585 Hypochlorhydria, which may be present in patients with also required with calcium -channel blockers, which may membranes for I to 4 weeks after the drug is stopped. Small AIDS, can reduce absorption of itraconazole. In this case increase the risk of congestive heart failure if given together, amounts are distributed into breast milk. absorption may be improved by giving itraconazole with an and nisoldipine in particular is considered contra-indicated. Itraconazole is metabolised in the liver mainly by acidic drink, such as a cola beverage. Use with the statins is also best avoided because of the risk of cytochrome P450 isoenzyme CYP3A4. The major metabo­ muscle damage. lite, hydroxyitraconazole, has antifungal activity compar­ Breast feeding. Licensed product information does not Reviews of drug interactions vvith azole antifungals. able with that of itraconazole. Itraconazole is also excreted recommend breast feeding while receiving itraconazole Baciewicz FA. Ketoconazole and lluconazole drug as inactive metabolites in the bile or urine; 3 to 18% is although only small amounts of itraconazole are distribu­ Intern Med 1993; 153: 1970-6. excreted in the faeces as unchanged drug. Small amounts 2. Lomae.;;tro BM, on drug interactions with awle ted into breast milk. are eliminated in the stratum corneum and hair. Itracon­ antifungal agents. Ann 1998; 32: 915-28. 3. Venkatakrishnan K, et a!. Effects of the antifungal on oxidative azole is not removed by dialysis. Porphyria. The Drug Database for Acute Porphyria, com­ drug metabolism: clinical relevance. Clin 2000; 38: 111- The elimination half-life after a single 100-mg dose has piled by the Norwegian Porphyria Centre (NAPOS) and 80. been reported as 20 hours, increasing to 30 to 40 hours with the Porphyria Centre Sweden, classifies itraconazole as continued use. probably porphyrinogenic; it should be prescribed only for Immunosuppressants. Fatal hepatitis occurred in a 68- compelling reasons and precautions should be considered year-old woman 1 after 2 months of use of itraconazole P.r�p�r<:Jii<:J':lS. in all patients.1 and leflunomide. The authors suggested that the combined hepatotoxicity of both drugs might have accounted for ProprietaryPreparations (details are given in Volume B) l. The Drug Database for Acute Porphyria. Available at http://www. this. drugs-porphyria.org (accessed 14/10/ll) Single-ingredient Preparations. Arg.: Itrac; Micotenk; Nitridazol; l. A, et al. Fatal hepatitis with leflunomide and itraconazole. Am 1 Panastat; Salimidin; Sporanox; Austral.: Sporanox; Austria: 113: 352-3 . Itrabene; Sporanox; Belg.: Sporanox; Braz.: Estiranox; Fungo­ Interactions nax; ltraconolt; Itracotan; Itrahexal; Itralex; Itraspor; Itrazol; Enzyme-inducing drugs such as carbamazepine, isoniazid, Metal ions. Didanosine in a formulation containing alu­ Neo Itrax; Sporanox; Spozol; Traconal; Tracozont; Tratzol; nevirapine, phenobarbital, phenytoin, rifabutin, rifampicin, minium and magnesium ion buffering agents could reduce Traxonol; Canad.: Sporanox; Chile: Itodal; Sporanox; Teramic; or St John's wort may decrease plasma concentrations of the absorption of itraconazole due to the resultant increase China: Mei Fu Sporanox (J!Ji&f=t!i): Yi Qi Kang itraconazole sufficiently to reduce its efficacy. Conversely, in gastric pH. 1 �); Cz. : Cladostad;(9iem): Prokanazol; Sporanox; Denm.: Itrastad; (§Nid­;;;; dazol; Sporanox; Sporanox; Sporanox; Itracolt; enzyme inhibitors such as clarithromycin, erythromycin, I. Moreno F, et al. Itraconazole-didanosine excipient interaction. lAMA Fin.: Fr.: Ger.: 269: Itraconbeta; Itradenn; Sempera; Slro:.; Assosept-S; Bevona­ HIV-protease inhibitors, including ritonavir-boosted HIV­ 199 3; 1508. Gr.: zole; Brovicton; Deratil; Etrel; Fansidol; Flunol; Fungonazol; protease inhibitors, may increase plasma concentrations of Fungospor; Idranox; Inrozol; Isoflon; Itrabest; Itracon; Itraco­ itraconazole. Use of drugs that reduce stomach acidity, such Antimicrobial Action nal; Itralfa; Itraproton; Itraspor; Itraviron; Itrazol; Laverio; Lor­ as antimuscarinics, antacids, proton pump inhibitors, and Itraconazole is a triazole antifungal drug that in sensitive enzo!; Mesmor; Micronazol; Mycodrox; Neo-Candimyk; Promi­ histamine H -receptor antagonists, may reduce the 2 fungi inhibits cytochrome P450-dependent enzymes nox; Soprazon; Sporanox; Sporizole; Stas; Sterginox; Zetilox; absorption of itraconazole. resulting in impairment of ergosterol synthesis in fungal Hong Kong: Aranox; Inox; Itracon; Itranstad; Quali-itrazole; Like other triazole antifungals, itraconazole is a potent Sporacidt; Sporanox; Cladostad; Itraconep; Itragen; cell membranes. It has a slightly wider spectrum of activity Hung.: inhibitor of the cytochrome P450 isoenzyme CYP3A4, and