Product Information
Registration Status: ActiveEDURANT FILM-COATED TABLET 25mg is approved to be sold in Singapore with effective from 2013-11-06. It is marketed by JOHNSON & JOHNSON PTE LTD, with the registration number of SIN14363P.
This product contains Rilpivirine 25mg in the form of TABLET, FILM-COATED. It is approved for ORAL use.
This product is manufactured by Janssen-Cilag S.p.A in ITALY.
It is a Prescription Only Medicine that can only be obtained from a doctor or a dentist, or a pharmacist with a prescription from a Singapore-registered doctor or dentist.
Description
Rilpivirine is non-nucleoside reverse transcriptase inhibitor (NNRTI) which is used for the treatment of HIV-1 infections in treatment-naive patients.[A31328] It is a diarylpyrimidine derivative, a class of molecules that resemble pyrimidine nucleotides found in DNA.[A31329] The internal conformational flexibility of rilpivirine and the plasticity of it interacting binding site gives it a very high potency and an unlikely generation of resistance compared to other NNRTI's.[A31331] Rilpivirine was developed by Tilbotec, Inc. and FDA approved on May 20, 2011.[L1030] On November 21, 2017, Rilpivirine, in combination with dolutegravir, was approved as part of the first complete treatment regimen with only two drugs for the treatment of adults with HIV-1 named Juluca.[L1031]
Indication
Rilpivirine, in combination with other agents, is indicated for the treatment of HIV-1 infections in antiretroviral treatment-naive patients with HIV-1 RNA ≤100,000 copies/mL and CD4+ cell count >200 cells/mm3.[L1030] The FDA combination therapy approval of rilpivirine and dolutegravir is indicated for adults with HIV-1 infections whose virus is currently suppressed (< 50 copies/ml) on a stable regimen for at least six months, without history of treatment failure and no known substitutions associated to resistance to any of the two components of the therapy.[L1031]
Mechanism of Action
Rilpivirine is a non-competitive NNRTI that binds to reverse transcriptase. Its binding results in the blockage of RNA and DNA- dependent DNA polymerase activities, like HIV-1 replication. It does not present activity against human DNA polymerases α, β and γ.[L1032] Rilpivirine binds to the HIV-1 reverse transcriptase (RT) and its flexible structure around the aromatic rings allows the adaptation to changes in the non-nucleoside RT binding pocket.[A31335]
Pharmacokinetics
- Absorption
- Absorption of rilpivirine is characterized by a lag time followed by a linear increase in plasma concentration. Under fasting conditions, the Cmax of rilpivirine can be decreased even by 46% while its AUC can be reduced by 43%. When given with a protein-rich drink the Cmax and AUC of rilpivirine is decreased by 50%. Therefore, it is recommended to consume rilpiviridine with a non-protein-rich meal. The average Tmax of various rilpivirine concentrations is 3-4 h.[A31331] The reported AUC in patients from clinical studies is 2235 ng h/ml.[FDA label]
- Distribution
- In VIH-1 patients, the apparent volume of distribution in the central compartment was determined to be 152-173 L.[L1032]
- Metabolism
- Mainly hepatically metabolized by CYP3A. Because it is highly protein bound, its free plasma concentration is very small thus is unlikely to inhibit cytochrome proteins to a clinically relevant degree despite being an inhibitor of CYP3A4, CYP2C19, and CYP2B6.[A7414]
- Elimination
Clearance
In HIV-1 patients, the apparent oral clearance is estimated to be 10.5-11.8 L/h.[L1032]
Toxicity
Rilpivirine did not induce chromosomal damage in vivo. It did not show any effect on mating or fertility in animal studies. On the other hand, mice studies have result positive for the formation of hepatocellular neoplasms which can be rodent-specific.[FDA label]
Active Ingredient/Synonyms
4-{[4-({4-[(E)-2-cyanovinyl]-2,6-dimethylphenyl}amino)pyrimidin-2-yl]amino}benzonitrile | Rilpivirine |
Source of information: Drugbank (External Link). Last updated on: 3rd July 18. *Trade Name used in the content below may not be the same as the HSA-registered product.