indinavir sulfate
Crixivan

Available forms
Available by prescription only
Capsules: 100 mg, 200 mg, 333 mg, and 400 mg

Indications and dosages
 Treatment of patients with HIV infection when antiretroviral therapy is warranted. Adults: 800 mg P.O. q 8 hours with other antiretrovirals. Don’t use indinavir as monotherapy.
≡ Dosage adjustment. Reduce dosage to 600 mg P.O. q 8 hours in patients with mild to moderate hepatic insufficiency resulting from cirrhosis.

Pharmacodynamics
Antiviral action: Indinavir sulfate inhibits HIV protease, an enzyme required for the proteolytic cleavage of viral polyprotein precursors into individual functional proteins found in infectious HIV. By binding to the protease active site, indinavir prevents cleavage of the viral polyproteins, resulting in formation of immature noninfectious viral particles.

Pharmacokinetics
Absorption: Rapidly absorbed in GI tract when administered on an empty stomach. A meal high in calories, fat, and protein significantly interferes with drug absorption, whereas lighter meals don’t.
Distribution: About 60% is plasma protein-bound.
Metabolism: Metabolized to at least seven metabolites. Cytochrome P-450 3A4 (CYP3A4) is the major enzyme responsible for formation of the oxidative metabolites.
Excretion: Less than 20% is excreted unchanged in urine.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug or its components. Use cautiously in patients with hepatic insufficiency resulting from cirrhosis.

Interactions
Drug-drug. Amprenavir, saquinavir: Increases plasma levels of these drugs. Dosage adjustments are probably not needed when used together.
Carbamazepine: Decreases indinavir’s area under the curve. Consider an alternative drug.
Clarithromycin: Alters plasma clarithromycin levels. Dosage adjustments are probably not needed when used together.
Delavirdine, itraconazole, ketoconazole: Causes an increase in the plasma levels of indinavir. Consider a dosage reduction of indinavir to 600 mg every 8 hours.
Didanosine: A normal gastric pH may be needed for optimal absorption of indinavir. Administer this drug and indinavir at least 1 hour apart on an empty stomach.
Efavirenz, nevirapine: Decreases plasma indinavir levels. Increase indinavir to 1,000 mg every 8 hours.
HMG-CoA reductase inhibitors: Increases levels of these drugs and increases risk of myopathy and rhabdomyolysis. Avoid use together.
Lopinavir/ritonavir fixed combination: Increases plasma levels of indinavir. Adjust indinavir dosage to 600 mg bid.
Midazolam, triazolam: Competition for CYP3A4 by indinavir could result in inhibition of the metabolism of these drugs and create the potential for serious or life-threatening events, such as arrhythmias or prolonged sedation. Don’t give these drugs with indinavir.
Nelfinavir: Increases indinavir levels by 50%, and nelfinavir levels by 80%. Limited data suggest adjusting the dose of indinavir to 1,200 mg b.i.d. and nelfinavir to 1,250 mg b.i.d. Monitor patient closely.
Rifabutin: Increases plasma rifabutin levels and decreases indinavir levels. Give indinavir 1,000 mg q 8 hours and decrease rifabutin dose to either 150 mg daily or 300 mg two to three times a week.
Rifampin: Is a potent inducer of CYP3A4, which could markedly diminish plasma indinavir levels. Don’t use together.
Ritonavir: Increases indinavir levels two- to fivefold. Adjust dosages. Give indinavir 400 mg b.i.d. and ritonavir 400 mg b.i.d.; or, indinavir 800 mg b.i.d. and ritonavir 100 to 200 mg b.i.d.
Sildenafil: Increases plasma sildenafil levels, and increases adverse effects (hypotension, visual changes, and priapism). Don’t exceed 25 mg of sildenafil in a 48-hour period.
Drug-herb. St. John’s wort: Reduces plasma indinavir levels by more than 50%. Warn patient not to use together.
Drug-food. Grapefruit juice: May decrease plasma levels and therapeutic effect of indinavir. Advise patient to take with liquid other than grapefruit juice.

Adverse reactions
CNS: malaise, headache, insomnia, dizziness, somnolence, asthenia, fatigue.
GI: abdominal pain, nausea, diarrhea, vomiting, acid regurgitation, anorexia, dry mouth, taste perversion.
GU: nephrolithiasis, hematuria.
Hematologic: anemia, thrombocytopenia, neutropenia.
Hepatic: hyperbilirubinemia; jaundice.
Musculoskeletal: flank pain, back pain.

Effects on lab test results
• May increase ALT, AST, bilirubin, amylase, and glucose levels.
• May decrease hemoglobin, hematocrit, and neutrophil and platelet counts.

Overdose and treatment
Acute or chronic overdose may cause renal and GI effects.
 Treatment is supportive, and the patient is observed closely. It’s not known whether indinavir is removed by hemodialysis or peritoneal dialysis.

Special considerations
• Dosage of indinavir is the same whether drug is used alone or with other antiretrovirals. However, antiretroviral activity of indinavir may be increased when used with approved reverse transcriptase inhibitors.
• When administering indinavir with rifabutin, reduce the dose of rifabutin by half. However, when administering indinavir with ketoconazole, decrease dose of indinavir to 600 mg q 8 hours.
• Drug may cause nephrolithiasis. If signs and symptoms of nephrolithiasis occur, consider stopping drug for 1 to 3 days during the acute phase. To prevent nephrolithiasis, patient should maintain adequate hydration.
Breast-feeding patients
• Drug may appear in breast milk. Because of the potential for indinavir to cause adverse effects in breast-fed infants and to prevent transmitting the infection to the infant, breast-feeding isn’t recommended.
Pediatric patients
• Safety and efficacy in children haven’t been established.

Patient education
• Inform patient that indinavir isn’t a cure for HIV infection and that opportunistic infections and other complications of HIV disease may continue to develop. Also tell him that drug hasn’t been shown to reduce risk of transmitting HIV to others through sexual contact or blood contamination.
• Caution patient not to adjust dosage or discontinue indinavir therapy without medical approval.
• Advise patient that, if a dose of indinavir is missed, therapy should be resumed with the next dose and that a double dose shouldn’t be taken.
• Instruct patient to take drug on an empty stomach with water 1 hour before or 2 hours after a meal. Or, he may take it with other liquids (such as skim milk, juice, coffee, or tea) or with a light meal. Inform patient that a meal high in calories, fat, and protein reduces the absorption of indinavir.
• Tell patient to store capsules in the original container and to keep the desiccant in the bottle because the capsules are sensitive to moisture.
• Instruct patient to drink at least six 8-oz glasses of fluid (1.5 L) daily.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use