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).
| 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.
