Long-Term Efficacy and Safety of Efavirenz Dose Reduction to 200 mg Once Daily in a Caucasian Patient with HIV

• Published in: Clinical drug investigation 2010-01, Vol.30 (6), p.405-411
• Main Authors: Figueroa, Salvador Cabrera, Gómez, Alicia Iglesias, Martín, Almudena Sánchez, de la Paz Valverde Merino, María, Hurlé, Alfonso Domínguez-Gil, Sánchez, Miguel Cordero
• Format: Article
• Language: English
• Subjects: Anti-HIV Agents - administration & dosage; Anti-HIV Agents - adverse effects; Anti-HIV Agents - pharmacokinetics; Aryl Hydrocarbon Hydroxylases - genetics; Benzoxazines - administration & dosage; Benzoxazines - adverse effects; Benzoxazines - pharmacokinetics; Case Report; Cytochrome P-450 CYP2B6; Dose-Response Relationship, Drug; European Continental Ancestry Group; Follow-Up Studies; HIV Infections - drug therapy; HIV Infections - virology; Humans; Internal Medicine; Male; Medicine; Medicine & Public Health; Middle Aged; Oxidoreductases, N-Demethylating - genetics; Pharmacology/Toxicology; Pharmacotherapy; Polymorphism, Genetic; Time Factors
• ISSN: 1173-2563; 1179-1918
• DOI: 10.1007/BF03256910

A 48-year-old Caucasian male patient presented with severe adverse drug events (ADEs) while being treated with a standard dose (600 mg/day) of efavirenz. The patient’s clinical course was favourable; however, he also described intense nightmares, cramps in his legs and anxiety disturbances that made him highly irritable. Measurement of the patient’s efavirenz plasma concentrations revealed a mean minimum steady-state concentration during a dosage interval (C min,ss ) of 12.7 mg/L, which was much higher than that recommended for this drug (therapeutic range 1–4 mg/L). Consequently, the dose of efavirenz was reduced to 400 mg/day, which resulted in a decrease in the frequency of ADEs. Subsequent genotype testing showed that the patient was homozygous for both the CYP2B6- G516T (T/T) and CYP2B6- A785G (G/G) alleles; these polymorphisms are associated with reduced enzymatic activity and elevated efavirenz plasma concentrations. Because of this and the fact that the patient’s mean efavirenz C min,ss was still high (4.6 mg/L), a second dosage reduction was undertaken, to 200 mg/day. This also resulted in a reduction in ADEs. At present, the patient’s CD4 + levels remain stable, his viral load continues to be undetectable and the mean efavirenz C min,ss is within the therapeutic range (2.7 mg/L).