ISENTRESS
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ISENTRESS (ISENTRESS).
Inhibitor of HIV-1 integrase, blocking strand transfer step of retroviral DNA integration into host genome.
| Metabolism | Primarily glucuronidation via UGT1A1; minor CYP3A4 metabolism. |
| Excretion | Renal (approximately 51% as unchanged drug via glomerular filtration and active tubular secretion) and fecal (approximately 32% as unchanged drug). |
| Half-life | Terminal elimination half-life is approximately 7–12 hours; no significant accumulation with twice-daily dosing. |
| Protein binding | Approximately 83% bound to human plasma proteins, primarily albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Apparent volume of distribution is 1.7–2.3 L/kg, indicating extensive tissue distribution and intracellular penetration. |
| Bioavailability | Oral bioavailability is approximately 60–70%; absorption is not significantly affected by food. |
| Onset of Action | Oral (tablet): Time to maximal suppression of HIV RNA is approximately 2–4 weeks after starting therapy. |
| Duration of Action | Twice-daily dosing maintains effective intracellular concentrations throughout the 12-hour dosing interval; continuous suppression requires strict adherence. |
| Action Class | Integrase (HIV) inhibitors |
| Brand Substitutes | Zepdon 400mg Tablet |
400 mg orally twice daily.
| Dosage form | POWDER |
| Renal impairment | CrCl <30 mL/min: 400 mg orally twice daily (no dose adjustment needed based on pharmacokinetics; use with caution in severe renal impairment). |
| Liver impairment | Mild to moderate hepatic impairment (Child-Pugh A or B): no dose adjustment. Severe hepatic impairment (Child-Pugh C): not recommended due to lack of data. |
| Pediatric use | Body weight ≥25 kg: 400 mg orally twice daily. Body weight ≥10 kg to <25 kg: 75 mg or 100 mg (using oral granules) twice daily based on weight bands: 10-15 kg: 75 mg; 15-20 kg: 100 mg; 20-25 kg: 150 mg. Body weight 3-10 kg: 50 mg (using oral granules) twice daily. |
| Geriatric use | No specific dose adjustment recommended; monitor renal function as age-related decline may increase exposure. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ISENTRESS (ISENTRESS).
| Breastfeeding | Raltegravir is excreted into human breast milk; estimated infant daily dose is 0.03-0.08 mg/kg (approximately 1-3% of maternal dose). Milk-to-plasma ratio is approximately 0.03. Breastfeeding is not recommended for mothers with HIV in developed countries due to risk of HIV transmission. In settings where breastfeeding is practiced, raltegravir is one of the preferred agents due to low infant exposure. |
| Teratogenic Risk | Isentress (raltegravir) is classified as FDA Pregnancy Category B. Human data are limited, but no increased risk of major birth defects has been observed in first trimester exposures. Animal studies show no teratogenicity at clinically relevant doses. Due to the benefit of HIV treatment in pregnancy, use is recommended. Adequate and well-controlled studies in pregnant women are not available. |
■ FDA Black Box Warning
None
| Serious Effects |
["Concurrent administration with drugs that are strong UGT1A1 inducers (e.g., rifampin) due to decreased raltegravir levels"]
| Precautions | ["Severe, potentially life-threatening skin reactions (Stevens-Johnson syndrome, hypersensitivity reactions)","Immune reconstitution syndrome","Myopathy/rhabdomyolysis","QT prolongation"] |
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| Fetal Monitoring | Monitor HIV RNA viral load and CD4 count at least every trimester and at delivery. Assess liver function tests and complete blood count periodically. Fetal monitoring includes ultrasound for growth and anatomy per standard obstetric care. No specific fetal monitoring beyond routine is required for raltegravir alone. |
| Fertility Effects | No known adverse effects on fertility in animal studies. In humans, no data suggest impaired fertility in men or women. HIV infection itself may affect fertility, but treatment with antiretrovirals including raltegravir may improve reproductive health. |