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. Adverse effects
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. QT prolongation of the heart rhythm has been observed at very high doses, but is not clinically relevant at standard doses of the drug. Pharmacology
Mechanism of action
Rilpivirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI). Pharmacokinetics
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.
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. Chemistry
Like etravirine, a second-generation NNRTI approved in 2008, rilpivirine is a diarylpyrimidine (DAPY).The tablets contain rilpivirine hydrochloride, while the injection contains free rilpivirine. History
Rilpivirine entered phase III clinical trials in April 2008, and was approved for use in the United States in May 2011 under the brand name Edurant.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. References
External links
"Rilpivirine". Drug Information Portal. U.S. National Library of Medicine. "Rilpivirine hydrochloride". Drug Information Portal. U.S. National Library of Medicine.