Efavirenz

FDA label

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Renal Undefined

Hepatic Not recommended in moderate or severe hepatic impairment (Child-Pugh B or C); mild impairment — no dose adjustment, use caution

Instructions

• Take once daily on an empty stomach, preferably at bedtime (food increases levels and adverse reactions; bedtime dosing improves CNS tolerability).
• Swallow tablets intact with liquid; tablets must not be broken or crushed.
• Must be given in combination with other antiretrovirals — never as a single agent or sole addition to a failing regimen (rapid resistance).
• With rifampin in patients >=50 kg: increase efavirenz to 800 mg QD.
• With voriconazole: decrease efavirenz to 300 mg QD using the capsule formulation and increase voriconazole to 400 mg q12h.
• Monitor hepatic function before and during treatment.
• Females of reproductive potential: pregnancy test before initiation; effective contraception (incl. barrier) during treatment and for 12 weeks after stopping.

Contraindications

• Coadministration with elbasvir/grazoprevir

Cautions

• Serious psychiatric symptoms: severe depression (2.4%), suicidal ideation (0.7%), suicide attempts, aggression, paranoid and manic reactions; postmarketing suicide, delusions, psychosis-like behavior, catatonia — seek immediate evaluation.
• Nervous system symptoms in 53%: dizziness, insomnia, impaired concentration, somnolence, abnormal dreams; begin days 1-2, usually resolve in 2-4 weeks; late-onset neurotoxicity (ataxia, encephalopathy) may occur months-years later, incl. with CYP2B6 polymorphisms; additive CNS effects with alcohol/psychoactive drugs.
• QTc prolongation: consider alternatives with drugs with known torsade risk or patients at higher risk.
• Embryo-fetal toxicity: avoid first-trimester use; avoid pregnancy on therapy.
• Hepatotoxicity incl. hepatic failure (a few cases without pre-existing liver disease): monitor LFTs, esp. with hepatitis B/C or hepatotoxic drugs.
• Rash 26%: usually onset within 1-2 weeks, resolves within 4 weeks; discontinue for severe rash; Grade 4 rash (erythema multiforme, SJS) 0.1%; rash more frequent/severe in pediatric patients.
• Convulsions: caution with history of seizures.
• Lipid elevations (total cholesterol, triglycerides): monitor before therapy and periodically.
• Do not coadminister with Atripla (contains efavirenz) unless needed for rifampin dose adjustment.
• Immune reconstitution syndrome; redistribution/accumulation of body fat.

Adverse reactions

• Impaired concentration
• Abnormal dreams
• Rash (26%)
• Dizziness (28%)
• Nausea
• Headache
• Fatigue
• Insomnia
• Vomiting
• Depression (19%)
• Anxiety (13%)

Pregnancy Avoid first-trimester use — retrospective neural tube defect reports and monkey malformations at near-human exposures; APR shows no overall increase in birth defects (2.3%); pregnancy registry 1-800-258-4263; pregnancy test before starting and contraception during + 12 weeks after.

Lactation Breastfeeding not recommended (risk of postnatal HIV-1 transmission).