium carbonate with raltegravir administered as a once daily dose (high dose regimen) is not recommended. Coadministration may result in decreased plasma concentrations of raltegravir, which may lead to HIV treatment failure or the development of viral resistance. Calcium carbonate may be given with other dosage regimens of raltegravir with no dose adjustments necessary. In a drug interaction study (n = 19), the AUC of raltegravir, given as a single 1200 mg dose, was decreased by 72% (90% CI, 68% to 76%) when administered with a calcium carbonate antacid.
Rasagiline: (Moderate) Monitor for dopaminergic adverse effects during concurrent use of rasagiline and famotidine. Coadministration may result in increased rasagiline concentrations. A dose reduction of rasagiline may be necessary. Rasagiline is primarily metabolized by CYP1A2; famotidine is a weak CYP1A2 inhibitor. When administered with a strong CYP1A2 inhibitor, the AUC of rasagiline was increased by 83%.
Relugolix; Estradiol; Norethindrone acetate: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Rifampin: (Moderate) Concomitant use of calcium carbonate and rifampin may decrease the absorption of rifampin. Daily doses of rifampin should be given at least 1 hour before the ingestion of calcium carbonate.
Rilpivirine: (Moderate) Coadministration with famotidine may significantly decrease rilpivirine plasma concentrations, potentially resulting in treatment failure. To decrease the risk of virologic failure, avoid use of famotidine for at least 12 hours before and at least 4 hours after administering rilpivirine. (Moderate) Concurrent administration of rilpivirine and antacids may significantly decrease rilpivirine plasma concentrations, potentially resulting in treatment failure. To decrease the risk of virologic failure, avoid use of antacids for at least 2 hours before and at least 4 hours after administering rilpivirine.
Riociguat: (Major) Separate administration of riociguat from antacids by at least 1 hour. Antacids such as aluminum hydroxide/magnesium hydroxide decrease riociguat absorption.
Risedronate: (Major) Use of H2-blockers with delayed-release risedronate tablets (Atelvia) is not recommended. Co-administration of drugs that raise stomach pH increases risedronate bioavailability due to faster release of the drug from the enteric coated tablet. This interaction does not apply to risedronate immediate-release tablets. (Moderate) Separate administration of oral risedronate and calcium-containing supplements by at least 2 hours. Calcium will interfere with the absorption of oral risedronate.
Rocuronium: (Moderate) Concomitant use of neuromuscular blockers and calcium may result in resistance to neuromuscular blockade. Calcium antagonizes the potentiating effect of magnesium on neuromuscular blockade. Also, calcium triggers acetylcholine release, and therefore, may both reduce the sensitivity to neuromuscular blockers and decrease the duration of neuromuscular blockade.
Rosuvastatin: (Moderate) While not specifically reported with calcium carbonate, antacids (aluminum hydroxide; magnesium hydroxide combination) have been shown to reduce rosuvastatin plasma concentrations by 54%. When the antacid is given 2 hours after rosuvastatin, no significant change in rosuvastatin plasma concentrations is observed.
Rosuvastatin; Ezetimibe: (Moderate) While not specifically reported with calcium carbonate, antacids (aluminum hydroxide; magnesium hydroxide combination) have been shown to reduce rosuvastatin plasma concentrations by 54%. When the antacid is given 2 hours after rosuvastatin, no significant change in rosuvastatin plasma concentrations is observed. (Minor) Antacids (e.g., 20 ml aluminum hydroxide; magnesium hydroxide) have no significant effect on the oral bioavailability of total ezetimibe (ezetimibe plus ezetimibe-glucuronide), ezetimibe-glucuronide, or ezetimibe based on AUC values. However, the peak plasma concentration (Cmax) of total ezetimibe is decreased by 30%. The effect of the antacids in this regard is not expected to have a significant effect on the ability of ezetimibe to lower cholesterol. However, to limit any potential interaction, it would be prudent to administer ezetimibe at least 1 hour before or 2 hours after administering antacids.
Sarecycline: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of these antibiotics will be significantly reduced by other orally administered compounds that contain calcium salts, particularly if the time of administration is within 60 minutes of each other. Calcium salts and tetracyclines should not be administered within 1 to 2 hours of each other, although doxycycline chelates less with calcium than other tetracyclines.
