Dosing and uses of Edurant (rilpivirine)
Adult dosage forms and strengths
tablet
- 25mg
HIV-1 Infection
Indicated in combination with other antiretroviral agents for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in treatment-naïve adult patients with HIV-1 RNA <100,000 copies/mL
25 mg PO qDay; administer with a meaL
Renal & Hepatic Impairment
Renal impairment
- Mild-to-moderate renal impairment: No dose adjustment required
- Severe renal impairment or ESRD: Used with caution and with increased monitoring for adverse effects, plasma concentrations may be increased because of altered drug absorption, distribution, and metabolism secondary to renal dysfunction
- Dialysis: Highly bound to plasma proteins, unlikely to be significantly removed by hemodialysis or peritoneal dialysis
Hepatic impairment
- Mild-to-moderate hepatic impairment (Child-Pugh Classes A and B): No dose adjustment required
- Severe hepatic impairment (Child-Pugh Class C): Has not been studied
Pediatric dosage forms and strengths
tablet
- 25mg
HIV-1 Infection
Indicated in combination with other antiretroviral agents for treatment of HIV-1 infection in treatment-naïve adolescents aged 12-17 yr with HIV-1 RNA ≤100,000 copies/mL
<12 years: Safety and efficacy not established
12-17 years (weight ≥35 kg): 25 mg PO qDay; administer with a meaL
Edurant (rilpivirine) adverse (side) effects
1-10%
Depressive disorders (4%)
Insomnia (3%)
Headache (3%)
Rash (3%)
Increased AST (2%; grade 3 or higher)
ALT increased (19%)
Abnormal dreams (1%)
Nausea (1%)
Suicidal ideation (4-8%)
Abdominal pain (1%)
Vomiting (1%)
Fatigue (1%)
Dizziness (1%)
Posmarketing reports
Severe skin and hypersensitivity reactions including DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms)
Warnings
Contraindications
Hypersensitivity
Coadministration with drugs (eg, CYP inducers like phenobarbital, dexamethasone, oxcarbazepine, phenytoin, or carbamazepine) where significant decreases in rilpivirine plasma concentrations may occur, which may result in loss of virologic response and possible resistance and cross-resistance to other NNRTIs
Contraindicated with drugs that increase gastric pH (eg, esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole) that may decrease rilpivirine absorption and result in decreased rilpivirine plasma concentrations
Cautions
Coadministration with other NNRTIs may either increase or decrease rilpivirine; avoid use with other NNRTIs
Supratherapeutic doses (ie, 75 mg and 300 mg qDay) have been shown to prolong the QTc interval; caution when coadministered with a drug known to increase risk of Torsade de Pointes
May increase risk for depressive disorders
Hepatic adverse effects reported; patients with underlying hepatitis B or C, or marked increased transaminases prior to treatment may be at increased risk; monitor for hepatotoxicity before initiating and during treatment
Redistribution/accumulation of body fat, including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and “cushingoid appearance” have been observed in patients receiving antiretroviral therapy
Immune reconstitution syndrome: During initial phase of combination ART treatment, patients whose immune system responds may develop an inflammatory response to indolent or residual opportunistic infections (eg, Mycobacterium avium complex, CMV, Pneumocystis pneumonia, TB)
Severe skin and hypersensitivity reactions reported, including cases of drug reaction with eosinophilia and systemic symptoms (DRESS), with rilpivirine-containing regimens; immediately discontinue treatment if hypersensitivity or rash with systemic symptoms or elevations in hepatic serum biochemistries develop and closely monitor clinical status, including hepatic serum biochemistries
Use caution in patients taking major CYP3A inducers or drugs that increase gastric pH
Virologic failure & resistance
- More rilpivirine treated individuals with HIV-1 RNA >100,000 copies/mL at the start of therapy experienced virologic failure compared to those with <100,000 copies/mL
- Observed virologic failure rate in rilpivirine treated individuals conferred a higher rate of overall treatment resistance and cross-resistance to the NNRTI class compared to efavirenz
- More individuals treated with rilpivirine developed lamivudine/emtricitabine associated resistance compared to efavirenz
Pregnancy and lactation
Pregnancy category: B; Antiretroviral Pregnancy Registry 1-800-258-4263
Lactation: Unknown whether distributed in human breast milk; The CDC recommends that mothers should not breastfeed their infants because of risk of postnatal HIV transmission
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Edurant (rilpivirine)
Mechanism of action
Antiviral agent; diarylpyrimidine non-nucleoside reverse transcriptase inhibitor (NNRTI) of HIV-1
Inhibits HIV-1 replication by noncompetitive inhibition of HIV-1 reverse transcriptase
Does not inhibit the human cellular DNA polymerases alpha, beta, and gamma
Absorption
Bioavailability: Absolute bioavailability unknown
Peak Plasma Time: 4-5 hr
Peak Plasma Concentration: 80 ng/mL (mean)
AUC: 2397 ng•h/mL (mean)
Food: Exposure ~40% lower when taken in a fasted condition as compared to a normal caloric meal (533 kcal) or high-fat high-caloric meal (928 kcal); when taken with only a protein-rich nutritional drink, exposures were 50% lower than when taken with a meaL
Distribution
Protein Bound: 99.7% (primarily to albumin)
Metabolism
Metabolized primarily by CYP3A
Elimination
Half-life: 50 hr
Excretion: feces (85%), urine (6.1%) bile, other
