Numeta G13%E and Numeta G16%E emulsion for infusion

• Because of the risk of hypermagnesaemia (high blood levels of magnesium), the nutrition preparation Numeta G13%E has been suspended until a reformulated preparation is made available. Numeta G13%E is given into a vein to provide nutritional support in premature babies who cannot be fed by mouth or with a feeding tube.
• The nutrition preparation Numeta G16%E can continue to be used in full-term newborns and children up to two years, however the doctor will monitor the levels of magnesium in the child's blood before giving the preparation and at appropriate intervals thereafter. The doctor will stop giving Numeta G16%E if magnesium levels are high, or will give Numeta at a slower rate.
• Severe hypermagnesaemia is rare but can have adverse clinical consequences. Doctors will monitor newborns and children who are receiving Numeta G16%E for symptoms of hypermagnesaemia such as weakness, nausea and vomiting, breathing difficulties, hypotension (low blood pressure) and arrhythmias (irregular heart beat).
• Parents who have any questions or concerns should speak to the treating doctor or other healthcare professional.

For Numeta G13%E:

• Following several reports of hypermagnesaemia in preterm infants, the nutrition preparation Numeta G13%E has been suspended until a reformulated preparation is made available. While Numeta G13%E is suspended, healthcare professionals should use alternative nutrition solutions, which may include authorised standardised or individually prepared solutions.

For Numeta G16%E:

• The benefit-risk balance of the nutrition preparation Numeta G16%E, used in full-term newborns and children up to two years, remains positive. However, healthcare professionals should be aware of the potential risk for hypermagnesaemia. This risk is increased in patients with reduced renal function, and in newborn infants of mothers who were receiving supplemental magnesium prior to delivery.
• When giving Numeta G16%E, doctors should monitor serum magnesium levels, along with other electrolyte levels at baseline and at appropriate intervals thereafter. This should be done in accordance with routine clinical practice and the clinical needs of the individual patient.
• Doctors should also monitor patients for signs and symptoms of hypermagnesaemia such as nausea, vomiting and flushing, generalised weakness, respiratory failure, hypotension and arrhythmias. Clinical signs may not be identifiable unless hypermagnesaemia is severe.
• In case of hypermagnesaemia, the infusion of Numeta G16%E should be stopped or infusion rate reduced and alternative fluids, nutrition and electrolytes prescribed as deemed clinically appropriate.

Further information about the EU-wide safety review:

• The company marketing Numeta identified 14 case reports of hypermagnesaemia with Numeta G13%E. Magnesium levels mainly ranged from 1.025 mmol/l to > 1.5 mmol/l and no clinical signs or symptoms were reported for any of the cases.
• The appropriate parenteral magnesium intake in preterm infants is uncertain. However, widely recognised guidelines^1,2 recommend a parenteral magnesium intake of 0.15-0.25 mmol/kg/day. The maximum total licensed amount of magnesium that can be delivered to preterm infants using Numeta G13%E is 0.55 mmol/kg/day, which is above this recommended intake.
• The company identified one case of hypermagnesaemia associated with Numeta G16%E. This report was confounded by the fact that additional magnesium may have been given.
• The maximum total amount of magnesium that can be delivered to term infants using Numeta G16%E according to its product information is 0.3 mmol/kg/day. Although this is within the recommendations reported in the literature as a whole, it is slightly more than suggested by some recognised guidelines^1,2,3 (0.15-0.25 mmol/kg/day and 0.2 mmol/kg/day for term infant to one year of age, 0.15-0.25 mmol/kg/day and 0.1 mmol/kg/day for children from one year to two years of age).

References:

1. Canada T, Crill C, Guenter P. American Society for Parenteral and Enteral Nutrition parenteral nutrition handbook. Silver Spring,Maryland: American Society for Parenteral and Enteral Nutrition. 2009; 167.
2. Mirtallo J., Canada T., Johnson D., Kumpf V., Petersen C., Sacks G., Seres D., Guenter P, Task Force for the Revision of Safe Practices for Parenteral Nutrition. Safe practices for parenteral nutrition. JPEN J Parenter Enteral Nutr 2004; 28(6):S39-S70.
3. Koletzko B., Goulet O., Hunt J., Krohn K., Shamir R. Guidelines on paediatric parenteral nutrition of the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and the European Society for Clinical Nutrition and Metabolism (ESPEN), supported by the European Society of Paediatric Research (ESPR). J Pediatric Gastroenterology Nutrition 2005; 41: S1-S87.

Numeta G13%E and Numeta G16%E (glucose, lipids, aminoacids and electrolytes) are parenteral nutrition solutions. Parenteral nutrition is the providing of nutrients and fluids through a vein in patients who cannot be fed by mouth or by enteral nutrition (the use of a feeding tube passed directly into the gut). Parenteral nutrition is necessary in premature neonates and in some full-term babies in order to prevent complications such as growth retardation and breathing complications and to promote the normal development of the brain.

Numeta G13%E and Numeta G16%E have been authorised since 2011 via national procedures in the following Member States: Austria, Belgium, the Czech Republic, Denmark, Finland, France, Germany, Greece, Ireland, Italy, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Spain, Sweden and the United Kingdom.

The review of Numeta G13%E and Numeta G16%E was initiated on 13 June 2013 at the request of Sweden, under Article 107i of Directive 2001/83/EC, also known as the urgent Union procedure.

The review was conducted by the Pharmacovigilance Risk Assessment Committee (PRAC). As the review only covers nationally authorised medicines, the PRAC recommendation was forwarded to the Coordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh), which adopted a final position. The CMDh is a medicines regulatory body representing the EU Member States.