Scopolamine: (Major) Avoid concomitant use of calcium carbonate and anticholinergics. Antacids may interfere with the absorption of anticholinergics.
Secretin: (Major) Discontinue use of H2-blockers at least 2 days before administering secretin. Patients who are receiving H2-blockers at the time of stimulation testing may be hyperresponsive to secretin stimulation, falsely suggesting gastrinoma.
Segesterone Acetate; Ethinyl Estradiol: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
Selpercatinib: (Major) Avoid coadministration of selpercatinib with calcium carbonate due to the risk of decreased selpercatinib exposure which may reduce its efficacy. If concomitant use is unavoidable, take selpercatinib 2 hours before or 2 hours after administration of calcium carbonate. Coadministration with acid-reducing agents decreases selpercatinib plasma concentrations. (Major) Avoid coadministration of selpercatinib with famotidine due to the risk of decreased selpercatinib exposure which may reduce its efficacy. If concomitant use is unavoidable, take selpercatinib 2 hours before or 10 hours after administration of famotidine. Coadministration with acid-reducing agents decreases selpercatinib plasma concentrations; however, no clinically significant differences in the pharmacokinetics of selpercatinib were observed when given under fasting conditions with multiple daily doses of another H2-receptor antagonist given 10 hours prior to and 2 hours after the selpercatinib dose.
Sodium Ferric Gluconate Complex; ferric pyrophosphate citrate: (Moderate) Antacids (e.g., calcium carbonate, aluminum hydroxide, or magnesium hydroxide) may decrease the absorption of oral iron preparations (e.g., iron salts or polysaccharide-iron complex). At higher pH values, iron is more readily ionized to its ferric state and is more poorly absorbed. Doses of antacids and iron should be taken as far apart as possible to minimize the potential for interaction. (Minor) The bioavailability of oral iron salts is influenced by gastric pH, and the concomitant administration of H2-blockers can decrease iron absorption. The non-heme ferric form of iron needs an acidic intragastric pH to be reduced to ferrous and to be absorbed. Iron salts and polysaccharide-iron complex provide non-heme iron. H2-blockers have long-lasting effects on the secretion of gastric acid and thus, increase the pH of the stomach. The increase in intragastric pH can interfere with the absorption of iron salts.
Sodium Fluoride: (Moderate) Absorption of sodium fluoride may be reduced by concomitant use of antacids that contain magnesium, aluminum, or calcium. An interval of at least 2 hours is advisable between administration of sodium fluoride and antacids.
Sodium Phosphate Monobasic Monohydrate; Sodium Phosphate Dibasic Anhydrous: (Moderate) The concomitant use of oral sodium phosphate monobasic monohydrate; sodium phosphate dibasic anhydrous preparations in conjunction with antacids containing calcium (e.g., calcium carbonate, calcium salts) may bind the phosphate in the stomach and reduce its absorption. If the patient requires multiple mineral supplements or concurrent use of antacids, it is prudent to separate the administration of sodium phosphate salts from calcium containing products by at least one hour.
Sodium Polystyrene Sulfonate: (Major) Simultaneous oral administration of cation-donating antacids or laxatives may reduce the potassium exchange capability of sodium polystyrene sulfonate. Examples of cation-donating antacids and laxatives include aluminum hydroxide, calcium carbonate, magnesium carbonate, magnesium citrate, and magnesium hydroxide. Patients who received concomitant oral sodium polystyrene sulfonate and non-absorbable cation-donating antacids and laxatives have developed systemic alkalosis. Intestinal obstruction due to concretions of aluminum hydroxide when used in combination with sodium polystyrene sulfonate has also been reported. One case of grand mal seizure has been reported in a patient with chronic hypocalcemia of renal failure who was given sodium polystyrene with magnesium hydroxide as laxative. Normally, antacids like magnesium hydroxide and calcium carbonate neutralize hydrochloric acid in the stomach, forming magnesium chloride and calcium chloride. As these compounds enter the small intestine, they react with bicarbonate, forming magnesium carbonate and calcium carbonate, which are insoluble. If polystyrene is administered, it blocks this reaction by binding to the magnesium and calcium ions before they can react with the bicarbonate. More hydrogen ions are lost from the stomach than are lost from the intestine, resulting in metabolic alkalosis. Rectal administration of sodium polystyrene sulfonate may reduce the severity of these interactions.
