Smoflipid 20 % 1 000 ml Emulsion for intravenous infusion

To supply energy and essential fatty acids and omega-3 fatty acids, as part of a parenteral regimen to patients, when oral or enteral nutrition is impossible, insufficient or contraindicated.

Posology
The patientu2019s ability to eliminate the fat infused, should govern the dosage and infusion rate.
Adults
The standard dose is 1,0 to 2,0 g fat/kg body weight/day, corresponding to 5-10 ml /kg body weight/day. The infusion rate of 0,125 g fat/kg body weight/hour, corresponding to 0,63 ml SMOFlipid/kg body weight/hour, is recommended and should not exceed 0,15 g fat/kg body weight/hour, corresponding to 0,75 ml SMOFlipid/kg body weight/hour.
Neonates and infants
The initial dose should be 0,5 u2013 1,0 g fat/kg body weight/day followed by a successive increase by 0,5 u2013 1,0 g fat/kg body weight/day up to 3,0 g fat/kg body weight/day. It is recommended not to exceed a daily dose of 3 g fat/kg body weight/day, corresponding to 15 ml SMOFlipid/kg body weight/day. The rate of infusion should not exceed 0,125 g fat/kg body weight/hour. In premature and low birth weight neonates, SMOFlipid should be infused continuously over about 24 hours.
Children
It is recommended not to exceed a daily dose of 3 g fat/kg body weight/day, corresponding to 15 ml SMOFlipid/kg body weight/day. The daily dose should be increased gradually during the first week of administration.
Method of administration
For intravenous infusion into a peripheral or central vein.

• Hypersensitivity to fish, egg, soya or peanut protein or to any of the active substances or excipients listed in section 6.1
• Severe hyperlipidaemia
• Severe liver insufficiency
• Severe blood coagulation disorders
• Severe renal insufficiency without access to haemofiltration or dialysis
• Acute shock
• General contraindications to infusion therapy: acute pulmonary oedema, fluid overload, decompensated cardiac insufficiency
• Unstable conditions (e.g. severe post-traumatic conditions, uncompensated diabetes mellitus, acute myocardial infarction, stroke, embolism, metabolic acidosis, severe sepsis and hypotonic dehydration).

The capacity to eliminate fat is individual and should therefore be monitored according to the routines of the clinician. This is in general done by checking the triglyceride levels. Special caution should be taken in patients with a marked risk for hyperlipidaemia (e.g. patients with high lipid dosage and severe sepsis). The concentration of triglycerides in serum should not exceed 3 mmol/l during infusion. Reduction of the dosage or cessation of the lipid emulsion should be considered if serum or plasma triglyceride concentrations during or after infusion exceed 3 mmol/l. An overdose may lead to fat overload syndrome, see section 4.8. SMOFlipid contains soya-bean oil, fish oil and egg phospholipids, which may rarely cause allergic reactions. Cross allergic reaction has been observed between soya-bean and peanut. Any sign or symptom of anaphylactic reaction (such as fever, shivering, rash or dyspnoea) should lead to immediate interruption of the infusion. SMOFlipid should be given with caution in conditions of impaired lipid metabolism, which may occur in patients with renal failure, diabetes mellitus, pancreatitis, impaired liver function, hypothyroidism, and sepsis. Clinical data in patients with diabetes mellitus or renal failure are limited. Administration of medium-chain fatty acids alone can result in metabolic acidosis. This risk is to a great extent eliminated by the simultaneous infusion of the long-chain fatty acids included in SMOFlipid. Concomitant administration of carbohydrates will further eliminate this risk. Hence, simultaneous infusion of carbohydrate or a carbohydrate-containing amino acid solution is recommended. Laboratory tests generally associated with monitoring of intravenous nutrition should be checked regularly. These include blood glucose levels, liver function tests, acid base metabolism, fluid balance, full blood count and electrolytes. SMOFlipid should be given with caution to neonates and premature neonates with hyperbilirubinaemia and cases with pulmonary hypertension. In neonates, particularly premature neonates on long term parenteral nutrition, blood platelet counts, liver function tests and serum triglycerides should be monitored. Light exposure of solutions for intravenous parenteral nutrition, especially after admixture with trace elements and/or vitamins, may have adverse effects on clinical outcome in neonates, due to generation of peroxides and other degradation products. When used in neonates and children below 2 years, SMOFlipid should be protected from ambient light until administration is completed (see sections 6.3 and 6.6). High levels of lipids in plasma may interfere with some laboratory blood tests, e.g. haemoglobin. Monitoring of triglycerides and blood glucose levels are recommended to avoid elevated levels, which may be harmful. At present there is limited experience of SMOFlipid treatment for more than 14 days. SMOFlipid contains up to 5 mmol sodium per 1 000 ml. To be taken into consideration by patients on a controlled sodium diet. The addition of other medicines or substances to SMOFlipid should generally be avoided unless compatibility has been proven (see sections 6.2 and 6.6).

