Severe adverse effects of bromocriptine in lactation inhibition: a pharmacovigilance survey

Abstract

Objective To assess the nature and conditions of the occurrence of adverse drug reactions (ADRs) of bromocriptine, which is used to inhibit lactation.Design Observational study.Setting Cases from the French pharmacovigilance database and the marketing authorisation holders.Sample Serious ADRs reported between 1994 and 2010 in association with bromocriptine used for lactation inhibition in France.Methods Each case was checked to confirm the bromocriptine indication, the seriousness of the ADR, the modalities of bromocriptine use, and to identify possible associated predisposing factors.Main outcome measures Number and description of serious ADRs, with a particular focus on misuse and associated predisposing factors.Results Among 105 serious ADRs, including two fatal cases, the most frequent were cardiovascular (70.5%), neurological (14.3%), and psychiatric (8.6%) disorders. Cardiovascular disorders primarily consisted of ischaemic manifestations (n = 47): acute ischaemic stroke (n = 18, one death), myocardial infarction (n = 11, one death), and reversible postpartum cerebral angiopathy (n = 10). Misuse was identified in 52 cases (70.3%) of cardiovascular disorders, and mostly consisted of bromocriptine continuation despite the occurrence of first symptoms suggesting an ADR or the absence of a progressive titration of bromocriptine. About half of these women had cardiovascular predisposing factors, mainly tobacco smoking, overweight or obesity, or a history of hypertension or preeclampsia.Conclusions This survey, together with published data, provides further evidence that serious ADRs still occur after bromocriptine use in lactation inhibition, and that most of these ADRs could have been avoided. The use of bromocriptine should therefore be limited to cases where no other options are available to inhibit lactation.

Effects of postnatal bromocriptine injection on thyroid function and prolactinemia of rats at adulthood

“…BRO is used in humans to treat a prolactinoma even during pregnancy and weaning (Bernard et al, 2015;Almalki et al, 2015). BRO crosses the the placenta and is transferred by milk.…”

“…The D2-like receptors inhibit adenylyl cyclase and are the targets for most of the common drugs used to treat Parkinson's disease. Bromocriptine (BRO) is a D2 agonist that inhibits PRL production and release, and is used in the management of prolactinomas (Seeman and Van, 1994), to treat type 2 diabetes (Liang et al, 2015) and for the suppression of lactation Neuropeptides xxx (2016) xxx-xxx (Verma et al, 2006;Bernard et al, 2015). In addition, dopamine has not only been used to treat shock in adults, but also in neonates (Noori and Seri, 2012;Saini et al, 2014), who have more plastic, therefore susceptible, dopaminergic neurons than adults.…”

Safe and Effective Use of Pharmacologic and Device Therapy for Peripartum Cardiomyopathy

“…A new drug application for bromocriptine for postpartum lactation prevention was withdrawn due to reports of myocardial infarction and stroke . Similar events were observed in a 2015 retrospective French pharmacovigilance study analyzing serious adverse effects associated with bromocriptine .…”

Predicting neurological Adverse Drug Reactions based on biological, chemical and phenotypic properties of drugs using machine learning models

“…Tetracyclines have been associated with neurotoxicity and neuromuscular blockage in addition to other neurotoxic events 18 . Irinotecan in combination with oxaliplatin induced various neurologic complications 19 , treatment with amiodarone induced polyneuropathy and other neurological complications 20 , severe axonal neuropathy and sensorimotor neuropathy was observed following treatment with arsenic trioxide 21 and a 14.3% of serious neurological side effects were observed on administration of bromocriptine 22 . Mild neurologic adverse events were detected on treatment with docetaxel 23 , severe neuropsychiatric manifestations were found to be associated with azithromycin 24 , nitrofurantoin was reported to cause sensorimotor polyneuropathy when used in children 25 , cases of neurosensory adverse effects were observed on treatment with phenylbutazone 26 and use of cocaine 27 , paclitaxel 28 and tacrolimus 29 is associated with severe neurotoxicity.…”