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Drug Interactions between Complete Acid Reducer plus Antacid and selpercatinib

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Major

famotidine selpercatinib

Applies to: Complete Acid Reducer plus Antacid (calcium carbonate / famotidine / magnesium hydroxide) and selpercatinib

GENERALLY AVOID: Coadministration with drugs that increase gastric pH may significantly decrease the oral bioavailability of selpercatinib and reduce its concentrations in plasma. According to the product labeling, the aqueous solubility of selpercatinib is pH-dependent, from freely soluble at low pH to slightly soluble at neutral pH. When a single dose of selpercatinib (160 mg) was administered under fasted conditions with multiple daily doses of the proton pump inhibitor omeprazole (40 mg once daily), selpercatinib peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 88% and 69%, respectively, compared to selpercatinib administered alone while fasting. The interaction may also occur with other acid reducing or neutralizing agents and may result in diminished anti-tumor activity of selpercatinib. However, no clinically significant differences in selpercatinib pharmacokinetics were observed when coadministered under fasted conditions with multiple daily doses of ranitidine given 10 hours prior to and 2 hours after the selpercatinib dose.

MANAGEMENT: Concomitant use of selpercatinib with H2-receptor antagonists should generally be avoided. If coadministration is required, the manufacturer recommends taking selpercatinib 2 hours before or 10 hours after the H2-receptor antagonist to minimize the clinical impact of the interaction.

References (4)
  1. (2024) "Product Information. Retevmo (selpercatinib)." Lilly, Eli and Company
  2. (2023) "Product Information. Retevmo (selpercatinib)." Eli Lilly Australia Pty Ltd, vA1.0
  3. (2024) "Product Information. Retsevmo (selpercatinib)." Eli Lilly and Company Ltd
  4. (2024) "Product Information. Retevmo (selpercatinib)." Loxo Oncology Inc
Major

calcium carbonate selpercatinib

Applies to: Complete Acid Reducer plus Antacid (calcium carbonate / famotidine / magnesium hydroxide) and selpercatinib

GENERALLY AVOID: Coadministration with drugs that increase gastric pH may significantly decrease the oral bioavailability of selpercatinib and reduce its concentrations in plasma. According to the product labeling, the aqueous solubility of selpercatinib is pH-dependent, from freely soluble at low pH to slightly soluble at neutral pH. When a single dose of selpercatinib (160 mg) was administered under fasted conditions with multiple daily doses of the proton pump inhibitor omeprazole (40 mg once daily), selpercatinib peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 88% and 69%, respectively, compared to selpercatinib administered alone while fasting. The interaction may also occur with other acid reducing or neutralizing agents and may result in diminished anti-tumor activity of selpercatinib.

MANAGEMENT: Concomitant use of selpercatinib with locally-acting antacids or other agents with acid neutralizing or reducing effects should generally be avoided. If coadministration is required, the manufacturer recommends taking selpercatinib 2 hours before or 2 hours after the antacid.

References (4)
  1. (2024) "Product Information. Retevmo (selpercatinib)." Lilly, Eli and Company
  2. (2023) "Product Information. Retevmo (selpercatinib)." Eli Lilly Australia Pty Ltd, vA1.0
  3. (2024) "Product Information. Retsevmo (selpercatinib)." Eli Lilly and Company Ltd
  4. (2024) "Product Information. Retevmo (selpercatinib)." Loxo Oncology Inc
Major

magnesium hydroxide selpercatinib

Applies to: Complete Acid Reducer plus Antacid (calcium carbonate / famotidine / magnesium hydroxide) and selpercatinib

GENERALLY AVOID: Coadministration with drugs that increase gastric pH may significantly decrease the oral bioavailability of selpercatinib and reduce its concentrations in plasma. According to the product labeling, the aqueous solubility of selpercatinib is pH-dependent, from freely soluble at low pH to slightly soluble at neutral pH. When a single dose of selpercatinib (160 mg) was administered under fasted conditions with multiple daily doses of the proton pump inhibitor omeprazole (40 mg once daily), selpercatinib peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 88% and 69%, respectively, compared to selpercatinib administered alone while fasting. The interaction may also occur with other acid reducing or neutralizing agents and may result in diminished anti-tumor activity of selpercatinib.

MANAGEMENT: Concomitant use of selpercatinib with locally-acting antacids or other agents with acid neutralizing or reducing effects should generally be avoided. If coadministration is required, the manufacturer recommends taking selpercatinib 2 hours before or 2 hours after the antacid.

