RILPIVIRINE HYDROCHLORIDE
Clinical safety rating: safe
Proton pump inhibitors are contraindicated as they significantly decrease levels Can cause depressive disorders and hepatotoxicity.
Rilpivirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) of HIV-1. It binds to HIV-1 reverse transcriptase, causing a conformational change that inhibits enzyme activity and prevents viral RNA conversion to DNA.
| Metabolism | Primarily metabolized by CYP3A4; minor contributions from CYP2C8 and CYP2C19. |
| Excretion | Primarily hepatic metabolism (CYP3A4), with 85% of dose excreted in feces (unchanged drug and metabolites) and 6.1% in urine (unchanged drug). Renal elimination of unchanged drug is <1%. |
| Half-life | Terminal elimination half-life is approximately 34.6 hours (range 25–56 hours), supporting once-daily dosing. Steady-state reached in ~2 weeks. |
| Protein binding | Approximately 99.7% bound to albumin. |
| Volume of Distribution | Apparent volume of distribution (Vd/F) is 0.95 L/kg (mean; ~72 L), indicating extensive tissue distribution into extravascular spaces. |
| Bioavailability | Oral bioavailability is approximately 35% (range 25–50%) under fed conditions; reduced by 40% when taken fasting. Absorption is pH-dependent with increased gastric pH reducing absorption. |
| Onset of Action | Oral: Time to maximum plasma concentration (Tmax) is 3–4 hours post-dose. Antiviral activity begins within days, but clinical efficacy is assessed after 4–8 weeks. |
| Duration of Action | Duration of antiviral effect is 24 hours with once-daily dosing due to sustained plasma levels above IC95 for wild-type HIV-1. Missed doses >24 hours may lead to virologic failure. |
| Molecular Weight | 366.84 |
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 | Child-Pugh Class A and B: No dose adjustment. Child-Pugh Class C: Not recommended. |
| Pediatric use | For patients weighing ≥35 kg and aged ≥12 years: 25 mg orally once daily with a meal. Not approved for children <12 years or <35 kg. |
| Geriatric use | No specific dose adjustment; monitor renal function and consider potential for increased adverse effects due to age-related changes. |
| 1st trimester | Rilpivirine is generally not recommended in first trimester due to lack of adequate data; use only if benefit outweighs risk. Clinical data limited. |
| 2nd trimester | Limited data suggest no increased risk of major malformations; consider use if alternative therapies are not suitable. |
| 3rd trimester | No specific risks reported; may be used if indicated, with monitoring for maternal and fetal effects. |
Clinical note
Proton pump inhibitors are contraindicated as they significantly decrease levels Can cause depressive disorders and hepatotoxicity.
| FDA category | Animal |
| Placental transfer | Rilpivirine crosses the placenta with a cord blood to maternal plasma concentration ratio of approximately 0.5-0.6, indicating moderate transfer. |
■ FDA Black Box Warning
None.
| Common Effects | Depression |
| Serious Effects |
Hypersensitivity to rilpivirine or any excipientsCoadministration with certain enzyme inducers (e.g., rifampin, carbamazepine, phenytoin, St. John's wort) due to significant decrease in rilpivirine exposure
| Precautions | Hepatotoxicity, including severe cases and hepatic failure, Risk of QT interval prolongation; avoid use with drugs that prolong QT or in patients with hypokalemia, hypomagnesemia, or congenital long QT syndrome, Severe skin and hypersensitivity reactions (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis), Depressive disorders, including suicidal ideation, Lipodystrophy and metabolic changes, Immune reconstitution syndrome, Decreased efficacy with high baseline viral load (>100,000 copies/mL) or low CD4 count (<200 cells/mm^3) |
| Food/Dietary |
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| Breastfeeding |
| Rilpivirine is excreted into human breast milk in low concentrations. The amount is likely insufficient to cause adverse effects in the infant, but caution is advised. Due to potential for HIV transmission, breastfeeding is discouraged in HIV-positive women in resource-rich settings; in resource-limited settings, WHO guidelines may support breastfeeding while on ART. |
| Lactation Rating | L3 |
| Teratogenic Risk | Insufficient human data; animal studies show no teratogenic effects at exposures up to 15 times human exposure. No increased risk of major birth defects observed in limited case series. Avoid in first trimester unless benefit outweighs risk. |
| Fetal Monitoring | Monitor for hepatotoxicity, renal function, and hypersensitivity reactions. Perform fetal ultrasound if used in pregnancy. |
| Fertility Effects | No evidence of impaired fertility in animal studies. Human data limited. |
| Must be taken with a meal (≥400 calories) to ensure adequate absorption. Avoid grapefruit juice as it may decrease drug levels. |
| Clinical Pearls | Rilpivirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) used in combination therapy for HIV-1 infection. It should always be used with a boosted protease inhibitor or integrase inhibitor. Avoid use with proton pump inhibitors; separate from H2 antagonists by at least 12 hours. Administer with a meal to ensure adequate absorption. Monitor for hepatotoxicity and hypersensitivity reactions. Use with caution in patients with severe hepatic impairment. |
| Patient Advice | Take this medication exactly as prescribed, once daily with a meal. · Do not use antacids within 2 hours before or 4 hours after taking rilpivirine. · Avoid proton pump inhibitors (e.g., omeprazole) while on this medication. · Do not change your dose or stop taking without consulting your doctor. · Report any signs of liver problems: yellowing skin or eyes, dark urine, pale stools, nausea, vomiting, or abdominal pain. · Rilpivirine does not cure HIV and you can still transmit the virus; use safe sex practices. · Tell your doctor about all other medicines, including over-the-counter drugs and supplements. |