Long-term efficacy and safety of efavirenz dose reduction to 200 mg once daily in a Caucasian patient with HIV.
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).
Cabrera Figueroa
Salvador
S
Pharmacy Service, University Hospital of Salamanca, Salamanca, Spain. scabrera@uach.cl
Iglesias Gómez
Alicia
A
Sánchez Martín
Almudena
A
de la Paz Valverde Merino
María
M
Domínguez-Gil Hurlé
Alfonso
A
Cordero Sánchez
Miguel
M
D000480:Alkynes; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D048588:Benzoxazines / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D003521:Cyclopropanes; D065702:Cytochrome P-450 CYP2B6; D004305:Dose-Response Relationship, Drug; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics; D011110:Polymorphism, Genetic; D013997:Time Factors; D044465:White People
D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D001189:Aryl Hydrocarbon Hydroxylases; C585599:CYP2B6 protein, human; D065702:Cytochrome P-450 CYP2B6; D010089:Oxidoreductases, N-Demethylating; C098320:efavirenz