|Trade names||Edurant, Rekambys|
|Drug class||Non-nucleoside reverse transcriptase inhibitor (NNRTI)|
|Side effects||Headache, trouble sleeping, dizziness, nausea, abnormal lipid levels, liver problems|
|By mouth, intramuscular|
|Typical dose||25 mg OD|
|Elimination half-life||tablets: 45 hours|
injection: 13–28 weeks
|Excretion||85% via faeces, 6% via urine|
|Chemical and physical data|
|Molar mass||366.428 g·mol−1|
|3D model (JSmol)|
|(what is this?)|
Rilpivirine, sold under the brand name Edurant among others, is a medication used to treat and prevent HIV/AIDS. Specifically it is used together with other antiviral medication for HIV-1. It is taken by mouth.
Common side effects include headache, trouble sleeping, dizziness, nausea, abnormal lipid levels, and liver problems. Other side effects may include drug reaction with eosinophilia and systemic symptoms (DRESS) and depression. Use during pregnancy appears safe, but as not been well studied. It is a non-nucleoside reverse transcriptase inhibitor (NNRTI) which blocks the enzyme reverse transcriptase.
Rilpivirine was approved for medical use in the United States and Europe in 2011. In the United Kingdom a month of medication costs the NHS about £200 as of 2021. This amount in the United States costs about 1,200 USD.
In the European Union, rilpivirine is approved in combination with cabotegravir for maintenance treatment of adults who have undetectable HIV levels in the blood (viral load less than 50 copies/ml) with their current antiretroviral treatment, and when the virus has not developed resistance to certain class of anti-HIV medicines called non-nucleoside reverse transcriptase inhibitors (NNRTIs) and integrase strand transfer inhibitors (INIs).
It is generally taken at a dose of 25 mg once per day.
The drug is available as tablets (brand name Edurant) and as a long-acting intramuscular injection to be given once every month or every two months (Rekambys). Before using the injection, the tablets are given for about four weeks to assess tolerability.
A fixed-dose medication combining rilpivirine with emtricitabine and tenofovir disoproxil (TDF) was approved by the U.S. Food and Drug Administration (FDA) in August 2011 under the brand name Complera, and was approved for use in the European Union with the brand name Eviplera in November 2011. This combination has been shown to have higher rates of virologic failure than emtricitabine/tenofovir/efavirenz in people with baseline HIV viral loads greater than 100,000 copies/mm3.[medical citation needed]
In January 2021, the U.S. Food and Drug Administration (FDA) approved cabotegravir/rilpivirine (brand name Cabenuva) for the treatment of HIV-1 infections in adults to replace a current antiretroviral regimen in those who are virologically suppressed on a stable antiretroviral regimen with no history of treatment failure and with no known or suspected resistance to either cabotegravir or rilpivirine. This is the first FDA-approved injectable, complete regimen for HIV-infected adults that is administered once a month. The label for rilpivirine tablets was revised to reflect the oral lead-in recommendations for use with cabotegravir.
Contraindications and interactions
The drug is contraindicated for use with drugs that induce the liver enzyme CYP3A4, such as carbamazepine, phenytoin, rifampicin, and St John's wort. Such drugs can accelerate the breaking down of rilpivirine, substantially decreasing its plasma concentrations and potentially resulting in loss of effectiveness and possible resistance. Some of these drugs also induce the enzyme UGT1A1 and thus reduce blood plasma concentrations of cabotegravir, further compromising the effectiveness of this combination therapy.
It is also contraindicated in combination with proton pump inhibitors because the increased gastric pH causes decreased rilpivirine absorption from the gut, with similar consequences as with CYP3A4 inducers.
The most common side effects of the injectable formulation are reactions at the injection site (in up to 84% of patients) such as pain and swelling, as well as headache (up to 12%) and fever or feeling hot (in 10%). Less common (under 10%) are depressive disorders, insomnia, and rashes. The most common side effects of the tablets are also depressive disorders (4.1%), headache (3.5%), insomnia (3.5%) and rashes (2.3%). All of these side effects occurred under combination therapies of rilpivirine with one or more other drugs against HIV.
Mechanism of action
When taken by mouth, rilpivirine reaches highest levels in the blood plasma after about four to five hours. Taking the drug without food lowers its plasma levels by 40% as compared to taking it with food, which is considered to be clinically relevant. Therefore, patients are advised to take the medication together with a meal. After injection into the muscle, the substance reaches highest plasma levels after three to four days.
Independently of the mode of application, rilpivirine is almost completely bound to plasma proteins (99.7%), mostly to albumin. It is metabolised mainly by the liver enzyme CYP3A4. Metabolites include several oxidation products, glucuronides, and glucuronides of oxidized metabolites. The biological half-life is approximately 45 hours for the tablets and 13 to 28 weeks for the injection.
Elimination has only been studied for oral administration: Most of the drug is excreted via the faeces (85%), partly in unchanged form (25%), partly in form of its metabolites (60%). A minor amount is excreted via the urine (6%), almost exclusively as metabolites.
On 15 October 2020, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for rilpivirine under the trade name Rekambys, intended for the treatment of human immunodeficiency virus type-1 (HIV-1) infection in combination with cabotegravir injection. It was approved for medical use in the European Union in December 2020. The two medicines are the first antiretrovirals that come in a long-acting injectable formulation. This means that instead of daily pills, people receive intramuscular injections monthly or every two months.
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