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

AIDS Rev. Apr-Jun 2013;15(2):87-101.


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).

Publication types

  • Review

MeSH terms

  • Anti-HIV Agents / administration & dosage*
  • Anti-HIV Agents / adverse effects
  • Anti-HIV Agents / therapeutic use
  • Drug Interactions
  • Drug Therapy, Combination
  • HIV Infections / drug therapy*
  • HIV Reverse Transcriptase / antagonists & inhibitors*
  • Humans
  • Nitriles / administration & dosage*
  • Nitriles / adverse effects
  • Nitriles / therapeutic use
  • Pyrimidines / administration & dosage*
  • Pyrimidines / adverse effects
  • Pyrimidines / therapeutic use
  • Rilpivirine


  • Anti-HIV Agents
  • Nitriles
  • Pyrimidines
  • HIV Reverse Transcriptase
  • Rilpivirine