Reactions 798 - 22 Apr 2000

★ O SRiluzole overdose

First report of neutropenia: case reportA 63-year-old woman developed neutropenia following an

inadvertent overdose of riluzole which she was receiving foramyotrophic lateral sclerosis.

The woman had been taking riluzole 50mg twice daily andamitriptyline for 6 weeks prior to presentation. She had alsobeen hospitalised 2 weeks prior to presentation for chest pain.A coronary angiogram at this time revealed no critical vesselstenosis. She was discharged with an inadvertent increase inher dosage of riluzole to 100mg twice daily. She was alsoreceiving aspirin and metoprolol. She began to experiencenausea, anorexia and low-grade fever 6 days after discharge,and was rehospitalised 10 days after starting the increaseddosage of riluzole.

The woman had a mild fever of 38.3°C and multiple discreteerythematous nodules on her forehead, posterior neck andright shin. She experienced atrial fibrillation, dysarthric speechand severe intrinsic hand muscle weakness with diffuselyhyperactive reflexes. Laboratory tests revealed that her WBCcount was 2.6 × 109/L with a differential of neutrophils 2.1%,band forms 4%, lymphocytes 34%, monocytes 55%,eosinophils 4% and basophils 2%. Her haemoglobin level was9.9 g/dl, her haematocrit was 29.8% and her platelet count was512 × 109/L.

The patient was treated with digoxin for her atrial fibrillation.Riluzole was discontinued on the second day ofhospitalisation. Further tests revealed bone marrowhypocellularity with maturation arrest in the myeloid series,typical for drug-induced agranulocytosis, and only rarematuration past the metamyelocyte stage. A chest x-rayrevealed right lower-lobe pneumonia. She received furthertreatment with filgrastim, ceftazidime and vancomycin.

After 6 days, the patient’s WBC and neutrophil counts hadincreased, and her fever and skin lesions resolved. She wasdischarged after 9 days of hospitalisation, but died 11 monthslater due to respiratory failure.

Author comment: ‘In our patient, several lines of evidenceraise the possibility of a causal relationship betweengranulocytopenia and riluzole, including restoration ofneutrophil function with riluzole discontinuation, bonemorrow biopsy findings typical for drug-induced effect, andlack of other suspect drug exposure.’North WA, et al. Reversible granulocytopenia in association with riluzole therapy.Annals of Pharmacotherapy 34: 322-324, Mar 2000 - USA 800823566

» Editorial comment: A search of AdisBase and Medline didnot reveal any previous case reports of neutropenia associatedwith riluzole.

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Reactions 22 Apr 2000 No. 7980114-9954/10/0798-0001/$14.95 Adis © 2010 Springer International Publishing AG. All rights reserved