Doravirine


Generic Medicine Info
Indications and Dosage
Oral
HIV-1 infection
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.
Special Patient Group
Patient taking moderate CYP3A inducers (e.g. rifabutin, dabrafenib, lesinurad, bosentan, thioridazine, nafcillin, modafinil, telotristat ethyl): 100 mg bid (approx 12 hours apart).
Administration
Tab: May be taken with or without food.
Contraindications
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

Chemical Structure Image
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.

Storage
Store between 20-25°C. Protect from moisture.
MIMS Class
ATC Classification
J05AG06 - doravirine ; Belongs to the class of non-nucleoside reverse transcriptase inhibitors. Used in the systemic treatment of viral infections.
References
Anon. Doravirine. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 26/02/2021.

Anon. Doravirine. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 26/02/2021.

Buckingham R (ed). Doravirine. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 26/02/2021.

Joint Formulary Committee. Doravirine. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 26/02/2021.

Pifeltro 100 mg Film-Coated Tablets (Merck Sharp & Dohme B.V.). European Medicines Agency [online]. Accessed 26/02/2021.

Pifeltro Film-Coated Tablets (Merck Sharp & Dohme [Asia] Ltd.). MIMS Hong Kong. http://www.mims.com/hongkong. Accessed 23/03/2021.

Pifeltro Tablet, Film Coated (Merck Sharp & Dohme Corp.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 26/02/2021.

Disclaimer: This information is independently developed by MIMS based on Doravirine from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2021 MIMS. All rights reserved. Powered by MIMS.com
Exclusive offer for doctors
Register for a MIMS account and receive free medical publications worth $768 a year.
Sign up for free
Already a member? Sign in