Drug Detail

Indinavir

Last Updated June 10, 2016

Trade Names

Crixivan

Drug Classification

HIV protease inhibitor antiretroviral

Formulations

400 mg capsules (as sulphate)

Indications and Pharmacology

Indication: treatment of HIV infection in combination with other antiretrovirals.

Mechanism of action*: inhibits HIV-1 protease activity by binding to active site to prevent cleavage of viral polyproteins.

Pharmacokinetics*: rapidly absorbed, metabolized in the liver by CYP3A4. Tmax: 0.8 hours; half-life: ~ 2 hours. Inhibits CYP3A4 enzyme. Weakly inhibits CYP2D6.

Dosage

Adult Dose: 800 mg every 8 hours, taken orally with water 1 hour before or 2 hours after a meal. Patients should consume 48 ounces of fluid daily to avoid renal calculi.

  • With ritonavir: 800 mg plus ritonavir 100 mg every 12 hours, independent of meals.
  • If administered concomitantly with ketoconazole or itraconazole: decrease indinavir dose to 600 mg every 8 hours.
  • If administered concomitantly with rifabutin or efavirenz: increase indinavir dose to 1000 mg every 8 hrs, dose reduce rifabutin to 150 mg every second day.
  • If administered concomitantly with delavirdine: consider decreasing indinavir dose to 600 mg every 8 hours.*
  • If administered concomitantly with didanosine: take agents at least 1 hour apart on empty stomach.*

Use in Renal or Hepatic Insufficiency:

  • No adjustment needed for renal insufficiency. Adequate hydration (1.5 liters every 24 hrs) needed to avoid renal calculi.*
  • Hepatic impairment: reduce dose to 600 mg every 8 hours.

Use in Pregnancy and Breastfeeding*: US Pregnancy Category C. Not recommended for use in pregnant women. It is not known whether indinavir is excreted in human breast milk.

Use in Children: Children 4-17 years (off label): 500 mg/m2 (maximum dose 800 mg) every 8 hours.

Warnings

See drug–drug interactions for medications that should not be coadministered.

Contraindicated in patients with hypersensitivity to indinavir or any of its components.

Maintain adequate hydration to avoid renal calculi.

Potential for nephrolithiasis/urolithiasis, with increased risk in paediatric patients; acute haemolytic anaemia; hepatitis; and new onset or exacerbation of diabetes mellitus, hyperglycaemia, and/or ketoacidosis.*

HIV cross-resistance with other PIs may occur.

Not recommended as first-line PI; if possible, switch to newer PIs such as atazanavir (or atazanavir/ritonavir) or darunavir/ritonavir or lopinavir/ritonavir.*

Drug–Drug Interactions

Contraindicated: alfuzosin, amiodarone, dihydroergotamine, ergonovine, ergotamine, methylergonovine, cisapride, lovastatin, simvastatin, pimozide, sildenafil for pulmonary arterial hypertension, oral midazolam, triazolam, alprazolam.*

Not recommended/use with extreme caution: sildenafil, tadalafil, vardenafil, St John’s wort, rifampicin, atazanavir.*

Increased concentrations of concomitant medication: ritonavir, saquinavir, antiarrhythmic agents (bepridil, systemic lidocaine, quinidine), trazodone, colchicine, quetiapine, dihydropyridine calcium channel blockers (felodipine, nifedipine, nicardipine), clarithromycin, bosentan, atorvastatin, rosuvastatin, immunosuppressants (cyclosporine, tacrolimus, sirolimus), salmeterol, fluticasone, parenteral midazolam, rifabutin, sildenafil, tadalafil, vardenafil.*

Increased concentrations of indinavir with concomitant medication: delavirdine, nelfinavir, ritonavir, clarithromycin, itraconazole, ketoconazole.*

Decreased concentrations of indinavir with concomitant medication: St John’s wort, rifampicin, efavirenz, nevirapine, anticonvulsants (carbamezapine, phenobarbital, phenytoin), rifabutin, venlafaxine.*

Drug interactions between indinavir and other antiretrovirals:

Considerations for Special Populations

Paediatric patients: higher incidence of nephrolithiasis.

Pregnancy: see above.

Adverse Effects

Nephrolithiasis/urolithiasis, haemolytic anaemia, hepatitis, hyperglycaemia, asymptomatic hyperbilirubinaemia, rash, upper respiratory infection, dry skin, pharyngitis, taste perversion, tubulointerstitial nephritis in patients with asymptomatic severe leucocyturia, fat maldistribution, possible increased bleeding in patients with haemophilia, immune reconstitution syndrome (including autoimmune disease), abdominal pain, fatigue, fever, nausea, diarrhoea, vomiting, headache, dizziness.

*Information from US prescribing information.
Recommendation of the Southern African HIV Clinicians Society.