Pharmacokinetic interactions between efavirenz and rifampicin in the treatment of HIV and tuberculosis: one size does not fit all.
The concomitant treatment of HIV-tuberculosis co-infection is complicated by pharmacological interactions between drugs, resulting in unpredictable drug levels. We monitored efavirenz levels in all tuberculosis-HIV-treated patients over 2 years. Using 800 mg/day of efavirenz, high levels and toxicity were detected in seven out of nine patients, necessitating reduction or discontinuation. Polymorphisms in cytochrome P450 2B6 may account for this. Therapeutic drug monitoring, dose reduction or a lower starting dose may be appropriate in some patients to abrogate toxicity.
Brennan-Benson
Paul
P
Clinical Infection Unit, Department of Genitourinary Medicine, St George's Hospital, London, UK.
Lyus
Richard
R
Harrison
Tom
T
Pakianathan
Mark
M
Macallan
Derek
D
D017088:AIDS-Related Opportunistic Infections / Q000150:complications / Q000188:drug therapy*; D000328:Adult; D000368:Aged; D000480:Alkynes; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D000904:Antibiotics, Antitubercular / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D048588:Benzoxazines; D003521:Cyclopropanes; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010078:Oxazines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D012293:Rifampin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D014376:Tuberculosis / Q000150:complications / Q000188:drug therapy*
D000480:Alkynes; D019380:Anti-HIV Agents; D000904:Antibiotics, Antitubercular; D048588:Benzoxazines; D003521:Cyclopropanes; D010078:Oxazines; C098320:efavirenz; D012293:Rifampin