Nutriflex Lipid Plus 1250 mL Intravenous infusion

Supply of the daily requirement of energy, essential fatty acids, amino acids, electrolytes and fluids during parenteral nutrition for patients with mild to moderately severe catabolism when oral or enteral nutrition is impossible, insufficient or contraindicated.

Posology
The dosage is adjusted according to the patientu2019s individual requirements. The maximum daily dose is 40 mL /kg body weight, corresponding to:
- 1,54 g amino acids /kg body weight per day
- 4,8 g glucose /kg body weight per day
- 1,6 g fat /kg body weight per day
It is recommended that Nutriflex u00ae Lipid Plus be administered continuously. A stepwise increase of the infusion rate over the first 30 minutes up to the desired infusion rate helps to avoid complications.
The maximum rate of infusion is 2,0 mL/kg body weight per hour, corresponding to
- 0,08 g amino acids /kg body weight per hour
- 0,24 g glucose /kg body weight per hour
- 0,08 g fat /kg body weight per hour
For a patient weighing 70 kg this corresponds to an infusion rate of 140 mL per hour. The amount of amino acid administered is then 5,4 g/hour, of glucose 16,8 g/hour and of lipid 5,6 g/hour.
In general, it is recommended that the maximum amount of energy should not exceed 40 kcal/kg body weight per day. If specially indicated e.g. for burned patients higher dosage is possible.
Method of administration
The ready-to-use emulsion is infused into a central vein. The emulsion should always be brought to room temperature prior to infusion. Only intact containers, with homogenous fat emulsions after gentle shaking, and clear solutions, are to be used.
Duration of use
The duration of treatment for the indications stated in not limited. During long-term administration of Nutriflexu00ae Lipid Plus it is necessary to supply appropriate replacement of trace elements and vitamins.

• Hypersensitivity to the active substances, to egg, peanut or soya protein or to any of the excipients listed in section 6.1
• Disturbances of amino acid metabolism
• Disturbances of lipid metabolism
• Hypokalaemia; hyponatraemia
• Unstable metabolism e.g. severe post aggression syndrome (an endocrine imbalance with glucose intolerance and peripheral resistance to insulin, which can result in persistent hyperglycaemic states with increased lipolysis and progressive proteolysis), unstabilised diabetes mellitus coma of unknown origin)
• Hyperglycaemia not responding to insulin doses of up to 6 units insulin/hour
• Acidosis
• Intrahepatic cholestasis
• Severe hepatic insufficiency
• Severe renal insufficiency
• Manifest cardiac insufficiency
• Aggravating haemorrhagic diatheses
• Acute myocardial infarction and stroke
• Acute event of thromboembolism, lipid embolism.

