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Drug Interactions between Tykerb and Vumon

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

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Interactions between your drugs

Moderate

teniposide lapatinib

Applies to: Vumon (teniposide) and Tykerb (lapatinib)

MONITOR: Coadministration with lapatinib may increase the plasma concentrations of drugs that are substrates of the CYP450 2C8 isoenzyme, CYP450 3A4 isoenzyme, and/or P-glycoprotein (P-gp) efflux transporter. The mechanism is decreased clearance via these routes due to inhibition by lapatinib. In cancer patients treated with lapatinib and paclitaxel, a CYP450 2C8 and P-gp substrate, 24-hour systemic exposure (AUC) of paclitaxel was increased by 23%. This increase may have been underestimated from the in vivo evaluation due to study design limitations. Lapatinib also increased the 24-hour AUC of midazolam, a CYP450 3A4 probe substrate, by 45% when midazolam was administered orally and 22% when administered intravenously. Likewise, lapatinib increased the AUC of single-dose digoxin, a P-gp probe substrate, by approximately 2.8-fold.

MANAGEMENT: Caution is advised if lapatinib must be used concurrently with medications that are substrates of the CYP450 2C8 isoenzyme, CYP450 3A4 isoenzyme, and/or P-gp efflux transporter, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever lapatinib is added to or withdrawn from therapy.

References

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

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

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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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