References (4)
  1. (2024) "Product Information. Retevmo (selpercatinib)." Lilly, Eli and Company
  2. (2023) "Product Information. Retevmo (selpercatinib)." Eli Lilly Australia Pty Ltd, vA1.0
  3. (2024) "Product Information. Retsevmo (selpercatinib)." Eli Lilly and Company Ltd
  4. (2024) "Product Information. Retevmo (selpercatinib)." Loxo Oncology Inc
Minor

famotidine calcium carbonate

Applies to: Complete Acid Reducer plus Antacid (calcium carbonate / famotidine / magnesium hydroxide) and Complete Acid Reducer plus Antacid (calcium carbonate / famotidine / magnesium hydroxide)

Antacids and some aluminum, calcium, and magnesium salts may decrease the plasma concentrations of H2-receptor antagonists during oral coadministration. The mechanism of interaction is unknown, but may involve reduced oral absorption due to increased gastric pH. Study data vary, with no changes to nearly 60% reductions in systemic exposures (AUCs) reported for cimetidine, famotidine, and ranitidine. The clinical significance has not been established. As a precaution, patients may consider taking H2-receptor antagonists one to two hours before antacids.

References (12)
  1. Donn KH, Eshelman FN, Plachetka JR, et al. (1984) "The effects of antacid and propantheline on the absorption of oral ranitidine." Pharmacotherapy, 4, p. 89-92
  2. Albin H, Vincon G, Demotes-Mainard F, et al. (1984) "Effect of aluminium phosphate on the bioavailability of cimetidine and prednisolone." Eur J Clin Pharmacol, 26, p. 271-3
  3. Lin JH, Chremos AN, Kanovsky SM, Schwartz S, Yeh KC, Kann J (1987) "Effects of antacids and food on absorption of famotidine." Br J Clin Pharmacol, 24, p. 551-3
  4. Bodemar G, Norlander B, Walan A (1979) "Diminished absorption of cimetidine caused by antacids." Lancet, 02/24/79, p. 444-5
  5. Steinberg WM, Lewis JH, Katz DM (1982) "Antacids inhibit absorption of cimetidine." N Engl J Med, 307, p. 400-4
  6. Barzaghi N, Gatti G, Crema F, Perucca E (1989) "Impaired bioavailability of famotidine given concurrently with a potent antacid." J Clin Pharmacol, 29, p. 670-2
  7. Russell WL, Lopez LM, Normann SA, et al. (1984) "Effect of antacids on predicted steady-state cimetidine concentrations." Dig Dis Sci, 29, p. 385-9
  8. Shelly DW, Doering PL, Russell WL, Guild RT, Lopez LM, Perrin J (1986) "Effect of concomitant antacid administration on plasma cimetidine concentrations during repetitive dosing." Drug Intell Clin Pharm, 20, p. 792-5
  9. Albin H, Vincon G, Begaud B, Bistue C, Perez P (1987) "Effect of aluminum phosphate on the bioavailability of ranitidine." Eur J Clin Pharmacol, 32, p. 97-9
  10. Mihaly GW, Marino AT, Webster LK, Jones DB, Louis WJ, Smallwood RA (1982) "High dose of antacid (Mylanta II) reduces bioavailability of ranitidine." Br Med J, 285, p. 998-9
  11. Covington TR, eds., Lawson LC, Young LL (1993) "Handbook of Nonprescription Drugs." Washington, DC: American Pharmaceutical Association
  12. Bachmann KA, Sullivan TJ, Jauregui L, Reese J, Miller K, Levine L (1994) "Drug interactions of h-2-receptor antagonists." Scand J Gastroenterol, 29, p. 14-9
Minor

famotidine magnesium hydroxide

Applies to: Complete Acid Reducer plus Antacid (calcium carbonate / famotidine / magnesium hydroxide) and Complete Acid Reducer plus Antacid (calcium carbonate / famotidine / magnesium hydroxide)

Antacids and some aluminum, calcium, and magnesium salts may decrease the plasma concentrations of H2-receptor antagonists during oral coadministration. The mechanism of interaction is unknown, but may involve reduced oral absorption due to increased gastric pH. Study data vary, with no changes to nearly 60% reductions in systemic exposures (AUCs) reported for cimetidine, famotidine, and ranitidine. The clinical significance has not been established. As a precaution, patients may consider taking H2-receptor antagonists one to two hours before antacids.

