Description
In May 2011, the U.S. FDA approved rilpivirine in combination with other
antiretroviral agents for the treatment of human immunodeficiency virus
(HIV) 1 infection in treatment-naive adult patients.
Rilpivirine is a member of the nonnucleoside reverse transcriptase inhibitor (NNRTI) class of anti-HIV
agents. It is highly potent against a range of wild-type HIV strains
(EC50=0.07–1.0 nM),～10–20 timesmore potent than the NNRTI efavirenz
(Sustiva), and active against HIV strains resistant to other NNRTIs. The
discovery of rilpivirine was guided by molecular modeling and X-ray
crystallography of HIV-1 RT complexed with inhibitors. The synthesis
of rilpivirine is accomplished by an efficient 6-step route in which the key
step is coupling of 4-((4-chloropyrimidin-2-yl)amino)benzonitrile with (E)-3-(4-amino-3,5-dimethylphenyl)acrylonitrile.
Chemical Properties
N/ABright Yellow Solid
Originator
Janssen (Belgium)
Uses
A novel non-nucleoside reverse transcriptase inhibitor. Rilpivirine seems to be well tolerated with less CNS disturbance than Efavirenz, and has non-teratogenic potential.
Definition
ChEBI: An aminopyrimidine that is pyrimidine-2,4-diamine in which the amino groups at positions 2 and 4 are substituted by 4-cyanophenyl and 4-[(E)-2-cyanovinyl]-2,6-dimethylphenyl groups respectively. Used for treatment of HIV.
Clinical Use
Non-nucleoside reverse transcriptase inhibitor:
Treatment of progressive or advanced HIV infection
in combination with at least two other antivirals
target
reverse transcriptase
Drug interactions
Potentially hazardous interactions with other drugs
Antibacterials: avoid with clarithromycin and
erythromycin - concentration possibly increased;
concentration decreased by rifampicin and rifabutin
- avoid with rifampicin, increase dose of rilpivirine
to 50 mg daily.
Antidepressants: concentration possibly reduced by
St John’s wort - avoid.
Antiepileptics: concentration possibly reduced
by carbamazepine, fosphenytoin, oxcarbazepine,
phenobarbital, primidone and phenytoin - avoid.
Corticosteroids: avoid with dexamethasone (except
as a single dose).
Orlistat: absorption possibly reduced by orlistat.
Ulcer-healing drugs: concentration possibly reduced
by esomeprazole, lansoprazole, omeprazole,
pantoprazole and rabeprazole - avoid; avoid
histamine H2
-antagonists for 12 hours before and 4
hours after rilpiverine.
Metabolism
Primarily undergoes oxidative metabolism mediated by
the cytochrome P450 (CYP) 3A system.
85% excreted via the faeces (25% as unchanged drug) and
6% via the urine.
References
[1] moss d m, liptrott n j, curley p, et al. rilpivirine inhibits drug transporters abcb1, slc22a1, and slc22a2 in vitro. antimicrobial agents and chemotherapy, 2013, 57(11): 5612-5618.
[2] garvey l, winston a. rilpivirine: a novel non-nucleoside reverse transcriptase inhibitor. 2009.
[3] weiss j, haefeli w e. potential of the novel antiretroviral drug rilpivirine to modulate the expression and function of drug transporters and drug-metabolising enzymes in vitro. international journal of antimicrobial agents, 2013, 41(5): 484-487.
[4] baert l, van’t klooster g, dries w, et al. development of a long-acting injectable formulation with nanoparticles of rilpivirine (tmc278) for hiv treatment. european journal of pharmaceutics and biopharmaceutics, 2009, 72(3): 502-508.
