Metoclopramide (various preparations)
Metoclopramide-containing medicinal products are approved in a number of Member States in various indications, including nausea and vomiting (for example, after chemotherapy or radiotherapy, surgery, or for migraine) and gastrointestinal motility disorders.
The European Medicines Agency (EMA) is recommending new directions for use, including reductions in dose and duration of therapy to minimize already known neurological risks.
Action at EU level
At the request of the French Medicines Agency (Agence nationale de sécurité du médicament et des produits de santé, ANSM), the Committee for Human Medicinal Products (CHMP) evaluated the benefit/risk profile of these drug products in all age groups.
The review confirmed the already well-established neurological risks, such as extrapyramidal disorders and tardive dyskenisia. The risk of short-term neurological reactions was found to be higher in children and increased with higher dosage and longer duration of therapy. Thus, the risk associated with its use outweighs its benefit in those indications requiring long-term therapy. In addition, very rare cases of serious cardiovascular reactions have been reported, particularly after injection.
The CHMP concluded that metoclopramide should now only be used for short-term therapy (for a maximum of five days). The preparations should no longer be used at all in children under one year of age and only as a second-line agent in children over one year of age for the prevention of delayed nausea and vomiting during chemotherapy and for the treatment of post-operative nausea and vomiting. In adults, it may be used in the future for the prevention of nausea and vomiting associated with chemotherapy or radiotherapy, surgical procedures, or migraine. In addition, the maximum recommended dosage for adults and children will be limited - higher-dose dosage forms will thus no longer be available.
A legally binding decision by the European Commission is expected within weeks.
Situation in Austria
In Austria, the following medicinal products containing metoclopramide are approved:
- Metoceolate 4 mg/ml drops.
- Metogastron 10 mg ampoules
- Metogastron 4 mg/ml drops
- Paspertin film-coated tablets
- Paspertin 10 mg ampoules
- Paspertin 4 mg/ml drops
- Paspertin 50 mg concentrate for infusion preparation
BASG has received a total of 22 case reports for all of the above preparations, two of which involved use in children or adolescents.
BASG recommendations for prescribers:
- To minimize the risk of neurologic and other adverse reactions, metoclopramide should be used only for a maximum duration of five days. Use in chronic conditions such as gastroparesis, dyspepsia, and gastroesophageal reflux should be discontinued, as should use as an adjunct to surgical or radiologic procedures.
- For adults, the indications remain prevention of post-operative nausea/vomiting, radiotherapy-induced nausea/vomiting, chemotherapy-induced delayed (not acute!) nausea/vomiting, and symptomatic treatment of nausea/vomiting, including its occurrence in acute migraine.
- For children, metoclopramide should only be used as a second-line agent for the prevention of delayed nausea/vomiting associated with chemotherapy and post-operative vomiting. Use in children less than one year of age is contraindicated.
- The Maximum Daily Dose for children and adults is 0.5 mg/kg body weight. The usual dosage for adults is 10 mg three times daily, and the recommended dosage for children is 0.1-0.15 mg/kg body weight up to three times daily.
- The use of oral liquid formulations carries a risk for overdose in children. Therefore, even the low-dose preparations remaining on the market should be administered using appropriate graduated syringes.
- Intravenous doses should be administered as a slow bolus over a duration of at least three minutes to minimize the risk for adverse reactions.
- Use in patients at increased risk for cardiovascular reactions should be done with great caution - especially when administered intravenously.
BASG recommendations for patients:
- Metoclopramide should not be used in children less than one year of age.
- In children over one year of age, metoclopramide-containing medicinal products may only be used to prevent nausea and vomiting occurring in the days following cancer therapy or surgery, provided that other medicines cannot be used.
- Metoclopramide should not be taken for more than five days in children and adults.
- The highest recommended daily dose for adults has been lowered to 30 mg per day - so some higher-dose preparations will not be available in the future.
- Patients currently being treated with metoclopramide are advised to see their treating physician in the near future to switch therapy if necessary.
Additional Information:European Medicines Agency Information, July 26, 2013.
