Antiretroviral NNRTI, enzyme inducer
Efavirenz is an antiretroviral medicine used to treat HIV infection, in combination with other medicines. In the first weeks it can cause dizziness, nightmares and difficulty concentrating, which tend to improve; taking it at night helps tolerate these effects.
Also known as: Sustiva, Stocrin
The combination of Praziquantel with Efavirenz is not recommended: it significantly reduces Praziquantel concentrations, with a risk of therapeutic failure.
Praziquantel is metabolised by CYP3A4 and efavirenz is a moderate CYP3A4 inducer: the praziquantel label documents the study with 20 volunteers in which efavirenz (400 mg/day for 13 days) reduced the mean praziquantel AUC by 77% (95% CI: 38–91%) and Cmax by 79% (95% CI: 41–92%), and classifies the combination as "avoid, unless the benefit outweighs the risks, due to the risk of a clinically significant decrease in praziquantel plasma concentrations which may lead to reduced therapeutic effect". If treatment cannot be delayed, consider stopping efavirenz 2–4 weeks before praziquantel (if possible) and monitor the anthelmintic efficacy; in practice, prefer an efavirenz alternative or another anthelmintic.
Efavirenz + praziquantel: efavirenz induces CYP3A4 and greatly reduces praziquantel levels (AUC −77%). Avoid; monitor efficacy.
Efavirenz, a moderate CYP3A4 inducer, accelerates the hepatic metabolism of Praziquantel, lowering its exposure.
Monitor the parasitological response and symptoms of the infection.
Treatment failure requires a therapeutic alternative.
Prefer an alternative; if unavoidable, closely monitor the parasitological response.
DailyMed/FDA (NIH/NLM) — approved Praziquantel label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=34ce1cdd-648e-4f1e-8512-bf3d4cc22eb9 ; approved Efavirenz label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=92603fa5-7a2c-4bfb-9a70-aadb4fba952c — with additional reference: Prontuário Terapêutico do INFARMED, INFARMED (11th ed., 2012)
Combining Efavirenz with Clarithromycin reduces Clarithromycin concentrations, compromising the antimicrobial response; there is also a risk of QT prolongation.
Efavirenz induces CYP3A4 and lowers clarithromycin concentrations by about 40%, while raising its active metabolite (14-hydroxyclarithromycin); the clinical significance is variable, but antibiotic efficacy may be compromised and the QT prolongation risk increases. In HIV patients receiving clarithromycin, consider an alternative (e.g. azithromycin, with less interaction) and monitor the clinical response.
Efavirenz + clarithromycin: efavirenz lowers clarithromycin levels (CYP3A4 induction) and raises the active metabolite; the QT may prolong. Monitor response and ECG.
Efavirenz, a CYP3A4 inducer, accelerates Clarithromycin metabolism (↓ Clarithromycin, ↑ of the metabolite), reducing its efficacy.
Watch for signs of uncontrolled infection and, with risk factors, the QT interval.
Worsening infection during treatment requires review of the antibiotic.
Consider an alternative antibiotic (e.g. azithromycin) to avoid the interaction and reduce the risk of QT prolongation.
DailyMed/FDA (NIH/NLM) — approved Efavirenz label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=92603fa5-7a2c-4bfb-9a70-aadb4fba952c ; approved Clarithromycin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d836ae7e-fdbf-4dcb-a90d-ede1dcbc3e67 — with additional reference: Prontuário Terapêutico do INFARMED, INFARMED (11th ed., 2012)
Combining Efavirenz with Carbamazepine reduces the concentrations of both drugs, risking failure in controlling epilepsy and HIV.
The interaction is bidirectional: carbamazepine induces CYP3A4 and lowers efavirenz concentrations, and efavirenz also induces CYP3A4, lowering carbamazepine levels. The result can be simultaneous loss of virological control and of seizure control. Whenever possible, choose another antiepileptic (e.g. levetiracetam, valproate) in patients on efavirenz; if the combination is unavoidable, monitor the viral load and carbamazepine levels, adjusting doses.
Efavirenz + carbamazepine: mutual CYP3A4 induction — both drugs can become subtherapeutic. Monitor levels and clinical response.
Efavirenz induces Carbamazepine metabolism and Carbamazepine induces Efavirenz metabolism, mutually lowering exposure.
Monitor seizure control and HIV viral load.
Worsening seizures or a detectable viral load require reassessment of the antiepileptic/antiretroviral regimen.
With no reliable dose recommendation, prefer an alternative antiepileptic when possible (e.g. valproate, levetiracetam).
