TELZIR ORAL SUSPENSION

Indications

• HIV infection (initiated by a specialist)
• HIV-1 infection in combination with other antiretroviral drugs

Dosage

Children: Child 6–17 years (body weight 25–39 kg): 18 mg/kg twice daily (max. per dose 700 mg); Child 6–17 years (body weight 40

Adults: 700 mg twice daily

Mechanism of action

Fosamprenavir is hydrolyzed to amprenavir by cellular phosphatases in the gut epithelium upon absorption. Amprenavir inhibits HIV-1 protease, an enzyme crucial for the processing of viral polypeptides during HIV replication. By binding to the active site of the HIV-1 protease, amprenavir prevents the cleavage of Gag and Gag-Pol polyprotein precursors, leading to the production of immature, non-infectious viral particles.

Pharmacodynamics

Fosamprenavir's pharmacodynamics involve its conversion to amprenavir, which functions as an antiretroviral protease inhibitor. This inhibition is critical in disrupting the lifecycle of HIV, ultimately reducing the viral load in the body. The slow release of amprenavir allows for less frequent dosing, improving patient compliance.

Pharmacokinetics

Fosamprenavir is well-absorbed following oral administration, and its bioavailability is enhanced by food. After administration, it is rapidly converted to amprenavir. The pharmacokinetics of amprenavir involve extensive hepatic metabolism primarily via cytochrome P450 3A4, with a half-life that supports twice-daily dosing. The drug's pharmacokinetic profile may be influenced by interactions with other medications, particularly those affecting the CYP450 enzyme system.

Adverse effects

• Oral paraesthesia
• Rash
• Increased risk of infection
• Leukopenia
• Lymphadenopathy
• Menstrual cycle irregularities
• Migraine
• Muscle weakness
• Myopathy
• Night sweats
• Pain
• Sexual dysfunction
• Atherosclerosis
• Atrioventricular block
• Cholangitis
• Constipation
• Deep vein thrombosis
• Haemorrhage
• Hyperbilirubinaemia
• Hypogonadism
• Myocardial infarction
• Nephritis
• Stomatitis
• Stroke
• Tinnitus
• Tremor
• Tricuspid valve incompetence
• Vasculitis
• Vertigo
• Visual impairment

Interactions

• Maraviroc - fosamprenavir may decrease the exposure to maraviroc

Precautions

• Caution in patients with cardiac conduction disorders
• Risk of pancreatitis
• Structural heart disease

Pregnancy

Manufacturer advises not to be initiated during pregnancy due to low darunavir exposure; women who become pregnant during therapy should be switched to an alternative regimen.

Breast-feeding

Use only if potential benefit outweighs risk.

Storage

Store in a cool, dry place away from direct sunlight.

Formulations

• Tablets: 700 mg

Mechanism of action

Fosamprenavir is a prodrug that is rapidly hydrolyzed to amprenavir by cellular phosphatases in the gut epithelium as it is absorbed. Amprenavir is an inhibitor of HIV-1 protease. During HIV replication, HIV protease cleaves viral polypeptide products of the Gag and Gag-Pol genes to form structural proteins of the virion core and essential viral enzymes. Amprenavir interferes with this process by binding to the active site of HIV-1 protease, thereby preventing the processing of viral Gag and Gag-Pol polyprotein precursors, resulting in the formation of immature non-infectious viral particles. Fosamprenavir is a prodrug of amprenavir, an inhibitor of HIV protease. ...Fosamprenavir is rapidly converted to amprenavir by cellular phosphatases in vivo. Amprenavir is an inhibitor of HIV-1 protease. Amprenavir binds to the active site of HIV-1 protease and thereby prevents the processing of viral Gag and Gag-Pol polyprotein precursors, resulting in the formation of immature noninfectious viral particles.

Pharmacodynamics

Fosamprenavir is hydrolyzed by cellular phosphatases to the antiretroviral protease inhibitor amprenavir. This hydrolysis allows for the slow release of amprenavir, reducing the number of pills a patient must take.