RALTEGRAVIR POTASSIUM
Clinical safety rating: safe
Animal studies have demonstrated safety
Raltegravir inhibits HIV integrase by binding to the integrase active site and blocking the strand transfer step of retroviral DNA integration, which is essential for viral replication.
| Metabolism | Primarily metabolized by glucuronidation via UGT1A1; minor metabolism by CYP3A4. |
| Excretion | Primarily hepatic metabolism via UGT1A1-mediated glucuronidation; <2% excreted unchanged in urine; approximately 51% of dose recovered in feces (as parent and metabolites) and 32% in urine (as metabolites); biliary/fecal elimination accounts for the majority. |
| Half-life | Terminal elimination half-life is approximately 9 hours (range 7–12 hours); supports twice-daily dosing; t1/2 is prolonged in hepatic impairment (Child-Pugh B/C) but no dose adjustment recommended. |
| Protein binding | Approximately 83% bound to human plasma proteins, predominantly albumin. |
| Volume of Distribution | Volume of distribution at steady state (Vss/F) is approximately 0.6 L/kg (total body water), indicating distribution into intracellular compartments; penetrates cerebrospinal fluid (CSF) achieving concentrations ~5–10% of plasma levels. |
| Bioavailability | Oral bioavailability is not precisely determined but is estimated to be high (≥60–70%) based on absorption and metabolism data; food may increase Cmax (up to 2-fold) but not AUC significantly; thus can be taken with or without food. |
| Onset of Action | Oral: Time to maximal plasma concentration (Tmax) is about 0.5–1.5 hours; antiviral effect typically observed within 1–2 weeks of therapy, with maximal viral suppression achieved by week 4–6. |
| Duration of Action | The drug is administered twice daily due to half-life; clinical effect on viral load maintained over dosing interval with sustained suppression; suboptimal adherence leads to rapid rebound of viremia. |
| Molecular Weight | 482.6 |
400 mg orally twice daily, with or without food. Administered as two 200 mg tablets or one 400 mg tablet.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for any degree of renal impairment, including end-stage renal disease on hemodialysis. |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh Class A or B). Not studied in severe hepatic impairment (Child-Pugh Class C); use with caution. |
| Pediatric use | For weight <3 kg: insufficient data. 3 kg to <4 kg: 50 mg twice daily. 4 kg to <6 kg: 80 mg twice daily. 6 kg to <10 kg: 100 mg twice daily. 10 kg to <14 kg: 150 mg twice daily. 14 kg to <20 kg: 200 mg twice daily. 20 kg to <28 kg: 250 mg twice daily. 28 kg to <40 kg: 300 mg twice daily. ≥40 kg: 400 mg twice daily. For children ≥2 years: can use oral granules for suspension or tablets. |
| Geriatric use | No specific dose adjustment recommended. Clinical studies did not include sufficient numbers of patients aged ≥65 years to determine if they respond differently. Use with caution due to potential comorbidities and renal/hepatic function decline. |
| 1st trimester | Limited human data; no teratogenicity in animal studies. Use if benefit outweighs risk. |
| 2nd trimester | No evidence of fetal harm in human studies; pharmacokinetics unchanged. |
| 3rd trimester | No evidence of fetal harm; may be used for HIV-1 treatment. |
Clinical note
Strong UGT1A1 inducers may decrease levels Can cause severe and potentially fatal skin reactions.
| Placental transfer | Crosses placenta; cord blood concentrations approximately 10-50% of maternal plasma. |
| Breastfeeding | Present in human milk at low concentrations; estimated infant dose <1% of maternal therapeutic dose. Consider benefit of breastfeeding versus potential risk of HIV transmission. |
| Lactation Rating |
■ FDA Black Box Warning
None.
| Common Effects | Headache |
| Serious Effects |
Hypersensitivity to raltegravir or any component
| Precautions | Severe skin and hypersensitivity reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported., Immune reconstitution syndrome may occur., Increased risk of creatine kinase elevation and myopathy/rhabdomyolysis., May cause liver enzyme elevations in patients with hepatitis B or C coinfection. |
| Food/Dietary | Raltegravir may be taken with or without food. There are no significant food interactions. However, high-fat meals may slightly increase absorption but not clinically relevant. |
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| Teratogenic Risk | First trimester: No increased risk of major birth defects based on data from >1000 exposed pregnancies; however, neural tube defects have been reported in animal studies at doses exceeding human exposure. Second and third trimesters: No evidence of fetal harm; raltegravir crosses the placenta with cord blood concentrations approximately equal to maternal plasma. |
| Fetal Monitoring | Monitor maternal HIV viral load and CD4 count regularly during pregnancy. Assess for maternal adverse effects such as hepatotoxicity, rash, and immune reconstitution syndrome. Consider fetal ultrasound for growth and well-being. |
| Fertility Effects | No adverse effects on fertility have been reported in animal studies. Human data are inadequate to determine impact on fertility. |
| Clinical Pearls | Raltegravir is a first-line integrase strand transfer inhibitor (INSTI) for HIV-1 treatment. It is often used in combination with two NRTIs. Unlike other INSTIs, raltegravir requires twice-daily dosing. It has a low potential for drug-drug interactions due to minimal CYP450 metabolism. Common adverse effects include insomnia, headache, and nausea. Raltegravir can be taken without regard to food. Monitor for elevation of creatine kinase and risk of myopathy/rhabdomyolysis, especially in patients on statins or with renal impairment. In pregnancy, raltegravir is preferred due to extensive safety data. |
| Patient Advice | Take raltegravir exactly as prescribed, twice daily, to maintain effective HIV suppression. · You may take this medication with or without food. · Do not miss doses; if you miss a dose, take it as soon as you remember unless it is almost time for your next dose. · Common side effects include difficulty sleeping, headache, nausea, and tiredness; report any muscle pain or weakness to your doctor. · Raltegravir does not cure HIV or prevent transmission; use barrier protection and avoid sharing needles. · Inform your doctor of all medications you take, including over-the-counter drugs and supplements. · Pregnant or planning pregnancy? This drug is safe to use during pregnancy. · Avoid alcohol or limit use as it may worsen side effects like nausea or dizziness. |