indinavir (Crixivan)
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Introduction
Tradename: Crixivan.
Indications
- treatment of HIV infection
- 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
- rapidly absorbed from GI tract in fasting state
- administration with meal high in calories, fat & protein decreases absorption >60%
- protein binding 60%
- penetrates the blood brain barrier into the CSF
- metabolized in liver by cyt P450 3A4 into 7 metabolites
- < 20% of dose is excreted unchanged in the urine
- elimination 1/2life is 1.8 hours +/- 0.4 hours
elimination via liver
elimination via kidney
1/2life = 1.8 hours
protein binding = 60 %
Adverse effects
- mild hyperbilirubinemia, largely unconjugated (10%)
- nephrolithiasis (fluid intake of > 2 L/day)
- renal insufficiency
- lipodystrophy syndrome[5]
- GI intolerance
- nausea
- rash
- headache
- drug adverse effects of antiretroviral protease inhibitors
- drug adverse effects of antiretroviral agents
Drug interactions
- rifampin & rifabutin
- not recommended for use with:
- ketoconazole in combination increases indinavir levels (decrease indinavir to 600 mg every 8 hours)
- itraconazole may affect indinavir
- didanosine may reduce absorption of indinavir unless taken > 2 hours apart
- any drug that inhibits cyt P450 3A4 may increase levels of indinavir
- any drug that induces cyt P450 3A4 may diminish levels of indinavir
- indinavir inhibits cyt P450 3A4, thus inhibits its own metabolism & metabolism of other cyt P450 3A4 substrates
- drug interaction(s) of fluticasone with HIV1 protease inhibitors
- drug interaction(s) of antiretroviral protease inhibitor in combination with ritonavir
- drug interaction(s) of statins with antiviral protease inhibitors
- drug interaction(s) of antibiotics with warfarin
Laboratory
Mechanism of action
- an inhibitor of HIV protease
- binds to active site of HIV protease(s)
- HIV protease inhibition prevents cleavage of viral proteins resulting in formation of immature non-infectious particles
- indinavir also inhibits cyt P450 3A4
- resistance may develop: cross-resistance with ritonavir & possibly nelfinavir
More general terms
Additional terms
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
- ↑ 5.0 5.1 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#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=220233&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 7.0 7.1 Prescriber's Letter 21(6): 2014 Oral Meds to Keep in Original Containers Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=300622&pb=PRL (subscription needed) http://www.prescribersletter.com
Database
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=60944
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=104877
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=3706
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=60958
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=394079