Isentress 100 mg

Indications

• HIV infection without resistance to other inhibitors
• HIV infection in combination with other antiretroviral agents

Dosage

Children: Refer to BNF for Children for specific dosing information based on age and weight.

Adults: The typical adult dosage is 400 mg taken orally twice daily. In some cases, a single daily dose of 800 mg may be appropriate, particularly in combination with certain other medications. Always refer to the BNF for specific dosing guidance.

Mechanism of action

Raltegravir inhibits the catalytic activity of HIV-1 integrase, an enzyme essential for viral replication. By blocking integrase, raltegravir prevents the integration of unintegrated linear HIV-1 DNA into the host cell genome, hindering the formation of the HIV-1 provirus necessary for the production of new viral particles.

Pharmacodynamics

Raltegravir demonstrates a dose-dependent inhibition of HIV replication. Its effectiveness is largely due to its ability to prevent the integration step of the viral life cycle, which is crucial for HIV propagation. The drug has been shown to have a rapid onset of action against HIV-1 and is generally well tolerated.

Pharmacokinetics

Raltegravir is primarily metabolized in the liver via glucuronidation. Its bioavailability is approximately 83%, and it reaches peak plasma concentrations within 1 to 3 hours after oral administration. The drug has a half-life of about 9 hours, allowing for dosing twice daily. It is excreted mainly via the feces, with minimal renal elimination.

Contra-indications

• Hypersensitivity to raltegravir or any of its excipients
• Severe hepatic impairment

Adverse effects

• Diarrhoea
• Fatigue
• Headache
• Nausea
• Rash
• Vomiting
• Dizziness
• Insomnia
• Tremor
• Visual impairment
• Weight increased
• Suicidal ideation (in patients with a history of depression or psychiatric illness)
• Osteonecrosis (especially in advanced HIV disease or prolonged exposure to antiretroviral therapy)
• Severe hypersensitivity reactions (including rash accompanied by fever, malaise, arthralgia, myalgia, blistering, oral lesions, conjunctivitis, angioedema, eosinophilia, or raised liver enzymes)

Interactions

• Antiepileptics (fosphenytoin, phenobarbital, phenytoin, primidone) may affect the exposure of raltegravir
• Rifampicin decreases the exposure of raltegravir
• Carbamazepine may affect the exposure of raltegravir
• Encorafenib may increase the exposure of raltegravir
• Atazanavir may increase the exposure of raltegravir
• Darunavir may increase the risk of rash when used with raltegravir

Precautions

• Caution in elderly patients due to limited information available
• Caution in patients with chronic hepatitis B or C
• Monitor for signs of hepatic side effects in patients with liver impairment
• Patients should be advised on the signs of hypersensitivity reactions

Pregnancy

Manufacturer advises to avoid unless essential; limited data available.

Breast-feeding

Caution advised as raltegravir may be excreted in breast milk.

Storage

Store in original container, at room temperature, away from moisture.

Formulations

• Tablets (50 mg)
• Chewable tablets
• Powder for oral suspension
• Powder and solvent for solution for injection

Mechanism of action

Raltegravir inhibits HIV integrase to prevent the viral genome being incorporated into the human genome. Raltegravir is primarily metabolized by glucuronidation. Raltegravir inhibits the catalytic activity of HIV-1 integrase, an HIV-1 encoded enzyme that is required for viral replication. Inhibition of integrase prevents the covalent insertion, or integration, of unintegrated linear HIV-1 DNA into the host cell genome preventing the formation of the HIV-1 provirus. The provirus is required to direct the production of progeny virus, so inhibiting integration prevents propagation of the viral infection. Raltegravir did not significantly inhibit human phosphoryltransferases including DNA polymerases alpha, beta, and gamma.