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Itraconazole and its Drug InteractionsBY: sadaf mumtaz | Category: Health | Submitted: 2012-07-10 01:37:36
Itraconazole belongs to the class Azoles and is an effective antifungal agent. Its pharmacologic properties include varied absorption due to the presence of food and low gastric pH; poor water solubility, an inhibitor of cytochrome450 system, decreased bioavailability, poor CNS penetration, and eliminated mainly through liver. Resistance developed with long-term use of Itraconazole. It is relatively non-toxic and cause only minor GI upset. It is available as capsule, oral solution and I.V. No effect on testosterone and glucocorticoid synthesis. Dose is 100-400mg/day.
Itraconazole is used for variety of superfacial mycoses as a prophylactic agent for spergillosis, Candidiasis in immunocompromised patients.
Mechanism of Action
It inhibits fungal p450 dependent enzyme and blocks ergosterol synthesis.
Cisapride, dofetilide, pimozide or quinidine, taking these medications with itraconazole can cause serious irregular heartbeat.
The effects of amphotericin B and azole antifungals would be expected to be antagonistic, and there is some clinical evidence that supports this suggestion and describes increased adverse effects.
An isolated study found that amphotericin B reduced the levels of itraconazole, and the combination may increase the incidence of hepatotoxicity.
A comparative study found that patients given itraconazole and amphotericin B had serum itraconazole levels of less than 1 microgram/mL, whereas those given itraconazole alone had serum itraconazole levels of 3.75 micrograms/mL, which suggests that amphotericin B may reduce itraconazole levels
A retrospective study of itraconazole use found that 11 of 12 leukaemic patients given amphotericin B and itraconazole had raised liver enzymes.These abnormalities resolved in 7 patients when the amphotericin B was discontinued. Itraconazole alone, given to another 8 patients did not cause liver enzyme abnormalities, even though it was used in high doses.
- Pages 233 and 237
Dexamethasone hepatically induces metabolism of ITZ.
Norfluoxetine inhibits CYP3A4, â†' ITZ concentrations.
Administer ITZ 2 hr after antacid dose. Note drug formulations containing antacid buffers.
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