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Drug Interactions between Actonel with Calcium and pexidartinib

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

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Interactions between your drugs

Moderate

calcium carbonate risedronate

Applies to: Actonel with Calcium (calcium carbonate / risedronate) and Actonel with Calcium (calcium carbonate / risedronate)

ADJUST DOSING INTERVAL: Products containing aluminum, calcium, magnesium and other polyvalent cations such as antacids or vitamin with mineral supplements are likely to interfere with the gastrointestinal absorption of oral bisphosphonates. For example, the bioavailability of tiludronate has been shown to decrease 80% during simultaneous administration with calcium, and 60% when aluminum- or magnesium-containing antacids were administered one hour before tiludronate.

MANAGEMENT: Antacids or other oral medications containing aluminum, calcium, magnesium and other polyvalent cations should be administered at least 30 minutes after the bisphosphonate dose.

References (6)
  1. (2001) "Product Information. Fosamax (alendronate)." Merck & Co., Inc
  2. Darcy PF (1995) "Nutrient-drug interactions." Adverse Drug React Toxicol Rev, 14, p. 233-54
  3. "Product Information. Skelid (tiludronate)." Sanofi Winthrop Pharmaceuticals
  4. (2001) "Product Information. Actonel (risedronate)." Procter and Gamble Pharmaceuticals
  5. (2001) "Product Information. Bonefos (clodronate)." Rhone-Poulenc Rorer Canada Inc
  6. (2005) "Product Information. Boniva (ibandronate)." Roche Laboratories
Moderate

calcium carbonate pexidartinib

Applies to: Actonel with Calcium (calcium carbonate / risedronate) and pexidartinib

ADJUST DOSING INTERVAL: Coadministration with acid-reducing agents may significantly decrease the bioavailability and therapeutic effects of pexidartinib. The proposed mechanism is a pH-dependent reduction in drug dissolution and/or absorption. Concomitant administration of esomeprazole, a proton pump inhibitor, decreased pexidartinib peak plasma concentration (Cmax) and systemic exposure (AUC) by 55% and 50%, respectively. The effect of coadministration with an H2-receptor antagonist or locally-acting antacids on pexidartinib pharmacokinetics is unknown.

MANAGEMENT: If acid-suppression therapy is required, pexidartinib may be administered 2 hours before or 2 hours after taking a locally-acting antacid, or if using an H2-receptor antagonist, administer pexidartinib at least 2 hours before or 10 hours after taking the H2-receptor antagonist. Concomitant use of pexidartinib with proton pump inhibitors should be avoided.

References (1)
  1. (2019) "Product Information. Turalio (pexidartinib)." Daiichi Sankyo, Inc.

Drug and food interactions

Major

pexidartinib food

Applies to: pexidartinib

ADJUST DOSING INTERVAL: The presence of food may increase the absorption and toxicity of pexidartinib. Administration of pexidartinib with a high-fat meal increased peak plasma concentration (Cmax) and systemic exposure (AUC) by 100% and prolonged the time to reach peak plasma concentration (Tmax) by 2.5 hours.

GENERALLY AVOID: Grapefruit or grapefruit juice may increase the plasma concentration and risk of adverse effects of pexidartinib, including potentially fatal hepatotoxicity. The mechanism is inhibition of CYP450 3A4-mediated metabolism of pexidartinib by certain compounds present in grapefruits. Concomitant administration of itraconazole, a strong CYP450 3A4 inhibitor, increased pexidartinib peak plasma concentration (Cmax) and systemic exposure (AUC) by 48% and 70%, respectively.

MANAGEMENT: Pexidartinib should be administered on an empty stomach, at least one hour before or two hours after a meal or snack. Consumption of grapefruit or grapefruit juice should generally be avoided during pexidartinib therapy. If concomitant use is unavoidable, the dose of pexidartinib should be reduced according to the manufacturer's recommendations. If concomitant use of grapefruit or grapefruit juice is discontinued, the dose of pexidartinib may be increased (after 3 plasma half-lives of a strong CYP450 3A4 inhibitor) to the dose that was used prior to consumption of grapefruit or grapefruit juice.

References (1)
  1. (2019) "Product Information. Turalio (pexidartinib)." Daiichi Sankyo, Inc.
Moderate

calcium carbonate food

Applies to: Actonel with Calcium (calcium carbonate / risedronate)

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
Moderate

risedronate food

Applies to: Actonel with Calcium (calcium carbonate / risedronate)

ADJUST DOSING INTERVAL: Food significantly decreases the bioavailability of risedronate, possibly to negligible levels.

MANAGEMENT: Risedronate should be administered with 180 to 240 mL (6 to 8 ounces) of plain water, at least 30 minutes before the first food, beverage, or medication of the day. Patients should remain upright for at least 30 minutes following administration of risedronate.

References (1)
  1. (2001) "Product Information. Actonel (risedronate)." Procter and Gamble Pharmaceuticals

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.


Report options

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.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.