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Drug Interactions between irinotecan and ritonavir

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

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Interactions between your drugs

Major

ritonavir irinotecan

Applies to: ritonavir and irinotecan

GENERALLY AVOID: Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of irinotecan and its active metabolite, SN-38. CYP450 3A4 is the isoenzyme 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, coadministration of ketoconazole, a potent CYP450 3A4 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: Concomitant use of irinotecan with potent CYP450 3A4 inhibitors should generally be avoided. Potent CYP450 3A4 inhibitors should be discontinued for at least one week before initiation of treatment with irinotecan.

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

Moderate

ritonavir food

Applies to: ritonavir

ADJUST DOSING INTERVAL: Administration with food may modestly affect the bioavailability of ritonavir from the various available formulations. When the oral solution was given under nonfasting conditions, peak ritonavir concentrations decreased 23% and the extent of absorption decreased 7% relative to fasting conditions. Dilution of the oral solution (within one hour of dosing) with 240 mL of chocolate milk or a nutritional supplement (Advera or Ensure) did not significantly affect the extent and rate of ritonavir absorption. When a single 100 mg dose of the tablet was administered with a high-fat meal (907 kcal; 52% fat, 15% protein, 33% carbohydrates), approximately 20% decreases in mean peak concentration (Cmax) and systemic exposure (AUC) were observed relative to administration after fasting. Similar decreases in Cmax and AUC were reported when the tablet was administered with a moderate-fat meal. In contrast, the extent of absorption of ritonavir from the soft gelatin capsule formulation was 13% higher when administered with a meal (615 KCal; 14.5% fat, 9% protein, and 76% carbohydrate) relative to fasting.

MANAGEMENT: Ritonavir should be taken with meals to enhance gastrointestinal tolerability.

References (1)
  1. (2001) "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical

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.

See also

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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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