Usage
Nelfinavir is an antiretroviral medication, specifically a protease inhibitor, primarily used in combination with other antiretroviral agents for the treatment of HIV-1 infection. It works by inhibiting the HIV protease enzyme, preventing the cleavage of viral proteins necessary for the formation of infectious viral particles. Although previously used in pediatric populations, current guidelines no longer recommend nelfinavir for children due to inferior potency and variable pharmacokinetics compared to other antiretroviral regimens.
Alternate Names
Viracept (brand name)
How It Works
Pharmacodynamics: Nelfinavir exerts its antiviral effect by inhibiting the HIV-1 protease enzyme. This inhibition prevents the processing of viral polyprotein precursors, resulting in the production of immature, non-infectious viral particles. Nelfinavir does not eradicate HIV, but it can reduce the viral load, improve immune function, and slow the progression of HIV-related disease.
Pharmacokinetics:
- Absorption: Nelfinavir is administered orally and its absorption is significantly enhanced when taken with food, especially meals with moderate to high fat content. Food increases both the extent and rate of absorption, reducing interindividual variability.
- Distribution: Nelfinavir is highly protein-bound (>98%) in plasma. The apparent volume of distribution is 2-7 L/kg.
- Metabolism: Primarily metabolized in the liver by the cytochrome P450 (CYP) system, specifically CYP3A4 and CYP2C19. Nelfinavir is a substrate and an inhibitor of CYP3A4, leading to potential drug interactions. It is metabolized to an active metabolite, M8. Impaired liver function significantly affects nelfinavir metabolism, necessitating dosage adjustments.
- Elimination: Mainly eliminated via the fecal route, with only a small portion (<2%) excreted unchanged in the urine. The terminal half-life is 3.5–5 hours.
Dosage
Standard Dosage
Adults: 1250 mg twice daily or 750 mg three times daily, taken with a meal.
Children: Nelfinavir is no longer recommended for pediatric use due to variable pharmacokinetics and inferior efficacy compared to other available antiretroviral agents.
Special Cases:
- Elderly Patients: No specific dosage adjustments are recommended based on age alone. However, consideration should be given to age-related changes in liver function.
- Patients with Renal Impairment: No dosage adjustment is necessary.
- Patients with Hepatic Dysfunction: Nelfinavir can be used with caution in patients with mild hepatic impairment (Child-Pugh A) without dose adjustment. Nelfinavir is not recommended for patients with moderate to severe hepatic impairment (Child-Pugh B or C).
- Patients with Comorbid Conditions: Careful monitoring for drug interactions and adverse events is warranted in patients with comorbid conditions, especially diabetes and other metabolic disorders.
Clinical Use Cases
Nelfinavir is not indicated for use in clinical settings such as intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations like status epilepticus or cardiac arrest. Its sole approved use is for chronic treatment of HIV-1 infection in combination with other antiretroviral agents.
Dosage Adjustments
Dosage adjustment may be necessary for patients with moderate to severe hepatic impairment, and concomitant use of certain medications that interact with CYP3A4 or CYP2C19.
Side Effects
Common Side Effects
Diarrhea, nausea, abdominal pain, flatulence, rash, lipodystrophy (changes in body fat distribution).
Rare but Serious Side Effects
New or worsening diabetes, hyperglycemia, increased bleeding in hemophiliac patients, Stevens-Johnson Syndrome, drug-induced liver injury.
Long-Term Effects
Lipodystrophy, dyslipidemia, insulin resistance, increased risk of cardiovascular disease.
Adverse Drug Reactions (ADR)
Severe skin reactions, hepatotoxicity, pancreatitis, new-onset diabetes mellitus or exacerbation of pre-existing diabetes.
Contraindications
Hypersensitivity to nelfinavir, concomitant use with medications highly dependent on CYP3A for clearance where elevated concentrations are associated with serious and/or life-threatening events (e.g., astemizole, terfenadine, cisapride, pimozide, midazolam, triazolam, ergot derivatives, simvastatin, lovastatin), moderate or severe hepatic impairment.
Drug Interactions
Nelfinavir is a substrate and inhibitor of CYP3A4 and a substrate of CYP2C19. It interacts with numerous medications including antiarrhythmics, anticonvulsants, antidepressants, antifungals, HMG-CoA reductase inhibitors, and other antiretrovirals. Concomitant use of certain drugs is contraindicated due to the risk of serious adverse effects. Consult a comprehensive drug interaction resource before co-administering nelfinavir with other medications.
Pregnancy and Breastfeeding
Pregnancy Category B. While not contraindicated, nelfinavir should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Nelfinavir is present in breast milk; breastfeeding is not recommended for HIV-infected mothers to prevent transmission of HIV to the infant.
Drug Profile Summary
- Mechanism of Action: HIV-1 protease inhibitor.
- Side Effects: Diarrhea, nausea, rash, lipodystrophy, hyperglycemia.
- Contraindications: Hypersensitivity, concomitant use with certain medications, moderate-severe hepatic impairment.
- Drug Interactions: Numerous, involving CYP3A4 and CYP2C19.
- Pregnancy & Breastfeeding: Category B; use with caution. Breastfeeding not recommended.
- Dosage: Adults: 1250 mg BID or 750 mg TID with food. Not recommended for children.
- Monitoring Parameters: HIV RNA viral load, CD4 cell count, liver function tests, blood glucose, lipid profile.
Popular Combinations
Nelfinavir was historically used in combination with nucleoside reverse transcriptase inhibitors (NRTIs). However, due to its limitations, nelfinavir is no longer a preferred component of combination antiretroviral therapy.
Precautions
Assess liver function, monitor for drug interactions, screen for diabetes and hyperglycemia, counsel patients about potential side effects and the importance of adherence to therapy.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Nelfinavir?
A: For adults, 1250 mg twice daily or 750 mg three times daily, taken with a meal. It is no longer recommended for pediatric use.
Q2: What is the mechanism of action of Nelfinavir?
A: Nelfinavir is a protease inhibitor that blocks the HIV protease enzyme, preventing the maturation of viral particles.
Q3: What are the common side effects of Nelfinavir?
A: Diarrhea, nausea, abdominal pain, flatulence, rash, and lipodystrophy are common side effects.
Q4: What are the serious side effects of Nelfinavir?
A: Serious side effects include new or worsening diabetes, hyperglycemia, increased bleeding in hemophiliac patients, drug-induced liver injury and severe skin reactions such as Steven Johnson’s Syndrome.
Q5: What are the contraindications for using Nelfinavir?
A: Contraindications include hypersensitivity to nelfinavir, co-administration with certain medications (e.g., astemizole, terfenadine, cisapride, pimozide, midazolam, triazolam, ergot derivatives, simvastatin, lovastatin), and moderate to severe hepatic impairment.
Q6: Does Nelfinavir interact with other medications?
A: Yes, Nelfinavir interacts with numerous medications metabolized by CYP3A4 and CYP2C19. Consult a drug interaction resource before prescribing.
Q7: Can Nelfinavir be used during pregnancy?
A: Nelfinavir is Pregnancy Category B. It should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Q8: Can Nelfinavir be used during breastfeeding?
A: Nelfinavir is present in breast milk. Breastfeeding is not recommended for HIV-infected mothers to prevent HIV transmission.
Q9: Is dose adjustment necessary for patients with renal impairment?
A: No dose adjustment is necessary for patients with renal impairment.
Q10: Is Nelfinavir still recommended for use in children?
A: No, current pediatric HIV treatment guidelines no longer recommend nelfinavir due to its inferior potency, variable pharmacokinetics, and the availability of safer and more effective alternatives.
