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Drug Interactions between telaprevir and Tykerb

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

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Interactions between your drugs

Major

lapatinib telaprevir

Applies to: Tykerb (lapatinib) and telaprevir

GENERALLY AVOID: Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of lapatinib, which is primarily metabolized by the isoenzyme. In healthy subjects, administration of lapatinib in combination with the CYP450 3A4 inhibitor ketoconazole (200 mg twice daily for 7 days) resulted in lapatinib systemic exposure (AUC) and half-life that were approximately 3.6- and 1.7-fold, respectively, of the control values.

MANAGEMENT: Concomitant use of lapatinib with potent CYP450 3A4 inhibitors should generally be avoided. Some authorities recommend avoiding concomitant use of lapatinib during and for 2 weeks after treatment with itraconazole. If coadministration is required, the manufacturer recommends reducing the lapatinib dosage to 500 mg once a day. Based on pharmacokinetic studies, this dosage is predicted to adjust the lapatinib 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 lapatinib dosage is adjusted upward to the indicated dosage (i.e., 1250 mg once a day).

References

  1. (2002) "Product Information. Sporanox (itraconazole)." Janssen Pharmaceuticals
  2. (2007) "Product Information. Tykerb (lapatinib)." Novartis Pharmaceuticals
  3. Cerner Multum, Inc. "Australian Product Information."

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Drug and food interactions

Moderate

lapatinib food

Applies to: Tykerb (lapatinib)

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of lapatinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits.

ADJUST DOSING INTERVAL: Food can significantly increase the oral bioavailability of lapatinib. According to the manufacturer, lapatinib peak plasma concentration (Cmax) was approximately 2.5- and 3-fold higher and systemic exposure (AUC) 3- and 4-fold higher when administered with a low fat meal (5% fat; 500 calories) or with a high-fat meal (50% fat; 1000 calories), respectively, compared to fasting. Dividing the daily dose also resulted in an approximately 2-fold higher systemic exposure at steady state compared to the same total dose administered once daily.

MANAGEMENT: Patients treated with lapatinib should preferably avoid the consumption of grapefruit or grapefruit juice. The manufacturer recommends that lapatinib be administered at least one hour before or one hour after a meal. The lapatinib dose is administered once daily and should not be divided.

References

  1. (2007) "Product Information. Tykerb (lapatinib)." Novartis Pharmaceuticals

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Moderate

telaprevir food

Applies to: telaprevir

ADJUST DOSING INTERVAL: Food significantly enhances the oral bioavailability of telaprevir. When given with a meal containing 533 kcal and 21 g fat, telaprevir systemic exposure (AUC) increased by 237% compared to administration under fasting conditions. The type of meal also affects the exposure to telaprevir. Relative to fasting, telaprevir AUC increased by approximately 117% with a low-fat meal (249 kcal; 3.6 g fat) and 330% with a high-fat meal (928 kcal; 56 g fat). In Phase 3 clinical trials, telaprevir doses were administered within 30 minutes of completing a meal or snack containing approximately 20 grams of fat.

MANAGEMENT: Telaprevir should be administered with food containing approximately 20 grams of fat. Patients should be advised that the fat content of the meal or snack is critical to the absorption of telaprevir. Food taken with telaprevir should be ingested within 30 minutes prior to each dose. Examples of some foods that could be taken with telaprevir include: bagel with cream cheese; half cup of nuts; 3 tablespoons of peanut butter; 1 cup of ice cream; 2 ounces of American or cheddar cheese; 2 ounces of potato chips; or half cup of trail mix.

References

  1. (2011) "Product Information. Incivek (telaprevir)." Vertex Pharmaceuticals

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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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