Eur J Clin Pharmacol (2003) 58: 717 DOI 10.1007/s00228-002-0552-4
L E T T ER TO TH E E D I T O R S
Raffaela Bertoli Æ Franc¸ois Girardin Æ Stefan Russmann Bernhard H. Lauterburg
Raynaud’s phenomenon induced by drugs acting on neurotransmission: two cases under reboxetine and one under tegaserod
Received: 6 August 2002 / Accepted: 9 December 2002 / Published online: 29 January 2003 Ó Springer-Verlag 2003
Keywords Reboxetine Æ Tegaserod Æ Antidepressants Æ Raynaud’s phenomenon Æ Peripheral ischemia Abbreviations RP Raynaud’s phenomenon Raynaud’s phenomenon (RP) is a common disease characterized by recurrent episodic vasospasms of the fingers and toes, typically triggered by exposure to cold and often associated with systemic diseases, endothelial damage, or drug exposure [1]. A 21-year-old woman started taking tegaserod (12 mg/day) in December. Two days later she experienced painful discoloration of the fingers after exposure to cold. In another case, a 41-year-old woman started taking reboxetine (8 mg/day) in September. Three months later, recurrent severe acrocyanosis of the nose and toes occurred upon exposure to cold, eventually leading to skin necrosis. In a third case, a 35-year-old woman started taking reboxetine (4 mg/day) in February and experienced cold-triggered painful discoloration of her fingers. After the dose was increased, these episodes occurred spontaneously and more frequently. In all patients symptoms disappeared completely after drug therapy was stopped. No concomitant drugs were taken and none of the patients had experienced RP before.
S. Russmann (&) Æ B.H. Lauterburg Department of Clinical Pharmacology and Regional Pharmacovigilance Center Bern, University of Bern, Murtenstrasse 35, 3010, Bern, Switzerland E-mail:
[email protected] Tel.: +41-31-6323191 Fax: +41-31-6324997 R. Bertoli Regional Pharmacovigilance Center Tessin, Lugano Regional Hospital, Via Tesserete 46, 6900, Lugano, Switzerland F. Girardin Department of Clinical Pharmacology and Regional Pharmacovigilance Center Geneva, University Hospital Geneva, 1211, Geneva 14, Switzerland
The temporal relationship to tegaserod or reboxetine and the rapid improvement upon dechallenge suggest drug-induced RP in all presented cases. Tegaserod is a selective partial 5-HT4-receptor agonist. Reboxetine is a selective noradrenalin re-uptake inhibitor, has some inhibitory effect on serotonin re-uptake and may impair redilatation of cutaneous vessels after vasoconstriction [2]. The WHO database for adverse drug reactions contains 18 reports of peripheral ischemia under reboxetine and none under tegaserod. There are also several reports of peripheral ischemia under other antidepressants and RP induced by the selective serotonin re-uptake inhibitor fluoxetine has been particularly well-documented [3]. The mechanism is not clear, but may be related to local and/or central effects on adrenalin and serotonin receptors [4]. Drugs affecting neurotransmission should therefore be considered in the etiological workup for RP occurring in close temporal relationship to their administration and particular care should be taken if these drugs are prescribed to patients with a previous history of RP.
References 1. Block JA, Sequeira W (2001) Raynaud’s phenomenon. Lancet 357:2042–2048 2. Siepmann M, Muck-Weymann M, Joraschky P, Kirch W (2001) The effects of reboxetine on autonomic and cognitive functions in healthy volunteers. Psychopharmacology (Berl) 157:202–207 3. Rudnick A, Modai I, Zelikovski A (1997) Fluoxetine-induced Raynaud’s phenomenon. Biol Psychiatry 41:1218–1221 4. Freedman RR, Baer RP, Mayes MD (1995) Blockade of vasospastic attacks by alpha 2-adrenergic but not alpha 1-adrenergic antagonists in idiopathic Raynaud’s disease. Circulation 92:1448–1451