References (12)
  1. Donn KH, Eshelman FN, Plachetka JR, et al. (1984) "The effects of antacid and propantheline on the absorption of oral ranitidine." Pharmacotherapy, 4, p. 89-92
  2. Albin H, Vincon G, Demotes-Mainard F, et al. (1984) "Effect of aluminium phosphate on the bioavailability of cimetidine and prednisolone." Eur J Clin Pharmacol, 26, p. 271-3
  3. Lin JH, Chremos AN, Kanovsky SM, Schwartz S, Yeh KC, Kann J (1987) "Effects of antacids and food on absorption of famotidine." Br J Clin Pharmacol, 24, p. 551-3
  4. Bodemar G, Norlander B, Walan A (1979) "Diminished absorption of cimetidine caused by antacids." Lancet, 02/24/79, p. 444-5
  5. Steinberg WM, Lewis JH, Katz DM (1982) "Antacids inhibit absorption of cimetidine." N Engl J Med, 307, p. 400-4
  6. Barzaghi N, Gatti G, Crema F, Perucca E (1989) "Impaired bioavailability of famotidine given concurrently with a potent antacid." J Clin Pharmacol, 29, p. 670-2
  7. Russell WL, Lopez LM, Normann SA, et al. (1984) "Effect of antacids on predicted steady-state cimetidine concentrations." Dig Dis Sci, 29, p. 385-9
  8. Shelly DW, Doering PL, Russell WL, Guild RT, Lopez LM, Perrin J (1986) "Effect of concomitant antacid administration on plasma cimetidine concentrations during repetitive dosing." Drug Intell Clin Pharm, 20, p. 792-5
  9. Albin H, Vincon G, Begaud B, Bistue C, Perez P (1987) "Effect of aluminum phosphate on the bioavailability of ranitidine." Eur J Clin Pharmacol, 32, p. 97-9
  10. Mihaly GW, Marino AT, Webster LK, Jones DB, Louis WJ, Smallwood RA (1982) "High dose of antacid (Mylanta II) reduces bioavailability of ranitidine." Br Med J, 285, p. 998-9
  11. Covington TR, eds., Lawson LC, Young LL (1993) "Handbook of Nonprescription Drugs." Washington, DC: American Pharmaceutical Association
  12. Bachmann KA, Sullivan TJ, Jauregui L, Reese J, Miller K, Levine L (1994) "Drug interactions of h-2-receptor antagonists." Scand J Gastroenterol, 29, p. 14-9

Drug and food interactions

Major

selpercatinib food

Applies to: selpercatinib

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of selpercatinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Inhibition of hepatic CYP450 3A4 may also contribute. The interaction has not been studied with grapefruit juice, but has been reported for other CYP450 3A4 inhibitors. When a single dose of selpercatinib (160 mg) was coadministered with multiple doses of itraconazole (200 mg once daily), a potent CYP450 3A4 inhibitor, selpercatinib peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 30% and 133%, respectively. Based on pharmacokinetic modeling, administration of multiple doses of selpercatinib (160 mg twice daily) with multiple doses of the moderate CYP450 3A4 inhibitors diltiazem (60 mg three times daily), fluconazole (200 mg once daily), or verapamil (80 mg three times daily) is predicted to increase selpercatinib Cmax by 46% to 76% and AUC by 60% to 99%. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Increased exposure to selpercatinib may increase the risk of serious adverse effects such as QT interval prolongation, liver transaminase and bilirubin elevations, hypertension, hemorrhage, edema, and hypersensitivity reactions (e.g., fever, rash, arthralgias/myalgias with concurrent decreased platelets or transaminitis).

MANAGEMENT: Until further information is available, it may be advisable for patients to limit or avoid consumption of grapefruit and grapefruit juice during treatment with selpercatinib.

References (4)
  1. (2024) "Product Information. Retevmo (selpercatinib)." Lilly, Eli and Company
  2. (2023) "Product Information. Retevmo (selpercatinib)." Eli Lilly Australia Pty Ltd, vA1.0
  3. (2024) "Product Information. Retsevmo (selpercatinib)." Eli Lilly and Company Ltd
  4. (2024) "Product Information. Retevmo (selpercatinib)." Loxo Oncology Inc
Moderate

calcium carbonate food

Applies to: Complete Acid Reducer plus Antacid (calcium carbonate / famotidine / magnesium hydroxide)

ADJUST DOSING INTERVAL: Administration with food may increase the absorption of calcium. However, foods high in oxalic acid (spinach or rhubarb), or phytic acid (bran and whole grains) may decrease calcium absorption.

MANAGEMENT: Calcium may be administered with food to increase absorption. Consider withholding calcium administration for at least 2 hours before or after consuming foods high in oxalic acid or phytic acid.

References (6)
  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. Canadian Pharmacists Association (2006) e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink
  3. Cerner Multum, Inc. "Australian Product Information."
  4. Agencia Española de Medicamentos y Productos Sanitarios Healthcare (2008) Centro de información online de medicamentos de la AEMPS - CIMA. https://cima.aemps.es/cima/publico/home.html
  5. Mangels AR (2014) "Bone nutrients for vegetarians." Am J Clin Nutr, 100, epub
  6. Davies NT (1979) "Anti-nutrient factors affecting mineral utilization." Proc Nutr Soc, 38, p. 121-8
Minor

famotidine food

Applies to: Complete Acid Reducer plus Antacid (calcium carbonate / famotidine / magnesium hydroxide)

H2 antagonists may reduce the clearance of nicotine. Cimetidine, 600 mg given twice a day for two days, reduced clearance of an intravenous nicotine dose by 30%. Ranitidine, 300 mg given twice a day for two days, reduced clearance by 10%. The clinical significance of this interaction is not known. Patients should be monitored for increased nicotine effects when using the patches or gum for smoking cessation and dosage adjustments should be made as appropriate.

References (1)
  1. Bendayan R, Sullivan JT, Shaw C, Frecker RC, Sellers EM (1990) "Effect of cimetidine and ranitidine on the hepatic and renal elimination of nicotine in humans." Eur J Clin Pharmacol, 38, p. 165-9

Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

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