Bromocriptine-containing medicines indicated in the prevention or suppression of physiological lactation post-partum - referral

Current status

European Commission final decision

Overview

 

Restrictions in use of bromocriptine for stopping breast milk production

The medicine should not be used routinely for preventing or stopping milk production after childbirth

On 20 August 2014, the Coordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh)¹ endorsed by majority recommendations on the use of bromocriptine-containing medicines by mouth to prevent or suppress breast milk production (lactation) after childbirth.

The CMDh agreed that the medicines should only be used for this purpose (in strengths up to 2.5 mg) when there are compelling medical reasons for stopping lactation, such as the need to avoid further distress after loss of the baby during or just after childbirth, or in mothers with HIV infection, who should not breastfeed.

Bromocriptine should not be used routinely for preventing or stopping milk production, and must not be used in women at increased risk of serious side effects, including women with various disorders that increase blood pressure or who have or have had heart disease or severe psychiatric disorders. Blood pressure should be monitored so that early signs of an increase can be detected and treatment stopped immediately.

The CMDh position followed a review by the EMA's Pharmacovigilance Risk Assessment Committee (PRAC) of available data on the safety and effectiveness of bromocriptine in controlling breast milk production after childbirth, which led to these recommendations. The review was triggered by concerns in France over increased reports of rare but potentially serious or fatal side effects, particularly cardiovascular side effects (such as heart attack and stroke), neurological side effects such as seizures (fits) and psychiatric side effects (such as hallucinations and manic episodes). Since lactation is a natural process that eventually stops if the infant is not breastfed, and other means of management are available, the French medicines agency (ANSM) asked the EMA to review the medicines and see if the benefits of such use still outweighed the risks.

As the CMDh position on bromocriptine was adopted by majority vote, it was sent to the European Commission, which took an EU-wide legally binding decision on 30 October 2014.

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¹The CMDh is a medicines regulatory body representing the European Union (EU) Member States.

Information to patients

• Medicines containing bromocriptine are licensed in many EU countries for use by mouth to prevent or stop milk production after childbirth in women who are not breastfeeding. Because of a possible risk of serious side effects, recommendations have been issued to clarify that these medicines should not be used routinely for preventing or stopping milk production.
• They should only be used for this purpose if there are medical reasons for doing so, for example to avoid further distress in women who lose a baby during or just after birth, or in women who have HIV infection (to avoid any risk of passing the virus on in breast milk).
• Bromocriptine should not be used to relieve symptoms of pain or swelling of the breasts after childbirth when such symptoms can be managed by measures such as breast support or applying ice, and the use of painkillers if needed.
• Women who are at greater risk of side effects, such as those who have a condition that increases blood pressure, or who have a history of serious mental illness, should not take bromocriptine.
• Blood pressure should be monitored in those who take the medicine (especially on the first day of taking it) so that early signs of problems can be detected, and the medicine stopped.
• Patients who develop chest pain or an unusually severe headache should consult their doctor urgently.
• Women who have any questions or concerns should consult their doctor or pharmacist.

Information to healthcare professionals

The following recommendations (some of which are already included in the product information) should be borne in mind when prescribing bromocriptine for the prevention or suppression of lactation.

• Bromocriptine should only be used orally in strengths up to 2.5 mg to inhibit lactation when medically indicated, such as in case of intrapartum loss, neonatal death or HIV infection of the mother. Products with strengths of 5 or 10 mg are not indicated for such use.
• Bromocriptine should not be used for the routine suppression of lactation, nor for the relief of symptoms of post-partum pain and engorgement, which can be adequately treated with non-pharmacological intervention (such as firm breast support, ice application) and simple analgesics.
• Use is contraindicated for patients with uncontrolled hypertension, hypertensive disorders of pregnancy (including eclampsia, pre-eclampsia or pregnancy-induced hypertension), hypertension post-partum and in the puerperium, a history of coronary artery disease or other severe cardiovascular conditions, or a history of severe psychiatric disorders.
• Blood pressure should be carefully monitored especially during the first day of therapy. If hypertension, suggestive chest pain, severe, progressive, or unremitting headache (with or without visual disturbance) or evidence of central nervous system toxicity develops, treatment should be discontinued and the patient evaluated promptly.

The above recommendations are based on a review of the available evidence of safety and efficacy of oral bromocriptine for prevention and suppression of lactation.

• Evidence from the clinical trials originally used to license the product as well as those in the published literature suggests that bromocriptine is efficacious in the prevention and inhibition of lactation. However, the data available were such that conclusions on the efficacy of bromocriptine in mastitis, breast engorgement and painful breast engorgement could not be made.
• On the basis of available safety data, a causal association between use of bromocriptine and serious cardiovascular, neurological or psychiatric events could not be excluded. However, the absolute number of cases reported post-marketing is low especially given the fact that bromocriptine has been available in the EU since 1973, with a substantial patient exposure; overall incidence rates are estimated to be between 0.005% and 0.04%.

The product information for bromocriptine-containing medicines has been updated accordingly.

More about the medicine

Bromocriptine is used to prevent or suppress milk production in women who have given birth. Women may not always breastfeed after childbirth for a variety of reasons ranging from stillbirth and HIV-infection of the mother to personal choice. Although milk production eventually stops, women in the meantime can experience breast engorgement, leakage of milk, discomfort and pain.

