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Drug Interactions between Lynparza and Telzir

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

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Interactions between your drugs

Major

fosamprenavir olaparib

Applies to: Telzir (fosamprenavir) and Lynparza (olaparib)

GENERALLY AVOID: Coadministration with moderate inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of olaparib, which is primarily metabolized by the isoenzyme. Simulations using physiologically-based pharmacokinetic (PBPK) models suggest that a moderate inhibitor (fluconazole) may increase olaparib peak plasma concentration (Cmax) and systemic exposure (AUC) by 1.1- and 2-fold, respectively. Increased exposure to olaparib may increase the risk of adverse effects such as hematologic toxicity, nausea, vomiting, diarrhea, anorexia, dyspepsia, and abdominal pain or discomfort.

MANAGEMENT Concomitant use of olaparib with moderate CYP450 3A4 inhibitors should be avoided whenever possible. If coadministration is required, dose reductions are recommended as follows: the olaparib tablet dosage should be reduced to 150 mg twice a day; the olaparib capsule dosage should be reduced to 200 mg twice a day. Specific dose recommendations for each formulation should be followed as the tablet and capsule formulations are not interchangeable due to differences in bioavailability. Once the CYP450 3A4 inhibitor has been discontinued for 3 to 5 elimination half-lives, the usual olaparib dose should be resumed.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. Cerner Multum, Inc. "Australian Product Information."
  3. (2014) "Product Information. Lynparza (olaparib)." Astra-Zeneca Pharmaceuticals

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Drug and food interactions

Major

olaparib food

Applies to: Lynparza (olaparib)

GENERALLY AVOID: Grapefruit juice may significantly increase the plasma concentrations of olaparib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. In a drug interaction study with 57 patients, olaparib systemic exposure (AUC) was increased approximately 2.7-fold by the potent CYP450 3A4 inhibitor itraconazole. Simulations using physiologically-based pharmacokinetic (PBPK) models suggest that a moderate inhibitor (fluconazole) may increase the AUC of olaparib by 2-fold. The interaction has not been studied with grapefruit juice. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Increased exposure to olaparib may increase the risk of adverse effects such as hematologic toxicity, nausea, vomiting, diarrhea, anorexia, dyspepsia, and abdominal pain or discomfort.

MANAGEMENT: Patients treated with olaparib should avoid consumption of grapefruit, grapefruit juice, starfruit (carambola), and Seville oranges.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. Cerner Multum, Inc. "Australian Product Information."
  3. (2014) "Product Information. Lynparza (olaparib)." Astra-Zeneca Pharmaceuticals

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Moderate

fosamprenavir food

Applies to: Telzir (fosamprenavir)

ADJUST DOSING INTERVAL: Food may reduce the systemic bioavailability of amprenavir from fosamprenavir oral suspension. The mechanism of interaction has not been described. According to the product labeling, administration of fosamprenavir oral suspension (1400 mg single dose) with a high-fat meal (967 kcal, 67 g fat, 33 g protein, 58 g carbohydrate) reduced amprenavir peak plasma concentration (Cmax) by 46% and systemic exposure (AUC) by 28% compared to administration in a fasted state. The time to reach peak plasma level (Tmax) was delayed by 0.72 hours. In contrast, the same high-fat meal did not affect the pharmacokinetics of amprenavir from fosamprenavir tablets.

MANAGEMENT: Fosamprenavir suspension should be administered on an empty stomach in adults, but with food in pediatric patients to aid palatability and compliance. If emesis occurs within 30 minutes after dosing the suspension, the dose should be repeated. Fosamprenavir tablets may be taken with or without food.

References

  1. (2003) "Product Information. Lexiva (fosamprenavir)." GlaxoSmithKline

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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.

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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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