Sofosbuvir; Velpatasvir: (Major) H2-blockers may be administered simultaneously with or 12 hours apart from velpatasvir. H2-blocker doses should not exceed doses comparable to famotidine 40 mg twice daily. Velpatasvir solubility decreases as pH increases; therefore, drugs that increase gastric pH are expected to decrease the concentrations of velpatasvir, potentially resulting in loss of antiviral efficacy. (Moderate) Separate the use of antacids (e.g., calcium carbonate) and sofosbuvir; velpatasvir administration by 4 hours. Velpatasvir solubility decreases as pH increases; therefore, drugs that increase gastric pH are expected to decrease the concentrations of velpatasvir, potentially resulting in loss of antiviral efficacy.
Sofosbuvir; Velpatasvir; Voxilaprevir: (Major) H2-blockers may be administered simultaneously with or 12 hours apart from velpatasvir. H2-blocker doses should not exceed doses comparable to famotidine 40 mg twice daily. Velpatasvir solubility decreases as pH increases; therefore, drugs that increase gastric pH are expected to decrease the concentrations of velpatasvir, potentially resulting in loss of antiviral efficacy. (Moderate) Separate the use of antacids (e.g., calcium carbonate) and sofosbuvir; velpatasvir administration by 4 hours. Velpatasvir solubility decreases as pH increases; therefore, drugs that increase gastric pH are expected to decrease the concentrations of velpatasvir, potentially resulting in loss of antiviral efficacy.
Sonidegib: (Moderate) Based on population PK analysis, the concomitant administration of a histamine-2-receptor antagonist such as famotidine decreases the geometric mean sonidegib steady-state AUC (0-24 hours) value by 34%.
Sotalol: (Moderate) Coadministration of antacids with sotalol reduces the Cmax and AUC of sotalol by 26% and 20%, respectively. This interaction results in a 25% reduction in the bradycardic effect of sotalol (measured at rest). Administer antacids two hours after the sotalol dose to avoid altering sotalol pharmacokinetics or pharmacodynamics.
Sotorasib: (Major) Avoid coadministration of sotorasib and gastric acid-reducing agents, such as H2-receptor antagonists. Coadministration may decrease sotorasib exposure resulting in decreased efficacy. If necessary, sotorasib may be administered 4 hours before or 10 hours after a locally acting antacid. Coadministration with an H2-receptor antagonist decreased sotorasib exposure by 38% under fed conditions. (Moderate) Avoid coadministration of sotorasib and gastric-reducing agents, such as antacids including calcium carbonate. Coadministration may decrease sotorasib exposure resulting in decreased efficacy. If coadministration with calcium carbonate is necessary, administer sotorasib 4 hours before or 10 hours after calcium carbonate.
Sparsentan: (Major) Avoid concurrent use of sparsentan and H2 receptor antagonists due to the risk for decreased sparsentan exposure which may reduce its efficacy. Medications that affect gastric pH may reduce sparsentan absorption.
Spironolactone; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium.
Succinylcholine: (Moderate) Concomitant use of neuromuscular blockers and calcium may result in resistance to neuromuscular blockade. Calcium antagonizes the potentiating effect of magnesium on neuromuscular blockade. Also, calcium triggers acetylcholine release, and therefore, may both reduce the sensitivity to neuromuscular blockers and decrease the duration of neuromuscular blockade.
Sucralfate: (Moderate) Oral antacids, including calcium carbonate, potentially interfere with gastric mucosal binding of sucralfate. This interaction can be minimized by staggering the doses of these agents as much as possible.
Sulfacetamide; Sulfur: (Major) Because edetate disodium chelates and lowers serum calcium, oral or parenteral calcium salts should not be administered concomitantly.
Sumatriptan; Naproxen: (Moderate) Avoid concomitant use of enteric-coated, delayed-release naproxen and H2-blockers due to the gastric pH elevating effects of H2-blockers. Enteric-coated, delayed-release naproxen tablets are designed to dissolve at a pH of 6 or more.
Telmisartan; Amlodipine: (Minor) Monitor blood pressure during concurrent use of calcium and calcium-channel blockers. Concomitant use may reduce the response to calcium-channel blockers.
Telmisartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium.
Teriparatide: (Moderate) Monitor serum calcium concentrations closely if concomitant use of calcium and teriparatide is necessary. Concomitant use may increase the risk of hypercalcemia.
