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Drug Interactions between bedaquiline and indinavir

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

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Interactions between your drugs

Moderate

indinavir bedaquiline

Applies to: indinavir and bedaquiline

GENERALLY AVOID: Coadministration with potent inhibitors of CYP450 3A4 may increase the plasma concentrations of bedaquiline, which is primarily metabolized by CYP450 3A4 to its less active N-monodesmethyl metabolite, M2. In healthy volunteers, administration of bedaquiline (400 mg once daily for 14 days) in combination with ketoconazole (400 mg once daily for 4 days) increased bedaquiline peak plasma concentration (Cmax), systemic exposure (AUC) and trough plasma concentration (Cmin) by 9%, 22% and 33%, respectively, compared to administration alone. The potential for increased risk of adverse reactions should be considered, including prolongation of the QT interval and liver enzyme and bilirubin elevations.

MANAGEMENT: The concomitant use of potent CYP450 3A4 inhibitors such as clarithromycin, cobicistat, conivaptan, delavirdine, nefazodone, telithromycin, and most protease inhibitors and azole antifungal agents given systemically for more than 14 consecutive days should generally be avoided during treatment with bedaquiline unless the benefit is anticipated to outweigh the risk. Appropriate clinical monitoring for bedaquiline-related adverse reactions is recommended if coadministration is required. ECG, serum electrolytes (potassium, magnesium, calcium), and liver function tests (ALT, AST, alkaline phosphatase, bilirubin) should be monitored before starting bedaquiline therapy and periodically during treatment in accordance with the product labeling. Hypokalemia, hypomagnesemia, and hypocalcemia must be corrected prior to bedaquiline administration. Bedaquiline should be interrupted in patients who develop clinically significant ventricular arrhythmia or a QTcF interval greater than 500 msec confirmed by repeat ECG. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope. Patients should also seek medical attention if they experience potential signs and symptoms of hepatotoxicity such as fever, rash, itching, anorexia, nausea, vomiting, fatigue, malaise, right upper quadrant pain, dark urine, pale stools, and jaundice.

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

Drug and food interactions

Moderate

indinavir food

Applies to: indinavir

ADJUST DOSING INTERVAL: According to the manufacturer, coadministration with a meal high in calories, fat, and protein reduces the absorption of indinavir. In ten patients given indinavir in this manner, the peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of indinavir decreased by an average of 84% and 77%, respectively. In contrast, grapefruit juice may have only minor effects on the oral bioavailability of indinavir. The manufacturer's package labeling states that administration of a single 400 mg dose of indinavir with 8 oz. of grapefruit juice decreased indinavir AUC by an average of 26%. Likewise, a study consisting of 14 HIV-infected subjects found no uniform nor significant changes in steady-state indinavir AUC during administration with double-strength grapefruit juice compared to water. There was, however, a delay in absorption (Tmax) due to grapefruit juice that is unlikely to be of clinical significance.

MANAGEMENT: To ensure maximal oral absorption, indinavir should be administered without food but with water 1 hour before or 2 hours after a meal. Alternatively, indinavir may be administered with other liquids such as skim milk, juice, coffee, or tea, or with a light meal (e.g., dry toast with jelly, juice, and coffee with skim milk and sugar; corn flakes, skim milk and sugar).

References (3)
  1. (2001) "Product Information. Crixivan (indinavir)." Merck & Co., Inc
  2. Yeh KC, Deutsch PJ, Haddix H, Hesney M, Hoagland V, Ju WD, Justice SJ, Osborne B, Sterrett AT, Stone JA, Woolf E, Waldman S (1998) "Single-dose pharmacokinetics of indinavir and the effect of food." Antimicrob Agents Chemother, 42, p. 332-8
  3. Shelton MJ, Wynn HE, Newitt RG, DiFrancesco R (2001) "Effects of grapefruit juice on pharmacokinetic exposure to indinavir in HIV-positive subjects." J Clin Pharmacol, 41, p. 435-42
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)
  1. (2013) "Product Information. Sirturo (bedaquiline)." Janssen Pharmaceuticals

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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