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Drug Interactions between irinotecan and pazopanib

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

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Interactions between your drugs

Moderate

irinotecan PAZOPanib

Applies to: irinotecan and pazopanib

MONITOR: Coadministration with inhibitors of CYP450 3A4 and/or UGT1A1 may increase the plasma concentrations of irinotecan and its active metabolite, SN-38. CYP450 3A4 and UGT1A1 are the isoenzymes responsible for the metabolic conversion of irinotecan to its inactive metabolite, APC. Inhibition of APC formation results in more irinotecan metabolism to SN-38, an active and toxic metabolite. High plasma levels of irinotecan and SN-38 may increase the risk of potentially fatal toxicities such as severe diarrhea, neutropenia, sepsis, and thromboembolism. In cancer patients receiving irinotecan, coadministration of ketoconazole, a potent CYP450 3A4 and UGT1A1 inhibitor, resulted in a 100% increase in the relative exposure to SN-38 and an 87% reduction in the exposure to APC. In HIV patients with Kaposi's sarcoma, coadministration of irinotecan with lopinavir-ritonavir decreased the clearance of irinotecan by 47%, increased the AUC of SN-38 by 204%, and decreased the AUC of APC by 81%.

MANAGEMENT: Caution is advised when irinotecan is prescribed with CYP450 3A4 or UGT1A1 inhibitors. Patients should be monitored for toxicities such as diarrhea, myelosuppression, thromboembolism, and interstitial lung disease, and the irinotecan dosage adjusted accordingly or treatment discontinued as necessary.

References (7)
  1. (2001) "Product Information. Camptosar (irinotecan)." Pharmacia and Upjohn
  2. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  3. Canadian Pharmacists Association (2006) e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink
  4. Corona G, Vaccher E, Sandron S, et al. (2008) "Lopinavir-ritonavir dramatically affects the pharmacokinetics of irinotecan in HIV patients with Kaposi's sarcoma." Clin Pharmacol Ther, 83, p. 601-6
  5. Cerner Multum, Inc. "Australian Product Information."
  6. Phansalker S, Desai AA, Bell D, et al. (2012) "High-priority drug-drug interactions for use in electronic health records." J Am Med Inform Assoc, 19, p. 735-43
  7. (2015) "Product Information. Onivyde (irinotecan liposomal)." Merrimack Pharmaceuticals

Drug and food interactions

Major

PAZOPanib food

Applies to: pazopanib

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of pazopanib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. Although not studied, the interaction may increase the risk of QT interval prolongation and torsade de pointes arrhythmia as well as severe and fatal hepatotoxicity associated with the use of pazopanib.

ADJUST DOSING INTERVAL: Food increases the oral bioavailability of pazopanib. The mechanism of interaction is unknown. Administration of pazopanib with a high-fat or low-fat meal results in an approximately 2-fold increase in peak plasma concentration (Cmax) and systemic exposure (AUC).

MANAGEMENT: Patients treated with pazopanib should avoid consumption of grapefruit, grapefruit juice, and any supplement containing grapefruit extract. Pazopanib should be administered at least one hour before or two hours after a meal.

References (1)
  1. (2009) "Product Information. Votrient (pazopanib)." GlaxoSmithKline

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.

Further information

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