table 1 below, lists drugs covered in this section by therapeutic group and drug class. If anti-infective is drug causing interaction, interaction is generally dealt with under affected drug. Also note that drugs such as 5-nitroimidazoles (e.g. metronidazole),which have actions against more than one type of organism (e.g. bacteria and protozoa) are covered under Antibacterials.
Intravenous amphotericin B causes important pharmacodynamic interactions via additive nephrotoxicity and myelotoxicity, and may increase cardiotoxicity of other drugs because of amphotericin-induced hypokalaemia. No important pharmacokinetic interactions are known. Lipid formulations such as liposomal amphotericin are less nephrotoxic than conventional amphotericin,and would therefore be expected to interact less frequently. Orally administered amphotericin is not absorbed systemically,and no interactions are known.
The most important interactions affecting and caused by azole antifungals are those resulting from inhibition and induction of cytochrome P450 isoenzymes
Fluconazole is principally (80%) excreted unchanged in urine, so is less affected by enzyme inducers and inhibitors than some other azoles. Fluconazole is a potent inhibitor of CYP2C9 and CYP2C19,and generally only inhibits CYP3A4 at high doses (greater than 200mg daily). Interactions are less likely with single doses used for genital candidiasis than with longer term use.
Itraconazole is extensively metabolised by CYP3A4,and its metabolism may become saturated with multiple dosing. Itraconazole and its major metabolite,hydroxy-itraconazole are potent inhibitors of CYP3A4.
Ketoconazole is extensively metabolised,particularly by CYP3A4. It is also a potent inhibitor of CYP3A4.
Miconazole is a potent inhibitor of CYP2C9. Because this azole is generally used topically as pessaries, skin cream, or an oral gel, it is less likely to cause interactions, although it should be noted that interactions with warfarin, , have been reported, particularly for oral gel.
Posaconazole is metabolised via UDP glucuronidation,and may also be a substrate for P-glycoprotein. Posaconazole is an inhibitor of CYP3A4.
Voriconazole is metabolised by CYP2C19,CYP2C9, and to a lesser extent by CYP3A4. Voriconazole is an inhibitor of CYP2C9,CYP2C19 and CYP3A4.
An number of other azole antifungals are only used topically in form of skin creams or intravaginal preparations, and have not been associated with drug interactions, presumably since their systemic absorption is so low, see Azoles; Topical + Miscellaneous interaction.
Fluconazole, ketoconazole and voriconazole have been associated with prolongation of QT interval, although generally not to a clinically relevant extent. However, they may also raise levels of other drugs that prolong QT interval, and these combinations are often contraindicated, see Antihistamines + Azoles interaction.
1. Venkatakrishnan K,von Moltke LL, Greenblatt DJ. Effects of the antifungal agents on oxidative drug metabolism: clinical relevance. Clin Pharmacokinet (2000) 38, 111–80.
table 1 below Anthelmintics,antifungals and antimalarials and other antiprotozoals
Albendazole,Flubendazole, Mebendazole, Tiabendazole (Thiabendazole)
Diethylcarbamazine,Ivermectin, Levamisole, Niclosamide, Oxamniquine, Piperazine, Praziquantel, Pyrantel
Naftifine,Terbinafine
Bifonazole,* Butoconazole,* Chlormidazole,* Clotrimazole,* Econazole,* Fenticonazole,* Isoconazole,* Ketoconazole,Miconazole, Oxiconazole,* Sertaconazole,* Sulconazole,* Tioconazole*
Fluconazole,Itraconazole, Posaconazole, Terconazole,* Voriconazole
Anidulafungin,Caspofungin
