CRIXIVAN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for CRIXIVAN (CRIXIVAN).
Indinavir is a specific, potent, reversible inhibitor of HIV-1 protease. It binds to the active site of the viral protease, preventing the cleavage of viral polyprotein precursors into functional proteins, resulting in the formation of immature, non-infectious virions.
| Metabolism | Indinavir is primarily metabolized by cytochrome P450 3A4 (CYP3A4) in the liver. |
| Excretion | Primarily fecal (78-82%) with approximately 20% renal excretion of unchanged drug. |
| Half-life | Terminal elimination half-life is 1.8 to 2.5 hours in healthy adults; requires dosing every 8 hours. |
| Protein binding | Approximately 60% bound to plasma proteins, mainly to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution is about 2.1 L/kg, indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability is approximately 60-70% under fed conditions; reduced when taken with high-fat meals. |
| Onset of Action | Oral: max serum concentration reached in 0.6-0.8 hours post-dose. |
| Duration of Action | Duration of action is approximately 8 hours, necessitating thrice-daily dosing to maintain therapeutic levels. |
800 mg orally every 8 hours on an empty stomach (1 hour before or 2 hours after meals) or with a light meal.
| Dosage form | CAPSULE |
| Renal impairment | No dose adjustment required for renal impairment. Not significantly removed by hemodialysis. |
| Liver impairment | Mild to moderate hepatic impairment (Child-Pugh A or B): 600 mg orally every 8 hours. Severe hepatic impairment (Child-Pugh C): contraindicated. |
| Pediatric use | Age ≥2 years: 500 mg/m2 orally every 8 hours (maximum 800 mg every 8 hours). For children unable to swallow capsules, use oral solution (not available in US). |
| Geriatric use | No specific dose adjustment recommended; monitor renal function and potential for increased adverse effects due to age-related changes. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for CRIXIVAN (CRIXIVAN).
| Breastfeeding | Indinavir is excreted in human milk; M/P ratio not reported. Breastfeeding is not recommended in HIV-infected women in the US due to risk of postnatal transmission of HIV; manufacturers advise against breastfeeding. |
| Teratogenic Risk | Crixivan (indinavir) is classified as FDA Pregnancy Category C. First trimester: Limited human data; animal studies show no evidence of teratogenicity at systemic exposures up to 0.8 times human AUC at recommended dose. Second/third trimesters: No evidence of increased risk of major malformations; cases of hyperbilirubinemia and early neonatal death reported with protease inhibitors, but not specifically with indinavir. Overall, risk of untreated HIV outweighs potential risks. |
■ FDA Black Box Warning
None
| Serious Effects |
["Concomitant use with drugs highly dependent on CYP3A4 for clearance (e.g., alfuzosin, amiodarone, ergot derivatives, lovastatin, simvastatin, pimozide, sildenafil for pulmonary hypertension, triazolam, midazolam oral) due to risk of serious adverse events.","Concomitant use with St. John's wort or rifampin.","Severe hepatic insufficiency (Child-Pugh class B or C)."]
| Precautions | ["Nephrolithiasis/urolithiasis: Hydrate adequately (at least 1.5 liters of fluid daily).","Hepatotoxicity: Including cases of acute hepatic failure; monitor hepatic enzymes.","Hyperbilirubinemia: Often due to indirect bilirubin elevations, typically benign but may occur with other serious events.","Hemolytic anemia: Rare, discontinue if diagnosed.","Diabetes mellitus/hyperglycemia: New-onset or exacerbation.","Immune reconstitution syndrome: Including autoimmune disorders.","Fat redistribution/accumulation: Central adiposity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, breast enlargement, cushingoid appearance.","Total cholesterol and triglyceride elevations.","Increased bleeding in hemophiliacs.","Pancreatitis.","Rash: Including severe reactions (Stevens-Johnson syndrome)."] |
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| Fetal Monitoring | Monitor maternal: viral load, CD4 count, serum bilirubin (indinavir may cause unconjugated hyperbilirubinemia), renal function (risk of nephrolithiasis), and liver function. Fetal/neonatal: ultrasound growth monitoring, screen for neonatal hyperbilirubinemia and kernicterus. |
| Fertility Effects | No human studies on fertility effects. In animal studies, no adverse effects on fertility at systemic exposures up to 0.8 times human AUC. |