PTPS-DSA-04-2013

Drug Safety Alert Domperidone Off Label Use in nursing mother

(Unknown Risk to Infants) Ref: US-FDA, EMA

Obaid Ali, R.Ph., Ph. D, Deputy Director, Drugs Regulatory Authority of Pakistan

Training and Pharmacy Services November 2013

OA, DDC, DRAP, Nov 06th 2013

SUMMARY

Domperidone (An EMA Approved Drug for GI related issue) is now under microscope due to its

reported association with Cardiac issues in EMA. US-FDA did not approved drug for any

indication issued Drug Safety Alert due to its potential Off label use/misuse and abuse as

Lactation Elevator by Health Care Professionals and Nursing mother in US. Since, indication is

not approved in any country and Investigations about Cardiac issue is underway in EMA

therefore, public awareness message need to be issued and take similar action of EMA may be

follow, unless local sufficient data speaks to conclude in special regulatory action accordingly.

DOMPERIDONE

DRAP has kept eye close on going Scrutiny in Europe to ensure similar regulatory

action as it happen. Local sufficient data is not available to evaluate Benefit-Risk

Balance of Domperidone-containing medicines and to decide Continuation with

or without Label Change or Withdrawn.

What is Domperidone?

Domperidone-containing medicines used to relieve symptoms of nausea and vomiting, fullness,

abdominal discomfort and heartburn. However increase lactation in breast-feeding mothers is

one of the off-label uses and not approved in any country of the world.

What is Off Label Use?

Authorized Physicians or Health Care Providers are not discouraged for an Off label use of

drugs, if it does not cross the regulatory boundaries. However, promotion or claim of use in any

indication, which is not approved, is a regulatory violation across the world at the end of

company.

OA, DDC, DRAP, Nov 06th 2013

When and where it is approved?

Domperidone have been authorized in a number of countries including several European

Countries since the 1970s and are widely available as over-the-counter or prescription-only

medicines in tablets, oral suspension and suppositories dosage form. It is not approved by US-

FDA and not legally allowed to use in any form in USA.

How Domperidone works?

Domperidone works by blocking receptors for the neurotransmitter dopamine found in the gut

and in the part of the brain linked to vomiting. This results in an increase in the action of the

muscles in the stomach so that food moves more effectively through the stomach into the

intestine, which helps prevent vomiting and reduces feelings of sickness, bloating and fullness.

What is the risk associated with Domperidone to Infant:

Domperidone is excreted in breast milk that could expose a breastfeeding infant to unknown

risks. There is no safety study available for its use in nursing mother.

What is the regulatory update of Domperidone in USA-FDA?

In 2004, the FDA warned clinicians and breast-feeding mothers not to use Domperidone to boost

milk production because of the risk for adverse events. US-FDA referred reports of cardiac

arrhythmias, cardiac arrest, and sudden death in patients receiving an intravenous form of

Domperidone that has been discontinued in several countries. In 2013, FDA issued a safety Alert

and warned Health Care Professionals and breastfeeding women not to use an unapproved drug,

Domperidone (that is illegally available in some of compounding Pharmacies or Outside USA)

due to associated potential public health risk.

What is the regulatory update of Domperidone in EMA?

In March 2013, upon request of drug regulators in Belgium, who learned of new cases of

cardiotoxicity and proposed that the drug be contraindicated for patients with QT prolongation,

significant electrolyte disturbances, or underlying cardiac diseases such as congestive heart

failure. The Pharmacovigilance Risk Assessment Committee (PRAC) of EMA started safety

review of Domperidone. PRAC of EMA responsible for the evaluation of safety issues for

OA, DDC, DRAP, Nov 06th 2013

human medicines, which will make a set of recommendations. Recommendation will be process

and sent to EU for final decision.

What is DRAP’s Position?

Although it is not promoted or use in increase of milk in nursing mother as per information

available but issuance of safety alert will damage potential of off label use. Considering

protection of public is shared responsibility, DRAP recommends manufacturer and government

together issue public serving message to keep away breastfeeding women and Health Care

Professionals from misuse, abuse and off label use of Domperidone.