efavirenz + emtricitabine + tenofovir disoproxil maleate: clinical use

Prescribing considerations

• Confirm sustained virological suppression, treatment history and absence of significant resistance to all components.
• Use separate preparations if an individual component needs modification.
• Review renal, hepatic, psychiatric, cardiac and bone risks and complete an interaction check.
• Assess hepatitis B status before stopping because withdrawal can precipitate severe hepatitis exacerbation.
• Food increases efavirenz exposure; advise empty-stomach administration.

Contraindications and cautions

• Hypersensitivity to an active substance or excipient.
• Severe hepatic impairment.
• Specified high-risk QT conditions, severe electrolyte disturbance or concurrent QT-prolonging medicines listed in the product information.
• Concurrent voriconazole, elbasvir/grazoprevir, St John’s wort and specified medicines carrying life-threatening CYP3A4-mediated interaction risks.
• Moderate or severe renal impairment, because the components cannot be adjusted independently.

Monitoring

• HIV viral load, adherence, resistance and treatment failure
• Creatinine clearance and serum phosphate; tubular-function tests if renal toxicity is suspected
• Liver function, particularly with viral hepatitis or underlying liver disease
• Mood, behaviour, sleep and other neuropsychiatric effects
• Bone pain, muscle weakness, fracture risk and possible proximal tubulopathy
• Blood lipids and glucose as clinically appropriate

Clinical pharmacology

Efavirenz non-competitively inhibits HIV-1 reverse transcriptase and induces CYP3A4, CYP2B6 and UGT1A1. Intracellular emtricitabine triphosphate and tenofovir diphosphate competitively inhibit reverse transcriptase and terminate viral DNA chains. Emtricitabine and tenofovir are predominantly eliminated by the kidneys.

Formulation and product differences

• The selected Mylan product contains tenofovir disoproxil as the maleate salt.
• It is a pink, capsule-shaped film-coated tablet marked “M” and “TME”, intended to be swallowed whole.
• It contains lactose monohydrate and sodium metabisulfite; sodium metabisulfite can rarely cause hypersensitivity reactions or bronchospasm.
• Pack presentations may be bottles or blisters; not every authorised pack size is necessarily marketed.

Tablet

Route: Oral

Strengths: 600 mg + 200 mg + 245 mg