raltegravir
Brand: Isentress, Isentress HD
Prototype: dolutegravir
Drug Class: HIV integrase strand transfer inhibitor (INSTI)
Drug Family: antiretroviral
Subclass: first-generation integrase inhibitor
Organ Systems: infectious-disease
Mechanism of Action
First-in-class INSTI; binds the active site of HIV integrase with a divalent metal chelation mechanism, blocking the strand transfer of HIV DNA into the host chromosome; does not inhibit CYP3A4, making it the INSTI with the fewest metabolic drug interactions.
HIV integrase (strand transfer step)
Indications
- HIV-1 infection (treatment-naïve and experienced)
- HIV-1 infection in pregnant women near delivery (rapid ART initiation)
Contraindications
- raltegravir hypersensitivity
Adverse Effects
Common
- nausea
- headache
- diarrhea
- fatigue
Serious
- severe skin reactions (SJS, TEN — rare)
- elevated CPK, rhabdomyolysis
- hypersensitivity reactions
- immune reconstitution inflammatory syndrome
Pharmacokinetics (ADME)
| Absorption | moderate bioavailability; administer with or without food (HD tablet requires feeding) |
| Distribution | widely distributed; 83% protein-bound |
| Metabolism | primarily UGT1A1 (glucuronidation) — NO significant CYP3A4 involvement |
| Excretion | fecal (51%) and renal (32%) |
| Half-life | 9 hours |
| Onset | 1–2 hours |
| Peak | 1–1.5 hours |
| Duration | twice daily (standard) or once-daily HD 1200 mg |
| Protein Binding | 83% |
| Vd | moderate |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| rifampin | UGT1A1 induction reduces raltegravir AUC by 40–61%; increase raltegravir to 800 mg BID with rifampin | major |
| polyvalent cations (antacids with calcium, magnesium) | chelation reduces absorption; take separately | moderate |
Nursing Considerations
- Raltegravir's lack of CYP3A4 metabolism makes it the preferred INSTI for patients with complex drug interactions involving CYP3A4.
- Twice-daily dosing of standard tablets can be challenging for adherence; the HD formulation (1200 mg once-daily) offers a once-daily option.
- Monitor CPK in patients with myopathy risk; rhabdomyolysis has been reported.
- Administer antacids separately by ≥2–4 hours to avoid chelation.
Clinical Pearls
- Raltegravir was the first FDA-approved INSTI, proving the integrase inhibitor concept in HIV therapy; its lack of CYP3A4 metabolism distinguishes it pharmacokinetically from subsequent INSTIs (dolutegravir, bictegravir) but lower genetic barrier to resistance limits its use.
- Due to its lack of pharmacokinetic boosting requirements and minimal drug interactions, raltegravir is a preferred regimen component during pregnancy when initiating antiretroviral therapy late in pregnancy.
Safety Profile
Pregnancy use-with-caution
Lactation avoid
Renal Adjustment Not required
Hepatic Adjustment Not required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.