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Drug Interactions between Lanoxin and olaparib

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

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Interactions between your drugs

Moderate

digoxin olaparib

Applies to: Lanoxin (digoxin) and olaparib

MONITOR: Based on in vitro inhibition data, coadministration with olaparib may increase the plasma concentrations of drugs that are substrates of CYP450 3A4 (e.g., cisapride, ergot alkaloids, fentanyl, lovastatin, oral midazolam, pimozide, quetiapine, simvastatin, triazolam, vinca alkaloids), P-gp (e.g., colchicine, dabigatran, digoxin), breast cancer resistance protein (BCRP) (e.g., rosuvastatin), OATP1B1 (e.g., eluxadoline, glyburide, repaglinide, statins, valsartan), or organic cation transporter 1 or 2 (OCT1, OCT2) (e.g., metformin). The proposed mechanism is decreased clearance due to inhibition of the corresponding metabolizing enzyme and/or efflux/uptake transporter by olaparib.

MANAGEMENT: Caution is advised if olaparib must be used concomitantly with drugs that are substrates of the affected enzymes or transporters, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever olaparib is added to or withdrawn from therapy.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  2. Cerner Multum, Inc. "Australian Product Information." O 0

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Drug and food interactions

Major

olaparib food

Applies to: 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." O 0
  2. Cerner Multum, Inc. "Australian Product Information." O 0
  3. "Product Information. Lynparza (olaparib)." Astra-Zeneca Pharmaceuticals (2014):

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Minor

digoxin food

Applies to: Lanoxin (digoxin)

Administration of digoxin with a high-fiber meal has been shown to decrease its bioavailability by almost 20%. Fiber can sequester up to 45% of the drug when given orally. Patients should be advised to maintain a regular diet without significant fluctuation in fiber intake while digoxin is being titrated.

Grapefruit juice may modestly increase the plasma concentrations of digoxin. The mechanism is increased absorption of digoxin due to mild inhibition of intestinal P-glycoprotein by certain compounds present in grapefruits. In 12 healthy volunteers, administration of grapefruit juice with and 30 minutes before, as well as 3.5, 7.5, and 11.5 hours after a single digoxin dose (0.5 mg) increased the mean area under the plasma concentration-time curve (AUC) of digoxin by just 9% compared to administration with water. Moreover, P-glycoprotein genetic polymorphism does not appear to influence the magnitude of the effects of grapefruit juice on digoxin. Thus, the interaction is unlikely to be of clinical significance.

References

  1. Darcy PF "Nutrient-drug interactions." Adverse Drug React Toxicol Rev 14 (1995): 233-54
  2. Becquemont L, Verstuyft C, Kerb R, et al. "Effect of grapefruit juice on digoxin pharmacokinetics in humans." Clin Pharmacol Ther 70 (2001): 311-6

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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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