On account of its composition Nutriflex u00ae Lipid Plus should not be used for neonates, infants and children under 2 years of age.
General contraindications to parenteral nutrition include:
- Unstable circulatory status
- Acute phases of cardiac infarction and stroke
- Unstable metabolic condition (e.g. severe postaggression 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, e.g. hyperhydration, hyperkalaemia, acidosis, 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 of symptoms 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 u00ae Lipid Plus. Fasting lipaemia should be excluded in patients with suspected disturbances of lipid metabolism before starting infusion. The administration of lipids is contraindicated if there is fasting lipaemia. The presence of hypertriglyceridaemia 12 hours after lipid administration also indicates a disturbance of lipid metabolism.
Patients with impaired lipid metabolism Nutriflex u00ae Lipid Plus should be administered cautiously to patients with disturbances of lipid metabolism, e.g. renal insufficiency, diabetes mellitus, pancreatitis, impaired liver function, hypothyroidism, sepsis and metabolic syndrome. If Nutriflex u00ae Lipid Plus is given to patients with these conditions close monitoring of serum triglycerides is mandatory. Depending on the patientu2019s metabolic condition, occasional hypertriglyceridaemia or increases of the blood glucose concentration may occur. If the plasma triglyceride concentration rises to more than 3 mmol/L during administration of lipid it is recommended that the infusion rate should be reduced. Should the plasma triglyceride concentration remain above 3 mmol/L the administration should be stopped until the level normalises.
The administration of Nutriflex u00ae Lipid Plus 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. A dose reduction or 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. Adequate supplementation of electrolytes according to deviations from normal values is necessary. Intravenous infusion of amino acids is accompanied by increased urinary excretion of the trace elements, especially copper and, in particular zinc. This should be considered in the dosing of trace elements, especially during long-term intravenous nutrition. Controls of the serum electrolytes, the water balance, acid-base balance, and of blood cell counts, coagulation status, renal and hepatic function are necessary. Substitution of electrolytes, vitamins and trace elements may be necessary as required. As Nutriflex u00ae Lipid Plus contains zinc, magnesium, calcium and phosphate, care should be taken when it is co-administered with solutions containing these substances.
Nutriflex u00ae Lipid Plus should not be given simultaneously with blood in the same infusion set due to the risk of pseudoagglutination. Nutriflex u00ae Lipid Plus 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). As with all intravenous solutions strict aseptic precautions are necessary for the infusion of Nutriflex u00ae Lipid Plus.
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 or renal function
Like all large-volume infusion solutions, Nutriflex u00ae Lipid Plus should be administered with caution to patients with impaired renal function. There is only limited experience of its use in patients with diabetes mellitus or renal failure.
Nutriflex u00ae Lipid Plus contains sodium Nutriflex u00ae Lipid Plus contains 1150 mg sodium per 1250 mL bag, equivalent to 58 % of the WHO recommended maximum daily intake of 2 g sodium for an adult. The maximum daily dose of Nutriflex u00ae Lipid Plus for a 70 kg adult is equivalent to 129 % of the WHO recommended maximum daily intake for sodium. Nutriflex u00ae Lipid Plus is considered high in sodium. This should be particularly taken into account for those on a low salt diet.
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 medication, 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 agents. Potassium-containing solutions like Nutriflex u00ae Lipid Plus should be used with caution in patients receiving drugs 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 u00ae Lipid Plus should not be given simultaneously with blood in the same infusion set due to the risk of pseudoagglutination (see also section 4.4). Solutions containing amino acids, carbohydrate and lipids should not be mixed with other solutions due to the risk for incompatibilities or microbial contamination. Concomitant infusion with other medicines should also be avoided due to the risk of incompatibilities (see section 6.2).

Pregnancy
Safety and efficacy have not yet been established. Nutriflex u00ae Lipid Plus is manufactured with soybean oil that contains phytosterols in concentrations that could lead to disturbances of fertility.
Lactation
Breastfeeding is not recommended if women need parenteral nutrition.
Fertility
No data from the use of Nutriflex Lipid Plus available.

Nutriflex u00ae Lipid Plus 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 u00ae Lipid Plus.
Blood and lymphatic system disorders:
Less frequent: Hypercoagulation. Frequency unknown: Hypokalaemia, hypophosphataemia, hypomagnesaemia, hypermagnesaemia, 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. Frequency unknown: Respiratory distress.
Gastrointestinal disorders:
Less frequent: Nausea, vomiting.
Hepatobiliary disorders:
Frequency unknown: Cholestasis.
Skin and subcutaneous tissue disorders:
Less frequent: Erythema, sweating. Frequency unknown: Bluish discoloration of the skin due to reduced oxygen content of the blood (cyanosis).
Musculoskeletal and connective tissue disorders:
Less frequent: Pain in the back, bones, chest and lumbar region.
Cardiac disorders:
Frequency unknown: Fall or increase in blood pressure.
General disorders and administration site conditions:
Frequent: Thrombophlebitis. Less frequent: Elevated body temperature, feeling cold, chills, fat overload syndrome (see details below). Frequency unknown: Infection of the injection site which can lead to septicaemia; irritation at the injection site.
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 u2018fat overload syndromeu2019, 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, leucopenia, 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 u00ae Lipid Plus 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, glycosuria, dehydration, hyperosmolality, hyperglycaemic- hyperosmolar coma.
Symptoms of lipid overdose:
Refer to section 4.8.
Treatment
Immediate cessation of infusion is indicated in the case of 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.