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HIV NUTRITION UPDATE
VOLUME 6, ISSUE 6

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By William Palumbo, MS, RD, CDN

 
Pharmacologic Classification
 
Crixivan is an inhibitor of HIV infection. It is classified as a  protease inhibitor.

Dosage and Administration   

The recommended dosage is 800 mg (two 400 mg capsules) orally every 8 hours. The dosage is the same whether Crixivan is used alone or in combination with other antiretroviral agents. It must be taken at intervals of 8 hours. For optimal absorption, take Crixivan without food but with water 1 hour before or 2 hours after a meal. Alternatively, Crixivan may be taken with other liquids such as skim milk, juice, or with a light meal, e.g. dry toast with jelly. To ensure adequate hydration, the patient should drink at least 1.5 liters (about 48 ounces) of liquids during the course of 24 hours.
 
Concomitant Administration

Crixivan administration needs to be adjusted when the following medications are used in conjunction: Rifabutin, Ketoconazole, and Didanosine. Rifampin should not be coadministered with Crixivan. Administration of Crixivan (800 mg every 8 hours) with rifampin (600 mg once daily) for one week resulted in an 89% +-9% decrease in Crixivan plasma concentration.

Indications For Use

Crixivan in combination with antiretroviral agents is indicated for the treatment of HIV infection. This indication is based on clinical trials that demonstrated: 1) a reduction in the risk of AIDS defining illnesses or death; 2) a prolonged suppression of HIV RNA.

Pharmacodynamics

HIV protease is an enzyme required for the proteolytic cleavage of the viral polyprotein precursors into the individual functional proteins found in infectious HIV. Crixivan 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 noninfectious viral particles.
 
    Pharmacokinetics

    Absorption: Crixivan is rapidly absorbed in the fasted state with a time to peak plasma concentration of 0.8 to 0.3 hours. Effects of Food on Oral Absorption: Administration of Crixivan with a meal high in calories, fat, and protein (784 kcal, 48.6 grams fat, 31.3 grams protein) resulted in a 77% +-8% reduction of plasma concentration. Distribution: Crixivan was approximately 60% bound to human plasma proteins. Metabolism: Seven metabolites have been identified, one glucuronide conjugate and six oxidative metabolites. In vitro studies indicate that cytochrome P450 3A4 (CYP3A4) is the major enzyme responsible for formation of the oxidative metabolites. Elimination:   Less than 20% of Crixivan is excreted unchanged in the urine. 

    Drug Interactions

    Special Populations: hepatic insufficiency- Patients with mild to moderate hepatic insufficiency and clinical cirrhosis had evidence of decreased metabolism of Crixivan resulting in 60% higher plasma concentrations following a single 400 mg dose.

     Warning:  Nephrolithiasis has occurred with Crixivan therapy. In some cases, nephrolithiasis has been associated with renal insufficiency or acute renal failure. Adequate hydration is recommended in all patients treated with Crixivan.

    New onset diabetes mellitus, exacerbation of pre-existing diabetes mellitus and hyperglycemia have been reported during surveillance in HIV-infected patients receiving protease inhibitor therapy.

    Adverse Reactions

    Taste changes, nausea, vomiting, regurgitation, abdominal pain, diarrhea, nephrolithiasis, asymptomatic hyperbilirubinemia (total bilirubin >2.5mg/dL), kidney stones, lipodystrophy, new onset diabetes mellitus, and hypertriglyceridemia. 

    Nutrient-Herb Interactions

    Patients should avoid the use of St. John’s Wort to limit possible nutrient-herb interactions.

    Sources

    Pronsky ZM, Meyer SA, Fields-Gardner C. HIV Medications Food Interactions (And So Much More). Second Edition. Birchrunville, PA; 2001:81.
     
    Crixivan Package Insert. 2000; Merck & Co: Whitehouse Station, NJ 08889. 

    HIV Prescribing Guide. 1998. Glaxo Wellcome.

    Herr SM. Herb-Drug Interaction Handbook. First Edition. Nassau, NY;2000:184.

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5/10/2002