No

Antiretroviral Agent, Protease Inhibitor

In combination with other antiretroviral therapy in the treatment of HIV infection

B

Breast-feeding/lactation: Animal studies suggest that nelfinavir may be excreted in human milk; the CDC advises against breast-feeding by HIV-infected mothers to avoid postnatal transmission of the virus to the infant

Hypersensitivity to nelfinavir or product components; phenylketonuria; concurrent therapy with terfenadine, astemizole, cisapride, triazolam, or midazolam

Avoid use of powder in phenylketonurics since contains phenylalanine; use extreme caution when administered to patients with hepatic insufficiency since nelfinavir is metabolized in the liver and excreted predominantly in the feces; avoid use, if possible, with amiodarone, quinidine, ergot derivatives, terfenadine, astemizole, cisapride, triazolam, or midazolam. Concurrent use with some anticonvulsants may significantly limit nelfinavir's effectiveness. Warn patients that redistribution of body fat can occur.

Protease inhibitors cause dyslipidemia which includes elevated cholesterol and triglycerides and a redistribution of body fat centrally to cause "protease paunch", buffalo hump, facial atrophy, and breast enlargement. These agents also cause hyperglycemia.

1% to 10%:

Central nervous system: Decreased concentration

Dermatologic: Rash

Gastrointestinal: Nausea, flatulence, abdominal pain

Neuromuscular & skeletal: Weakness

<1%: Anxiety, depression, dizziness, emotional lability, hyperkinesia, insomnia, migraine, seizures, sleep disorder, somnolence, suicide ideation, fever, headache, malaise, dermatitis, pruritus, urticaria, increased LFTs, hyperlipemia, hyperuricemia, hypoglycemia, anorexia, dyspepsia, epigastric pain, mouth ulceration, GI bleeding, pancreatitis, vomiting, kidney calculus, sexual dysfunction, anemia, leukopenia, thrombocytopenia, hepatitis, arthralgia, arthritis, cramps, myalgia, myasthenia, myopathy, paresthesia, back pain, dyspnea, pharyngitis, rhinitis, sinusitis, diaphoresis, allergy, redistribution of body fat, jaundice, metabolic acidosis.

No data available; however, unabsorbed drug should be removed via gastric lavage and activated charcoal; significant symptoms beyond gastrointestinal disturbances are likely following acute overdose; hemodialysis will not be effective due to high protein binding of nelfinavir

CYP3A3/4 enzyme substrate; CYP3A3/4 enzyme inducer; CYP3A3/4 enzyme inhibitor

Nelfinavir inhibits the metabolism of cisapride and astemizole and should, therefore, not be administered concurrently due to risk of life-threatening cardiac arrhythmias.

A 20% increase in rifabutin plasma AUC has been observed when coadministered with nelfinavir (decrease rifabutin's dose by 50%).

An increase in midazolam and triazolam serum levels may occur resulting in significant oversedation when administered with nelfinavir. These drugs should not be administered together. Use caution with other benzodiazepines.

Amiodarone, quinidine, and ergot alkaloids: Serum levels/toxicity may be increased by nelfinavir - avoid concurrent use.

Indinavir and ritonavir may increase nelfinavir plasma concentrations resulting in potential increases in side effects (the safety of these combinations have not been established).

Nelfinavir increases indinavir concentrations

Decreased effect:

Rifampin decreases nelfinavir's plasma AUC by ~82%; the two drugs should not be administered together.

Ethinyl estradiol concentrations are decreased by nelfinavir.

Oral contraceptives: Serum levels of the hormones in oral contraceptives may decrease significantly with administration of nelfinavir. Patients should use alternative methods of contraceptives during nelfinavir therapy.

Norethindrone concentrations are decreased by nelfinavir.

Phenobarbital, phenytoin, and carbamazepine may decrease serum levels and consequently effectiveness of nelfinavir.

