EDURANT PED
Clinical safety rating: caution
Comprehensive clinical and safety monograph for EDURANT PED (EDURANT PED).
Edurant PED is a non-nucleoside reverse transcriptase inhibitor (NNRTI) of HIV-1. It binds to reverse transcriptase, causing a conformational change that inhibits the enzyme's RNA-dependent and DNA-dependent DNA polymerase activities, thereby blocking viral replication.
| Metabolism | Primarily metabolized by cytochrome P450 3A4 (CYP3A4). |
| Excretion | Rilpivirine is primarily metabolized by CYP3A4; after oral administration, approximately 85% of the dose is recovered in feces (mainly as unchanged drug and metabolites) and 6% in urine. Less than 1% is excreted unchanged in urine. |
| Half-life | Terminal elimination half-life is approximately 50 hours (range 34-73 h). This long half-life supports once-daily dosing and allows for sustained plasma concentrations. |
| Protein binding | Rilpivirine is approximately 99.7% bound to plasma proteins, primarily to albumin. |
| Volume of Distribution | Volume of distribution (Vd) is 152 L (approximately 2.2 L/kg). This large Vd indicates extensive tissue distribution, including penetration into lymphoid tissues and cerebrospinal fluid. |
| Bioavailability | Oral bioavailability is approximately 90% (range 75-95%) under fed conditions, but is significantly reduced (by about 40-50%) when taken with a high-fat meal. Rilpivirine should be taken with a meal to optimize absorption. |
| Onset of Action | Rilpivirine reaches steady-state plasma concentrations within approximately 2-4 weeks. Antiviral activity occurs promptly after achieving therapeutic concentrations, but full virologic suppression is typically observed after 2-4 weeks of once-daily dosing. |
| Duration of Action | Duration of action is approximately 24 hours due to the long half-life, allowing once-daily administration. If a dose is missed, the drug remains at subtherapeutic concentrations for an extended period, increasing risk of resistance. |
25 mg orally once daily with a meal.
| Dosage form | TABLET, FOR SUSPENSION |
| 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 (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment. Not recommended in severe hepatic impairment (Child-Pugh C). |
| Pediatric use | Approved for pediatric patients weighing ≥35 kg: 25 mg orally once daily with a meal. Not recommended for patients <12 years or weight <35 kg due to insufficient data. |
| Geriatric use | No specific dose adjustment; use with caution due to potential for decreased renal function and increased comorbidities. Monitor renal function and consider risk of QT prolongation. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for EDURANT PED (EDURANT PED).
| Breastfeeding | It is not known whether rilpivirine is excreted in human breast milk. Rilpivirine is present in the milk of lactating rats, and the milk-to-plasma ratio ranged from 0.7 to 5.9. Because of the potential for HIV transmission and adverse effects in nursing infants, mothers should be instructed not to breastfeed if they are receiving EDURANT PED. |
| Teratogenic Risk | Rilpivirine, the active ingredient in EDURANT PED, is classified as FDA Pregnancy Category B. In animal studies, no evidence of teratogenicity or fetal harm was observed at exposures up to 15 times the human exposure. However, there are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, EDURANT PED should be used during pregnancy only if clearly needed. Limited human data from the Antiretroviral Pregnancy Registry show no increased risk of major birth defects with first-trimester exposure compared to background rates. |
■ FDA Black Box Warning
None
| Serious Effects |
["Coadministration with potent CYP3A4 inducers (e.g., carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifampin, rifapentine, St. John's wort) due to decreased rilpivirine exposure and loss of virologic response.","Coadministration with proton pump inhibitors (e.g., esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole) due to significant reduction in rilpivirine absorption."]
| Precautions | ["Severe, life-threatening skin reactions (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis) have been reported; discontinue if rash with systemic symptoms or severe rash develops.","Hepatotoxicity: Elevations in liver enzymes and hepatic adverse events may occur; monitor liver function tests in patients with underlying hepatic disease or co-infected with hepatitis B or C.","Depressive disorders: New onset or worsening depression has been reported; monitor for psychiatric symptoms.","Lipid elevation: Increases in total cholesterol and triglycerides may occur; monitor lipid levels.","Immune reconstitution syndrome: May occur during initial treatment; monitor for inflammatory reactions.","Fat redistribution: Accumulation or loss of body fat may occur."] |
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| Fetal Monitoring | Monitor liver function tests (AST, ALT) and renal function (serum creatinine) periodically during pregnancy, as pregnancy may affect hepatic and renal function. Assess HIV RNA viral load and CD4 count at least every trimester to ensure adequate virologic response. Monitor for signs of depression or suicidality, as psychiatric adverse events have been reported with rilpivirine. Fetal monitoring should include standard prenatal ultrasound assessments. Consider ECG monitoring if risk factors for QTc prolongation are present, as rilpivirine may prolong the QTc interval. |
| Fertility Effects | In animal studies, rilpivirine had no effects on mating or fertility in male and female rats at doses up to 20 mg/kg/day (approximately 10 times the human exposure). There are no human data on the effect of rilpivirine on fertility. Based on animal data, EDURANT PED is not expected to impair fertility in humans. |