Usage
- Raltegravir is prescribed, in combination with other antiretroviral agents, for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults, adolescents, children, and infants from 4 weeks of age and older.
- Pharmacological Classification: Antiretroviral, Integrase Strand Transfer Inhibitor (INSTI)
- Mechanism of Action: Raltegravir inhibits HIV integrase, an enzyme essential for viral replication. By preventing the integration of viral DNA into the host cell’s DNA, raltegravir blocks the formation of new HIV-1 virions.
Alternate Names
- International Nonproprietary Name (INN): Raltegravir potassium (amorphous)
- Brand Names: Isentress, Isentress HD
How It Works
- Pharmacodynamics: Raltegravir exerts its antiviral effect by targeting the integration step of the HIV-1 replication cycle. It specifically inhibits HIV-1 integrase, preventing the insertion of viral DNA into the host cell’s genome. This action effectively halts viral replication and reduces the viral load in infected individuals.
- Pharmacokinetics:
- Absorption: Raltegravir is rapidly absorbed after oral administration, reaching peak plasma concentrations (Cmax) in approximately 3 hours. Food does not significantly affect absorption.
- Metabolism: Raltegravir is primarily metabolized via glucuronidation by uridine diphosphate glucuronosyltransferase (UGT) 1A1. It is not a substrate of cytochrome P450 (CYP) enzymes.
- Elimination: Raltegravir is eliminated primarily through hepatic metabolism and subsequent excretion in the feces (approximately 82%), with a smaller portion excreted in the urine (approximately 18%).
- Mode of Action: Raltegravir binds to the integrase enzyme at the viral DNA-integrase complex, preventing the strand transfer step of integration. This prevents the insertion of viral DNA into host cellular DNA.
- Receptor Binding/Enzyme Inhibition: Raltegravir is a highly specific inhibitor of HIV-1 integrase. It does not inhibit human polymerases or other cellular enzymes.
- Elimination Pathways: Primarily hepatic metabolism via UGT1A1 glucuronidation, followed by fecal and urinary excretion.
Dosage
Standard Dosage
Adults:
- Isentress: 400 mg orally twice daily.
- Isentress HD: 1200 mg (two 600 mg tablets) orally once daily for treatment-naïve patients or those virologically suppressed on an initial regimen of raltegravir 400 mg twice daily. Do not use the 400 mg tablet to administer the once daily regimen.
- With rifampin: 800 mg twice daily.
Children:
- Neonates (birth to 4 weeks) weighing 2kg or more: Raltegravir Oral Suspension according to weight-based dosing (see detailed source information provided, as dosing varies by weight and week of life).
- 4 weeks and older, weighing between 3 kg and less than 25 kg: Weight-based dosing of oral suspension or chewable tablets, approximately 6 mg/kg twice daily (max 300mg twice daily for chewable tablets, and 100 mg twice daily for oral suspension). See detailed source information provided, as dosing varies by weight band.
- At least 25 kg: 400 mg twice daily (one 400-mg film-coated tablet twice daily). If unable to swallow tablets, use chewable tablets according to the weight based guidance (up to 300 mg twice daily).
- At least 40 kg: 400 mg twice daily (one 400-mg film-coated tablet twice daily) or 1200 mg once daily (two 600-mg film-coated tablets once daily).
Special Cases:
- Elderly Patients: Use with caution due to potential age-related changes in hepatic, renal, or cardiac function.
- Patients with Renal Impairment: No dosage adjustment is necessary.
- Patients with Hepatic Dysfunction (Mild to Moderate): No dosage adjustment required for twice daily dosing. HD formulation is not recommended in patients with hepatic impairment. Severe hepatic impairment has not been studied.
- Patients with Comorbid Conditions: Individualized assessment is required. For example, patients with tuberculosis may require dose adjustment if receiving rifampin.
Clinical Use Cases Raltegravir is not indicated for use in these clinical scenarios as described in the prompt: intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations (e.g. status epilepticus or cardiac arrest.) It is used for HIV-1 infection treatment only, and should not be used in these circumstances.
