Dosing and uses of Crixivan, IDV (indinavir)
Adult dosage forms and strengths
capsules
- 100mg
- 200mg
- 400mg
HIV Infection
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
Renal Impairment
Dose adjustment not studied
Hepatic Impairment
Mild-to-moderate: 600 mg PO q8hr
Pediatric dosage forms and strengths
capsules
- 100mg
- 200mg
- 400mg
HIV-1 Infection (Off-label)
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
Crixivan, IDV (indinavir) adverse (side) effects
>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
Postmarketing Reports
Body as a whole: Redistribution/accumulation of body fat
Cardiovascular system: Cardiovascular disorders including myocardial infarction and angina pectoris; cerebrovascular disorder
Digestive system: Liver function abnormalities; hepatitis including reports of hepatic failure; pancreatitis; jaundice; abdominal distention; dyspepsia
Hematologic: Increased spontaneous bleeding in patients with hemophilia, acute hemolytic anemia
Endocrine/metabolic: New onset diabetes mellitus, exacerbation of pre-existing diabetes mellitus, hyperglycemia
Hypersensitivity: Anaphylactoid reactions; urticaria; vasculitis
Musculoskeletal system: Arthralgia, periarthritis
Nervous system/psychiatric: Oral paresthesia; depression
Skin and skin appendage: Rash including erythema multiforme and Stevens-Johnson syndrome; hyperpigmentation; alopecia; ingrown toenails and/or paronychia; pruritus
Urogenital system: Nephrolithiasis/urolithiasis, in some cases resulting in renal insufficiency or acute renal failure, pyelonephritis with or without bacteremia; nephritis sometimes with indinavir crystal deposits; renal insufficiency; renal failure; leukocyturia, crystalluria; dysuria
Laboratory abnormalities: Increased serum triglycerides; increased serum cholesteroL
Warnings
Contraindications
Hypersensitivity
Drugs that are contraindicated with indinavir include alpha1-adrenoreptor agonists (eg, alfuzosin), antiarrhythmics (amiodarone, bepridil, flecainide, propafenone, quinidine), rifampin, voriconazole, ergot derivatives (dihydroergotamine, ergonovine, ergotamine, methylergonovine), cisapride, St. John’s wort, lovastatin, simvastatin, lurasidone, pimozide, sildenafil (when used for pulmonary artery hypertension), midazolam, and triazolam
Cautions
Proper hydration required (1.5 L liquids/day) to counter risk of nephrolithiasis/urolithiasis (much higher in children)
Risks of fat redistribution, hemolytic anemia, hyperglycemia, hyperbilirubinemia, immune reconstitution syndrome if used in combination w/ other antiretroviral drugs
Separate from didanosine by 1 hr
Monitor: LFTs q6-12week
Pregnancy and lactation
Pregnancy category: C
Lactation: excretion in milk unknown; contraindicated
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Crixivan, IDV (indinavir)
Mechanism of action
Protease Inhibitor; inhibits cleavage of Gag-Pol polyprotein precursors, which in turn causes the formation of immature, noninfectious viral particles; combination use recommended
Pharmacokinetics
Absorption: administration with high fat, high calorie diet resulted in a reduction in AUC & in maximum serum concentration (77% & 84% respectively); lighter meal resulted in little or no change in these parameters
Protein Bound: 60%
Metabolism: hepatic via CYP3A4; 7 metabolites of indinavir identified
Bioavailability: good
Half-life, elimination: 1.8±0.4 hr
Peak Plasma Time: 0.8±0.3 hr
Excretion: Urine (19%); feces (83%)
Administration
Oral 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
