ISENTRESS HD
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ISENTRESS HD (ISENTRESS HD).
Integrase strand transfer inhibitor (INSTI). Inhibits the catalytic activity of HIV-1 integrase, preventing integration of viral DNA into host genome.
| Metabolism | Primarily metabolized by UGT1A1 (glucuronidation), with minor contribution from CYP3A4. Raltegravir is a substrate of P-glycoprotein (P-gp). |
| Excretion | Primarily hepatic metabolism via UGT1A1 with glucuronidation; 51% excreted in feces (mainly as parent drug) and 32% in urine (mostly as metabolites). |
| Half-life | Terminal elimination half-life is approximately 12.9 hours in adults, supporting twice-daily dosing. Prolonged in hepatic impairment. |
| Protein binding | Approximately 83% bound to human plasma proteins, primarily albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Mean volume of distribution is 2.9 L/kg, indicating extensive extravascular distribution including into tissues such as the central nervous system. |
| Bioavailability | Absolute bioavailability not determined; relative bioavailability of the 600 mg tablet is comparable to the 400 mg tablet. Absorption is rapid, with mean peak plasma concentrations reached in 2–3 hours. |
| Onset of Action | Within 1–2 hours after oral administration; maximal viral suppression achieved within 2–4 weeks when used in combination therapy. |
| Duration of Action | Dosing interval is 12 hours; steady-state achieved within 2 days. Duration of suppressive effect is dependent on adherence and combination regimen. |
600 mg orally twice daily, with or without food.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). For severe renal impairment (CrCl <30 mL/min), data insufficient to recommend dose adjustment; use with caution. Not recommended in ESRD not on dialysis. |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B). Not studied in severe hepatic impairment (Child-Pugh C). |
| Pediatric use | For body weight ≥25 kg: 600 mg orally twice daily. For body weight <25 kg: use the appropriate formulation (e.g., ISENTRESS chewable tablets or oral granules) according to prescribing information. |
| Geriatric use | No specific dose adjustment recommended for elderly patients; select dose with caution due to age-related renal and hepatic decline, and monitor for adverse effects. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ISENTRESS HD (ISENTRESS HD).
| Breastfeeding | Raltegravir is excreted into human breast milk. The milk-to-plasma (M/P) ratio is approximately 0.3-0.6. Limited data suggest infant exposure is low, with estimated relative infant dose of 2-3% of maternal weight-adjusted dose. The American Academy of Pediatrics considers raltegravir compatible with breastfeeding. However, in the US, breastfeeding is not recommended for HIV-positive mothers due to risk of HIV transmission. |
| Teratogenic Risk | Isentress HD (raltegravir) is classified as FDA Pregnancy Category B. Studies in animals have not demonstrated teratogenic risk. In humans, data from the Antiretroviral Pregnancy Registry do not show an increased risk of major birth defects compared to the background rate. First trimester exposure shows no significant increase in malformations. Second and third trimester exposure is considered safe, with no known fetal toxicity. However, there is a theoretical risk of mitochondrial dysfunction with prolonged in utero exposure, but clinical significance is uncertain. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Concomitant administration with aluminum- or magnesium-containing antacids (reduces raltegravir absorption); may be given separated by 2 hours","Severe hypersensitivity (e.g., Stevens-Johnson syndrome) to raltegravir or any component"]
| Precautions | ["Immune reconstitution syndrome","Potential for drug interactions with strong UGT1A1 inducers (e.g., rifampin), which may reduce raltegravir levels and require dose adjustment","Hypersensitivity reactions (rash, severe skin reactions including Stevens-Johnson syndrome)","Myopathy/rhabdomyolysis (rare)","Hepatotoxicity (including liver enzyme elevations) in patients with underlying liver disease or co-infection with hepatitis B/C","Decreased bone mineral density reported"] |
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| Fetal Monitoring | Monitor maternal viral load every 2-4 weeks during pregnancy, especially near delivery. CD4+ count should be monitored every 3 months. Fetal ultrasound for growth and development is recommended at 18-20 weeks and again in third trimester. Hepatic and renal function tests should be performed periodically. Monitor for signs of drug-induced hepatitis or rash. |
| Fertility Effects | No significant adverse effects on fertility have been reported in animal studies or human data. Raltegravir does not affect spermatogenesis or ovulation. It is not known to impair female or male fertility. No dose adjustment is required for fertility treatment. |