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Drug Interactions between Epitol and lapatinib

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

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Interactions between your drugs

Major

carBAMazepine lapatinib

Applies to: Epitol (carbamazepine) and lapatinib

GENERALLY AVOID: Coadministration with potent inducers of CYP450 3A4 may significantly decrease the plasma concentrations of lapatinib, which is primarily metabolized by the isoenzyme. In 24 healthy subjects, administration of a single 250 mg oral dose of lapatinib following treatment with the potent CYP450 3A4 inducer carbamazepine (100 mg twice daily for 3 days, then 200 mg twice daily for 17 days) decreased mean lapatinib peak plasma concentration (Cmax) and systemic exposure (AUC) by 59% and 72%, respectively, compared to administration of lapatinib alone. Reduced efficacy of lapatinib may occur.

MANAGEMENT: Concomitant use of lapatinib with potent CYP450 3A4 inducers should generally be avoided. If coadministration is required, a gradual dosage increase of lapatinib should be considered. The prescribing information recommends titrating the lapatinib dosage gradually from 1250 mg/day up to 4500 mg/day or from 1500 mg/day up to 5500 mg/day depending on the indication and patient tolerability. Based on pharmacokinetic studies, this dosage recommendation is predicted to adjust the lapatinib systemic exposure (AUC) to the range observed without inducers. However, clinical data are lacking. The dosage of lapatinib should be reduced over approximately 2 weeks to the indicated dosage following discontinuation of the potent CYP450 3A4 inducer.

References

  1. (2023) "Product Information. Tykerb (lapatinib)." Novartis Pharmaceuticals
  2. (2022) "Product Information. Tykerb (lapatinib)." Novartis Pharmaceuticals Canada Inc
  3. (2022) "Product Information. Tyverb (lapatinib)." Novartis Pharmaceuticals UK Ltd
  4. (2022) "Product Information. Tykerb (laPAtinib)." Novartis Pharmaceuticals Australia Pty Ltd
  5. Smith DA, Koch KM, Arya N, Bowen CJ, Herendeen JM, Beelan A (2009) "Effects of ketoconazole and carbamazepine on lapatinib pharmacokinetics in healthy subjects." Br J Clin Pharmacol, 67, p. 421-6
View all 5 references

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Drug and food interactions

Moderate

carBAMazepine food

Applies to: Epitol (carbamazepine)

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of carbamazepine. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

In a small, randomized, crossover study, the administration of carbamazepine with grapefruit juice (compared to water) increased plasma drug concentrations by approximately 40%. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits.

MANAGEMENT: Patients receiving carbamazepine should be advised to avoid or limit consumption of alcohol. Given the drug's narrow therapeutic index, patients receiving carbamazepine therapy should preferably avoid the regular consumption of grapefruits and grapefruit juice to prevent any undue fluctuations in plasma drug levels. Patients should be advised to report signs of carbamazepine toxicity (nausea, visual disturbances, dizziness, or ataxia) to their physicians.

References

  1. (2002) "Product Information. Tegretol (carbamazepine)." Novartis Pharmaceuticals
  2. Garg SK, Kumar N, Bhargava VK, Prabhakar SK (1998) "Effect of grapefruit juice on carbamazepine bioavailability in patients with epilepsy." Clin Pharmacol Ther, 64, p. 286-8
  3. Bailey DG, Dresser GR, Kreeft JH, Munoz C, Freeman DJ, Bend JR (2000) "Grapefruit-felodipine interaction: Effect of unprocessed fruit and probable active ingredients." Clin Pharmacol Ther, 68, p. 468-77

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