Nutriflex Omega Specialized 1000 mL/625 mL/1875 mL Infusion

Supply of energy, essential fatty acids including omega-3 and omega 6-fatty acids, amino acids, electrolytes and fluids for parenteral nutrition of patients in states of moderate to severe catabolism when oral or enteral nutrition is impossible, insufficient or contraindicated. NUTRIFLEX OMEGA SPECIALIZED is indicated in adults.

Posology
The dosage should be adapted to the patientsu2019 individual requirements. It is recommended that NUTRIFLEX OMEGA SPECIALIZED be administered continuously. A stepwise increase of the infusion rate over the first 30 minutes up to the desired infusion rate avoids possible complications.

Adult
The maximum daily dose amounts to 35 mL/kg body weight, corresponding to:
2,0 g amino acids per kg body weight per day
5,04 g glucose per kg body weight per day
1,4 g lipid per kg body weight per day.
The maximum rate of infusion is 1,7 mL/kg body weight per hour, corresponding to:
0,1 g amino acids per kg body weight per hour
0,24 g glucose per kg body weight per hour
0,07 g lipid per kg body weight per hour.
For a patient weighing 70 kg this corresponds to a maximum infusion rate of 119 mL per hour. The amount of substrate administered is then 6,8 g of amino acids per hour, 17,1 g of glucose per hour and 4,8 g of lipids per hour.

Paediatric population
Newborn infants, infants and toddlers less than two years of age NUTRIFLEX OMEGA SPECIALIZED is contraindicated in newborn infants, infants and toddlers 2 years and adolescents have not been established.

Patients with renal/hepatic impairment
The doses should be adjusted individually in patients with hepatic or renal insufficiency (see also section 4.4).

Patient with intradialytic parenteral nutrition (IDPN)
Intradialytic parenteral nutrition is intended for non-acutely ill malnourished dialysis patients where nutritional counselling or treatment with oral nutritional supplements was ineffective. The selection of the appropriate NUTRIFLEX OMEGA SPECIALIZED volume to be used for IDPN should be guided by the gap between spontaneous intakes and the recommended intakes. Additionally, metabolic tolerance needs to be taken into consideration. For NUTRIFLEX OMEGA SPECIALIZED in patients on IDPN, the maximum hourly infusion rate is 2,3 mL/kg/hour, corresponding to 0,13 g/kg/hour amino acids, 0,33 g/kg/hour glucose, and 0,092 g/kg/hour lipids administered over 4 hours. Taking into consideration the known amino acid (retention rate 73 %) and glucose losses (25 g/ 4-hour dialysis session) during dialysis, the patient will finally receive 0,095 g/kg amino acids, 0,25 g/kg glucose and 0,093 g/kg lipids in a 4-hour dialysis session. This corresponds to 27 g of amino acids, 70 g of glucose, 26 g of lipids and 644 mL of fluid for a 70 kg patient.

Duration of treatment
The duration of treatment for the indications stated is not limited. During the administration of NUTRIFLEX OMEGA SPECIALIZED it is necessary to provide an appropriate amount of trace elements and vitamins.

Duration of infusion of one single bag
The recommended duration of infusion for a parenteral nutrition bag is maximum 24h.

Method of administration
Intravenous use. For central venous infusion only. During intradialytic parenteral nutrition (IDPN) the bag should be administered through the venous drip chamber of the extracorporeal circulation lines.

• hypersensitivity to the active substances, to egg, fish, peanut or soya protein or to any of the excipients listed in section 6.1
• inborn errors of amino acid metabolism
• severe hypertriglyceridaemia (u2265 1000 mg/dL or 11,4 mmol/L)
• severe coagulopathy
• hyperglycaemia not responding to insulin doses of up to 6 units insulin/hour
• acidosis
• intrahepatic cholestasis
• severe hepatic insufficiency
• severe renal insufficiency in absence of renal replacement therapy
• aggravating haemorrhagic diatheses
• acute thrombo-embolic events, lipid embolism.

On account of its composition NUTRIFLEX OMEGA SPECIALIZED must not be used in newborn infants, infants and toddlers under 2 years of age.

General contraindications to parenteral nutrition include:

• unstable circulatory status with vital threat (states of collapse and shock)
• acute phases of cardiac infarction and stroke
• unstable metabolic condition (e.g. severe post-aggression syndrome, coma of unknown origin)
• inadequate cellular oxygen supply
• disturbances of the electrolyte and fluid balance
• acute pulmonary oedema
• decompensated cardiac insufficiency.

Caution should be exercised in cases of increased serum osmolarity. Disturbances of the fluid, electrolyte or acid-base balance must be corrected before the start of infusion.

Too rapid infusion can lead to fluid overload with pathological serum electrolyte concentrations, hyperhydration and pulmonary oedema. Any sign or symptom of anaphylactic reaction (such as fever, shivering, rash or dyspnoea) should lead to immediate interruption of the infusion.

