Other safety alerts
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| Singapore: Restrictions on the use of metoclopramide-containing products |
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The Singapore Health Sciences Authority (HSA) had issued a Dear Healthcare Professional Letter in July 2015 and its amendment in March 2016 to healthcare professionals regarding new restrictions on the use of metoclopramide-containing products in order to reduce the risk of neurological and other dose-related adverse reactions. This article serves as a consolidation of the two letters and a reminder on the restrictions and revised indications for its use.
Metoclopramide is a pro-kinetic drug that has been licensed in Singapore since 1989 for the prevention and treatment of nausea and vomiting due to various conditions. In Singapore, there are 12 registered metoclopramide-containing products, which are available in various dosage forms such as tablets, syrups and injections.
In December 2011, a benefit-risk assessment of metoclopramide use in different age groups in the European Union (EU) was initiated by the European Medicines Agency (EMA), following concerns from the French National Agency for the Safety of Medicine and Health Products (ANSM) regarding the benefit-risk balance of metoclopramide. In order to minimise the risk of potentially serious neurological adverse reactions, the EMA’s Committee for Medicinal Products for Human Use (CHMP) recommended restrictions on the indications, dose and duration of use of metoclopramide-containing products in the EU. It was recommended that the use of metoclopramide should be restricted to the short term (i.e. up to 5 days). Indications involving long-term treatment (e.g., gastroparesis, dyspepsia) were no longer supported. As it is indicative that adverse events increased with dose, the dose should be restricted to the minimum effective dose with a recommended maximum daily dose of 30 mg and 0.5mg/kg, in adults and children, respectively. In addition, metoclopramide should be contraindicated in children below one year of age due to increased risks of extrapyramidal disorders and methaemoglobinaemia.
The United States Food and Drug Administration (US FDA) and Health Canada have reported the increased risk of irreversible tardive dyskinesia beyond 12 weeks of metoclopramide treatment in 2009 and 2011. Both agencies retained the indications involving long-term treatment but recommended that the maximum treatment duration for metoclopramide should not exceed 12 weeks. The Australian Therapeutic Goods Administration (TGA) adopted the CHMP’s recommendations in February 2015, including restricting the use to short-term indications with a maximum treatment duration of 5 days. In addition, both Health Canada and TGA have recommended that the maximum daily dose of metoclopramide should not exceed 30 mg in adults and 0.5 mg/kg in children, and that the product should be contraindicated in children below one year of age.
In Singapore, nearly 1 in 5 neurological adverse reports associated with metoclopramide received by HSA from 1993 to August 2014 were reported in children. Overall, the local incidence rate of neurological side effects in adults and children did not exceed those reported overseas.
HSA has reviewed the benefits versus the risks of metoclopramide and is recommending the following restrictions on the indications, dose and duration of use of metoclopramide-containing products in Singapore:
In adults, metoclopramide will be indicated for the following:
• the prevention of nausea and vomiting associated with chemotherapy and radiotherapy with low and minimal emetogenicity
• the prevention of post-operative nausea and vomiting (only via the parenteral route)
• the symptomatic treatment of acute migraine induced nausea and vomiting
• the adjunct treatment of gastroparesis
• the management of dyspepsia and gastroesophageal reflux disorder when other treatment options are unsuitable (only via the oral route)
• as an adjuvant to surgical and radiological procedures.
The recommended maximum daily dose is 30 mg by the oral, intravenous or intramuscular route. In children (aged one to 18 years old), metoclopramide should be restricted to the second-line treatment of established post-operative nausea and vomiting (only via the intravenous route). The recommended maximum daily dose is 0.5 mg/kg. Metoclopramide is contraindicated in infants less than one year of age.
Treatment should be kept as short as possible, in accordance to one’s clinical judgement. Treatment duration beyond 12 weeks should be avoided unless the therapeutic benefit is judged to outweigh the risk to the patient.
Intravenous doses should be administered as a slow bolus (over at least three minutes).
HSA is working with the companies of metoclopramide-containing products to update their local package inserts with the new restrictions.
Please refer to the following website in HSA for details:
http://www.hsa.gov.sg/content/hsa/../restrictions-on-theuseofmetoclopramidecontainingproducts.html
In Hong Kong, there are 33 registered pharmaceutical products containing metoclopramide, and are prescription only medicines. Related news was previously issued by various overseas drug regulatory authorities, and was posted on the Drug Office website since July 2013, and the latest update was posted on 29 March 2016. Letters to inform local healthcare professionals were issued on 29 July 2013. So far, the Department of Health (DH) has not received any adverse drug reaction report related to metoclopramide. In September 2014, the Registration Committee of the Pharmacy and Poisons Board (the Committee) decided that the sales pack label and/or package insert of metoclopramide-containing products should be updated to include the appropriate safety information. The HSA's consolidated reminder is similar to EMA's recommendation in 2013 which has already been discussed by the Committee. DH will remain vigilant on any further update related to metoclopramide.
Ends/ Thursday, September 22, 2016
Issued at HKT 16:00
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