Tetracycline: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of these antibiotics will be significantly reduced by other orally administered compounds that contain calcium salts, particularly if the time of administration is within 60 minutes of each other. Calcium salts and tetracyclines should not be administered within 1 to 2 hours of each other, although doxycycline chelates less with calcium than other tetracyclines.
Tetracyclines: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of these antibiotics will be significantly reduced by other orally administered compounds that contain calcium salts, particularly if the time of administration is within 60 minutes of each other. Calcium salts and tetracyclines should not be administered within 1 to 2 hours of each other, although doxycycline chelates less with calcium than other tetracyclines.
Thalidomide: (Moderate) Thalidomide and other agents that slow cardiac conduction such as H2-blockers should be used cautiously due to the potential for additive bradycardia.
Theophylline, Aminophylline: (Minor) Aminophylline is a prodrug of theophylline, and is primarily metabolized in the liver by the CYP1A2 isoenzyme. In general, famotidine does not interact with aminophylline and does not affect theophylline levels in most patients. One small study documented a significant decrease in theophylline clearance after therapy with famotidine. Be alert for any evidence of interaction, and monitor the patients aminophylline therapy as per standard of care or if side effects are reported. (Minor) Theophylline is primarily metabolized in the liver by the CYP1A2 isoenzyme. In general, famotidine does not interact with theophylline and does not affect theophylline levels in most patients. One small study documented a significant decrease in theophylline clearance after therapy with famotidine. Be alert for any evidence of interaction, and monitor the patients theophylline therapy as per standard of care or if side effects are reported.
Thiazide diuretics: (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium.
Thiothixene: (Major) Antacids may reduce the oral availablility of thiothixene. To avoid this, administer thiothixene at least 1 hour before or 2 hours after the antacid.
Thyroid hormones: (Moderate) Thyroid hormones should be administered at least 4 hours before or after the ingestion of oral calcium supplements. Calcium salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption. Some case reports have described clinical hypothyroidism resulting from coadministration of thyroid hormones with oral calcium supplements.
Tipranavir: (Moderate) Concurrent administration of tipranavir and ritonavir with antacids results in decreased tipranavir concentrations. Administer tipranavir and ritonavir 2 hours before or 1 hour after antacids.
Tizanidine: (Major) Avoid concomitant use of tizanidine and famotidine as increased tizanidine exposure may occur. If use together is necessary, initiate tizanidine at 2 mg and increase by 2 to 4 mg/day based on clinical response. Discontinue tizanidine if hypotension, bradycardia, or excessive drowsiness occurs. Tizanidine is a CYP1A2 substrate and famotidine is a weak CYP1A2 inhibitor.
Trandolapril; Verapamil: (Minor) Monitor blood pressure during concurrent use of calcium and calcium-channel blockers. Concomitant use may reduce the response to calcium-channel blockers.
Triamterene; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium.
Trihexyphenidyl: (Major) Avoid concomitant use of calcium carbonate and anticholinergics. Antacids may interfere with the absorption of anticholinergics.
Valproic Acid, Divalproex Sodium: (Minor) Antacids may increase valproic acid AUC. Patients should be monitored for adverse effects in this situation.
Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum calcium concentration during concomitant calcium and thiazide diuretic use due to the risk for hypercalcemia. Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and slight increases in serum calcium.
Vecuronium: (Moderate) Concomitant use of neuromuscular blockers and calcium may result in resistance to neuromuscular blockade. Calcium antagonizes the potentiating effect of magnesium on neuromuscular blockade. Also, calcium triggers acetylcholine release, and therefore, may both reduce the sensitivity to neuromuscular blockers and decrease the duration of neuromuscular blockade.
Verapamil: (Minor) Monitor blood pressure during concurrent use of calcium and calcium-channel blockers. Concomitant use may reduce the response to calcium-channel blockers.
Vitamin A: (Minor) Doses in excess of 1,500 to 2,000 mcg per day of Vitamin A may lead to bone loss and will counteract the effects of supplementation with calcium salts.
Vitamin D analogs: (Moderate) Monitor serum calcium concentrations during concomitant use of high doses of calcium and vitamin D analogs; a dosage adjustment of the vitamin D analog may be needed. Hypercalcemia may be exacerbated by concomitant administration.
