Pharmacovigilance

European Medicines Agency recommends changes to the use of metoclopramide

01.08.2013

The European Medicines Agency’s Committee on Medicinal Products for Human Use has recommended changes to the use of metoclopramide-containing medicines in the European Union (EU), including restricting the dose and duration of use of the medicine to minimise the known risks of potentially serious neurological side effects. Metoclopramide-containing medicines have been authorised separately in individual Member States of the EU, with differing licensed indications such as nausea and vomiting of various causes (for example after treatment with anticancer chemotherapy or radiotherapy, after surgery, or associated with migraine) and gastrointestinal motility disorders (conditions in which the normal passage of food through the gut is delayed).

The review of metoclopramide was carried out at the request of the French medicines regulatory agency (ANSM), following continued safety concerns over side effects and concerns over efficacy. The review confirmed the well-known risks of neurological effects such as short-term extrapyramidal disorders, a group of involuntary movement disorders that may include muscle spasms (often involving the head and neck), and tardive dyskinesia (uncontrollable movements such as grimacing and twitching). The risk of acute (short-term) neurological effects is higher in children, although tardive dyskinesia is reported more often in the elderly, and the risk is increased at high doses or with long-term treatment. The evidence indicated that these risks outweighed the benefits of metoclopramide in conditions requiring long-term treatment. There have also been very rare cases of serious effects on the heart or circulation, particularly after injection.

The Committee recommended that metoclopramide should only be prescribed for short-term use (up to five days), that it should not be used in children below one year of age and that in children over one year of age, it should only be used as a second-choice treatment (after other treatments have been considered or tried) for the prevention of delayed nausea and vomiting after chemotherapy and for the treatment of post-operative nausea and vomiting. In adults, it may be used for the prevention and treatment of nausea and vomiting such as that associated with chemotherapy, radiotherapy, surgery and in the management of migraine. In addition, the maximum recommended doses in adults and children should be restricted, and higher strength formulations removed from the market.

There are no approved strengths of metoclopramide-containing medicines in the Republic of Croatia, that should be the subject to recall. The above mentioned changes will in a shortest time be included in the Summary of Product Characteristics and Package Leaflet of metoclopramide containing medicines. Detailed recommendations for patients and healthcare professionals are available bellow. The CHMP redommendation will now be sent to the European Commission for the sadoption of a legally binding decision throughout the European Union (EU).

Information to patients

• Metoclopramide is used to prevent or treat nausea and vomiting (feeling or being sick), including nausea and vomiting that may result from anticancer medicines or radiation treatment, surgery, or an attack of migraine. It is given by injection, by mouth, or as suppositories.
• Metoclopramide is known to sometimes cause short-term side effects on the nervous system that result in unintentional movements such as twitches and nervous tics and these are commoner in children and young people, and at high doses. Other nervous-system side effects may occur when metoclopramide is used for prolonged periods and may occur more often in the elderly.
• Use in children is therefore now restricted to prevention of nausea and vomiting that occurs in the days after treatment with anticancer medicines, or to treat nausea and vomiting after surgery, and only when other treatments do not work or cannot be used.
• Metoclopramide should no longer be used in children under one year old.
• For both adults and children, metoclopramide should only be used for a maximum of 5 days.
• The recommended maximum dose of the medicine has been lowered in adults to a total of 30 mg a day, and some high dose products will be removed from the market as they will no longer be needed.
• In other longer-lasting conditions, the benefits of this medicine do not outweigh the risks of side effects. Therefore, it should no longer be used to treat conditions such as indigestion, heartburn and acid reflux, or chronic (long-term) disorders due to slow emptying of the stomach.
• If you are taking metoclopramide (especially for long-term conditions) you will have your treatment reviewed by your doctor at your next scheduled appointment, and in some cases you may be recommended a different treatment. Patients who have any questions should discuss them with their doctor or pharmacist.

Information to healthcare professionals

• In order to minimise the risks of neurological and other adverse reactions, metoclopramide should only be prescribed for short-term use (up to five days). It should no longer be used in chronic conditions such as gastroparesis, dyspepsia and gastro-oesophageal reflux disease, nor as an adjunct in surgical and radiological procedures.
• In adults, metoclopramide remains indicated for prevention of postoperative nausea and vomiting (PONV), radiotherapy-induced nausea and vomiting and delayed (but not acute) chemotherapy-induced nausea and vomiting, and for symptomatic treatment of nausea and vomiting including that associated with acute migraine (where it may also be used to improve absorption of oral analgesics).
• In children, metoclopramide should only be used as a second-line option for prevention of delayed chemotherapy-induced nausea and vomiting and treatment of established PONV. Use is contra-indicated in children under one year of age.
• For adults and children the maximum dose in 24 hours is 0.5 mg per kg body weight; in adults, the usual dose of conventional formulations (all routes) is 10 mg up to three times daily. In children the recommended dose is 0.1 to 0.15 mg per kg body weight, repeated up to three times daily. A dosing table for use in children will be included in the product information.
• Oral liquid formulations have been particularly associated with overdose in children. Oral liquids containing more than 1 mg/ml will be withdrawn from the market, and oral doses of remaining formulations should be administered using an appropriately designed graduated oral syringe to ensure accuracy.
• Intravenous formulations with concentrations above 5 mg/ml and suppositories containing 20 mg will also be withdrawn.
• Intravenous doses should be administered as a slow bolus over at least three minutes to reduce the risk of adverse effects.
• Given very rare reports of serious cardiovascular reactions associated with metoclopramide, particularly via the intravenous route, special care should be taken in populations likely to be at increased risk, including the elderly, patients with cardiac conduction disturbances, uncorrected electrolyte imbalance or bradycardia, and those taking other drugs known to prolong the QT interval.
• Patients who are currently taking regular metoclopramide should have their treatment reviewed at a routine (non-urgent) medical appointment.

We remind healthcare professionals that they should report any adverse reaction to HALMED, as well as quality defect. Patients who have developed any adverse reaction to medicinal product may report it directly to HALMED via form or on-line application, with recommendation regarding any adverse reaction they discover to consult with their doctor or pharmacist about the continuation of their therapy.