No

Antiretroviral Agent, Protease Inhibitor

Treatment of HIV infection; should always be used as part of a multidrug regimen (at least three antiretroviral agents)

C

Clinical effects on the fetus: Administer during pregnancy only if benefits to mother outweigh risks to the fetus; hyperbilirubinemia may be exacerbated in neonates

Breast-feeding/lactation: HIV-infected mothers are discouraged from breast-feeding to decrease potential transmission of HIV

Hypersensitivity to the drug or its components

Because indinavir may cause nephrolithiasis the drug should be discontinued if signs and symptoms occur. Indinavir should not be administered concurrently with terfenadine, astemizole, cisapride, triazolam, and midazolam because of competition for metabolism of these drugs through the CYP3A4 system, and potential serious or life-threatening events. Patients with hepatic insufficiency due to cirrhosis should have dose reduction. Warn patients about fat redistribution that 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.

Central nervous system: Headache (5.6%), insomnia (3.1%)

Gastrointestinal: Mild elevation of indirect bilirubin (10%), abdominal pain (8.7%), nausea (11.7%), diarrhea/vomiting (4% to 5%), taste perversion (2.6%)

Neuromuscular & skeletal: Weakness (3.6%), flank pain (2.6%)

Renal: Kidney stones (2% to 3%)

<1%: Malaise, dizziness, somnolence, anorexia, xerostomia, decreased hemoglobin, pancreatitis, urticaria, depression, increased serum cholesterol

CYP3A3/4 enzyme substrate; CYP3A3/4 enzyme inhibitor

Increased toxicity: Gastric pH is lowered and absorption may be decreased when didanosine and indinavir are taken <1 hour apart; a reduction of dose is often required when coadministered with ketoconazole; astemizole and cisapride should be avoided with indinavir due to life-threatening cardiotoxicity; benzodiazepines with indinavir may result in prolonged sedation and respiratory depression; ketoconazole, itraconazole, nelfinavir, ritonavir, and delavirdine increased indinavir levels. Indinavir inhibits the metabolism of HMG-CoA reductase inhibitors (atorvastatin, cerivastatin, lovastatin, simvastatin) which increases the risk of rhabdomyolysis. Indinavir increases the AUC of amprenavir.

Drug-Herb interactions: St John's wort (hypericum) appears to induce CYP3A enzymes and has lead to 57% reductions in indinavir AUCs and 81% reductions in trough serum concentrations, which may lead to treatment failures

Capsules are sensitive to moisture; medication should be stored and used in the original container and the desiccant should remain in the bottle

Indinavir is a human immunodeficiency virus protease inhibitor, binding to the protease activity site and inhibiting the activity of this enzyme. HIV protease is an enzyme required for the cleavage of viral polyprotein precursors into individual functional proteins found in infectious HIV. Inhibition prevents cleavage of these polyproteins resulting in the formation of immature noninfectious viral particles.

Absorption: Administration of indinavir with a high fat, high calorie diet resulted in a reduction in AUC and in maximum serum concentration (77% and 84% respectively). Administration with a lighter meal resulted in little or no change in these parameters.

Protein binding: 60% in the plasma

Metabolism: Highly metabolized by the cytochrome P-450 3A4 enzymes; seven metabolites of indinavir have been identified

Bioavailability: Oral: Good; T_max: 0.8 ± 0.3 hour

Half-life: 1.8 ± 0.4 hour

Elimination: In feces and urine

Adults: Oral: 800 mg every 8 hours

Meals high in calories, fat, and protein result in a significant decrease in drug levels; grapefruit juice may decrease indinavir's AUC

Monitor viral load, CD4 count, triglycerides, cholesterol, glucose

May cause insomnia; may rarely cause dizziness or drowsiness

Contraindicated with midazolam and triazolam; use caution with other benzodiazepines; may produce additive sedation and respiratory depression

No information available to require special precautions

No effects or complications reported

Take as directed, around-the-clock, with a large glass of water, preferably 1 hour before or 2 hours after meals. Maintain adequate hydration (2-3 L/day of fluids unless instructed to restrict fluid intake). If indinavir and didanosine are prescribed together, take at least 1 hour apart on an empty stomach. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant. Do not breast-feed.

Administer around-the-clock to avoid significant fluctuation in serum levels; administer with plenty of water

Capsule: 200 mg, 333 mg, 400 mg

CDC and the National Foundation for Infectious Disease, "Update: Provisional Public Health Service Recommendations for Chemoprophylaxis After Occupational Exposure to HIV," MMWR Morb Mortal Wkly Rep, 1996, 45(22):468-80.

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

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.

Mueller BU, Smith S, Sleasman J, et al, "A Phase I/II Study of the Protease Inhibitor Indinavir (MK-0639) in Children With HIV Infection," Int Conf AIDS, 1996, 11:37.

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

Stein DS, Fish DG, Bilello JA, et al, "A 24-Week Open-Label Phase I/II Evaluation of the HIV Protease Inhibitor MK-639 (Indinavir)," AIDS, 1996, 10(5):485-92.

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.