Omicral; Orungal; India: Biospore; Candistat; Canditral; Ful­ than ketoconazole. It is active against Aspergillus spp., may increase plasma concentrations of other drugs reliant cover; Fungicap; Itaspor; Itra; Itracan; Itrazen; Itrole; Indon.: Blastomyces dermatitidis, Candidaspp., Coccidioides immitis, upon it for their metabolism. This increases the risk of Forcanox; Fungitrazol; Furolnokt; Itzol; Mycotrazol; Nufatrac; Cryptococcus neoformans, Epidermophytonspp., Histoplasma adverse effects and such combinations should be given with Petrazole; Sporacid; Sporanox; Sporax; Spyrocon; Trachon; Tra­ capsulatum, Malassezia fu rfu r, Microsporum spp., Paracocci­ caution and careful monitoring, if at all. Drugs so affected cor; Unitrac; Zitrazolt; Irl.: Sporanox; Israel: Itranol; Sporanox; dioides brasiliensis, Sporothrix schenckii, and Trichophyton spp. may include: Ital. : Sporanox; Tranizolo; Trazer; Triasporin; Jpn: Itrizole; Itraconazole also has son1e antiprotozoal activity against antiarrhythmics such as disopyramide, dofetilide and Malaysia: Canditral; Inox; Itracon; Sporanox; Unitrac; Mex.: • Leishmania spp. Carexant; Conamed; Congox; Derusil; Ergospharmat; Fitocyd; quinidine Acquired resistance to itraconazole is rare but ketocon­ Fuzoltec; Imazolt; Iqcona; Isoporum; Isox; Itracosid; Itranax; antidepressants such as reboxetine • azole�resistant strains of Candida albicans have been found to Lozartil; Rixtal; Seritral; Silicsan; Sinozol; Solmavin; Sporanox; antiepileptics such as carbamazepine (which in turn • be cross resistant to itraconazole. Steitraz; Trax; Z-Fin; Zitriasol; Zolken; Zotril; Neth.: Trisporal; decreases the concentration of the antifungal, see above) Norw.: Sporanox; NZ: Itcozol; Itrazole; Sporanox; Philipp.: antihistamines such as astemizole, mizolastine, and • Microbiological interactions. Synergistic antifungal effects In ox; Sporanox; Pol. : ItraGen; ItraMerck; Orungal; Trioxal; terfenadine were seen in vitro with terbinafine and itraconazole against Port.: Fungizol; Itracic; Sporanox; Unisens; Rus.: Canditral antimalarials such as halofantrine (KaH,[{JIT}Jarr); Irunine (11pyHHH); Itramicol (UrpaM.llKOJI); Itrazol • strains of Candida albicans1 and Scedosporium prolzficans. 2 antimigraine drugs such as dihydroergotamine, ergo­ (Urpa3oJI); Miconihol (MHKOHHXOJI); Orungal (OpyHrarr); Orun­ • For effects on the antifungal activity of azoles when given metrine, ergotamine, methylergometrine, and eletriptan gamin (OpyHraMrrH); Orunit (OpyHHT); Rumycoz (PyMHK03); with amphotericin B, see p. 572.3. Teknazol (TeKH<l3orr); Adco-Sporozole; Sporanox; Tris­ • the antimycobacterial rifabutin (which again also S.Afr. : decreases antifungal concentrations) l. Barchiesi F, et al. In vitro activities of terbinafine in combination with poral; Singapore: Canditral; Hitrazole; Sporanox; Unitrac; fluconazole and itraconazole against isolates of Candida albkans with Spain: Canadiol; Hongoseril; Oromict; Sporanox; Swed.: antineop/astics such as busulfan, docetaxel, trimetrexate, reduced su�ceptibility to azoles. Antimicrob Agents Chemother 1997; 41: • Sporanox; Gosegyne G; Itraderm; Sporanox; Can­ and the vinca alkaloids 1812-14. Switz.: Thai.: antipsychotics such as pimozide and sertindole 2. Meletiadis J, et al. In vitro interaction of terhinaline with itrawnawle ditralt; Iconat; Itra; Itracon; Itrasix; Itrazole; Norspor; Spazol; • Sporal; Sporlabt; Spornar; Funit; Itraspor; Sporanox; anxio/ytics and sedatives such as buspirone Antimicrob Agents Turk.: • Sporex; UK: Sporanox; Ukr.: Funit (<llyHHT); Itracon (lfrpaKOH); benzodiazepines such as alprazolam, brotizolam, diaze­ • ltral (11Tp''-'); Orunzol (OpyH3on)t Sporagal (Cnoparan); Trioxal pam, rnidazolam, and triazolam Resistance. For a discussion of increasing resistance of (TpnoKcaJI)t; USA: Onmel; Sporanox; Venez.: Fungosin; calcium-channel blockers such as bepridil, verapamil, and : • Candida spp. to azoles, see under Antimicrobial Action of Sporanox. the dihydropyridines felodipine, nifedipine, and nisoldi­ Fluconazole, p. 580.2. Decreased susceptibility to itracon­ pine (see also below) Mex. : Gitrasek; Sepia; Sporasec; azole and cross-resistance to fluconazole has been reported Multi-ingredient Preparations. some corticosteroids such as budesonide, dexamethasone, Venez. : Sporasec. • in C. albicans isolated from patients with AIDS given long­ fluticasone and methylprednisolone term prophylaxis with itraconazole.1 Aspergillus fu migatus the coumarin anticoagulant warfarin • resistant to hraconazole has also been seen.2•3 the gastrointestinal prokinetic cisapride • l. Goldman M, et a!. Does long-term itraconazole prophylaxis result in in Ketoconazole (BAN, USAN, r/NN) • HIV-protease inhibitors such as indinavir, ritonavir, and vitro azoic resistance