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 (Cmax), 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, Cmax, 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%.