SUMMARY OF PRODUCT CHARACTERISTICS. Medical conditions that require parenteral nutrition for supply of energy and essential fatty acids.

Transcription

1 SUMMARY OF PRODUCT CHARACTERISTICS 1. NAME OF THE MEDICINAL PRODUCT Alphalipid 200 mg/ml emulsion for infusion 2. QUALITATIVE AND QUANTITATIVE COMPOSITION 1000 ml of the emulsion contain: Soya-bean oil, refined Energy content: 200 g 2000 kcal/l (8.4 MJ/l) Excipient with known effect: Sodium 0.03 mg/ml (see section 4.4) For the full list of excipients, see section PHARMACEUTICAL FORM Alphalipid is a milky white emulsion for infusion. Osmolality: about 350 mosm/kg water ph: CLINICAL PARTICULARS 4.1 Therapeutic indications Medical conditions that require parenteral nutrition for supply of energy and essential fatty acids. 4.2 Posology and method of administration Posology Adults The patient s ability to eliminate the infused fat should determine the dosage (see Treatment monitoring below). The quantity of fat administered intravenously should normally not exceed 3 g/kg bodyweight/day. The highest permitted infusion rate is 1.6 ml/min, equivalent to an infusion time of at least 5 hours for 500 ml. Paediatric population The child s ability to eliminate fat should determine the dosage (see Treatment monitoring below). The recommended daily dose is g fat/kg bodyweight. The infusion rate should not exceed 0.17 g fat/kg bodyweight/hour (4 g fat/kg per 24 hours). In premature and very low birth weight infants Alphalipid should preferably be administered continuously over 24 hours. The initial dosage should be g fat/kg bodyweight/day. The dose should then be increased gradually by g fat/kg Page 1

2 bodyweight/day up to 2 g fat/kg bodyweight/day. The dosage may be increased to 4 g/kg/day only under close monitoring of serum triglyceride concentrations, liver function and oxygen saturation. Method of administration Alphalipid should be administered as an intravenous infusion. Treatment monitoring Adults: where intravenous fat emulsion is indicated for more than a week, the patient s ability to eliminate fat should be checked. A sample of blood should be taken before the start of the infusion and centrifuged. If the plasma is milky or opalescent, the planned infusion should be postponed. Be aware that hypertriglyceridaemia may pass undetected with this method. In patients in whom impaired fat tolerance may be expected, measurement of the serum triglyceride concentration is therefore recommended. The elimination of fat should be checked daily in the medical conditions mentioned in section 4.4. Paediatric population: in infants treated with Alphalipid the ability to eliminate fat should be tested regularly. In infants receiving long-term parenteral nutrition, particularly premature infants, platelet count, liver function and serum triglycerides should be monitored daily. Specific measurement of the serum triglyceride concentration is recommended for this group. 4.3 Contraindications Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. Hypersensitivity to egg protein. Hypersensitivity to soya-bean protein or peanut protein. Alphalipid contains soya-bean oil. Cross-allergy occurs between peanuts and soya-beans. Acute shock. Conditions involving severe hyperlipidaemia. Severe hepatic failure. Haemophagocytic syndrome. 4.4 Special warnings and precautions for use Caution should be observed in conditions with impaired fat metabolism, such as renal impairment, uncontrolled diabetes, pancreatitis, hepatic impairment, hypothyroidism (if hypertriglyceridaemia is present) and sepsis. If Alphalipid is given in these conditions, the serum triglyceride concentration should be monitored closely. Paediatric population Alphalipid should be given with caution to neonates and premature infants with hyperbilirubinaemia and in cases of suspected pulmonary hypertension. Interference with serological testing Alphalipid may interfere with certain laboratory tests (bilirubin, lactate dehydrogenase, oxygen saturation, Hb, etc.) if blood is sampled before the administered fat has been cleared from the blood. In most patients fat is cleared from the blood 5-6 hours after the end of the infusion. This medicinal product contains 0,65 mmol sodium (15 mg) per 500 ml, i.e. essentially sodium- free. Page 2

3 4.5 Interaction with other medicinal products and other forms of interaction Certain medicinal products such as insulin can affect the body s lipase system. This type of interaction, however, is considered to be of limited clinical significance. Heparin in clinical doses causes a transient increase in lipolysis in plasma, resulting in a transient decrease in triglyceride clearance due to depletion of lipoprotein lipase. Soya-bean oil has a natural content of vitamin K 1. This is considered important only in patients treated with coumarin derivatives, which interact with vitamin K Fertility, pregnancy and lactation Pregnancy Data on a limited number of exposed pregnancies indicate no adverse effects of Alphalipid on pregnancy or on the health of the fetus/newborn child. To date, no other relevant epidemiological data are available. Caution should be exercised when prescribing to pregnant women. Breastfeeding There is insufficient information on the excretion of soya-bean oil in human milk. Fertility There is insufficient information on the effect on fertility. 4.7 Effects on ability to drive and use machines Alphalipid has no or negligible influence on the ability to drive and use machines. 4.8 Undesirable effects The following frequencies are taken as a basis when evaluating undesirable effects: Very common: 1/10 Common: 1/100 to <1/10 Uncommon: 1/1000 to <1/100 Rare: 1/10,000 to <1/1,000 Very rare: <1/10,000 Not known: cannot be estimated from the available data Following undesirable effects were reported for the reference soya-bean emulsion for infusion: System organ class Frequency Event Blood and lymphatic system disorders Rare Haemolysis, reticulocytosis, thrombocytopenia (in association with long-term treatment in infants) Vascular disorders Rare Hypertension, hypotension Respiratory, thoracic and mediastinal disorders Rare Tachypnoea Hepatobiliary disorders Rare Hepatic impairment Page 3

