Indinavir
Mechanism :
Indinavir inhibits the HIV viral protease enzyme which prevents cleavage of the gag-pol polyprotein, resulting in non-infectious, immature viral particles.
Indication :
- Treatment of HIV-1 infection in combination with reverse transcriptase inhibitor (RTI) nucleoside analogues.
Contraindications :
In patients with clinically significant hypersensitivity to any of its components.
Dosing :
4 to 15 years:
234 to 500 mg/m² thrice a day. Administer with water, 1 hour before or 2 hours after a meal.
Safety and efficacy is not established in neonates and infants.
Adverse Effect :
Increased spontaneous bleeding in patients with haemophilia, liver function abnormalities, pancreatitis; dyspepsia, arthralgia, new onset diabetes mellitus, exacerbation of pre-existing diabetes mellitus, hyperglycemia, anaphylactoid reactions, urticaria, vasculitis, depression, oral paraesthesia, rash including erythema multiforme and Stevens-Johnson syndrome, hyperpigmentation, alopecia, paronychia, ingrown toenails, pruritus, redistribution/accumulation of body fat, urolithiasis, nephrolithiasis, increased serum cholesterol, increased serum triglycerides, myocardial infarction.
Interaction :
CYP3A4 Drugs: Indinavir is an inhibitor of the cytochrome P450 isoform CYP3A4. Coadministration with drugs primarily metabolized by CYP3A4 may result in increased plasma concentrations of the other drug, which could increase or prolong its therapeutic and adverse effects. Indinavir is metabolized by CYP3A4. Drugs that induce CYP3A4 activity would be expected to increase the clearance of indinavir, resulting in lowered plasma concentrations of indinavir. Coadministration of drugs that inhibit CYP3A4 may decrease the clearance of indinavir and may result in increased plasma concentrations of indinavir.
Dosage adjustments for indinavir when administered in combination therapy:
Delavirdine, Itraconazole, or Ketoconazole: Reduce indinavir dose to 600 mg every 8 hours.
Efavirenz: Increase indinavir dose to 1000 mg every 8 hours.
Lopinavir and Ritonavir: Indinavir 600 mg twice daily.
Nevirapine: Increase indinavir dose to 1000 mg every 8 hours.
Rifabutin: Reduce rifabutin to 1/2 the standard dose plus increase indinavir to 1000 mg every 8 hours.
Ritonavir: Adjustments necessary for both agents:
Ritonavir 100-200 mg twice daily plus indinavir 800 mg twice daily or
Ritonavir 400 mg twice daily plus indinavir 400 mg twice daily.
Renal Dose :
Dose in Renal Impairment GFR (mL/min)
| 20-50 | Dose as in normal renal function Monitor closely |
| 10-20 | Dose as in normal renal function Monitor closely |
| <10 | Dose as in normal renal function Monitor closely |
Dose in Patients undergoing Renal Replacement Therapies
| CAPD | Unlikely to be dialysed. Dose as in GFR<10 mL/min |
| HD | Not dialysed. Dose as in GFR<10 mL/min |
| HDF/High flux | Not dialysed. Dose as in GFR<10 mL/min |
| CAV/VVHD | Unlikely to be dialysed. Dose as in GFR=10–20 mL/min |
Hepatic Dose :
For Adults
Mild and moderate hepatic impairment: Reduce the recommended dose to 600 mg PO every 8 hours.
Dose in severe hepatic impairment has not been studied.