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 |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for EDURANT (EDURANT).
| Breastfeeding | Unknown if excreted in human breast milk. M/P ratio not established. Use with caution in breastfeeding women only if clearly needed due to potential for HIV transmission and adverse effects in nursing infant. |
| 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 |
■ FDA Black Box Warning
None
| Serious Effects |
["Coadministration with drugs that significantly induce CYP3A4 (e.g., rifampin, carbamazepine, phenytoin, St. John's wort)","Coadministration with drugs that increase gastric pH (e.g., proton pump inhibitors)","Severe hepatic impairment (Child-Pugh Class C)"]
| 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"] |
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| 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. |