INTELENCE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for INTELENCE (INTELENCE).
Non-nucleoside reverse transcriptase inhibitor (NNRTI). Binds directly to HIV-1 reverse transcriptase, causing allosteric inhibition of RNA-dependent and DNA-dependent DNA polymerase activities.
| Metabolism | Primarily metabolized by CYP3A (CYP3A4) and to a lesser extent by CYP2C9 and CYP2C19. |
| Excretion | Primarily fecal (76.6% as unchanged drug or metabolites) with minor renal excretion (19.6%, of which 1.2% is unchanged). Biliary elimination of metabolites may occur. |
| Half-life | Terminal elimination half-life is approximately 40 hours (range 30-60 hours). This supports once-daily dosing with 400 mg (two 200 mg tablets) after initial twice-daily dosing for 2 weeks, but note that etravirine is only approved for twice-daily dosing (200 mg twice daily) in treatment-experienced patients. |
| Protein binding | 99.9% bound to plasma proteins, primarily alpha-1-acid glycoprotein and albumin. |
| Volume of Distribution | Apparent volume of distribution is approximately 2.9 L/kg (range 2.5-3.5 L/kg), indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability is not precisely determined due to lack of an intravenous formulation; absorption is enhanced with food (50% increase in AUC compared to fasting). |
| Onset of Action | No immediate onset; as a non-nucleoside reverse transcriptase inhibitor (NNRTI), it inhibits HIV-1 replication after reaching steady-state concentrations (achieved in ~2 weeks). Steady-state is reached in 14 days with twice-daily dosing. |
| Duration of Action | With twice-daily dosing, plasma concentrations remain above the protein-binding-adjusted 90% inhibitory concentration (IC90) for wild-type HIV-1 throughout the dosing interval. Duration of antiviral effect is continuous with adherence. |
| Molecular Weight | 435.29 |
200 mg orally twice daily after a meal.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. Not studied in severe renal impairment or ESRD. |
| Liver impairment | Mild to moderate hepatic impairment (Child-Pugh Class A or B): no adjustment. Severe hepatic impairment (Child-Pugh Class C): not recommended. |
| Pediatric use | Body weight ≥25 kg: 200 mg twice daily; 16 to <25 kg: 150 mg twice daily; 10 to <16 kg: 100 mg twice daily. Administer after a meal. |
| Geriatric use | No specific dose adjustment; use with caution due to age-related hepatic, renal, or cardiac dysfunction and potential for drug interactions. |
| 1st trimester | No adequate studies in pregnant women; use only if potential benefit justifies risk. Antiretroviral Pregnancy Registry data do not show increased risk of major birth defects. |
| 2nd trimester | No evidence of fetal harm in animal studies; use if needed. Registry data do not indicate increased risk. |
| 3rd trimester | Safe to use; no known adverse effects on fetus. Recommended as part of combination therapy for HIV in pregnancy. |
Clinical note
Comprehensive clinical and safety monograph for INTELENCE (INTELENCE).
| Placental transfer | Etravirine crosses the placenta with cord blood concentrations approximately 50% of maternal plasma levels. |
| Breastfeeding | Breastfeeding is not recommended in HIV-infected women due to risk of postnatal transmission. Etravirine is present in human milk at low levels; potential for infant adverse effects unknown. |
■ FDA Black Box Warning
No black box warning.
| Serious Effects |
Severe hepatic impairment (Child-Pugh Class C)Concomitant use with strong CYP3A4 inducers (e.g., carbamazepine, phenobarbital, phenytoin, rifampin, rifapentine)Hypersensitivity to etravirine or any excipients
| Precautions | Severe skin and hypersensitivity reactions (including Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis) have been reported., Hepatotoxicity has been reported, including in patients with no pre-existing hepatic disease., Immune reconstitution syndrome has been reported., Lipodystrophy and redistribution of body fat may occur. |
| Food/Dietary | Etravirine should be taken with food to increase bioavailability. A standard meal (e.g., breakfast or dinner) is sufficient. Avoid high-fat meals if gastrointestinal upset occurs. No specific food restrictions otherwise. |
Loading safety data…
| Lactation Rating | L4 (possibly hazardous) - avoid breastfeeding while on this drug |
| Teratogenic Risk | Pregnancy category B. No evidence of teratogenicity in animal studies; no adequate human studies. Avoid in first trimester due to theoretical risk; use only if benefit outweighs risk. |
| Fetal Monitoring | Monitor HIV viral load, CD4 count, hepatic function, and complete blood count throughout pregnancy. Fetal ultrasound for anomalies if exposure occurs. |
| Fertility Effects | No known effects on fertility in humans; animal studies show no impairment. |
| Clinical Pearls | INTELENCE (etravirine) is a non-nucleoside reverse transcriptase inhibitor (NNRTI) for HIV-1 treatment in treatment-experienced adults. It requires twice-daily dosing with food to enhance absorption. Avoid coadministration with certain NNRTIs (e.g., efavirenz, nevirapine) and potent CYP3A4 inducers. Monitor for severe skin reactions, including Stevens-Johnson syndrome, especially during first weeks. Dose adjustment needed with strong CYP3A4 inhibitors like ritonavir-boosted protease inhibitors. |
| Patient Advice | Take etravirine twice daily with a meal to ensure proper absorption. · Do not miss doses as this can lead to drug resistance. · Report any rash, fever, or blistering immediately as it may be a serious allergic reaction. · Inform your doctor of all other medications, including antacids, as they may interfere with etravirine. · Store at room temperature away from moisture and heat. |