Cabotegravir And Rilpivirine
Cabotegravir And Rilpivirine Uses, Dosage, Side Effects, Food Interaction and all others data.
Cabotegravir, or GSK1265744, is an HIV-1 integrase inhibitor that is prescribed with the non-nucleoside reverse transcriptase inhibitor, rilpivirine. Early research into cabotegravir showed it had lower oral bioavailability than dolutegravir. The devlopment of cabotegravir was later developed to create a long acting monthly intramuscular injection.
Cabotegravir was granted FDA approval on 21 January 2021.
Cabotegravir is an inhibitor of HIV integrase, which reduces viral replication. It has a long duration of action as the oral tablet is given daily and the intramuscular suspension is given monthly. Patients should be counselled regarding the risk of hypersensitivity, hepatotoxicity, and depression.
Rilpivirine is non-nucleoside reverse transcriptase inhibitor (NNRTI) which is used for the treatment of HIV-1 infections in treatment-naive patients. It is a diarylpyrimidine derivative. The internal conformational flexibility of rilpivirine and the plasticity of it interacting binding site gives it a very high potency and reduces the chance of resistance compared to other NNRTI's. Rilpivirine was developed by Tilbotec, Inc. and FDA approved on May 20, 2011. 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. Rilpivirine in combination with cabotegravir was granted FDA approval on 21 January 2021.
Rilpivirine is a non-nucleoside reverse transcriptase inhibitor that inhibits the replication of HIV-1. It has a long duration of action as the oral tablet is given daily and the intramuscular suspension is given monthly. Patients should be counselled regarding the risk of hypersensitivity reactions, hepatotoxicity, depressive disorders, and the redistribution or accumulation of body fat.
| Trade Name | Cabotegravir And Rilpivirine |
| Generic | cabotegravir + rilpivirine |
| Weight | 200mg + 300mg/ml |
| Type | Intramuscular suspension, extended release |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | United States |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Cabotegravir is an HIV-1 integrase inhibitor.
Oral cabotegravir is indicated in combination with rilpivirine for the short term treatment of HIV-1 in virologically suppressed adults with no history of treatment failure to assess tolerability of cabotegravir or who have missed an injected dose of cabotegravir. Intramuscular extended-release cabotegravir is indicated in combination with rilpivirine as a complete regimen for virologically suppressed adults with no history of treatment failure. The intramuscular form is meant to replace their current antiretroviral treatment.
Rilpivirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) used in combination with other antiretrovirals to specifically treat human immunodeficiency virus type 1 (HIV-1).
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. 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.
Cabotegravir And Rilpivirine is also used to associated treatment for these conditions: Human Immunodeficiency Virus Type 1 (HIV-1)Human Immunodeficiency Virus Type 1 (HIV-1) Infection
How Cabotegravir And Rilpivirine works
Cabotegravir binds to the active site of HIV integrase, preventing strand transfer of the viral genome into the host genome, and preventing replication of the virus.
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. Rilpivirine's flexible structure around the aromatic rings allows the adaptation to changes in the non-nucleoside RT binding pocket, reducing the likelihood of viral mutations conferring resistance.
Toxicity
Data regarding the toxicity of cabotegravir is not readily available. In the event of overdose, patients should have their vital signs monitored, including an ECG to monitor the QT interval. Treat patients symptomatically and supportively. As cabotegravir is highly protein bound, dialysis is not expected to remove a significant amount of the drug from plasma.
In the event of an overdose, contact a poison control centre. Patients should be treated with symptomatic and supportive measures, including monitoring of the QT interval. Dialysis is not expected to remove significant amounts of the drug from plasma as it is highly bound to albumin.
Volume of Distribution
Data regarding the volume of distribution of cabotegravir is not readily available.
In HIV-1 patients, the apparent volume of distribution in the central compartment was 152-173 L.
Elimination Route
Oral cabotegravir has a Tmax of 3 hours, reaches a Cmax of 8.0 µg/mL, and has an AUC of 145 µg*h/mL. Intramuscular extended-release cabotegravir has a Tmax of 7 days, reaches a Cmax of 8.0 µg/mL, and has an AUC of 1591 µg*h/mL.
Rilpivirine has a Tmax of 3-4 hours and has a mean AUC of 2235 ± 851 ng*h/mL. A 25mg dose reaches a Cmax of 247 ng/mL in healthy subjects and 138.6 ng/mL in patients with HIV-1.
Half Life
The mean half life of oral cabotegravir is 41 hours. The mean half life of intramuscular extended-release cabotegravir is 5.6-11.5 weeks.
Rilpivirine has a terminal half-life of 34-55 hours.
Clearance
Data regarding the clearance of cabotegravir is not readily available. Clearance in dogs was 0.34 mL/min/kg and in cynomolgus monkeys was 0.32 mL/min/kg.
In HIV-1 patients, the apparent total clearance is estimated to be 6.89-8.66 L/h.
Elimination Route
An oral radiolabelled dose of cabotegravir is 58.5% recovered in the feces and 26.8% recovered in the urine.
Rilpivirine is 85% eliminated in the feces and 6.1% eliminated in the urine. 25% of a dose is recovered in the feces as the unchanged parent drug, while 9
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