Antifungal azoles voriconazole

ANTIBIOTICS - macrolides (especially azithromycin, clarithromycin, parenteral erythromycin, telithromycin), quinupristin/ dalfbpristin 3. ANTICANCER AND IMMUNOMODULATING DRUGS - arsenic trioxide 4. ANTIDEPRESSANTS - TCAs, venlafaxine S. ANTIEMETICS-dolasetron 6. ANTIFUNGALS - fluconazole, posacon-azole, voriconazole 7. ANTIHISTAMINES-terfenadine, hydroxyzine, mizolastine... 

For details of interactions with individual antifungal azoles, see individual monographs (fluconazole, itraconazole, ketoconazole, miconazole, and voriconazole). 

Select azole antifungals (e.g., itraconazole, voriconazole, and posaconazole) and the echinocandins are available for IA treatment. For initial therapy of IA, voriconazole had higher response and survival rates than c-AMB.102 An advantage of voriconazole is its 96% oral bioavailability, making use of this oral drug an attractive and less expensive alternative. The dose of voriconazole was 6 mg/kg IV every 12 hours for two doses, followed by 4 mg/kg IV every 12 hours for at least 7 days, at which time oral voriconazole 200 mg every 12 hours could be administered. Common toxicities reported with voriconazole include infusion-related, transient visual disturbances (i.e., blurred vision, altered color perception, photophobia, and visual hallucinations), skin reactions (i.e., rash, pruritus, and photosensitivity), elevations in hepatic transaminases and alkaline phosphatase, nausea, and headache.102 In addition, voriconazole increases the serum concentrations of medications cleared by cytochrome P-450 2C9, 2C19, and 3A4 (e.g., cyclophosphamide and calcineurin inhibitors) concomitant voriconazole-sirolimus should be avoided.103... 

The azole derivatives for systemic administration include the imidazoles ketoconazole and miconazole and the triazoles fluconazole, itraconazole, posaconazole and voriconazole. They are broad spectrum antifungals and have activity against several dermatophytes, Candida, Cryptococcus and other fungi that cause deep-seated infections. 

Therapy of fungal arthritis consists of amphotericin B in combination with surgical debridement. Azole antifungal agents including itraconazole, fluconazole, voriconazole, and posaconazole, are promising in the therapy of fungal arthritis. 

Clinical Use. Voriconazole (Vfend) is similar chemically to other azole antifungals such as fluconazole. Voriconazole has a broad antifungal spectrum, and is administered systemically to treat aspergillosis and other serious fungal infections caused by Scedospo-rium apiospermum and Fusarium,31... 

Elerbrecht R. Voriconazole therapeutic review of a new azole antifungal. Expert Rev Anti Infect Ther. 2004 2 485 197. 

CARBAMAZEPINE ANTIFUNGALS - ITRACONAZOLE, KETOCONAZOLE, MICONAZOLE, POSACONAZOLE, VORICONAZOLE 1 plasma concentrations of itraconazole and of its active metabolite, ketoconazole, posaconazole and voriconazole, with risk of therapeutic failure, t carbamazepine plasma concentrations These azoles are highly lipophilic, and clearance is heavily dependent upon metabolism by CYP isoenzymes. Carbamazepine is a powerful inducer of CYP3A4 and other CYP isoenzymes (CYP2C18/19, CYP1A2), and the result is very low or undetectable plasma levels. Inhibition of P-gp t bioavailability of carbamazepine Avoid co-administration of posaconazole or voriconazole with carbamazepine. Watch for inadequate therapeutic effects, and t dose of itraconazole. Higher doses of itraconazole may not overcome this interaction. Consider use of the less lipophilic fluconazole, which is less dependent on CYP metabolism. Necessary to monitor carbamazepine levels... 

These antifungals are inhibitors of the CYP3A4 isoenzyme but the inhibiting potencies of azoles vary itraconazole and ketoconazole are considered to be more potent than posaconazole and voriconazole, which in turn are more potent than fluconazole. Fluconazole, itraconazole and voriconazole also inhibit CYP2C9 and CYP2C19. 

Voriconazole is contraindicated in patients with known hypersensitivity to voriconazole or its components. There is no information regarding cross-sensitivity between voriconazole and other azole antifungal agents. Caution should be used when prescribing voriconazole to patients with hypersensitivity to other azoles. Refer to Table 11-14 for drug interactions. 

B. Azole antifungals include systemic agents such as keto-conazole, fluconazole, itraconazole, and voriconazole. Topical agents used for the treatment of vaginal candidiasis and thrush include miconazole and clotrimazole. The pharmacologic properties of the systemic azoles differ considerably. Ketoconazole, the first oral azole developed, has poor bioavailability and requires an acidic environment for enhanced absorption. Thus, initial studies required ketoconazole to be administered with a cola to increase bioavailability. Fluconazole, unlike itraconazole and ketoconazole, is hydrophillic and has increased penetration across the blood-brain barrier. Fluconazole is also the only azole that is renally eliminated. 

Resistance to other antifungal agents such as amphotericin B has been observed less frequently in clinical fungal isolates however, the molecular basis of this resistance is not currently well understood. To solve the problems associated with antifungal resistance a number of novel azole drugs (e.g. voriconazole) and novel classes of drug (e.g echinocandins) have been developed (see Chapter 12). 

Clinically important, potentially hazardous interactions with amphetamines, aprepitant, astemizole, atazanavir, azithromycin, azole antifungals, clarithromycin, darunavir, dirithromycin, erythromycin, fluoxetine, fosamprenavir, grapefruit juice, imatinib, indinavir, itraconazole, ketoconazole, methylphenidate, nefazodone, nelfinavir, nilotinib, pemoline, phenothiazines, protease inhibitors, quinidine, ritonavir, saquinavir, sertraline, sparfloxacin, sulpiride, telithromycin, thioridazine, tipranavir, tricyclic antidepressants, troleandomycin, voriconazole, zileuton, ziprasidone... 

Azole antifungal agents (ketoconazole. Itraconazole, ketoconazole, and voriconazole concentrations may be... 

In more advanced esophageal disease, oral azoles may be ineffective. Until recently, intravenous amphotericin B deoxycholate has been the alternative for patients with endoscopically proven disease who have failed fluconazole or itraconazole therapy.22 2" Moderate disease may be treated adequately with low- to moderate-dose amphotericin B for 10 days, although higher doses may be necessary for patients with AIDS or advanced disease. " Voriconzole, a new triazole antifungal available in both oral and intravenous preparations, produces comparable clinical response to fluconazole. Voriconazole has been associated with more side effects and multiple pharmacokinetic drug interactions. " ... 

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