Source: Health Products Regulatory Authority (ZA) Revision Year: 2023 Publisher: Viatris Healthcare (Pty) Ltd, 4 Brewery Street, Isando, Johannesburg, 1600, Gauteng, South Africa
A.20.2.8 Antiviral medicines
Pharmacotherapeutic group: Antivirals for systemic use, non-nucleoside reverse transcriptase inhibitors
ATC code: J05AG03
Efavirenz is a selective non-nucleoside reverse transcriptase inhibitor (NNRTI) of human immunodeficiency virus type 1 HIV-1. Efavirenz is a non-competitive inhibitor of HIV-1 reverse transcriptase (RT) with respect to template, primer or nucleoside triphosphates, with a small component of competitive inhibition. HIV-2 RT and human cellular DNA polymerases alpha, beta, gamma and delta are not inhibited by concentrations of efavirenz.
Peak efavirenz plasma concentrations of 1,6-9,1 µM were attained by 5 hours following single oral doses of 100 mg to 1600 mg administered to uninfected volunteers. Dose-related increases in Cmax and AUC were seen for doses up to 1600 mg; the increases were less than proportional suggesting diminished absorption at higher doses.
In HIV-infected patients at steady state, mean Cmax mean Cmin and mean AUC were linear with 200 mg, 400 mg and 600 mg daily doses and steady state was reached in 6 to 10 days, in 35 patients receiving efavirenz 600 mg once daily, steady-state Cmax was 12,9 μM, steady state Cmin was 5,6 μM, and AUC was 184 μM•h.
Efavirenz is highly bound (approximately 99,5–99,75%) to human plasma proteins, predominantly albumin. In HIV-1 infected patients who received efavirenz 200 to 600 mg once daily for at least one month, cerebrospinal fluid concentrations ranged from 0,26 to 1,19% (mean 0,69%) of the corresponding plasma concentration. This proportion is approximately three-fold higher than the non-protein-bound (free) fraction of efavirenz in plasma.
Efavirenz is principally metabolised by the cytochrome P450 system to hydroxylated metabolites with subsequent glucuronidation of these hydroxylated metabolites. These metabolites are inactive against HIV-1. CYP3A4 and CYP2B6 are the major isozymes responsible for efavirenz metabolism. Efavirenz has been shown to induce P450 enzymes, resulting in the induction of its own metabolism.
Efavirenz has a long terminal half-life of 52 to 76 hours after single doses, and 40-55 hours after multiple doses. Approximately 14-34% of a radio-labelled dose of efavirenz was recovered in the urine and 16-61% was recovered in faeces, mainly in the form of metabolites.
The pharmacokinetics of efavirenz has not been adequately studied in patients with hepatic impairment (see section 4.4).
The pharmacokinetics of efavirenz has not been studied in patients with renal insufficiency. However, less than 1% of efavirenz is excreted unchanged in the urine, so the impact of renal impairment on efavirenz elimination should be minimal.
Pharmacokinetics of efavirenz has not been studied in subjects aged 65 and over to establish whether they respond differently.
The pharmacokinetics of efavirenz in paediatric patients was similar to adults.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
