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Drug Interactions between bedaquiline and Epitol

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

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Interactions between your drugs

Major

carBAMazepine bedaquiline

Applies to: Epitol (carbamazepine) and 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."
  2. (2013) "Product Information. Sirturo (bedaquiline)." Janssen Pharmaceuticals

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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

bedaquiline food

Applies to: 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. (2013) "Product Information. Sirturo (bedaquiline)." Janssen 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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