The CHMP’s 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 and tardive dyskinesia. The risk of acute 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. The CHMP also noted that there have been very rare cases of serious effects on the heart or circulation, particularly after injection.
In view of the known risk of neurological and other adverse effects, particularly in children and young people, the CHMP concluded that the indications for metoclopramide should be restricted to those involving short-term use, at a maximum dose of 0.5 mg per kg body weight daily, and where there is sufficient evidence of efficacy. The product information will be amended accordingly, and prescribers will receive further communication at a national level.
The following detailed information is provided for healthcare professionals (direct from source):
- In order to minimise the risks of neurological and other adverse reactions, metoclopramide should only be prescribed for short-term use (up to 5 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 post-operative 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 1 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 3 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 3 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 QT interval.
- Patients who are currently taking regular metoclopramide should have their treatment reviewed at a routine (non-urgent) medical appointment.