Inherited long QT syndrome revealed by antifungals drug-drug interaction.
A 14-year-old Tahitian girl with acute myeloid leukaemia and a suspected mucormucosis infection was treated with intravenous voriconazole and caspofungin. Because of worsening of fungal infection, voriconazole was switched to posaconazole. During the switch, the patient presented with QT interval prolongation with 'torsades de pointes' and reversible cardiac arrest. Voriconazole plasma level measured 15 h after the last administration was 7 mg/L. Genotyping suggested that the patient was an extensive metabolizer with respect to CYP2C9 and CYP2C19. The association of antifungal agents with pro-arrhythmogenic drugs and other risk factors led to torsades de pointes and the revealing of inherited QT syndrome.
Eiden
C
C
Department of Medical Pharmacology and Toxicology, Lapeyronie Hospital, Montpellier, France.
Peyrière
H
H
Tichit
R
R
Cociglio
M
M
Amedro
P
P
Blayac
J-P
JP
Margueritte
G
G
Hillaire-Buys
D
D
D000208:Acute Disease; D000293:Adolescent; D000935:Antifungal Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D065731:Cytochrome P-450 CYP2C19; D065729:Cytochrome P-450 CYP2C9; D005260:Female; D005838:Genotype; D006801:Humans; D007275:Injections, Intravenous; D007951:Leukemia, Myeloid / Q000150:complications; D008133:Long QT Syndrome / Q000139:chemically induced* / Q000150:complications / Q000235:genetics; D006899:Mixed Function Oxygenases / Q000235:genetics; D009091:Mucormycosis / Q000150:complications / Q000188:drug therapy; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D016171:Torsades de Pointes / Q000139:chemically induced* / Q000150:complications; D014230:Triazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D065819:Voriconazole
D000935:Antifungal Agents; D011743:Pyrimidines; D014230:Triazoles; C101425:posaconazole; D006899:Mixed Function Oxygenases; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D065819:Voriconazole