NELFIN-250 250MG TABLET

Indications

• HIV infection
• AIDS-related complex

Dosage

Children: Refer to BNF for Children for specific dosing guidelines.

Adults: Refer to BNF for specific dosing guidelines.

Mechanism of action

Nelfinavir acts as a competitive inhibitor of the HIV protease enzyme, which is essential for the cleavage of the viral polyprotein precursors into functional proteins. By binding reversibly to the active site of the HIV protease, nelfinavir prevents the enzyme from processing the Gag-pol polyprotein. This inhibition leads to the production of immature, non-infectious viral particles, thereby reducing the infectivity of the virus.

Pharmacodynamics

Nelfinavir exhibits potent antiviral activity against Human Immunodeficiency Virus Type 1 (HIV-1). As a protease inhibitor, it specifically targets the HIV-1 protease enzyme, blocking its function and leading to the accumulation of immature viral particles. Its effectiveness is enhanced when used in combination with other antiretroviral agents, which is a common practice in HIV treatment regimens.

Pharmacokinetics

Nelfinavir is well absorbed following oral administration, with peak plasma concentrations typically achieved within 1 to 3 hours. It undergoes extensive hepatic metabolism, primarily via the cytochrome P450 system. The drug has a relatively short half-life, necessitating multiple daily doses to maintain effective plasma levels. It is also important to note that nelfinavir's pharmacokinetics can be influenced by food intake, and it is often recommended to take it with meals to enhance absorption.

Contra-indications

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

Adverse effects

• Diarrhea
• Nausea
• Vomiting
• Abdominal pain
• Rash
• Altered liver function tests
• Hyperlipidemia

Interactions

• May interact with other protease inhibitors, leading to altered efficacy or increased toxicity
• Caution with drugs that are substrates, inducers, or inhibitors of CYP450 enzymes
• Anticonvulsants may reduce nelfinavir levels
• Rifampicin may significantly reduce nelfinavir plasma concentrations

Precautions

• Monitor liver function regularly during therapy
• Use with caution in patients with a history of pancreatitis
• Consider potential for drug interactions with concomitant medications

Pregnancy

Nelfinavir should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is not recommended as a first-line therapy.

Breast-feeding

Nelfinavir is excreted in breast milk. Caution should be exercised when administering nelfinavir to a nursing mother.

Storage

Store in a cool, dry place away from light. Keep out of reach of children.

Formulations

• Tablets: 250 mg

Mechanism of action

HIV viral protease is an important enzyme for HIV maturation and pathogenicity since HIV produces its structural and key proteins in the form of a polyprotein that needs to be cleaved by a protease. HIV protease is synthesized as part of the Gag-pol polyprotein, where Gag encodes for the capsid and matrix protein to form the outer protein shell, and Pol encodes for the reverse transcriptase and integrase protein to synthesize and incorporate its genome into host cells. The Gag-pol polyprotein undergoes proteolytic cleavage by HIV protease to produce 66 molecular species which will assume conformational changes to become fully active. Inhibition of protease, therefore, prevents HIV virion from fully maturing and becoming infective. Nelfinavir is a competitive inhibitor of the HIV protease by reversibly binding to the active site of the enzyme, preventing it from interacting with its substrate to produce mature and infectious viral particles.

Pharmacodynamics

Nelfinavir is a protease inhibitor with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Protease inhibitors block the part of HIV called protease. HIV-1 protease is an enzyme required for the proteolytic cleavage of the viral polyprotein precursors into the individual functional proteins found in infectious HIV-1. Nelfinavir binds to the protease active site and inhibits the activity of the enzyme. This inhibition prevents cleavage of the viral polyproteins resulting in the formation of immature non-infectious viral particles. Protease inhibitors are almost always used in combination with at least two other anti-HIV drugs.