title: [Drug interactions in critically-ill patients. An important factor in the use of micafungin?].
abstract: Currently there are three main drug groups for the prevention and treatment of fungal infections: polyenes (amphotericin B deoxycholate or its lipid formulations), azoles (fluconazole, itraconazole or posaconazole) and echinocandins (caspofungin, micafungin and anidulafungin). However, a major characteristic to be evaluated when choosing an antifungal agent -apart from antifungal spectrum, pharmacokinetics and adverse effects- is the absence of significant drug interactions. Amphotericin B lacks interactions but may cause renal dysfunction, leading to the accumulation of renally metabolized drugs. Nephrotoxicity is significantly lower with lipid formulations, especially with liposomal amphotericin B. Azoles modify the metabolism of a wide range of drugs by inhibiting their biotransformation or altering their distribution and elimination. These drugs are metabolized in the liver through the P450 cytochrome complex, inhibiting several isoenzymes, especially CYP3A4, the main drug-metabolizing enzyme. Moreover, itraconazole and posaconazole are substrates and inhibitors of the transporter protein, P-glycoprotein. Fluconazole is the azole with the fewest drug-drug interactions. The echinocandins have increased the therapeutic arsenal and a particular feature of these drugs is their safety, due to the absence of severe adverse effects and the scarce number of interactions. The echinocandin with the highest number of interactions is caspofungin. Micafungin is an echinocandin lacking in relevant interactions and consequently its dosage requires no adjustment in any of its indications. This drug can be used both in adults and in the pediatric population, including neonates.
authors.affiliation: Unidad Clínica de Cuidados Críticos y Urgencias, Unidad de Cuidados Intensivos, Hospital Universitario Virgen del Rocío, Sevilla, España. jgarnachom@telefonica.net
authors.forename: José
authors.initials: J
authors.lastname: Garnacho-Montero
authors.forename: Francisco
authors.initials: F
authors.lastname: Jiménez Parrilla
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors; D000328:Adult; D000666:Amphotericin B / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D000935:Antifungal Agents / Q000009:adverse effects / Q000145:classification / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002648:Child; D016638:Critical Illness; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D065692:Cytochrome P-450 CYP3A Inhibitors; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D054714:Echinocandins / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D007231:Infant, Newborn; D055666:Lipopeptides / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000077551:Micafungin; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D009181:Mycoses / Q000150:complications / Q000188:drug therapy*; D014230:Triazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000935:Antifungal Agents; D065692:Cytochrome P-450 CYP3A Inhibitors; D054714:Echinocandins; D055666:Lipopeptides; D014230:Triazoles; D000666:Amphotericin B; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D000077551:Micafungin