Treatment of Tuberculosis with Rifampin Induces Opioid Withdrawal in Patients Maintained on Buprenorphine

Potential buprenorphine interactions with medications for tuberculosis (TB), HIV, and other common comorbid illnesses among opioid-dependent patients are important to identify. Rifampin, a cytochrome P 450 enzyme-inducing medication used to treat TB, has the potential to decrease buprenorphine levels, leading to clinical withdrawal symptoms and possibly relapse. In this pharmacokinetic study, investigators compared the impact of 15 days of either rifampin (n=12) or rifabutin (n=9), another TB medication, coadministered with buprenorphine-naloxone (BUP/NLX) in BUP/NLX-maintained patients with TB.

• Both rifampin and rifabutin decreased buprenorphine pharmacokinetic measures, including area under the curve (AUC), maximum plasma concentration (C_max), and trough plasma concentration (C₂₄).

• Rifampin, but not rifabutin, was associated with significant decreases in pharmacokinetic parameters of norbuprenorphine (an active buprenorphine metabolite), including AUC, C_max, and C₂₄.

• Clinical opioid withdrawal was observed in 6 of the 12 rifampin-administered subjects as early as 6 days after starting rifampin. Withdrawal was not observed in rifabutin-administered subjects.

• Increased BUP/NLX offered to participants in withdrawal alleviated symptoms with dose increases of 25–100%.

Comments:

This important study describes withdrawal symptoms among BUP/NLX-maintained patients being treated for TB with rifampin. Rifabutin did not cause withdrawal, however, it is expensive, which may preclude widespread use. Clinicians need to be aware of the BUP/NLX-rifampin interaction and pre-empt possible relapse or treatment dropout with patient counseling. Although dose adjustments of BUP/NLX may alleviate withdrawal symptoms in patients treated with rifampin, longer term studies are needed to confirm the efficacy of this approach.

Hillary Kunins, MD, MPH, MS

Reference:

McCance-Katz EF, Moody DE, Prathikanti S, et al. Rifampin, but not rifabutin, may produce opiate withdrawal in buprenorphine-maintained patients. Drug Alcohol Depend. May 18, 2011 (E-pub ahead of print). doi: 10.1016/j.drugalcdep.2011.04.013.