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. |
| Molecular Weight | 366.42 |
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 | Rilpivirine is not recommended during the first trimester due to limited data; however, if benefit outweighs risk, it may be used. No increased risk of major malformations observed in small studies. |
| 2nd trimester | Use with caution; data limited but no evidence of fetal harm from animal studies. Pharmacokinetic changes in pregnancy may require dose adjustment. |
| 3rd trimester | Use with caution; placental transfer occurs. Monitor for maternal viral suppression and potential neonatal effects. |
Clinical note
Proton pump inhibitors are contraindicated as they significantly decrease levels Can cause depressive disorders and hepatotoxicity.
| Placental transfer | Rilpivirine crosses the placenta; animal studies show transfer to fetus. Human data limited but measurable cord blood concentrations. |
| Breastfeeding | Rilpivirine is excreted into human milk at low concentrations; however, the potential for HIV transmission via breastfeeding contraindicates breastfeeding in HIV-positive mothers. In HIV-negative mothers, caution is advised due to unknown effects on infant. |
■ FDA Black Box Warning
There are no FDA boxed warnings for rilpivirine.
| Common Effects | Depression |
| Serious Effects |
Hypersensitivity to rilpivirine or any componentCoadministration with drugs that induce CYP3A4 (e.g., rifampin, carbamazepine, phenytoin, St. John's wort)Coadministration with proton pump inhibitors (e.g., omeprazole, esomeprazole, lansoprazole)
| 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. |
Loading safety data…
| Lactation Rating | L3 (Moderately Safe) or Avoid in HIV+ due to transmission risk |
| 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. |
| 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. |
| Food/Dietary |
| Rilpivirine must be taken with a meal (≥400 kcal) to achieve adequate absorption. A protein-rich meal or a standard meal (e.g., breakfast) is sufficient. Grapefruit juice may increase rilpivirine levels, but clinical significance is unknown; avoid excessive grapefruit juice consumption. |
| Clinical Pearls | Rilpivirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) with a long half-life (~50 hours). It must be taken with a meal to ensure adequate absorption. Avoid coadministration with proton pump inhibitors; separate antacids by at least 4 hours and H2 receptor antagonists by at least 12 hours. Rilpivirine is associated with a lower risk of neuropsychiatric side effects compared to efavirenz. Use with caution in patients with severe hepatic impairment (Child-Pugh class C). |
| Patient Advice | Take rilpivirine exactly once daily, always with a meal (not just a snack) to ensure the medication works properly. · Do not take antacids within 4 hours before or 4 hours after taking rilpivirine. · Separate H2 blockers (e.g., famotidine) by at least 12 hours before or 4 hours after rilpivirine. · Avoid proton pump inhibitors (e.g., omeprazole) while taking rilpivirine. · Tell your doctor if you have liver problems, depression, or are pregnant or breastfeeding. · Rilpivirine does not cure HIV or prevent transmission; use condoms and practice safe sex. |