The serum triglyceride concentration should be monitored when infusing NUTRIFLEX OMEGA SPECIALIZED. Depending on the patientu2019s metabolic condition, occasional hypertriglyceridaemia may occur. If the plasma triglyceride concentration exceeds 4,6 mmol/L (400 mg/dL) during administration of lipids, it is recommended to reduce the infusion rate. The infusion must be interrupted if the plasma triglyceride concentration exceeds 11,4 mmol/L (1000 mg/dL), as these levels have been associated with acute pancreatitis.

Patients with impaired lipid metabolism NUTRIFLEX OMEGA SPECIALIZED should be administered cautiously to patients with disturbances of lipid metabolism with increased serum triglycerides, e.g. renal insufficiency, diabetes mellitus, pancreatitis, impaired hepatic function, hypothyroidism (with hypertriglyceridaemia), sepsis and metabolic syndrome. If NUTRIFLEX OMEGA SPECIALIZED is given to patients with these conditions, more frequent monitoring of serum triglycerides is necessary to assure triglyceride elimination and stable triglyceride levels below 11,4 mmol/L (1000 mg/dL).

In combined hyperlipidaemias and in metabolic syndrome, triglyceride levels react to glucose, lipids and overnutrition. Adjust dose accordingly. Assess and monitor other lipid and glucose sources, and drugs interfering with their metabolism. The presence of hypertriglyceridaemia 12 hours after lipid administration also indicates a disturbance of lipid metabolism.

The administration of NUTRIFLEX OMEGA SPECIALIZED can lead to hyperglycaemia. The blood glucose level should be monitored. If there is hyperglycaemia, the rate of infusion should be reduced or insulin should be administered. If the patient is receiving other intravenous glucose solutions concurrently, the amount of additionally administered glucose has to be taken into account. An interruption of administration of the emulsion may be indicated if the blood glucose concentration rises to above 14 mmol/L (250 mg/dL) during administration.

Refeeding or repletion of malnourished or depleted patients may cause hypokalaemia, hypophosphataemia and hypomagnesaemia. Close monitoring of serum electrolytes is mandatory. Adequate supplementation of electrolytes according to deviations from normal values is necessary. Controls of the serum electrolytes, the water balance, the acid-base balance, and of blood cell counts, coagulation status, hepatic and renal function are necessary. Substitution of electrolytes, vitamins and trace elements may be necessary as required. As NUTRIFLEX OMEGA SPECIALIZED contains zinc, magnesium, calcium and phosphate, care should be taken when it is co-administered with solutions containing these substances.

NUTRIFLEX OMEGA SPECIALIZED is a preparation of complex composition. It is, therefore, strongly advisable not to add other solutions (as long as compatibility is not proven u2013 see section 6.2). NUTRIFLEX OMEGA SPECIALIZED should not be given simultaneously with blood in the same infusion set due to the risk of pseudo-agglutination (see also section 4.5).

Strict aseptic precautions are necessary for the infusion of NUTRIFLEX OMEGA SPECIALIZED.

Paediatric population
There is as yet no clinical experience of the use of NUTRIFLEX OMEGA SPECIALIZED in children and adolescents.

Elderly patients
Basically, the same dosage as for adults applies, but caution should be exercised in patients suffering from further diseases like cardiac insufficiency or renal insufficiency that may frequently be associated with advanced age.

Patients with diabetes mellitus, impaired cardiac or renal function NUTRIFLEX OMEGA SPECIALIZED should be administered with caution to patients with impaired cardiac or renal function. There is only limited experience of its use in patients with diabetes mellitus or renal failure.

NUTRIFLEX OMEGA SPECIALIZED contains sodium
This medicinal product contains 771 mg sodium per 625 mL bag, equivalent to 39 % of the WHO recommended maximum daily intake of 2 g sodium for an adult. The maximum daily dose of this product for a 70 kg adult is equivalent to 151 % of the WHO recommended maximum daily intake for sodium. NUTRIFLEX OMEGA SPECIALIZED is considered high in sodium. This should be particularly taken into account for those on a low salt diet. Guidelines for parenteral nutrition recommend a daily supply of 60 u2013 150 mmol (1,0 u2013 1,5 mmoL/kg/d) of sodium. NUTRIFLEX OMEGA SPECIALIZED provides between 33,5 to 100,5 mmol of sodium. Thus, the product provides sufficient amounts of sodium in good agreement with the sodium recommendation for parenteral nutrition.

Interference with laboratory tests
The fat content may interfere with certain laboratory measurements (e.g. bilirubin, lactate dehydrogenase, oxygen saturation) if blood is sampled before fat has been adequately cleared from the blood stream.