Bromocriptine is a dopamine receptor agonist. It mimics some of the actions of dopamine, a hormone that regulates the release of another hormone, prolactin, which in turn controls lactation. As a result, bromocriptine prevents the secretion of prolactin, thereby preventing or suppressing milk production.

Bromocriptine is also used to treat other conditions, such as hyperprolactinaemia (high levels of prolactin in the body) and Parkinson's disease; however these uses are not covered by this review.

Bromocriptine medicines have been authorised via national procedures for various indications in the following EU Member States: Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Lithuania, Luxemburg, Netherlands, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden and United Kingdom, as well as Norway. They are available on prescription for use by mouth in forms such as tablets and capsules, and have been marketed under various trade names (such as Parlodel) and as generics.

More about the procedure

The review of oral bromocriptine was initiated at the request of France on 17 July 2013, under Article 31 of Directive 2001/83/EC.

A review of these data was first conducted by the Pharmacovigilance Risk Assessment Committee (PRAC). The PRAC recommendations were sent to Co-ordination Group for Mutual Recognition and Decentralised Procedures - Human (CMDh), which adopted a final position. The CMDh, a body representing EU Member States, is responsible for ensuring harmonised safety standards for medicines authorised via national procedures across the EU.

As the CMDh position was adopted by majority vote, it was sent to the European Commission, which took an EU-wide legally binding decision on 30 October 2014.

Bromocriptine Article-31 referral - CMDh endorses restricted use of bromocriptine for stopping breast milk production

Key facts

About this medicine

• Approved name:
  Bromocriptine-containing medicines indicated in the prevention or suppression of physiological lactation post-partum
• International non-proprietary name (INN) or common name:
  bromocriptine

About this procedure

• Current status:
  European Commission final decision
• Reference number:
  EMEA/H/A-31/1379
• Type:
  Article 31 referrals

  This type of referral is triggered when the interest of the Union is involved, following concerns relating to the quality, safety or efficacy of a medicine or a class of medicines.

• Authorisation model:
  Nationally authorised product(s)
• Decision making model:
  PRAC-CMDh

Key dates and outcomes

• Procedure start date:
  05/09/2013
• PRAC recommendation date:
  10/07/2014
• CHMP opinion date:
  20/08/2014
• EC decision date:
  30/10/2014
• Outcome:
  Variation

All documents

Procedure started

Bromocriptine Article-31 referral - Annex I

Reference Number: EMA/541119/2013

Bromocriptine Article-31 referral - PRAC list of questions

AdoptedReference Number: EMA/PRAC/493207/2013

Bromocriptine Article-31 referral - Notification

Bromocriptine Article-31 referral - Review started

Reference Number: EMA/533713/2013

Bromocriptine Article-31 referral - Timetable for the procedure

Reference Number: EMA/PRAC/493206/2013 rev. 2

Recommendation provided by Pharmacovigilance Risk Assessment Committee

Bromocriptine Article-31 referral - PRAC assessment report

Bromocriptine Article-31 referral - PRAC recommends restricted use of bromocriptine for stopping breast milk production

Reference Number: EMA/409529/2014

Position provided by CMDh

Bromocriptine Article-31 referral - CMDh endorses restricted use of bromocriptine for stopping breast milk production

Bromocriptine Article-31 referral - CMDh endorses restricted use of bromocriptine for stopping breast milk production

European Commission final decision

Bromocriptine Article-31 referral - Restrictions in use of bromocriptine for stopping breast milk production

Reference Number: EMA/698187/2014

Bromocriptine Article-31 referral - Annex I

Bromocriptine Article-31 referral - Annex II

Bromocriptine Article-31 referral - CMDh divergent position

Bromocriptine Article-31 referral - Annex III

Description of documents published

Please note that some of the listed documents apply only to certain procedures.

• Overview - lay-language summary of the stage of the procedure
• Notification – a letter from a Member State, the European Commission or the marketing authorisation holder requesting the initiation of the procedure
• Scientific background – further background information from the triggering Member State on the issues leading to the initiation of the procedure (if applicable)
• List of questions – questions agreed by the Committee requesting further information from the marketing authorisation holder(s) / applicant(s) to evaluate the issues identified
• Timetable for the procedure – agreed timeframe to respond to the list of questions, to assess the issues and to adopt a conclusion
• List of medicines concerned by the procedure – medicine(s) / active substance(s) concerned, and marketing authorisation holder(s) / applicant(s)
• List of questions to be addressed by the stakeholders – call for data to be submitted by stakeholders (e.g. healthcare professionals, patient organisations, individual patients) (if applicable)
• Stakeholder submission form – form to be used by stakeholders to submit data (if applicable)
• Scientific conclusions – scientific conclusions of the PRAC and/or CHMP and/or CMDh
• Assessment report – PRAC or CHMP assessment and conclusions on the issues investigated, including divergent positions (if applicable)
• Divergent positions – divergent positions of the CHMP or CMDh members for pharmacovigilance procedures (if applicable)
• Changes to the summary of product characteristics, labelling and package leaflet (amended sections or fully revised version) (if applicable)
• Condition(s) to the marketing authorisation(s) – condition(s) for the safe and effective use of the medicine(s) (if applicable)
• Condition for lifting the suspension – condition to be fulfilled for the suspension of the marketing authorisation(s) to be lifted (if applicable)
• Timetable for implementation of CMDh position – agreed timeframe to submit and finalise the variation(s) implementing the outcome of the procedure (if applicable)

Note that older documents may have different titles.