efavirenz
Regulatory sources consulted
Approved indications
- Combination antiviral treatment of HIV-1 in adults, adolescents, and children aged 3 years or older with suitable weight for the formulation.
Contraindications
Absolute
- Hypersensitivity to efavirenz.
- Severe hepatic impairment.
- Concomitant elbasvir/grazoprevir.
- Concomitant St John’s wort.
Clinical warnings
- It may cause severe neuropsychiatric symptoms, suicidal ideation, seizures, and late-onset encephalopathy; assess history and new symptoms. — CIMA/AEMPS, ficha técnica 79191
- Risk of severe rash, hepatotoxicity, and QT prolongation; monitor the liver and avoid risky combinations. — CIMA/AEMPS, ficha técnica 79191
Drug interactions
- HighVoriconazole
Mechanism: Efavirenz reduces voriconazole and voriconazole increases efavirenz.
Recommendation: If combined, use voriconazole 400 mg every 12 hours and efavirenz 300 mg once daily using capsules; monitor efficacy and toxicity.
CIMA/AEMPS, ficha técnica 79191
- HighCYP2B6/CYP3A4 inducers or substrates and QT-prolonging drugs
Mechanism: Efavirenz has multiple induction/inhibition interactions and may add QT risk.
Recommendation: Review each combination and monitor levels, response, or ECG as appropriate.
CIMA/AEMPS, ficha técnica 79191
- HighRifampicin
Mechanism: It reduces efavirenz exposure.
Recommendation: In people weighing at least 50 kg, increase efavirenz to 800 mg once daily while rifampicin is used.
CIMA/AEMPS, ficha técnica 79191
Adverse events
Common (≥1%)
Dizziness, insomnia, somnolence, impaired concentration, abnormal dreams, and rash
Rare but serious
Stevens-Johnson syndrome, liver failure, suicidal behavior, seizures, and encephalopathy
Pregnancy and lactation
It must not be used during pregnancy unless the clinical situation requires treatment. Perform a pregnancy test before starting. Use barrier contraception in addition to hormonal contraception during treatment and for 12 weeks afterward. Do not breastfeed during HIV treatment.
Recent literature (PubMed)
The provision of long-acting reversible contraceptive (LARC) methods is one of the best tools available to avoid high rates of unplanned pregnancy (UP), a public health problem that affects millions of women worldwide. In this review we provide an update regarding subdermal contraceptive implants including etonogestrel (ENG) and levonorgestrel (LNG) implants. Implants have been shown to be one of the most effective forms of contraceptive, with failure in only 4/1000 women for up to five years. Thus, their provision is an excellent strategy for reducing UPs. After a single intervention, implants provide long-term contraception with minimal side effects. Implants have few contraindications, but care must be taken to check for drug interactions with topiramate, rifampin and efavirenz. Although the ENG implant is approved for up to three years of use, research is ongoing into the possibility of extending its use beyond that period.
Dengue, caused by dengue virus (DENV), is now endemic in nearly 100 countries and infection incidence is reported in another 30 countries. Yearly an estimated 400 million cases and 2200 deaths are reported. Effective vaccines against DENV are limited and there has been significant focus on the development of effective antiviral against the disease. The World Health Organization has initiated research programs to prioritize the development and optimization of antiviral agents against several viruses including Flaviviridae. A significant effort has been taken by the researchers to develop effective antivirals against DENV. Several potential small-molecule inhibitors like efavirenz, tipranavir and dasabuvir have been tested against envelope and non-structural proteins of DENV, and are in clinical trials around the world. We recently developed one small molecule, namely 7D, targeting the host PF4-CXCR3 axis. 7D inhibited all 4 serotypes of DENV in vitro and specifically DENV2 infection in two different mice models. Although the development of dengue vaccines remains a high priority, antibody cross reactivity among the serotypes and resulting antibody-dependent enhancement (ADE) of infection are major concerns that have limited the development of effective vaccine against DENV. Therefore, there has been a significant emphasis on the development of antiviral drugs against dengue. This review article describes the rescue effects of some of the small molecule inhibitors to viral/host factors associated with DENV pathogenesis.
Although single-tablet, oral bictegravir, emtricitabine, and tenofovir alafenamide or dolutegravir and lamivudine are preferred regimens in several major guidelines and are widely used in many countries, they have not been compared in a fully powered trial. This study aimed to prospectively compare the 48-week results of dolutegravir and lamivudine versus bictegravir, emtricitabine, and tenofovir alafenamide as maintenance therapies for people with HIV. PASO-DOBLE is a randomised, multicentre, open-label, non-inferiority trial done over 48 weeks at 30 sites in Spain. Adults (aged ≥18 years) with HIV-1, without previous viral failure, who had reached virological suppression on oral regimens containing at least one pill a day, cobicistat, efavirenz, or tenofovir disoproxil fumarate and no previous use of dolutegravir or bictegravir, and plasma HIV-1 RNA <50 copies per mL for at least 24 weeks were eligible. Participants were randomly assigned (1:1) to switch regimens to dolutegravir 50 mg and lamivudine 300 mg or bictegravir 50 mg, emtricitabine 200 mg, and tenofovir alafenamide 25 mg once daily, using random block permutation, stratified by tenofovir alafenamide presence at baseline and sex assigned at birth. The primary endpoint was the proportion of participants with HIV RNA ≥50 copies per mL at week 48 in the intention-to-treat exposed population (ie, all participants who received at least one dose of study medication). The primary and safety analysis was done in the intention-to-treat exposed population. The non-inferiority margin was 4%. This trial is registered with ClinicalTrials.govNCT04884139 and is incomplete. Between July 14, 2021, and March 24, 2023, 553 participants initiated dolutegravir and lamivudine (n=277) or bictegravir, emtricitabine, and tenofovir alafenamide (n=276). The difference in the proportion of participants with HIV RNA ≥50 copies per mL between the dolutegravir and lamivudine group (six [2%] of 277) and bictegravir, emtricitabine, and t
Pharmacogenetic testing can identify patients who may benefit from personalized drug treatment. However, clinical uptake of pharmacogenetic testing has been limited. Clinical practice guidelines recommend biomarker tests that the guideline authors deem to have demonstrated clinical utility, meaning that testing improves treatment outcomes. The objective of this narrative review is to describe the current status of pharmacogenetic testing recommendations within clinical practice guidelines in the US. Guidelines were reviewed for pharmacogenetic testing recommendations for 21 gene-drug pairs that have well-established drug response associations and all of which are categorized as clinically actionable by the Clinical Pharmacogenetics Implementation Consortium. The degree of consistency within and between organizations in pharmacogenetic testing recommendations was assessed. Relatively few clinical practice guidelines that provide a pharmacogenetic testing recommendation were identified. Testing recommendations for HLA-B*57:01 before initiation of abacavir and G6PD before initiation of rasburicase, both of which are included in drug labeling, were mostly consistent across guidelines. Gene-drug pairs with at least one clinical practice guideline recommending testing or stating that testing could be considered included CYP2C19-clopidogrel, CYP2D6-codeine, CYP2D6-tramadol, CYP2B6-efavirenz, TPMT-thiopurines, and NUDT15-thiopurines. Testing recommendations for the same gene-drug pair were often inconsistent between organizations and sometimes inconsistent between different guidelines from the same organization. A standardized approach to evaluating the evidence of clinical utility for pharmacogenetic testing may increase the inclusion and consistency of pharmacogenetic testing recommendations in clinical practice guidelines, which could benefit patients and society by increasing clinical use of pharmacogenetic testing. Efavirenz is excreted into breastmilk and small amount