Nelfinavir's effectiveness may be decreased with concomitant nevirapine

Store at room temperature

Inhibits the HIV-1 protease; inhibition of the viral protease prevents cleavage of the gag-pol polyprotein resulting in the production of immature, noninfectious virus

Absorption: Food increases plasma concentration-time curve (AUC) by two- to threefold

Distribution: V_d: 2-7 L/kg

Metabolism: Via multiple cytochrome P-450 isoforms (eg, CYP3A); major metabolite has activity comparable to the parent drug

Protein binding: 98%

Half-life: 3.5-5 hours

Time to peak serum concentration: 2-4 hours

Elimination: 98% to 99% excreted in the feces (78% as metabolites and 22% as unchanged nelfinavir); 1% to 2% excreted in the urine

Oral:

Adults: 750 mg 3 times/day with meals

Dosing adjustment in renal impairment: No adjustment needed

Dosing adjustment in hepatic impairment: Use caution when administering to patients with hepatic impairment since eliminated predominantly by the liver

Liver function tests, viral load, CD4 count, triglycerides, cholesterol, glucose

May cause dizziness, anxiety, insomnia, difficulty concentrating, depression, and suicidal ideation

May rarely cause leukopenia; use caution with clozapine and carbamazepine; concurrent use with midazolam and triazolam may produce oversedation; barbiturates and carbamazepine may decrease the effectiveness of nelfinavir

No information available to require special precautions

<1% of patients experience mouth ulcers

This is not a cure for HIV and has not been shown to reduce the risk of transmitting HIV to others. The long-term effects of use are not known. Should be taken as scheduled with food (mix powder with nonacidic, noncitric fluids and do not store reconstituted powder mixture for longer than 6 hours). If you miss a dose, take as soon as possible and return to regular schedule (never take a double dose). Frequent blood tests may be required with prolonged therapy. You may experience nausea and vomiting (small frequent meals, frequent mouth care, sucking lozenges, or chewing gum may help). Report rash; respiratory difficulty; CNS changes (migraine, confusion, suicidal ideation); muscular or skeletal pain, weakness, or tremors; or other adverse reactions. Use appropriate barrier contraceptive measures (as alternative to oral contraceptives) to reduce risk of transmitting infection and potential pregnancy. Breast-feeding precautions: Do not breast-feed.

If diarrhea occurs, it may be treated with OTC antidiarrheals

Powder, oral: 50 mg/g (contains 11.2 mg phenylalanine)

Tablet, film coated: 250 mg

Deeks SG, Smith M, Holodniy M, et al, "HIV-1 Protease Inhibitors. A Review for Clinicians," JAMA, 1997, 277(2):145-53.

Havlir DV and Lange JM, "New Antiretrovirals and New Combinations," AIDS, 1998, 12(Suppl A):S165-74.

Hilts AE and Fish DN, "Dosage Adjustment of Antiretroviral Agents in Patients With Organ Dysfunction," Am J Health Syst Pharm, 1998, 55:2528-33.

Kakuda TN, Struble KA, and Piscitelli SC, "Protease Inhibitors for the Treatment of Human Immunodeficiency Virus Infection," Am J Health Syst Pharm, 1998, 55(3):233-54.

Kaufman MB and Simionatto C, "A Review of Protease Inhibitor-Induced Hyperglycemia," Pharmacotherapy, 1999, 19(1):114-7.

Kaul DR, Cinti SK, Carver PL, et al, "HIV Protease Inhibitors: Advances in Therapy and Adverse Reactions, Including Metabolic Complications," Pharmacotherapy, 1999, 19(3):281-98.

McDonald CK and Kuritzkes DR, "Human Immunodeficiency Virus Type 1 Protease Inhibitors," Arch Intern Med, 1997, 157(9):951-9.

Perry CM and Benfield P, "Nelfinavir," Drugs, 1997, 54(1):81-7.

Rana KZ and Dudley MN, "Human Immunodeficiency Virus Protease Inhibitors," Pharmacotherapy, 1999, 19(1):35-59.

Working Group on Antiretroviral Therapy and Medical Management of HIV-Infected Children, "Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection," March 1, 1999, http://www.hivatis.org.