Risk of cardiovascular, neurological and psychiatric adverse effects associated with bromocriptine

HSA would like to remind healthcare professionals about the risk of cardiovascular, neurological and psychiatric adverse effects that are known to be associated with the use of bromocriptine. These rare but potentially serious or fatal adverse effects were highlighted by the European Medicines Agency’s (EMA) Pharmacovigilance Risk Assessment Committee (PRAC) in its recently completed safety review, which advised against the routine use of bromocriptine-containing medicines for the prevention or suppression of lactation, as well as for relieving symptoms of pain or swelling of the breasts postpartum.¹

Bromocriptine is a dopamine agonist that has been authorised across Europe for use in the prevention and suppression of lactation postpartum. However, locally, it is not licensed for such use and is not recommended for the routine prevention or suppression of puerperal breast engorgement.

In Singapore, bromocriptine (Parlodel®, Novartis (Singapore) Pte Ltd) has been registered since May 1988 for the treatment of Parkinson’s disease, prolactinomas, acromegaly, hyperprolactinaemia in men, as well as menstrual cycle disorders and female infertility. There are also several generic brands of bromocriptine registered locally, namely Apo-bromocriptine® (Pharmaforte Singapore Pte Ltd), Brameston® (Goldplus Universal Pte Ltd) and Bromocriptin-Richter® (Pharmline Marketing Pte Ltd).

EMA’s review of bromocriptine-containing medicines

In September 2013, EMA’s PRAC initiated a safety review of bromocriptine-containing medicines for the prevention or suppression of lactation postpartum.² This review was requested by the French medicines agency (ANSM) following concerns of rare but potentially serious or fatal adverse effects associated with the use of bromocriptine. These included cardiovascular diseases (e.g., heart attack and stroke), neurological effects (e.g., fits) and psychiatric effects (e.g., hallucinations and manic episodes) that were observed from the French pharmacovigilance database and global safety databases of companies for the period 1985 to 2012. ANSM considered that the risk of these events was not acceptable in view of the availability of alternative means of management, and that breast milk production will naturally cease if the mother stops breastfeeding her infant.

In July 2014, the PRAC completed its review,¹ taking into consideration available data from post-marketing spontaneous case reports, clinical trials and published literature relating to cardiovascular, neurological and psychiatric risks following treatment with bromocriptine-containing medicines in postpartum lactation inhibition. The outcome of the review concluded that although bromocriptine was effective for the prevention or suppression of lactation postpartum, an association between bromocriptine treatment and adverse events such as heart attack, stroke, fits, and psychiatric disorders could not be ruled out. PRAC recommended that bromocriptine (up to 2.5mg) should only be used in the presence of compelling medical reasons for stopping lactation. Bromocriptine should not be used routinely for prevention or suppression of lactation, nor to relieve symptoms of pain or swelling of the breasts postpartum.

In addition, women at high risk of serious adverse effects, such as those with severe psychiatric disorders and those with disorders that increase blood pressure, should not be treated with bromocriptine. Blood pressure monitoring is recommended in patients using bromocriptine to detect early signs of problems that may warrant discontinuation of the treatment.

Local situation and HSA’s advisory

To date, HSA has received two non-serious adverse reaction reports associated with the use of bromocriptine for the suppression of lactation (off-label use). The adverse reactions reported included rash, facial oedema and peripheral oedema.

HSA would like to highlight to healthcare professionals that bromocriptine-containing products are not licensed locally for the prevention and suppression of lactation postpartum. Bromocriptine-containing products are also not recommended for use in the routine prevention or suppression of puerperal breast engorgement as such symptoms can usually be treated with simple analgesics and managed by non-pharmacological interventions such as firm breast support or ice application.

There are existing warnings regarding cardiovascular, neurological and psychiatric concerns in the local package inserts of bromocriptine-containing products, including the need for periodic blood pressure monitoring. Healthcare professionals are advised to take into consideration these labelled warnings when prescribing bromocriptine to patients. They should also be aware of the above safety review by PRAC and its recommendations on the use of bromocriptine for suppression of lactation as authorised in Europe.

References

Healthcare professional, Industry member, Therapeutic Products

Published: 26 Dec 2014

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