Dosage Adjustments
- Rifampin Co-administration: 800 mg twice daily in adults. No data are available for pediatric patients.
Side Effects
Common Side Effects
- Headache, nausea, diarrhea, fatigue, insomnia, vomiting, abdominal pain.
Rare but Serious Side Effects
- Severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis), hypersensitivity reactions, rhabdomyolysis, hepatotoxicity, depression, suicidal thoughts.
Long-Term Effects
- Myopathy, increased creatine kinase, increased risk of certain infections with immune reconstitution.
Adverse Drug Reactions (ADR)
- As noted above, severe skin and hypersensitivity reactions, hepatotoxicity, rhabdomyolysis, and suicidal ideation require immediate intervention.
Contraindications
- Hypersensitivity to raltegravir.
Drug Interactions
- Rifampin: Decreases raltegravir concentrations. Dosage adjustment is required.
- Drugs that induce or inhibit UGT1A1: May alter raltegravir plasma levels.
- Antacids containing aluminum, magnesium, or calcium: Should not be taken concurrently with raltegravir.
Pregnancy and Breastfeeding
- Limited data is available for pregnancy. Raltegravir should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Drug Profile Summary
- Mechanism of Action: Integrase strand transfer inhibitor.
- Side Effects: Nausea, diarrhea, headache, fatigue, insomnia, rare but serious skin reactions.
- Contraindications: Hypersensitivity.
- Drug Interactions: Rifampin, UGT1A1 inducers/inhibitors, antacids containing aluminum, magnesium, or calcium.
- Pregnancy & Breastfeeding: Limited data available; use only if benefit outweighs risk.
- Dosage: Adults: 400 mg BID or 1200 mg QD; Pediatric: weight-based dosing.
- Monitoring Parameters: HIV-1 RNA viral load, CD4+ cell count, liver function tests, creatine kinase.
Popular Combinations
Raltegravir is commonly used in combination with other antiretroviral agents, such as nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) and other INSTIs, to create a complete antiretroviral regimen. Specific combinations are chosen based on individual patient factors, including resistance testing and other medications.
Precautions
- General Precautions: Monitor for signs of hypersensitivity, skin reactions, hepatotoxicity, and myopathy.
- Specific Populations: as described in other sections.
- Lifestyle Considerations: Adherence to prescribed dosing schedule is crucial for maintaining viral suppression and preventing drug resistance.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Raltegravir?
A: Adults: 400 mg twice daily or 1200 mg once daily (HD formulation). Children: weight-based dosing (see detailed dosage section).
Q2: How does Raltegravir work?
A: It inhibits HIV-1 integrase, preventing the integration of viral DNA into the host cell’s DNA and blocking viral replication.
Q3: What are the most common side effects of Raltegravir?
A: Headache, nausea, diarrhea, and fatigue.
Q4: Are there any serious side effects I should be aware of?
A: Yes, although rare, serious side effects can include severe skin reactions, hypersensitivity reactions, muscle damage (rhabdomyolysis), liver toxicity and suicidal thoughts.
Q5: What are the contraindications to Raltegravir?
A: Known hypersensitivity to raltegravir.
Q6: Does Raltegravir interact with other medications?
A: Yes, notably rifampin. Other interactions include drugs that affect the UGT1A1 metabolic pathway.
Q7: Can Raltegravir be used during pregnancy and breastfeeding?
A: Limited data available. Use only if the potential benefit justifies the potential risk to the fetus or neonate.
Q8: What monitoring parameters are important for patients taking Raltegravir?
A: HIV-1 RNA viral load, CD4+ T-cell count, liver function tests, creatine kinase, and monitoring for any signs of hypersensitivity or skin reactions.
Q9: What is the difference between Isentress and Isentress HD?
A: Isentress is the 400 mg twice-daily formulation, whereas Isentress HD is the 600 mg tablet, taken as two tablets (1200 mg) once daily in certain patients.
A: No. These formulations are not bioequivalent and should not be substituted for one another. They have different pharmacokinetic profiles, resulting in different levels of drug absorption. Consult specific guidelines for each formulation.
