Rilpivirine

Structural formula
General
Non-proprietary name	Rilpivirine
other names	4 - {[4 - ({4 - [( E ) -2-cyanovinyl] -2,6-dimethylphenyl} amino) -2-pyrimidinyl] amino} benzonitrile ( IUPAC ) Rilpivirinum ( Latin )
Molecular formula	C 22 H 18 N 6
External identifiers / databases
CAS number 500287-72-9 EC number 695-719-5 ECHA InfoCard 100.224.394 PubChem 6451164 ChemSpider 4953643 DrugBank DB05083 Wikidata Q421547
Drug information
Drug class	Antivirals , non-nucleoside reverse transcriptase inhibitors
Mechanism of action	non-competitive inhibition of reverse transcriptase
properties
Molar mass	366.42 g · mol -1
safety instructions
GHS labeling of hazardous substances Caution H and P phrases H: 302-319-410 P: ?
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Rilpivirine (RLP) was developed by Tibotec and is a drug used to treat HIV- infected patients as part of combination therapy for HIV .

Rilvipivirine is a diaryl pyrimidine (DAPY) analog from the group of non-nucleoside reverse transcriptase inhibitors (NNRTIs).

Compared to the NNRTIs 1st generation rilpivirine has the advantage that it is effective against most strains in which these NNRTIs fail. In addition, studies show significantly fewer side effects of the CNS . Against this background, it is likely that rilpivirine - together with other 2nd generation NNRTIs (e.g. etravirine) - could replace the classic NNRTIs in the future.

Approval as a drug

Rilpivirine was approved by the FDA in the USA under the trade name Edurant in May 2011 , followed by approval for the EU in November 2011 . For the fixed combination with emtricitabine and tenofovir as a once-daily therapy regimen, approvals have been granted under the names Complera (USA, August 2011) and Eviplera (EU, November 2011).

The additional benefit of Edurant on the basis of Section 35a SGB ​​V ( AMNOG ) ( early benefit assessment ) was assessed by the Federal Joint Committee (G-BA) : According to this, adult patients who have not been previously treated for antiretroviral have a viral load of 100,000 HIV-1 RNA copies for Edurant / ml provided proof of a minor added benefit compared to the ACT ( etravirine ). The added benefit for Eviplera is classified as minor. Compared to the appropriate comparative therapy, there is a moderate improvement in the therapy-relevant benefit, since a relevant avoidance of dermatological and neurological side effects is achieved. The preliminary assessment by the Institute for Quality and Efficiency in Health Care (IQWiG) had seen a higher additional benefit for the monopreparation.

pharmacology

Rilpivirine belongs to the class of non-nucleoside reverse transcriptase inhibitors (NNRTIs). The active ingredient binds non-competitively to the reverse transcriptase of HIV-I , near the substrate binding site for nucleosides . This blocks the catalytically active binding site. Only a few nucleosides can bind and the polymerization is slowed down significantly.

Resistances

Rilpivirine has the advantage over other NNRTIs that it is effective against most strains that other NNRTIs fail.

Pharmacokinetics

Rilpivirine is subject to oxidative metabolism by the cytochrome P450 system of the liver (especially CYP3A4 ). The terminal half-life of 34 to 55 hours allows a single dose per day. In general, the maximum plasma concentration is reached within 4-5 hours after oral administration. Concomitant use of CYP3A4 inducers can therefore lead to lower plasma concentrations of rilpivirine, which may result in a loss of therapeutic effect. Substances that inhibit CYP3A4 can lead to increased plasma concentrations of rilpivirine. An increased pH value in the stomach (e.g. due to proton pump inhibitors ) is associated with reduced bioavailability . The bioavailability is particularly dependent on the diet: when taken with a protein drink it drops by 50%, when taken without food it drops by 40%. It is therefore recommended to take it 10 minutes after breakfast with bread, butter, jam and cheese / ham.

Therapeutic drug monitoring (TDM)

Decreased plasma concentrations ( effective levels ) of rilpivirine can cause HIV therapy to fail. Regular monitoring of plasma concentrations is therefore recommended.

Trade names

Monopreparation

Edurant ^®

Combination preparation

Eviplera ^®

Odefsey ^®

literature

• PA Janssen, PJ Lewi, E. Arnold et al .: In search of a novel anti-HIV drug: multidisciplinary coordination in the discovery of 4 - [[4 - [[4 - [(1E) -2-cyanoethenyl] -2.6] -dimethylphenyl] amino] -2-pyrimidinyl] amino] benzonitriles (R278474, rilpivirine) . In: J Med Chem. 48, 2005, pp. 1901-1909.

Individual evidence

1. ↑ There is not yet a harmonized classification for this substance . A labeling of 4 - ((4 - ((4 - [(E) -2-cyanoethenyl] - 2,6-dimethylphenyl) amino) pyrimidin-2-yl) amino) benzonitrile in the classification is derived from a self-classification by the distributor and Labeling Inventory of the European Chemicals Agency (ECHA), accessed on July 11, 2020.
2. ↑ ^{a b} Summary of the European public assessment report (EPAR) for Edurant of the European Medicines Agency (EMA) (English)
3. ↑ Pozniak 2007.
4. ↑ New on the market - Rilpivirin , Pharmazeutische Zeitung Online
5. ↑ Gilead receives European marketing authorization for Eviplera®, a new, once-daily combined preparation in the form of a single tablet for treatment-naïve adults with HIV-1 infection ( Memento of February 7, 2015 in the Internet Archive ), finanzen.net, November 29, 2011 .
6. ↑ Federal Joint Committee: Early Benefit Assessment (Section 35a SGB V) .
7. ↑ Federal Joint Committee: Resolutions on the benefit assessment of drugs with new active ingredients according to Section 35a SGB V - Rilpivirine (PDF; 108 kB) of July 5, 2012.
8. ↑ Federal Joint Committee: Resolutions on the benefit assessment of drugs with new active ingredients according to Section 35a SGB V - Emtricitabine, Rilpivirine, Tenofovir Disoproxil (PDF; 112 kB) from July 5, 2012.
9. ↑ Rilpivirine in HIV: additional benefit for monopreparation proven , press release Institute for Quality and Efficiency in Health Care (IQWiG).
10. ↑ Federal Joint Committee: Drugs Directive / Annex XII: Rilpivirine of July 5, 2012.
11. ↑ Zeynep Ofluoglu, Anke Heithoff, Ricarda Rockel-Witschonke, Nina Ciemniak Ziba Mahdizadeh: rilpivirine for the treatment of HIV-1 in treatment-naïve antiretroviral adults . In: Förtbildungstelegramm Pharmazie. 6 (6), 2012, pp. 195-209.
12. ↑ ^{a b} Analysis spectrum - Rilpivirin , Labor Lademannbogen

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