EDURANT
Clinical safety rating: caution
Comprehensive clinical and safety monograph for EDURANT (EDURANT).
Rilpivirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) that binds to HIV-1 reverse transcriptase, causing conformational changes that inhibit enzyme activity and viral replication.
| Metabolism | Primarily metabolized by CYP3A4; minor contributions from CYP1A1, CYP1A2, CYP2C19, and CYP2C9. |
| Excretion | Renal (~25% unchanged) and fecal (~60% as metabolites); total recovery ~85% |
| Half-life | Terminal half-life 38 hours (range 25-57 h); supports once-daily dosing, steady state at ~7 days |
| Protein binding | ~99.7% bound to albumin and alpha-1-acid glycoprotein |
| Volume of Distribution | Vd/F 0.66 L/kg (oral), indicating extensive tissue distribution (approx. 50 L in 70 kg adult) |
| Bioavailability | Oral absolute bioavailability not determined; ~100% relative to solution; food effect: 2-fold increase with meal, requires administration with food |
| Onset of Action | Oral: Not applicable; steady-state viral suppression typically by 4 weeks |
| Duration of Action | Once-daily dosing maintains therapeutic concentrations throughout 24-hour interval; viral suppression sustained with adherence |
| 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 for use in severe renal impairment (CrCl <30 mL/min) or end-stage renal disease. |
| Liver impairment | No dose adjustment required for mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment. Not recommended for use in severe hepatic impairment (Child-Pugh C). |
| Pediatric use | Approved for use in pediatric patients aged 12 years and older weighing at least 35 kg: 25 mg orally once daily with a meal. Not approved for children under 12 years or weighing less than 35 kg. |
| Geriatric use | No specific dose adjustment required based solely on age; clinical studies included limited numbers of patients ≥65 years. Monitor renal function due to age-related decline and potential for other comorbidities. |
| 1st trimester | Insufficient human data; animal studies show no evidence of teratogenicity at clinically relevant exposures. Use only if benefit outweighs risk. |
| 2nd trimester | Limited human data; no known risk of fetal harm based on available studies. Preferred NNRTI in pregnancy due to favorable safety profile. |
| 3rd trimester | No adverse fetal effects reported; pharmacokinetics may be altered in pregnancy, dose adjustments may be needed. |
Clinical note
Comprehensive clinical and safety monograph for EDURANT (EDURANT).
| Placental transfer | Rilpivirine crosses the placenta in humans; cord blood concentrations are approximately 60-70% of maternal concentrations. |
| Breastfeeding | Rilpivirine is excreted in human breast milk in low concentrations. The WHO recommends exclusive breastfeeding for infants of HIV-positive mothers on effective ART. However, potential for viral transmission through breastfeeding exists regardless of maternal therapy. Only use if benefits to mother outweigh potential risks to infant. |
■ FDA Black Box Warning
None
| Serious Effects |
History of hypersensitivity to rilpivirine or any component of the formulationCoadministration with drugs that significantly reduce rilpivirine exposure (e.g., rifampin, rifapentine, carbamazepine, oxcarbazepine, phenobarbital, phenytoin, systemic dexamethasone at doses >4 mg once daily, St. John's wort)
| Precautions | Hepatotoxicity: elevation of liver enzymes, especially in patients with HBV or HCV co-infection, Depressive disorders: increased risk of depression, suicidal ideation, Skin reactions: severe rash, including Stevens-Johnson syndrome, QT interval prolongation: use with caution in patients at risk of Torsades de Pointes, Fat redistribution and immune reconstitution syndrome, Increased risk of adverse reactions when co-administered with strong CYP3A4 inducers or inhibitors |
| Food/Dietary | Rilpivirine must be administered with a meal containing at least 400 kilocalories. A meal enhances absorption; without food, AUC decreases by ~50% and Cmax decreases. The type of meal (high-fat vs low-fat) does not significantly affect absorption as long as caloric content is adequate. Grapefruit juice has no known significant interaction with rilpivirine. |
Loading safety data…
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | Insufficient human data; animal studies show no evidence of teratogenicity at exposures up to 10 times the human exposure. No known fetal risk in any trimester. |
| Fetal Monitoring | Monitor HIV viral load and CD4+ count throughout pregnancy and postpartum. Assess liver function tests and renal function. No specific fetal monitoring required. |
| Fertility Effects | No significant adverse effects on fertility observed in animal studies. No human data on fertility impact. |
| Clinical Pearls | Edurant (rilpivirine) is a non-nucleoside reverse transcriptase inhibitor (NNRTI) for HIV-1 treatment, always used as part of combination antiretroviral therapy. It must be taken with a meal (≥400 kcal) to ensure adequate absorption; without food, exposure decreases by ~50%. It is not recommended for patients with viral load >100,000 copies/mL at initiation due to higher risk of virologic failure. Co-administration with proton pump inhibitors is contraindicated due to significant reduction in rilpivirine concentrations. Use with H2-receptor antagonists requires staggered dosing (12 hours apart). Caution with QTc-prolonging drugs; rilpivirine may prolong QTc interval. |
| Patient Advice | Take this medication exactly as prescribed, always with a meal (at least 400 calories) to ensure it works properly. · Never skip doses; missing doses can lead to drug resistance. · Avoid taking this drug with proton pump inhibitors (e.g., omeprazole, esomeprazole). · If you take an H2-blocker (e.g., famotidine, ranitidine), take Edurant at least 12 hours before or after the H2-blocker. · Tell your doctor about all other medications, including over-the-counter drugs and supplements, to avoid interactions. · This drug does not cure HIV; you can still transmit the virus to others. Use safer sex practices and do not share needles. · Attend all lab appointments to monitor viral load and CD4 count. · Report any symptoms of liver problems (dark urine, jaundice, nausea) or rash immediately. |