itraconazole (Sporanox, Tulsura)
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Introduction
Tradename: Sporanox. In general, itraconazole is 10-100 times more potent than fluconazole.
Indications
- preferred agent for treatment of nonmeningeal histoplasmosis
- onychomycosis
- dermatophytes, tinea versicolor
- griseofulvin-resistant ringworm
- Candida
- pulmonary infections or extrapulmonary infections caused by:
- neutropenic fever[6]
Contraindications
- concurrent therapy with:
- may lead to prolongation of QT interval, tachycardia & ventricular fibrillation
Dosage
- systemic infection
- onychomycosis
- 200 mg PO QD for 3 months
- 200 mg PO BID for 1st 7 days of the month
- 3 months for onychomycosis of fingernails
- 4 months for onychomycosis of toenails
- 100-200 mg PO BID. Max 800 mg/day
- intravenous infusion:
- dilute in normal saline
- 200 mg BID (not for bolus injection)
- infuse 200 mg over 60 minutes
Tabs: 100 mg.
Solution: for injection
- 25 mL containing 200 mg itraconazole
- mix with 50 mL normal saline (provided)
Liquid: formulation has both topical & systemic effect
Dosage adjustment in renal failure
Table
| creatinine clearance | dosage |
|---|---|
| > 50-90 mL/min | 100% |
| 10-50 mL/min | 100% |
| < 10 mL/min | 50% |
Pharmacokinetics
- oral absorption is increased by gastric acidity
- food increases absorption
- antacids decrease absorption
- 99% is bound to albumin
- concentrations are higher in tissue than in serum
- metabolized by liver by cyt P450 3A4
- also strongly inhibits cyt P450 3A4
- 1/2life 24-28 hours
- therapeutic level > 1 ug/mL
elimination via liver
1/2life = >40 hours
Monitor
- liver function tests
- patients with hepatic dysfunction
- consider monitoring in all patients[8]
Antimicrobial activity
Antifungal activity:
- Candida albicans
- Candida krusei
- Candida tropicalis
- Cryptococcus
- Histoplasma capsulatum
- Blastomyces dermatitidis
- Sporothrix
- Penicillium marneffei
- Aspergillus
- Coccidioides immitis
- Phaeohyphomycosis
- Fusarium (+/-)
Adverse effects
- generally well tolerated at 200 mg QD
- GI distress at 400 mg/day
- nausea/vomiting 10%
- hypertriglyceridemia 9%
- hypokalemia 6%
- increased serum transaminases 5%
- rash 2%
- hepatotoxicity
- hypertension
- headache
- decreased libido
- congestive heart failure[4]
- at least one side effect in 39%
Drug interactions
- hepatic cytochrome P450 induction by itraconazole decreases serum level of:
- rifampin
- rifabutin (+/-)
- carbamazepine
- itraconazole increases plasma levels of:
- phenytoin
- cyclosporine
- midazolam
- triazolam
- saquinavir (possibly)
- coadministration may increase levels of itraconazole:
- coadministration may decrease levels of itraconazole
- antacids, H2 blockers (cimetidine, famotidine, ranitidine) 5 & proton pump inhibitors (omeprazole, lansoprazole) may diminish absorption of itraconazole by as much as 60%
- HMG CoA reductase inhibitors (simvastatin, lovastatin etc) in combination may result in rhabdomyolysis
- may increase effects of warfarin
- terfenadine, astemizole, cisapride
- contraindicated
- may result in QT prolongation, tachycardia & ventricular fibrillation
- in general, drug interactions with fluconazole greater than with itraconazole
- any drug that inhibits cyt P450 3A4 may increase levels of itraconazole
- any drug that induces cyt P450 3A4 may diminish levels of itraconazole
- itraconazole inhibits cyt P450 3A4, thus inhibits its own metabolism & metabolism of other cyt P450 3A4 substrates
Mechanism of action
- inhibits fungal cytochrome P450
- inhibits synthesis of fungal cell wall ergosterol
- disrupts fungal cell wall
More general terms
Additional terms
- aspergillosis
- Blastomycosis
- candidiasis
- cytochrome P450 3A4 (cytochrome P450 C3, nifedipine oxidase, P450-PCN1, NF-25, CYP3A4)
- histoplasmosis (Ohio Valley fever)
- onychomycosis
- pityriasis
- Tinea versicolor (Pityriasis versicolor)
References
- ↑ The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
- ↑ Medical Knowledge Self Assessment Program (MKSAP) 11, American College of Physicians, Philadelphia 1998
- ↑ Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
- ↑ 4.0 4.1 Prescriber's Letter 8(6):33 2001
- ↑ 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
- ↑ 6.0 6.1 Journal Watch 21(21):171, 2001 Boogaerts et al, Ann Intern Med 135:412, 2001
- ↑ PDR 2000
- ↑ 8.0 8.1 Prescriber's Letter 17(7): 2010 Recommended Lab Monitoring for Common Medications Liver Function Test Scheduling Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=260704&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 9.0 9.1 Deprecated Reference