DailyMed/FDA (NIH/NLM) — approved Efavirenz label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=92603fa5-7a2c-4bfb-9a70-aadb4fba952c ; approved Carbamazepine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9f3d91cd-a959-4e07-a51b-8a4e9ba9ece2 — with additional reference: Prontuário Terapêutico do INFARMED, INFARMED (11th ed., 2012)
Combining Efavirenz with Warfarin may increase or decrease the anticoagulant effect, with a risk of bleeding or thrombosis.
Efavirenz induces CYP3A4 and CYP2C9 (among other isoenzymes), accelerating warfarin metabolism and reducing its plasma levels. The usual result is a decrease in the INR, with thrombosis risk if the dose is not adjusted; however, the effect varies between patients and there may be phases of INR instability in both directions. The INR should be monitored frequently at efavirenz initiation and discontinuation and the warfarin dose adjusted accordingly, with vigilance for thromboembolism and bleeding signs.
Efavirenz induces CYP2C9/CYP3A4 and can REDUCE the effect of warfarin. Monitor the INR when starting and stopping the antiretroviral and adjust the dose.
As an enzyme inducer, Efavirenz alters Warfarin metabolism; the net effect is variable between patients.
Frequent INR at start and dose changes.
A high INR or signs of bleeding/thrombosis require anticoagulant adjustment.
Monitor the INR and adjust the Warfarin dose during co-administration.
DailyMed/FDA (NIH/NLM) — approved Efavirenz label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=92603fa5-7a2c-4bfb-9a70-aadb4fba952c ; approved Warfarin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=541c9a70-adaf-4ef3-94ba-ad4e70dfa057 — with additional reference: Prontuário Terapêutico do INFARMED, INFARMED (11th ed., 2012)
Alcohol may potentiate efavirenz central nervous system effects and add hepatotoxicity.
Avoid or strongly limit alcohol intake during treatment.
DailyMed/FDA (NIH/NLM) — approved Efavirenz label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=92603fa5-7a2c-4bfb-9a70-aadb4fba952c
High-fat meals increase efavirenz absorption and may potentiate central nervous system adverse effects (dizziness, nightmares, insomnia).
Take efavirenz on an empty stomach, preferably at bedtime.
DailyMed/FDA (NIH/NLM) — approved Efavirenz label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=92603fa5-7a2c-4bfb-9a70-aadb4fba952c
Efavirenz causes neuropsychiatric effects (depression, suicidal ideation, psychosis), with increased risk in patients with prior psychiatric disease.
Monitor neuropsychiatric symptoms; stop with severe depression or suicidal ideation.
DailyMed/FDA (NIH/NLM) — approved Efavirenz label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=92603fa5-7a2c-4bfb-9a70-aadb4fba952c
Efavirenz is hepatotoxic, especially in the first months and in hepatitis B or C coinfection; prior liver disease increases the risk.
Monitor transaminases; stop if hepatitis symptoms occur.
DailyMed/FDA (NIH/NLM) — approved Efavirenz label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=92603fa5-7a2c-4bfb-9a70-aadb4fba952c
Efavirenz is teratogenic in primates (neural tube defects) and should be avoided in the 1st trimester; human data are limited.
Avoid in the 1st trimester; where possible, prefer an alternative (e.g. dolutegravir) in women of childbearing age.
Excreted into breast milk; in HIV infection breastfeeding is not recommended regardless of treatment.
Advise effective contraception during treatment (efavirenz may reduce the efficacy of hormonal contraceptives).
DailyMed/FDA (NIH/NLM) — approved Efavirenz label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=92603fa5-7a2c-4bfb-9a70-aadb4fba952c
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Non-nucleoside reverse transcriptase inhibitor (NNRTI) of HIV-1: binds directly to the reverse transcriptase enzyme, blocking viral DNA polymerisation. In combination with other antiretrovirals it reduces viral load and increases CD4. Non-linear pharmacokinetics with dose; neuropsychiatric effects are related to plasma concentrations.
Efavirenz binds to an allosteric site of HIV-1 reverse transcriptase, inducing a conformational change that inhibits both DNA-dependent and RNA-dependent polymerase activities — it does not compete with nucleosides. It is not active against HIV-2.
Peak plasma concentrations occur in 3–5 hours; steady state is reached in 6–10 days. Food (high-fat meal) increases AUC by 28% and Cmax by 79% — take on an empty stomach, preferably at night. Plasma protein binding is very high (~99.5–99.75%).
Efavirenz is metabolised mainly by the cytochrome P450 system to hydroxylated metabolites, subsequently glucuronidated (CYP3A and CYP2B6 are the major isozymes). It induces CYP enzymes (autoinduction): multiple 200–400 mg/day doses for 10 days result in 22–42% lower accumulation and a shorter terminal half-life.
The terminal half-life is 52–76 hours after single doses and 40–55 hours after multiple doses. Less than 1% is excreted unchanged in urine — the impact of renal impairment on elimination is minimal.
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
