RILPIVIRINE
Clinical safety rating: safe
Animal studies have demonstrated safety
Rilpivirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) that binds to HIV-1 reverse transcriptase, causing a conformational change that inhibits the enzyme's activity and prevents viral RNA-dependent DNA polymerization.
| Metabolism | Rilpivirine is primarily metabolized by CYP3A4 isoenzyme. |
| Excretion | Renal (1% unchanged, 6% as metabolites); Fecal (85% as metabolites, 25% unchanged) |
| Half-life | Terminal elimination half-life is approximately 50 hours (range 41–55 h), supporting once-daily dosing. |
| Protein binding | 99.7% bound primarily to albumin. |
| Volume of Distribution | 152 ± 52 L (approximately 2.2 L/kg), indicating extensive tissue distribution. |
| Bioavailability | Oral: bioavailability is not well established; however, absorption is variable (approximately 35–50%), with enhanced absorption when taken with a high-fat meal. |
| Onset of Action | Oral: Antiviral effect begins within 2–4 hours, with maximum viral suppression achieved by 4 weeks. |
| Duration of Action | Oral: Duration of antiviral activity is approximately 24 hours, consistent with once-daily dosing. |
25 mg orally once daily with a meal.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). Not recommended in severe renal impairment (CrCl <30 mL/min) or end-stage renal disease. |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh Class A or B). Contraindicated in severe hepatic impairment (Child-Pugh Class C). |
| Pediatric use | Approved for HIV-1 infection in patients aged ≥12 years and weighing ≥35 kg: 25 mg orally once daily with a meal. |
| Geriatric use | No specific dose adjustment; use with caution due to potential age-related renal and hepatic impairment. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Proton pump inhibitors are contraindicated as they significantly decrease levels Can cause depressive disorders and hepatotoxicity.
| Breastfeeding | Rilpivirine is excreted into human breast milk at low concentrations. Limited data suggest the M/P ratio is approximately 1.1. In HIV-infected women, breastfeeding is contraindicated to prevent HIV transmission to the infant. For HIV-negative women, caution is advised due to potential infant exposure; no adverse effects reported. |
| Teratogenic Risk | Rilpivirine is classified as FDA Pregnancy Category B. In animal studies, no teratogenic effects were observed at exposures up to 15 times the human AUC. Human data are limited; however, available studies (including the Antiretroviral Pregnancy Registry) have not shown an increased risk of major birth defects. First trimester: no evidence of increased malformations. Second/third trimesters: no known fetal risks; continued use recommended to prevent HIV transmission. No specific trimester-specific risks identified. |
■ FDA Black Box Warning
There are no FDA boxed warnings for rilpivirine.
| Common Effects | Depression |
| Serious Effects |
["Concomitant use with CYP3A4 inducers (e.g., carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine, systemic dexamethasone, St. John's wort), which significantly reduce rilpivirine plasma concentrations and lead to loss of virologic response.","Concomitant use with proton pump inhibitors (e.g., omeprazole, esomeprazole, lansoprazole, pantoprazole, rabeprazole) due to decreased absorption and reduced efficacy."]
| Precautions | ["Hepatotoxicity: Monitor liver function; risk in patients with underlying hepatitis B or C.","Depressive disorders: May cause or exacerbate depression; monitor for symptoms.","QT interval prolongation: Use with caution with drugs that prolong QT or in patients with pre-existing QT prolongation.","Severe skin and hypersensitivity reactions: Discontinue if signs of severe rash or hypersensitivity.","Lipid elevations: Increases in total cholesterol and LDL occur.","Hepatitis B/C co-infection: Increased risk of hepatic adverse events.","Fat redistribution: May occur."] |
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| Fetal Monitoring | Monitor maternal HIV viral load, CD4 count, and adherence to therapy. No specific fetal monitoring required beyond routine prenatal care. Consider hepatic function and renal function tests as part of standard regimen monitoring. |
| Fertility Effects | No evidence of impaired fertility in animal studies. In humans, no significant adverse effects on fertility have been reported. Rilpivirine may reduce the efficacy of hormonal contraceptives; alternative non-hormonal contraception is recommended. |