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indinavir (Crixivan)
Tradename: Crixivan.
Indication:
1) treatment of HIV infection
2) post-exposure prophylaxis against HIV
Dosage:
- 800 mg PO every 8 hours
- dosage should be reduced to 600 mg every 8 hours with mild to moderate liver failure secondary to cirrhosis
Tabs: 200 & 400 mg.
Storage:
- store in orginal container
- must be protected from moisture
- original container has a desiccant [7]
Pharmacokinetics:
1) rapidly absorbed from GI tract in fasting state
2) administration with meal high in calories, fat & protein decreases absorption >60%
3) protein binding 60%
4) penetrates the blood brain barrier into the CSF
5) metabolized in liver by cyt P450 3A4 into 7 metabolites
6) < 20% of dose is excreted unchanged in the urine
7) elimination 1/2life is 1.8 hours +/- 0.4 hours
Adverse effects:
1) mild hyperbilirubinemia, largely unconjugated (10%)
2) nephrolithiasis (fluid intake of > 2 L/day)
3) renal insufficiency
4) lipodystrophy syndrome [5]
5) GI intolerance
6) nausea
7) rash
8) headache
Drug interactions:
1) rifampin & rifabutin
a) may decrease effectiveness of indinavir
b) increased levels of rifampin & rifabutin
2) not recommended for use with:
a) terfenadine
b) astemizole
c) cisapride
d) triazolam
e) midazolam
f) ergot alkaloids
3) ketoconazole in combination increases indinavir levels (decrease indinavir to 600 mg every 8 hours)
4) itraconazole may affect indinavir
5) didanosine may reduce absorption of indinavir unless taken > 2 hours apart
6) any drug that inhibits cyt P450 3A4 may increase levels of indinavir
7) any drug that induces cyt P450 3A4 may diminish levels of indinavir
8) indinavir inhibits cyt P450 3A4, thus inhibits its own metabolism & metabolism of other cyt P450 3A4 substrates
Laboratory:
- indinavir in serum/plasma
Mechanism of action:
1) an inhibitor of HIV protease
2) binds to active site of HIV protease(s)
3) HIV protease inhibition prevents cleavage of viral proteins resulting in formation of immature non-infectious particles
4) indinavir also inhibits cyt P450 3A4
5) resistance may develop: cross-resistance with ritonavir & possibly nelfinavir
Interactions
drug interactions
drug adverse effects (more general classes)
Related
cytochrome P450 3A4 (cytochrome P450 C3, nifedipine oxidase, P450-PCN1, NF-25, CYP3A4)
General
antiretroviral protease inhibitor
Properties
INHIBITS: HIV protease
MISC-INFO: elimination route LIVER
KIDNEY
1/2life 1.8 HOURS
protein-binding 60%
pregnancy-category C
safety in lactation -
Database Correlations
PUBCHEM correlations
References
- The Pharmacological Basis of Therapeutics, 9th ed.
Gilman et al, eds. Permagon Press/McGraw Hill, 1996
- Physician's Desk Reference (PDR) 56th edition, Medical
Economics, 2002
- Drug Information & Medication Formulary, Veterans Affairs,
Central California Health Care System, 1st ed., Ravnan et al
eds, 1998
- Kaiser Permanente Northern California Regional Drug
Formulary, 1998
- Medical Knowledge Self Assessment Program (MKSAP) 11, 14,
American College of Physicians, Philadelphia 1998, 2006
- Prescriber's Letter 13(3): 2006
Cytochrome P450 drug interactions
Detail-Document#: 220233
(subscription needed) http://www.prescribersletter.com
- Prescriber's Letter 21(6): 2014
Oral Meds to Keep in Original Containers
Detail-Document#: 300622
(subscription needed) http://www.prescribersletter.com