doravirine + lamivudine + tenofovir disoproxil fumarate: clinical use

Prescribing considerations

• Confirm HIV-1 resistance history and suitability of all three fixed-dose components.
• Assess renal function and review nephrotoxic medicines before initiation.
• Test for hepatitis B before starting; plan follow-up after discontinuation in HIV/HBV coinfection.
• Consider renal tubular and bone toxicity risks, especially with osteoporosis, fractures or other renal risk factors.
• Review prescription, non-prescription and herbal products for CYP3A induction and renal interactions.
• Use caution in severe hepatic impairment because doravirine has not been studied in this group.

Contraindications and cautions

• Hypersensitivity to an active substance or excipient.
• Concomitant strong CYP3A inducers, including specified enzyme-inducing antiseizure medicines, rifampicin, rifapentine, St John’s wort, mitotane, enzalutamide and lumacaftor.
• Do not initiate when renal function is below the product threshold because the fixed components cannot be adjusted separately.
• Rare hereditary galactose intolerance, total lactase deficiency or glucose-galactose malabsorption.

Monitoring

• HIV viral load, treatment response and adherence.
• Renal function before treatment and as clinically appropriate; include serum phosphate and urine glucose/protein when renal risk is increased.
• Renal tubular dysfunction, persistent bone pain, fractures or muscle weakness.
• Hepatic clinical and laboratory follow-up for several months after discontinuation in HIV/HBV coinfection.
• Skin and mucosal symptoms suggesting a severe cutaneous adverse reaction.
• New inflammatory or autoimmune symptoms associated with immune reconstitution.

Clinical pharmacology

Doravirine is a CYP3A-metabolised non-nucleoside inhibitor of HIV-1 reverse transcriptase. Intracellular metabolites of lamivudine and tenofovir competitively inhibit reverse transcriptase and terminate viral DNA chains; lamivudine and tenofovir are primarily eliminated renally.

Formulation and product differences

• Available as a fixed-combination film-coated tablet containing all three active substances.
• The components cannot be adjusted separately within this formulation.
• The tablet contains lactose and should be swallowed whole.
• It may be taken with or without food.

Tablet

Route: Oral

Strengths: 100 mg + 300 mg + 245 mg