Indinavir

Indications

Indinavir is used for: HIV infection

Adult Dose

Oral HIV infection Adult: 800 mg PO q8hr With ritonavir: 800 mg PO q12hr plus ritonavir 100-200 mg q12hr Dosage Modifications Concomitant CYP3A4 inhibitor: 600 mg PO q8hr Concomitant administration with itraconazole, delavirdine, ketoconazole: 600 mg PO q8hr Concomitant administration with efavirenz: 1000 mg PO q8hr Concomitant administration with lopinavir and ritonavir: 600 mg PO q12hr Concomitant administration with nelfinavir: 1200 mg PO q12hr Concomitant administration with nevirapine: 1000 mg PO q8hr Concomitant administration with rifabutin: Reduce rifabutin dose to half of standard dose plus increase indinavir to 1000 mg PO q8hr Hepatic impairment: Mild-moderate (due to cirrhosis): 600 mg every 8 hr.

Child Dose

HIV-1 Infection Neonates/infants: Safety and efficacy not established; should not be administered to neonates due to the risks associated with hyperbilirubinemia 4-15 years (investigational): 500 mg/m² PO q8hr

Renal Dose

Dose adjustment not studied

Administration

Take on empty stomach, with water, 1 hr prior or 2 hr after meal May take with skim milk or low-fat meal If taking with ritonavir, may take without regard to meals

Contra Indications

Hypersensitivity. Severe hepatic impairment.

Precautions

Proper hydration required (1.5 L liquids/day) to counter risk of nephrolithiasis/urolithiasis (much higher in children). Hyperbilirubinaemia may be exacerbated. Diabetes; haemophilia. Monitor for signs of lipodystrophy. Pregnancy and lactation. Lactation: excretion in milk unknown; contraindicated

Pregnancy-Lactation

Pregnancy Category: C Lactation: excretion in milk unknown; contraindicated

Interactions

Reduced absorption with antacids. Increased concentrations with ketoconazole, delavirdine, nelfinavir and ritonavir. Reduced efficacy with nevirapine, efavirenz or rifampicin. Increased risk of myopathy with statins. Increased concentrations of phosphodiesterase-5 inhibitors. Potentially Fatal: Increased risk of cardiac arrhythmias with amiodarone, pimozide or cisapride. Increased sedation and respiratory depression with midazolam, alprazolam and triazolam. Increased risk of ergotism with ergot derivatives. Increased toxicity of drugs with narrow therapeutic index.

Adverse Effects

Side effects of Indinavir : >10% Nephrolithiasis/urolithiasis (29%, peds), Hyperbilirubinemia (14%), Nausea (12%), Pain (17%), Nephrolithiasis/urolithiasis (12%, adults) 1-10% Abdominal pain (9%), Thrombocytopenia (1%), Back pain (8%), Dysuria (2%), Headache (6%), Fever (2%), Dizziness (3%), Diarrhea/vomiting (4-5%), Weakness (4%), Malaise (2%), Insomnia (3%), Fatigue (2%), Taste perversion (3%), Flank pain (3%), Pruritus (4%), Neutropenia (2%), Cough (2%) <1% Angina, Erythema multiforme, Hepatitis, Crystaluria, Angina

Mechanism of Action

Indinavir binds reversibly to HIV-protease which prevents cleavage of the viral precursor polyproteins. As a result, immature viral particles incapable of infecting other cells are formed.