Amphotericin B,Natamycin,* Nystatin*
Amorolfine,* Butenafine,* Ciclopirox,* Flucytosine,Griseofulvin, Tolnaftate*
Amodiaquine,Chloroquine, Hydroxychloroquine
Mefloquine,Quinine
Artemether,Artemotil, Artesunate, Atovaquone, Halofantrine, Lumefantrine, Proguanil, Pyrimethamine, Sulfadoxine
Metronidazole,Ornidazole, Tinidazole
Furazolidone,Nifurtimox
Atovaquone,Diiodohydroxyquinoline, Diloxanide furoate, Eflornithine, Mepacrine, Pentamidine, Suramin
Anthelmintics,Antifungals and Antiprotozoals 209
| Table 1 Anthelmintics, antifungals and antimalarials and other antiprotozoals | |
| Group | Drugs |
| Anthelmintics | |
| Benzimidazole derivatives | Albendazole, Flubendazole, Mebendazole, Tiabendazole (Thiabendazole) |
| Organophosphorous compounds | Metrifonate (Metriphonate) |
| Other | Diethylcarbamazine, Ivermectin, Levamisole, Niclosamide, Oxamniquine, Piperazine, Praziquantel, Pyrantel |
| Antifungals | |
| Allylamines | Naftifine, Terbinafine |
| Azoles: | |
| Imidazoles | Bifonazole,* Butoconazole,* Chlormidazole,* Clotrimazole,* Econazole,* Fenticonazole,* Isoconazole,* Ketoconazole, Miconazole, Oxiconazole,* Sertaconazole,* Sulconazole,* Tioconazole* |
| Triazoles | Fluconazole, Itraconazole, Posaconazole, Terconazole,* Voriconazole |
| Echinocandins | Anidulafungin, Caspofungin |
| Polyene antibiotics | Amphotericin B, Natamycin,* Nystatin* |
| Other | Amorolfine,* Butenafine,* Ciclopirox,* Flucytosine, Griseofulvin, Tolnaftate* |
| Antimalarials | |
| 4-aminoquinolines | Amodiaquine, Chloroquine, Hydroxychloroquine |
| 8-aminoquinolines | Primaquine |
| 4-methanolquinolines | Mefloquine, Quinine |
| Other | Artemether, Artemotil, Artesunate, Atovaquone, Halofantrine, Lumefantrine, Proguanil, Pyrimethamine, Sulfadoxine |
| Antiprotozoals | |
| Antimony compounds | Sodium stibogluconate |
| Arsenicals | Melarsoprol |
| 5-nitroimidazoles†| Metronidazole, Ornidazole, Tinidazole |
| Nitrofuran | Furazolidone, Nifurtimox |
| Other | Atovaquone, Diiodohydroxyquinoline, Diloxanide furoate, Eflornithine, Mepacrine, Pentamidine, Suramin |
| Table 2 Anthelmintics, antifungals and antimalarials and other antiprotozoals | |
| Group | Drugs |
| Anthelmintics | |
| Benzimidazole derivatives | Albendazole, Flubendazole, Mebendazole, Tiabendazole (Thiabendazole) |
| Organophosphorous compounds | Metrifonate (Metriphonate) |
| Other | Diethylcarbamazine, Ivermectin, Levamisole, Niclosamide, Oxamniquine, Piperazine, Praziquantel, Pyrantel |
| Antifungals | |
| Allylamines | Naftifine, Terbinafine |
| Azoles: | |
| Imidazoles | Bifonazole,* Butoconazole,* Chlormidazole,* Clotrimazole,* Econazole,* Fenticonazole,* Isoconazole,* Ketoconazole, Miconazole, Oxiconazole,* Sertaconazole,* Sulconazole,* Tioconazole* |
| Triazoles | Fluconazole, Itraconazole, Posaconazole, Terconazole,* Voriconazole |
| Echinocandins | Anidulafungin, Caspofungin |
| Polyene antibiotics | Amphotericin B, Natamycin,* Nystatin* |
| Other | Amorolfine,* Butenafine,* Ciclopirox,* Flucytosine, Griseofulvin, Tolnaftate* |
| Antimalarials | |
| 4-aminoquinolines | Amodiaquine, Chloroquine, Hydroxychloroquine |
| 8-aminoquinolines | Primaquine |
| 4-methanolquinolines | Mefloquine, Quinine |
| Other | Artemether, Artemotil, Artesunate, Atovaquone, Halofantrine, Lumefantrine, Proguanil, Pyrimethamine, Sulfadoxine |
| Antiprotozoals | |
| Antimony compounds | Sodium stibogluconate |
| Arsenicals | Melarsoprol |
| 5-nitroimidazoles†| Metronidazole, Ornidazole, Tinidazole |
| Nitrofuran | Furazolidone, Nifurtimox |
| Other | Atovaquone, Diiodohydroxyquinoline, Diloxanide furoate, Eflornithine, Mepacrine, Pentamidine, Suramin |