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Drug Interactions between fosphenytoin and Sirturo

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

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Interactions between your drugs

Major

fosphenytoin bedaquiline

Applies to: fosphenytoin and Sirturo (bedaquiline)

GENERALLY AVOID: Coadministration with potent or moderate inducers of CYP450 3A4 may decrease the plasma concentrations of bedaquiline, which is primarily metabolized by CYP450 3A4 to the major N-monodesmethyl metabolite, M2. Because M2 is 4- to 6-fold less active than the parent drug in terms of antimycobacterial potency, the interaction may diminish the therapeutic effect of bedaquiline. In healthy volunteers, administration of a single 300 mg dose of bedaquiline in combination with rifampin 600 mg once daily for 21 days reduced bedaquiline systemic exposure (AUC) by 52% compared to administration alone. Another study involving healthy volunteers revealed a 20% decrease in the AUC and no change in the Cmax of bedaquiline (400 mg once) when administered with efavirenz (600 mg once daily for 27 days).

MANAGEMENT: The concomitant use of bedaquiline with potent or moderate CYP450 3A4 inducers should generally be avoided.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  2. "Product Information. Sirturo (bedaquiline)." Janssen Pharmaceuticals (2013):

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Drug and food interactions

Moderate

bedaquiline food

Applies to: Sirturo (bedaquiline)

ADJUST DOSING INTERVAL: Food enhances the oral bioavailability of bedaquiline. When administered with a standard meal containing approximately 22 grams of fat (558 total Kcal), the relative bioavailability of bedaquiline increased by approximately 2-fold compared to administration under fasted conditions.

GENERALLY AVOID: Coadministration with alcohol may increase the risk of hepatotoxicity associated with the use of bedaquiline. In clinical trials, hepatic adverse drug reactions developed in more bedaquiline-treated patients than in those who received other drugs used to treat tuberculosis. In patients receiving bedaquiline or placebo in combination with other drugs used to treat multidrug-resistant tuberculosis, reversible aminotransferase elevations of at least 3 times the upper limit of normal developed more frequently in the bedaquiline treatment group [10.8%] than in the placebo group [5.7%].

MANAGEMENT: To ensure maximal oral absorption, bedaquiline should be taken with food. Patients should avoid alcohol use during treatment.

References

  1. "Product Information. Sirturo (bedaquiline)." Janssen Pharmaceuticals (2013):

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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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