Some medicine, like insulin, may interfere with the bodyu2019s lipase system. This kind of interaction seems, however, to be of only limited clinical importance. Heparin given in clinical doses causes a transient release of lipoprotein lipase into the circulation. This may result initially in increased plasma lipolysis followed by a transient decrease in triglyceride clearance. Soya-bean oil has a natural content of vitamin K 1. This may interfere with the therapeutic effect of coumarin derivatives which should be closely monitored in patients treated with such medicines. NUTRIFLEX OMEGA SPECIALIZED should be used with caution in patients receiving medicines that increase serum potassium concentration, such as potassium-sparing diuretics (triamterene, amiloride, spironolactone), ACE inhibitors (e.g. captopril, enalapril), angiotensin-II-receptor antagonists (e.g. losartan, valsartan), ciclosporin and tacrolimus. Corticosteroids and ACTH are associated with sodium and fluid retention. NUTRIFLEX OMEGA SPECIALIZED should not be given simultaneously with blood in the same infusion set due to the risk of pseudoagglutination (see also section 4.4).

Pregnancy
There are no or limited amount of data from the use of NUTRIFLEX OMEGA SPECIALIZED in pregnant women. Animal studies are insufficient with respect to reproductive toxicity (see section 5.3). Parenteral nutrition may become necessary during pregnancy. NUTRIFLEX OMEGA SPECIALIZED should only be given to pregnant women after careful consideration.

Breast-feeding
Components/metabolites of NUTRIFLEX OMEGA SPECIALIZED are excreted in human milk, but at therapeutic doses no effects on the breastfed newborn/infants are anticipated. Nevertheless, breast-feeding is not recommended for mothers on parenteral nutrition.

Fertility
No data from the use of NUTRIFLEX OMEGA SPECIALIZED available.

NUTRIFLEX OMEGA SPECIALIZED has no or negligible influence on the ability to drive and use machines.

Under conditions of correct use, in terms of dosing monitoring, observation of safety restrictions and instructions, undesirable effects may still occur. The following listing includes a number of systemic reactions that may be associated with the use of NUTRIFLEX OMEGA SPECIALIZED. Undesirable effects are listed according to their frequencies as follows:

System organ class Frequency Undesirable effects

Blood and lymphatic system disorders: Less frequent Hypercoagulation

Frequency not known Leucopenia, Thrombocytopenia

Immune system disorders Less frequent Allergic reactions (e.g. anaphylactic reactions, dermal eruptions, laryngeal, oral and facial oedema)

Metabolism and nutrition disorders Less frequent Loss of Appetite, Hyperlipidaemia, Hyperglycaemia, Metabolic acidosis. (The frequency of these undesirable effects is dose-dependent and may be higher under the condition of absolute or relative lipid overdose)

Nervous system disorders Less frequent Headache, drowsiness

Vascular disorders Less frequent Hypertension or Hypotension, Flush

Respiratory, thoracic, and mediastinal disorders Less frequent Dyspnoea, Cyanosis

Gastrointestinal disorders Less frequent Nausea, Vomiting

Hepatobiliary disorders Frequency not known Cholestasis

Skin and subcutaneous tissue disorders Less frequent: Erythema, Sweating

Musculoskeletal and connective tissue disorders Less frequent Pain in back, Bones, Chest and lumbar region

General disorders and administration site conditions Less frequent Elevated Body Temperature, Feeling Cold, Chills, Fat Overload Syndrome (details see below).

Should adverse reactions occur, the infusion must be stopped. Should the triglyceride level rise to above 11,4 mmol/L (1000 mg/dL) during infusion, the infusion must be stopped. With levels above 4,6 mmol/L (400 mg/dL), the infusion may be continued at a reduced dosage (see section 4.4). If the infusion is restarted, the patient should be carefully monitored, especially at the beginning, and serum triglycerides should be determined at short intervals.

Information on particular undesirable effects
Nausea, vomiting and lack of appetite are symptoms often related to conditions for which parenteral nutrition is indicated, and may be associated with parenteral nutrition at the same time.

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 disorder 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 NUTRIFLEX OMEGA SPECIALIZED should be discontinued immediately.

Symptoms of fluid and electrolyte overdose
Hyperhydration, electrolyte imbalance and pulmonary oedema.

Symptoms of amino acid overdose
Renal amino acid losses with consecutive amino acid imbalances, sickness, vomiting and shivering.

Symptoms of glucose overdose
Hyperglycaemia, glucosuria, dehydration, hyperosmolality, hyperglycaemic-hyperosmolar coma.

Symptoms of lipid overdose
See section 4.8.

Treatment
Immediate cessation of infusion is indicated for overdose. Further therapeutic measures depend on the particular symptoms and their severity. When infusion is recommenced after the symptoms have declined it is recommended that the infusion rate be raised gradually with monitoring at frequent intervals.