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Clinical perspective on drug-drug interactions with the non-nucleoside reverse transcriptase inhibitor rilpivirine. 2013

Herta Crauwels, and Rolf P G van Heeswijk, and Marita Stevens, and Annemie Buelens, and Simon Vanveggel, and Katia Boven, and Richard Hoetelmans
Clinical Pharmacology, Janssen Infectious Diseases BVBA, Beerse, Belgium. hcrauwel@its.jnj.com

Rilpivirine (TMC278) is a non-nucleoside reverse transcriptase inhibitor approved in combination with other antiretrovirals for the treatment of HIV-1 infection in treatment-naive adults (Edurant(®) 25 mg once daily; Complera(®) [USA]/Eviplera(®) [EU] once daily single-tablet regimen). Rilpivirine should be administered with a meal to optimize bioavailability. Its solubility is pH dependent. Rilpivirine is primarily excreted via the feces with negligible renal elimination. Rilpivirine is predominantly metabolized by cytochrome P450 3A4. There is no clinically relevant effect of age, gender, bodyweight, race, estimated glomerular filtration rate, or hepatitis B/C coinfection status on rilpivirine pharmacokinetics in adults. Drug-drug interactions were investigated with cytochrome P450 3A substrates, inducers and inhibitors, drugs altering intragastric pH, antiretrovirals, and other often coadministered drugs. Rilpivirine 25 mg once daily does not have a clinically relevant effect on exposure of coadministered drugs. Coadministration with cytochrome P450 3A inhibitors (ketoconazole, ritonavir-boosted protease inhibitors, telaprevir) results in increased rilpivirine plasma concentrations, but these are not considered clinically relevant; no dose adjustments are required. Coadministration of rilpivirine with cytochrome P450 3A inducers (e.g. rifampin, rifabutin) or compounds increasing gastric pH (e.g. omeprazole, famotidine) results in decreased rilpivirine plasma concentrations, which may increase the risk of virologic failure and resistance development. Therefore, strong cytochrome P450 3A inducers and proton-pump inhibitors are contraindicated. Histamine-2 receptor antagonists and antacids can be coadministered with rilpivirine, provided doses are temporally separated. No dose adjustments are required when rilpivirine is coadministered with: acetaminophen, phosphodiesterase type 5 inhibitors (sildenafil, etc.), atorvastatin (and other statins), oral contraceptives (ethinyl estradiol, norethindrone), chlorzoxazone (cytochrome P450 2E1 substrate), methadone, digoxin, tenofovir disoproxil fumarate, didanosine and other nuceos(t)ide reverse transcriptase inhibitors, and HIV integrase inhibitors (raltegravir, dolutegravir, GSK1265744).

UI MeSH Term Description Entries
D009570 Nitriles Organic compounds containing the -CN radical. The concept is distinguished from CYANIDES, which denotes inorganic salts of HYDROGEN CYANIDE. Nitrile
D011743 Pyrimidines A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (CYTOSINE; THYMINE; and URACIL) and form the basic structure of the barbiturates.
D004347 Drug Interactions The action of a drug that may affect the activity, metabolism, or toxicity of another drug. Drug Interaction,Interaction, Drug,Interactions, Drug
D004359 Drug Therapy, Combination Therapy with two or more separate preparations given for a combined effect. Combination Chemotherapy,Polychemotherapy,Chemotherapy, Combination,Combination Drug Therapy,Drug Polytherapy,Therapy, Combination Drug,Chemotherapies, Combination,Combination Chemotherapies,Combination Drug Therapies,Drug Polytherapies,Drug Therapies, Combination,Polychemotherapies,Polytherapies, Drug,Polytherapy, Drug,Therapies, Combination Drug
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000068696 Rilpivirine A diarylpyrimidine derivative and REVERSE TRANSCRIPTASE INHIBITOR with antiviral activity against HIV-1 that is used in the treatment of HIV INFECTIONS. It is also used in combination with other ANTI-HIV AGENTS, since ANTIVIRAL DRUG RESISTANCE emerges rapidly when it is used alone. R278474,Rilpivirine HCl,Rilpivirine Hydrochloride,TMC 278,TMC-278,TMC278,278, TMC,HCl, Rilpivirine,Hydrochloride, Rilpivirine
D015658 HIV Infections Includes the spectrum of human immunodeficiency virus infections that range from asymptomatic seropositivity, thru AIDS-related complex (ARC), to acquired immunodeficiency syndrome (AIDS). HTLV-III Infections,HTLV-III-LAV Infections,T-Lymphotropic Virus Type III Infections, Human,HIV Coinfection,Coinfection, HIV,Coinfections, HIV,HIV Coinfections,HIV Infection,HTLV III Infections,HTLV III LAV Infections,HTLV-III Infection,HTLV-III-LAV Infection,Infection, HIV,Infection, HTLV-III,Infection, HTLV-III-LAV,Infections, HIV,Infections, HTLV-III,Infections, HTLV-III-LAV,T Lymphotropic Virus Type III Infections, Human
D054303 HIV Reverse Transcriptase A reverse transcriptase encoded by the POL GENE of HIV. It is a heterodimer of 66 kDa and 51 kDa subunits that are derived from a common precursor protein. The heterodimer also includes an RNAse H activity (RIBONUCLEASE H, HUMAN IMMUNODEFICIENCY VIRUS) that plays an essential role the viral replication process. Reverse Transcriptase, HIV,Reverse Transcriptase, Human Immunodeficiency Virus,Transcriptase, HIV Reverse
D019380 Anti-HIV Agents Agents used to treat AIDS and/or stop the spread of the HIV infection. These do not include drugs used to treat symptoms or opportunistic infections associated with AIDS. AIDS Drug,AIDS Drugs,Anti-AIDS Agents,Anti-AIDS Drug,Anti-HIV Agent,Anti-HIV Drug,Anti-AIDS Drugs,Anti-HIV Drugs,Agent, Anti-HIV,Agents, Anti-AIDS,Agents, Anti-HIV,Anti AIDS Agents,Anti AIDS Drug,Anti AIDS Drugs,Anti HIV Agent,Anti HIV Agents,Anti HIV Drug,Anti HIV Drugs,Drug, AIDS,Drug, Anti-AIDS,Drug, Anti-HIV,Drugs, AIDS,Drugs, Anti-AIDS,Drugs, Anti-HIV

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