Epistaxis and other haemorrhagic events associated  with the smoking cessation medicine varenicline: a case series  from two national pharmacovigilance centres.
OBJECTIVE
To present a case series of haemorrhagic events associated with varenicline identified from the New Zealand (NZ) and Netherlands national pharmacovigilance centres and propose a possible mechanism for these adverse events.


METHODS
Reports of epistaxis and other haemorrhagic events (in all system organ classes excluding gynaecological) associated with varenicline were identified and assessed in both the NZ Intensive Medicines Monitoring Programme (IMMP) and the Netherlands Pharmacovigilance Centre Lareb (Lareb). Additional reports were identified from the World Health Organisation Uppsala Monitoring Centre (WHO-UMC) datasets, and these also underwent causality assessment.


RESULTS
A total of 30 reports of haemorrhagic events were identified by the NZ IMMP (16 reports) and Lareb (14 reports). Six cases of epistaxis were identified, and four patients had a positive dechallenge on withdrawal of varenicline, suggesting a causal association. Another five reports of gingival bleeding were identified, with three patients having a positive dechallenge. Another patient who experienced haemoptysis while taking varenicline had a positive dechallenge and a positive rechallenge. In the WHO datasets, a further 49 reports of epistaxis, 39 reports of haemoptysis and 21 reports of thrombocytopenia were identified. A plausible mechanism for haemorrhagic events associated with varenicline may be a result of interaction with the serotonin (5-HT) receptor system and transporter.


CONCLUSIONS
This is the first specific investigation of haemorrhagic events associated with varenicline. The results of our assessment of reports identified by two national pharmacovigilance centres suggest that there may be causal relationship between varenicline and these adverse events.
Intensive Medicines Monitoring Programme, New Zealand Pharmacovigilance Centre, Department of Preventive and Social Medicine, University of Otago Medical School, PO Box 913, Dunedin 9054, New Zealand. mira.harrison-woolrych@otago.ac.nz
Mira
M
Harrison-Woolrych
Linda
L
Härmark
Ming
M
Tan
Simran
S
Maggo
Kees
K
van Grootheest
D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems; D000368:Aged; D001552:Benzazepines / Q000009:adverse effects*; D016208:Databases, Factual; D004844:Epistaxis / Q000139:chemically induced* / Q000453:epidemiology; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D009520:New Zealand / Q000453:epidemiology; D018722:Nicotinic Agonists / Q000009:adverse effects*; D060735:Pharmacovigilance; D011810:Quinoxalines / Q000009:adverse effects*; D016540:Smoking Cessation / Q000379:methods; D000068580:Varenicline; D055815:Young Adult
D001552:Benzazepines; D018722:Nicotinic Agonists; D011810:Quinoxalines; D000068580:Varenicline