Heparin given in clinical doses causes a transient increase in lipoprotein lipase release into the circulation. This may initially result in increased plasma lipolysis, followed by a transient decrease in triglyceride clearance. Soybean oil has a natural content of vitamin K 1. The content is however so low in SMOFlipid that it is not expected to significantly influence the coagulation process in patients treated with coumarin derivatives.

There are no data available on the use of SMOFlipid in pregnant or breastfeeding women. There are no studies available on reproductive toxicity in animals. SMOFlipid should only be given to pregnant and breastfeeding women after careful consideration.

Not relevant.

a. Summary of the safety profile
No information available.
b. Tabulated list of adverse reactions
Frequencies are defined as : Common (u2265 1/100 to < 1/10) Uncommon (u2265 1/1 000 to < 1/100) Rare (u2265 1/10 000 to < 1/1 000) Very rare (< 1/10 000)
Vascular disorders
Rare: Hypotension, hypertension
Respiratory, thoracic and mediastinal disorders
Rare: Dyspnoea
Gastrointestinal disorders
Uncommon: Lack of appetite, nausea, vomiting
Reproductive system and breast disorders
Very rare: Priapism
General disorders and administration site conditions
Common: Slight increase in body temperature
Uncommon: Chills
Immune system disorders
Rare: Hypersensitivity-reactions (e.g. anaphylactic or anaphylactoid reactions, skin rash, urticaria, flush, headache), heat or cold sensation, paleness, cyanosis, pain in the neck, back, bones, chest and loins. Should these side effects occur or should the triglyceride level during infusion rise above 3 mmol/l, the infusion of SMOFlipid should be stopped or, if necessary, continued at a reduced dosage. SMOFlipid should always be a part of a complete parenteral nutritional treatment including amino acids and glucose. Nausea, vomiting and hyperglycaemia are symptoms related to conditions indicating parenteral nutrition and may sometimes be associated with parenteral nutrition.
c. Description of selected adverse reactions
Fat overload syndrome: Impaired capacity to eliminate triglycerides can lead to u201cFat overload syndromeu201d which may be caused by overdose. Possible signs of metabolic overload must be observed. The cause may be genetic (individually different metabolism) or the fat metabolism may be affected by ongoing or previous illnesses. This syndrome may also appear during severe hypertriglyceridaemia, even at the recommended infusion rate, and in association with a sudden change in the patientu2019s clinical condition, such as renal function impairment or infection. The fat overload syndrome is characterised by hyperlipidaemia, fever, fat infiltration, hepatomegaly with or without icterus, splenomegaly, anaemia, leukopenia, thrombocytopenia, coagulation disorders, haemolysis and reticulocytosis, abnormal liver function tests and coma. The symptoms are usually reversible if the infusion of the fat emulsion is discontinued. Should signs of a fat overload syndrome occur, the infusion of SMOFlipid should be discontinued.

Overdose leading to fat overload syndrome may occur as a result of a too rapid infusion rate, or chronically at recommended rates of infusion in association with a change in the patientu2019s clinical conditions e.g. renal function impairment or infection. Overdosage may lead to side effects (see section 4.8). In these cases, the lipid infusion should be stopped or, if necessary, continued at a reduced dosage.