Brand Name: Isentress, Isentress HD
Pharmacologic Class
Integrase Strand Transfer Inhibitor (INSTI)
— an antiretroviral used in the management of HIV-1 infection.
Mechanism of Action
Raltegravir inhibits the HIV integrase enzyme, which is essential for viral replication.
- Specifically, it blocks the strand transfer step of viral DNA integration into the host genome.
- This prevents the formation of proviral DNA, halting viral replication and infection of new cells.
Therapeutic Indications
- Treatment of HIV-1 infection in adults and pediatric patients (≥4 weeks of age and ≥3 kg).
- Used in combination antiretroviral therapy (ART) with other agents (e.g., nucleoside reverse transcriptase inhibitors).
Available Formulations
| Formulation | Strength | Brand |
|---|---|---|
| Tablet (film-coated) | 400 mg | Isentress® |
| Chewable tablet | 25 mg, 100 mg | Isentress® |
| Tablet (HD) | 600 mg | Isentress HD® |
| Oral suspension | 10 mg/mL (single-use packets) | Isentress® |
Dosage (Adults)
| Formulation | Dose | Frequency |
|---|---|---|
| Standard tablets (400 mg) | 400 mg | Twice daily |
| HD tablets (600 mg) | 1,200 mg (two 600 mg tablets) | Once daily (with or without food) |
Note: Do not interchange the 400 mg BID and 1,200 mg QD regimens — pharmacokinetics differ.
Pediatric Dosing (Weight-Based)
- Chewable tablets or oral suspension may be used for children ≥4 weeks and ≥3 kg.
- Dosing varies by weight and formulation (refer to specific product monograph or DHHS HIV Guidelines).
Renal & Hepatic Considerations
| Organ Impairment | Adjustment Needed? | Notes |
|---|---|---|
| Renal impairment | No adjustment | Not renally eliminated. |
| Hepatic impairment | Caution in moderate-to-severe | Mainly metabolized hepatically (UGT1A1). Monitor closely. |
Pharmacokinetics
| Parameter | Details |
|---|---|
| Absorption | Rapid; Tmax ~1–3 h |
| Metabolism | Glucuronidation via UGT1A1 (not CYP450) |
| Elimination half-life | ~9 h (standard); ~12 h (HD formulation) |
| Excretion | Primarily fecal (51%), renal (32%) |
Major Drug Interactions
| Drug/Class | Effect | Recommendation |
|---|---|---|
| Rifampin | ↓ Raltegravir levels via UGT1A1 induction | Increase raltegravir dose to 800 mg BID. |
| Antacids with Al³⁺/Mg²⁺ | ↓ Absorption | Avoid coadministration; Ca²⁺-based antacids acceptable. |
| Efavirenz, tipranavir/ritonavir | Slight ↓ in levels | No dose adjustment but monitor virologic response. |
Adverse Effects
| Common | Serious/Rare |
|---|---|
| Headache, nausea, fatigue, insomnia | Rash, hypersensitivity, rhabdomyolysis, depression, elevated CPK, hepatotoxicity |
Monitoring Parameters
- HIV viral load and CD4+ count
- CPK (if myopathy symptoms)
- Liver function tests (ALT/AST)
- Adherence and tolerability
Contraindications: Hypersensitivity to raltegravir or formulation components.
Clinical Pearls
- No CYP450 interactions — suitable for patients on multiple concomitant drugs.
- Well tolerated compared to protease inhibitors.
- Can be used in pregnancy (category B; evidence supports safety).
- Rapid viral suppression — often used in initial ART regimens.
- Take with or without food.
Example Regimen (First-Line Combination)
- Raltegravir 400 mg PO BID
- Tenofovir disoproxil fumarate 300 mg / Emtricitabine 200 mg PO once daily
- → potent, well-tolerated triple therapy for HIV-1.
Synonyms
Isentress, Isentress HD