title: Severe pustular eruption associated with imatinib and voriconazole in a patient with chronic myeloid leukemia.
abstract: Imatinib is a specific and potent inhibitor of the BCR-ABL tyrosine kinase. Several clinical trials have demonstrated the efficacy of imatinib in chronic myeloid leukemia. Adverse cutaneous reactions induced by imatinib are frequent and may be dose related. We report a case of an unusual pustular eruption in a patient with chronic myeloid leukemia, who received high doses imatinib for blast crisis and later voriconazole for invasive pulmonary aspergillosis. At the time of his skin eruption, elevated plasma levels of imatinib were recorded. Imatinib is primarily metabolized by the cytochrome CYP3A4. Voriconazole is a cytochrome CYP3A4 inhibitor and can lead to high plasma levels of imatinib. This case suggests that severe drug reactions to imatinib may be related not only to imatinib doses, but also to elevated plasma drug levels resulting from pharmacokinetic interactions. The monitoring of imatinib plasma levels may be of help for identifying patients at risk for severe toxicity.
authors.affiliation: Dermatology Sevices, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors.forename: E
authors.initials: E
authors.lastname: Gambillara
authors.forename: E
authors.initials: E
authors.lastname: Laffitte
authors.forename: N
authors.initials: N
authors.lastname: Widmer
authors.forename: L A
authors.initials: LA
authors.lastname: Decosterd
authors.forename: M A
authors.initials: MA
authors.lastname: Duchosal
authors.forename: T
authors.initials: T
authors.lastname: Kovacsovics
authors.forename: R G
authors.initials: RG
authors.lastname: Panizzon
mesh_terms: D000328:Adult; D000935:Antifungal Agents / Q000009:adverse effects*; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000097:blood; D001228:Aspergillosis / Q000188:drug therapy; D001549:Benzamides; D051544:Cytochrome P-450 CYP3A; D065607:Cytochrome P-450 Enzyme Inhibitors; D003875:Drug Eruptions / Q000209:etiology*; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000009:adverse effects; D005076:Exanthema / Q000139:chemically induced*; D006801:Humans; D000068877:Imatinib Mesylate; D007509:Irritants / Q000009:adverse effects*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D008172:Lung Diseases, Fungal / Q000188:drug therapy; D008297:Male; D010879:Piperazines / Q000009:adverse effects* / Q000097:blood; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011743:Pyrimidines / Q000009:adverse effects* / Q000097:blood; D014230:Triazoles / Q000009:adverse effects*; D065819:Voriconazole
chemical_list: D000935:Antifungal Agents; D000970:Antineoplastic Agents; D001549:Benzamides; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D007509:Irritants; D010879:Piperazines; D011743:Pyrimidines; D014230:Triazoles; D000068877:Imatinib Mesylate; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D011505:Protein-Tyrosine Kinases; D065819:Voriconazole