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Drug Interactions between lapatinib and thiotepa

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

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Interactions between your drugs

Moderate

thiotepa lapatinib

Applies to: thiotepa and lapatinib

MONITOR: Coadministration with CYP450 3A4 and/or 2B6 inhibitors may increase plasma concentrations of thiotepa and decrease concentrations of its active metabolite triethylenephosphoramide (TEPA). Thiotepa is a prodrug that is primarily converted to TEPA by these isoenzymes. A pharmacokinetic study evaluating six breast cancer patients receiving high-dose chemotherapy (cyclophosphamide 1,500 mg/m2/day, thiotepa 120 mg/m2/day, and carboplatin AUC 5 mg min/mL/day) with the moderate CYP3A4 inhibitor aprepitant (125 mg one day before chemotherapy, then 80 mg daily during and for three days after) showed a 15% increase in total thiotepa exposure, a 33% decrease in TEPA formation, and 20% reduction in TEPA exposure.

MANAGEMENT: Caution and closer monitoring for decreased efficacy and adverse effects are advised when thiotepa is used concurrently with CYP450 3A4 and/or 2B6 inhibitors. Patients should be more closely monitored for thiotepa-related toxicities such as myelosuppression, cutaneous toxicity, and neurotoxicity.

References (5)
  1. de Jonge ME, Huitema AD, Holtkamp MJ, van Dam SM, Beijnen JH, Rodenhuis S (2005) "Aprepitant inhibits cyclophosphamide bioactivation and thiotepa metabolism" Cancer Chemother Pharmacol, 56, p. 370-8
  2. (2023) "Product Information. Thiotepa (thiotepa)." Meitheal Pharmaceuticals Inc.
  3. (2023) "Product Information. Tepadina (thiotepa)." Link Medical Products Pty Ltd T/A Link Pharmaceuticals, 3
  4. (2022) "Product Information. Thiotepa (thiotepa)." MSN Laboratories Europe Ltd
  5. (2021) "Product Information. Tepadina (thiotepa)." Adienne SA

Drug and food interactions

Moderate

lapatinib food

Applies to: 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

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