Regulatory Decision Summary for Smofkabiven Electrolyte Free, Smofkabiven extra Nitrogen Electrolyte Free

Overall, the benefit-risk profile was favorable for the use of SmofKabiven extra Nitrogen Electrolyte Free in parenteral nutrition of patients who require increased amino acid. The reviewed data show that SmofKabiven extra Nitrogen Electrolyte Free will enable the achievement of higher protein targets.

The claim of efficacy for SmofKabiven extra Nitrogen Electrolyte Free is based on the proven efficacy of SmofKabiven Electrolyte Free with which they share qualitatively same ingredients. SmofKabiven extra Nitrogen Electrolyte Free differs from SmofKabiven Electrolyte Free in that it has an increased amino acids content. The volumes of dextrose and lipid have been modified so that in the end the same concentration (i.e., amino acid 10%, dextrose 42%, and lipid 20%) are provided with the final admixture as with SmofKabiven Electrolyte Free.

The effectiveness of the proposed change to increase the amino acids (from 5.1 g to 6.5 g amino acids) which would provide a dosage in the range of 0.85 - 2.0 g amino acids/kg bw/day, is supported by clinical guidelines that recommend high-dose protein in critically ill patients. The American Society for Parenteral and Enteral Nutrition (ASPEN) and European Society for Clinical Nutrition and Metabolism (ESPEN) recommendations emphasize that acutely and critically ill patients are the patient groups with the highest protein requirements. While 0.8 g protein per kg body weight is sufficient for healthy adults, the needs rise to 1.0 - 1.3 g/kg body weight for patients in mild to moderate metabolic stress, for instance after elective surgery. In contrast, the recommended dosage for intensive care patients in their acute phase is 1.3 - 1.5 g/kg body weight or, in very severe catabolic condition or at increased losses, up to 2.0 (or even 2.5) g/kg bodyweight. The recommended dosage for SmofKabiven extra Nitrogen Electrolyte Free is in the range of 13 - 31 mL SmofKabiven extra Nitrogen Electrolyte Free /kg bw/day which corresponds to 0.85 - 2.0 g amino acids/kg bw/day. This dosage would cover the needs of protein in critically ill patients as recommended in above-mentioned clinical guidelines.

There is no direct measure of efficacy in parenteral nutrition; their efficacy is ascertained based on clinical outcomes. Published studies have shown that administration of parenteral nutrition with increased amino acid and reduced dextrose is associated with better clinical outcomes (e.g., decreased mortality risk, fewer infections, shorter duration of ventilator support, and reduced intensive care unit length of stay [ICU LOS]) than a regular parenteral nutrition solution.

Safety data are available from clinical trials and from post-marketing safety update reports received since launch of SmofKabiven Electrolyte Free and SmofKabiven extra Nitrogen Electrolyte Free. Since SmofKabiven extra Nitrogen Electrolyte Free has the same individual components as SmofKabiven Electrolyte Free, safety data available for the SmofKabiven Electrolyte Free apply to SmofKabiven extra Nitrogen Electrolyte Free.

The most reported adverse reactions in clinical trials and during the post-marketing include general disorders and administration site conditions (slight increase in body temperature, chills, dizziness, and headache), gastrointestinal disorders (lack of appetite, nausea, and vomiting), metabolism and nutrition disorders (elevated plasma levels of liver enzymes, hyperglycemia), and hepatobiliary disorders (hyperbilirubinemia).

In conclusion, SmofKabiven extra Nitrogen Electrolyte Free with its increased amino acid would cover the protein needs of critically ill patients as recommended by recent clinical guidelines. It is beneficial in some categories of patients, especially critically ill patients, and patients with morbid obesity, where it has been shown that increase of amino acid is associated with better clinical outcomes. No new safety issues have been identified in this submission. All adverse reactions identified during the approval process of SmofKabiven Electrolyte Free and post-marketing of SmofKabiven extra Nitrogen Electrolyte Free are addressed through labelling in the Product Monograph. Therefore, the data support the approval of SmofKabiven extra Nitrogen Electrolyte Free as a new total parenteral nutrition option in the management of patients with specific parenteral nutrition needs. A Notice of Compliance is recommended.