Reactions 1235 - 17 Jan 2009

★ X SAntineoplastics

Diarrhoea, neutropenia and ciclosporinaemia,interaction between ciclosporin and erlotinib(first report) leading to skin toxicity andneutropenia?: case report

A 53-year-old man receiving ciclosporin asimmunosuppression following a renal transplantexperienced diarrhoea, neutropenia and ciclosporinaemia,after receiving carboplatin and paclitaxel for metastaticpulmonary adenocarcinoma; he subsequently developedskin toxicity and neutropenia after initiating erlotinib for thesame indication.

The man with cirrhosis underwent transplantation in2002, followed by continuous treatment with ciclosporin[dosage not stated]. After the cancer diagnosis in 2007, hewas initiated on carboplatin and paclitaxel [dosages notstated]. Following the first administration, he sufferedgrade 3 diarrhoea and neutropenia, along with a highvariability of ciclosporinaemia [time to reaction onset notstated], and treatment was interrupted. He underwentradiotherapy, and then started on erlotinib 150mg daily.The dosage of ciclosporin was adjusted to maintain a bloodconcentration of 60–90 ng/mL. Eleven weeks after the startof erlotinib treatment, grade 1 skin toxicity and a persistentnonfebrile grade 1 neutropenia appeared. [Outcome notstated.]

Erlotinib was continued at the same dose. In order tomaintain ciclosporin blood concentrations in theestablished range, the dose was progressively increasedfrom 50mg twice daily to 75mg twice daily, then to 100mgtwice daily. At last follow-up, the man had been receivingerlotinib and ciclosporin for 1 year.

Author comment: "These data together indicate theabsence of any clinically relevant interference betweencyclosporine and erlotinib. However, the need of increasingthe drug dosage over time could suggest that long-termexposure of erlotinib might induce CYP 3A4 and suggest theusefulness of monitoring cyclosporine blood levels."De Pas T, et al. Erlotinib combined with cyclosporine in a liver-transplant recipientwith epidermal growth factor receptor-mutated non-small cell lung cancer. Journalof Thoracic Oncology 4: 138-139, No. 1, Jan 2009 - Italy 801135131

» Editorial comment: A search of AdisBase, Medline andEmbase did not reveal any previous case reports of aninteraction between ciclosporin and erlotinib. The WHOAdverse Drug Reactions database contained 13 reportsinvolving the concomitant use of ciclosporin and erlotinib.

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Reactions 17 Jan 2009 No. 12350114-9954/10/1235-0001/$14.95 © 2010 Adis Data Information BV. All rights reserved