Warfarin: (Moderate) Closely monitor the INR if coadministration of warfarin with famotidine is necessary as concurrent use may increase the exposure of warfarin leading to increased bleeding risk. Famotidine is a CYP1A2 inhibitor and the R-enantiomer of warfarin is a CYP1A2 substrate. The S-enantiomer of warfarin exhibits 2 to 5 times more anticoagulant activity than the R-enantiomer, but the R-enantiomer generally has a slower clearance.
As an antacid, calcium carbonate neutralizes gastric acidity resulting in increased gastric and duodenal pH. The calcium released from calcium carbonate is known to increase peristalsis in the esophagus, pushing the acid into the stomach and provide relief from symptoms of heartburn. Famotidine is a competitive inhibitor of histamine-2 (H2) receptors, which results in inhibition of gastric secretion. Both the acid concentration and volume of gastric secretion are suppressed by famotidine, while changes in pepsin secretion are proportional to volume output. Magnesium hydroxide rapidly reacts with gastric acid to form water and magnesium chloride, which neutralizes gastric acid.
Calcium carbonate; famotidine; magnesium hydroxide is administered orally. After absorption, approximately 50% of calcium in the serum is in the physiologically active ionized form; about 10% is complexed to phosphate, citrate, or other anions. The remaining 40% is bound to proteins, primarily albumin. Unabsorbed calcium from the small intestine is excreted in the feces. Renal excretion depends largely on glomerular filtration and calcium tubular reabsorption with more than 98% of calcium reabsorbed from the glomerular filtrate. This process is regulated by active vitamin D and parathyroid hormone (PTH). The amount excreted in the urine varies with the degree of calcium absorption, the rate of bone turnover, and renal conservation status. Calcium is excreted in the urine (roughly 20%). Plasma protein binding of famotidine is approximately 15% to 20%. There is no cumulative effect with repeat doses; plasma concentrations after multiple doses are similar to those after single doses. Famotidine undergoes minimal first-pass metabolism. The majority (65% to 70%) of a famotidine dose is excreted in the urine; 30% to 35% of the dose is metabolized by the liver. The S-oxide metabolite is the only metabolite identified in humans. Famotidine elimination half-life is 2.5 to 3.5 hours in adults with normal renal function. In the stomach, magnesium hydroxide reacts with hydrochloric acid to form magnesium chloride. Approximately 15% to 30% of the magnesium chloride is absorbed and rapidly excreted by the kidneys in patients with normal renal function. Any magnesium hydroxide that is not converted to magnesium chloride is subsequently changed in the small intestine to soluble but poorly absorbed salts. The magnesium that is not absorbed remains in the GI tract and is excreted in the feces.
Affected cytochrome P450 isoenzymes and drug transporters: CYP1A2, OAT1, OAT3, MATE-1
Famotidine is a weak inhibitor of CYP1A2. In vitro studies also indicate that famotidine is a substrate for human organic anion transporter (OAT) 1 and 3 and an inhibitor of multidrug and toxin extrusion protein 1 (MATE-1).
-Route-Specific Pharmacokinetics
Oral Route
Bioavailability of famotidine is approximately 40% to 45% in adults. Food may slightly increase and antacids may slightly decrease the bioavailability of famotidine; however, the effects are considered clinically insignificant. The onset of action of famotidine is usually within 1 hour after oral administration with maximum effects occurring within 1 to 3 hours depending on the dose. The duration of action of famotidine is roughly 10 to 12 hours. About 25% to 30% of an oral famotidine dose is excreted in urine as an unchanged drug.
-Special Populations
Renal Impairment
In adults with severe renal impairment (creatinine clearance less than 30 mL/minute), the systemic exposure (AUC) of famotidine increased at least 5-fold. In adults with moderate renal impairment (creatinine clearance 30 to 60 mL/minute), the AUC of famotidine increased at least 2-fold.
Pediatrics
Children and Adolescents
The mean oral bioavailability of famotidine in 8 pediatric patients 11 to 15 years of age was 50%. The mean half-life of famotidine was 2 to 3.4 hours in pediatric patients 1 to 15 years of age.
Geriatric
There are no clinically significant age-related changes in famotidine pharmacokinetics in elderly patients vs. younger adults. However, in elderly patients with decreased renal function, the clearance of famotidine may be reduced.