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Drug Interactions between ceritinib and temsirolimus

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

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Interactions between your drugs

Major

temsirolimus ceritinib

Applies to: temsirolimus and ceritinib

GENERALLY AVOID: Coadministration of temsirolimus with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of sirolimus, a major active metabolite of temsirolimus and known substrate of CYP450 3A4. According to the product labeling, administration of temsirolimus in combination with the CYP450 3A4 inhibitor ketoconazole resulted in a 2.2-fold and 3.1-fold increase in sirolimus peak plasma concentration (Cmax) and systemic exposure (AUC), respectively, compared to administration of temsirolimus alone. No significant effect on the pharmacokinetics of temsirolimus was reported.

MANAGEMENT: Concomitant use of temsirolimus with potent CYP450 3A4 inhibitors should generally be avoided. Some authorities recommend avoiding concomitant use of intravenous temsirolimus during and for 2 weeks after treatment with itraconazole (US). If coadministration is required, the manufacturer recommends reducing the temsirolimus dosage to 12.5 mg once a week. Based on pharmacokinetic studies, this dosage is predicted to adjust the sirolimus systemic exposure (AUC) to the range observed without inhibitors. However, clinical data are lacking. Following discontinuation of the potent CYP450 3A4 inhibitor, a washout period of approximately one week should be allowed before the temsirolimus dosage is adjusted upward to the normally recommended dosage (i.e., 25 mg once a week) or the dosage used prior to initiation of the CYP450 3A4 inhibitor.

References

  1. (2002) "Product Information. Sporanox (itraconazole)." Janssen Pharmaceuticals
  2. (2007) "Product Information. Torisel (temsirolimus)." Wyeth-Ayerst Laboratories
  3. Cerner Multum, Inc. "Australian Product Information."

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Drug and food interactions

Major

ceritinib food

Applies to: ceritinib

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of ceritinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Because ceritinib is associated with concentration-dependent prolongation of the QT interval, increased levels may potentiate the risk of ventricular arrhythmias such as torsade de pointes and sudden death. Other, more common side effects such as diarrhea, nausea, vomiting, abdominal pain, hyperglycemia, and bradycardia may also increase.

ADJUST DOSING INTERVAL: Food increases the oral bioavailability of ceritinib. The mechanism of interaction is unknown. Compared to the fast state, administration of a single 500 mg dose of ceritinib with a high-fat meal (approximately 1000 calories; 58 grams of fat) increased ceritinib peak plasma concentration (Cmax) and systemic exposure (AUC) by 41% and 73%, respectively, and administration with a low-fat meal (approximately 330 calories; 9 grams of fat) increased ceritinib Cmax and AUC by 43% and 58%, respectively. A dose of 600 mg or higher taken with a meal is expected to produce systemic exposure exceeding that from a 750 mg dose taken in the fasted state, which may lead to increased adverse effects.

MANAGEMENT: Patients treated with ceritinib should avoid consumption of grapefruit, grapefruit juice, and any supplement containing grapefruit extract. Ceritinib should be administered on an empty stomach (i.e., avoid administration within 2 hours of a meal).

References

  1. (2014) "Product Information. Zykadia (ceritinib)." Novartis Pharmaceuticals

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Moderate

temsirolimus food

Applies to: temsirolimus

GENERALLY AVOID: Coadministration of temsirolimus with grapefruit juice may increase the plasma concentrations of sirolimus, a major active metabolite of temsirolimus and known substrate of CYP450 3A4. The proposed mechanism is inhibition of CYP450 3A4-mediated metabolism by certain compounds present in grapefruits.

MANAGEMENT: Patients treated with temsirolimus should preferably avoid the consumption of grapefruit or grapefruit juice.

References

  1. (2007) "Product Information. Torisel (temsirolimus)." Wyeth-Ayerst Laboratories

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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

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

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