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Drug Interactions between fidaxomicin and venetoclax

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

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Interactions between your drugs

Moderate

fidaxomicin venetoclax

Applies to: fidaxomicin and venetoclax

MONITOR: Coadministration with fidaxomicin may increase the plasma concentrations of some orally administered drugs that are substrates of the P-glycoprotein (P-gp) transporter. In vitro, fidaxomicin and its main metabolite are substrates and inhibitors of P-gp, an efflux transporter expressed in the gastrointestinal tract. When digoxin, a P-gp substrate, was coadministered with fidaxomicin (200 mg twice daily) in healthy volunteers, digoxin peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 14% and 12%, respectively. Although the effect of fidaxomicin on digoxin exposure is not considered clinically relevant, a larger effect on P-gp substrates with lower bioavailability that may be more sensitive to intestinal P-gp inhibition, such as dabigatran etexilate, cannot be excluded.

MANAGEMENT: Caution is advised when fidaxomicin is used in combination with P-gp substrates that may be sensitive to intestinal P-gp inhibition.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  2. Cerner Multum, Inc. "Australian Product Information." O 0
  3. "Product Information. Dificid (fidaxomicin)." Optimer Pharmaceuticals (2011):
  4. Cerner Multum, Inc. "Canadian Product Information." O 0 (2015):
View all 4 references

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Drug and food interactions

Major

venetoclax food

Applies to: venetoclax

ADJUST DOSING INTERVAL: Food enhances the oral bioavailability of venetoclax. Relative to fasting conditions, venetoclax systemic exposure (AUC) increased by approximately 3.4-fold when administered with a low-fat meal and by 5.1- to 5.3-fold when administered with a high-fat meal.

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of venetoclax. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. 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 venetoclax exposure may potentiate the risk of tumor lysis syndrome, particularly at initiation of therapy and during the dosage ramp-up phase, as well as other adverse effects such as diarrhea, nausea, vomiting, neutropenia, anemia, and thrombocytopenia.

MANAGEMENT: Venetoclax should be administered with a meal and water at approximately the same time each day. Patients should avoid consumption of grapefruit products, Seville oranges, and starfruit during treatment with venetoclax.

References

  1. "Product Information. Venclexta (venetoclax)." AbbVie US LLC (2016):

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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

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