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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for INTELENCE (INTELENCE).
| Breastfeeding | Contraindicated during breastfeeding due to potential for HIV transmission and unknown drug excretion in human milk; M/P ratio not established. |
| 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 |
■ FDA Black Box Warning
No black box warning.
| Serious Effects |
["Concomitant use with strong CYP3A inducers (e.g., rifampin, carbamazepine, phenytoin, phenobarbital, St. John's wort)."]
| 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."] |
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| 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. |