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Drug Interactions between Tykerb and voriconazole

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

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Interactions between your drugs

Major

voriconazole lapatinib

Applies to: voriconazole and Tykerb (lapatinib)

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

Drug and food interactions

Moderate

voriconazole food

Applies to: voriconazole

ADJUST DOSING INTERVAL: Food reduces the oral absorption and bioavailability of voriconazole. According to the product labeling, administration of multiple doses of voriconazole with high-fat meals decreased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) by 34% and 24%, respectively, when the drug is administered as a tablet, and by 58% and 37%, respectively, when administered as the oral suspension.

MANAGEMENT: To ensure maximal oral absorption, voriconazole tablets and oral suspension should be taken at least one hour before or after a meal.

References (2)
  1. (2002) "Product Information. VFEND (voriconazole)." Pfizer U.S. Pharmaceuticals
  2. Wohlt PD, Zheng L, Gunderson S, Balzar SA, Johnson BD, Fish JT (2009) "Recommendations for the use of medications with continuous enteral nutrition." Am J Health Syst Pharm, 66, p. 1438-67
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)
  1. (2007) "Product Information. Tykerb (lapatinib)." Novartis 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.

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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