Adult: In combination with other antiretroviral agents for the treatment of patients who are antiretroviral-naive or who are previously treated with antiretroviral therapy: 100 mg once daily.
Hypersensitivity. Lactation. Concomitant use with strong CYP3A inducers.
Special Precautions
Patient taking moderate CYP3A inducers. Severe hepatic impairment. Pregnancy.
Adverse Reactions
Significant: Immune reconstitution syndrome. Gastrointestinal disorders: Abdominal pain, diarrhoea, flatulence, nausea, vomiting. General disorders and administration site conditions: Fatigue. Hepatobiliary disorders: Hepatocellular injury. Investigations: Increased ALT, AST, serum bilirubin. Nervous system disorders: Dizziness, headache, somnolence. Psychiatric disorders: Abnormal dreams, insomnia. Skin and subcutaneous tissue disorders: Rash.
Patient Counseling Information
This drug may cause fatigue, dizziness and somnolence, if affected, do not drive or operate machinery.
Monitoring Parameters
Monitor viral load and CD4 count. Evaluate for signs of immune reconstitution syndrome.
Drug Interactions
Moderate CYP3A inducers (e.g. rifabutin, dabrafenib, lesinurad, bosentan, thioridazine, nafcillin, modafinil, telotristat ethyl) and other NNRTIs (e.g. efavirenz, etravirine, nevirapine) may decrease doravirine concentrations. CYP3A inhibitors (e.g. azole antifungals, ritonavir) may increase doravirine plasma concentrations. May decrease exposure of drugs that are sensitive CYP3A substrates (e.g. midazolam, tacrolimus, sirolimus). Potentially Fatal: Concomitant administration of strong CYP3A inducers (e.g. carbamazepine, oxcarbazepine, phenobarbital, phenytoin, enzalutamide, rifampicin, rifapentine, mitotane, lumacaftor) may significantly decrease the plasma concentrations of doravirine.
Food Interaction
St. John’s wort may significantly decrease doravirine concentrations; avoid concomitant use.
Action
Description: Doravirine is a pyridinone non-nucleoside reverse transcriptase inhibitor (NNRTI) that inhibits HIV-1 replication by interfering with viral polymerase activities of reverse transcriptase (RT). It binds to a hydrophobic pocket in the p66 subunit of the p66/p51 heterodimer of the RT enzyme, causing conformational changes within the active site residues. This leads to an inactive conformation, thereby inhibiting the chemical step of a polymerisation reaction. Pharmacokinetics: Absorption: Bioavailability: Approx 64%. Time to peak plasma concentration: 2 hours. Distribution: Volume of distribution: 60.5 L. Plasma protein binding: Approx 76%. Metabolism: Metabolised in the liver mainly by the CYP3A4 isoenzyme. Excretion: Via urine (6% as unchanged drug); faeces (minor; as unchanged drug). Elimination half-life: Approx 15 hours.
Chemical Structure
Doravirine Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 58460047, Doravirine. https://pubchem.ncbi.nlm.nih.gov/compound/Doravirine. Accessed Mar. 25, 2021.
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