Long-term efficacy and safety of efavirenz dose reduction to 200 mg once daily in a Caucasian patient with HIV

Clin Drug Investig. 2010;30(6):405-11. doi: 10.1007/BF03256910.

Abstract

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).

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkynes
  • 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
  • Cyclopropanes
  • Cytochrome P-450 CYP2B6
  • Dose-Response Relationship, Drug
  • European Continental Ancestry Group
  • Follow-Up Studies
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • Humans
  • Male
  • Middle Aged
  • Oxidoreductases, N-Demethylating / genetics
  • Polymorphism, Genetic
  • Time Factors

Substances

  • Alkynes
  • Anti-HIV Agents
  • Benzoxazines
  • Cyclopropanes
  • Aryl Hydrocarbon Hydroxylases
  • CYP2B6 protein, human
  • Cytochrome P-450 CYP2B6
  • Oxidoreductases, N-Demethylating
  • efavirenz