efavirenz: clinical use

Prescribing considerations

• Review resistance history, interaction potential, psychiatric and seizure history, hepatic disease, cardiac rhythm risk, pregnancy potential and concomitant products.
• Food increases exposure; bedtime administration on an empty stomach may improve neuropsychiatric tolerability.
• Consider late-onset neurotoxicity, including ataxia and encephalopathy, even after prolonged treatment.

Contraindications and cautions

• Hypersensitivity to efavirenz or an excipient.
• Severe hepatic impairment.
• Specified high-risk CYP3A4 interactions, including midazolam, triazolam, pimozide and ergot alkaloids.
• Elbasvir/grazoprevir or St John’s wort.
• Relevant congenital or acquired QT-prolongation risk, serious rhythm disorders, major electrolyte disturbance or concomitant QT-prolonging medicines as detailed in the product information.

Monitoring

• Virological response and adherence.
• Neuropsychiatric symptoms, sleep disturbance and neurological function.
• Rash, especially during early treatment.
• Liver function, particularly with hepatic disease, viral hepatitis or hepatotoxic co-medication.
• Blood lipids, glucose and weight.
• ECG and electrolytes when clinically indicated.
• Pregnancy status where relevant before initiation.

Clinical pharmacology

Efavirenz is a non-competitive HIV-1 reverse-transcriptase inhibitor. It is principally metabolised by CYP2B6 and CYP3A4, has a long elimination phase, induces CYP3A4, CYP2B6 and UGT1A1, and can inhibit several CYP enzymes. CYP2B6 genetic variation may increase exposure and toxicity.

Formulation and product differences

• The selected product is a film-coated tablet intended to be swallowed whole with water.
• It contains lactose and is essentially sodium-free.
• The selected tablet is unsuitable for children below the product’s stated weight threshold; another formulation is required.

Tablet

Route: Oral

Strengths: 600 mg