4 System organ class Frequency Event Skin and subcutaneous tissue disorders Uncommon Flushing Rare Skin rash, urticaria Reproductive system and breast disorders Rare Priapism General disorders and administration site conditions Uncommon Rare Fever, chills, nausea Anaphylactic reaction, headache, abdominal pain, tiredness The rare side effects can occur during or following infusion (early effects) or after extended treatment. Early effects that occur at the recommended dose include allergic reactions, abdominal pain, haemolysis, headache, hypertension, hypotension, priapism, reticulocytosis, tachypnoea and tiredness. Effects reported in long-term treatment include thrombocytopenia in infants. Fat overload syndrome An impaired ability of the patient to eliminate Alphalipid can lead to fat overload syndrome, which may be caused by overdose. This syndrome may appear during severe hypertriglyceridaemia, even at the recommended infusion rate, and in association with a sudden change in the patient s clinical condition, such as renal function impairment or infection. Fat overload syndrome is characterised by hyperlipidaemia, fever, fat infiltration, hepatomegaly, splenomegaly, anaemia, leukopenia, thrombocytopenia, coagulation disorder and coma. The symptoms are usually reversible if the treatment is discontinued. Transient changes in liver function have been noted in association with intravenous nutrition, but the cause is unknown. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reaction via the national reporting system listed in Appendix V*. 4.9 Overdose See section 4.8 under Fat overload syndrome. A marked overdose of fat emulsions containing triglycerides can result in metabolic acidosis, particularly if carbohydrates are not given concomitantly. 5. PHARMACOLOGICAL PROPERTIES 5.1 Pharmacodynamic properties Pharmacotherapeutic group: Solutions for parenteral nutrition, fat emulsions, ATC code: B05BA02. Alphalipid is a fat emulsion for intravenous use containing soya-bean oil emulsified with egg phospholipids. Particle size and biological properties are similar to those of natural chylomicrons. Unlike chylomicrons, Alphalipid does not contain cholesterol esters or apolipoproteins, while its phospholipid content is significantly higher. Page 4

5 5.2 Pharmacokinetic properties The fat particles in Alphalipid are in principle distributed and eliminated in the same way as natural chylomicrons. 5.3 Preclinical safety data Refined soya-bean oil emulsion for infusion has been used clinically for many years. Its safety is based on clinical experience. 6. PHARMACEUTICAL PARTICULARS 6.1 List of excipients purified egg yolk phospholipids glycerol sodium oleate sodium hydroxide water for injections 6.2 Incompatibilities This medicinal product must not be mixed with other medicinal products except those mentioned in section Shelf life Shelf life in the unopened bottle: 2 years Shelf life in the opened container: Because of the risk of microbial contamination the product should be used immediately. Any unused infusion should be discarded. Shelf life after compounding: Chemical and physical in-use stability has been demonstrated for 4 weeks at 25 C under light protection. From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 to 8 C, unless compounding has taken place in controlled and validated aseptic conditions. Do not freeze the compounded emulsion. 6.4 Special precautions for storage Do not freeze. For storage conditions after compounding, see section 6.3. Page 5

6 6.5 Nature and contents of container Type II glass bottle with 100 ml, 250 ml or 500 ml infusion, closed with a chlorobutyl rubber stopper sealed with an aluminium capsule. Pack sizes: Glass bottle: 20 x 100 ml 20 x 250 ml 10 x 500 ml Not all pack sizes may be marketed. 6.6 Special precautions for disposal and other handling Do not use the product if the package is damaged. Do not use if you notice phase separation of the emulsion. Compounding Alphalipid may be compounded with medicinal products containing amino acids, glucose and electrolyte solutions under aseptic conditions to produce Intradialytic Parenteral Nutrition (IDPN) and Total Parenteral Nutrition (TPN) admixtures. Medicinal products with the volume of 5 ml and more should be mixed with Alphalipid at once, using an automatic filling system. Volumes below 5 ml may be added separately to the pre-mixture. These processes should be executed under aseptic conditions (see section 6.3). The table below shows the highest concentration of components for which the chemical and physical stability has been demonstrated (see section 6.3): Components Soya-bean oil [g] (source: Alphalipid) Composition for Intradialytic Parenteral Nutrition per 100 ml Composition for Total Parenteral Nutrition per 100 ml Amino acids [g] Glucose [g] Overall omega 3-fatty acids [g] max max Omega 3-fatty acids from fish oil [g] (source: Omegaven) Omega 3-fatty acids from soya-bean oil [g] (source: Alphalipid) max max max max Electrolytes 0 Sodium [mmol] Page 6

7 Calcium [mmol] Magnesium [mmol] Zinc [µmol] Potassium [mmol] Chloride [mmol] Phosphate [mmol] Acetate [mmol] Citrate [mmol] Malate [mmol] Saccharate [mmol] Gluconate [mmol] Water for injections can be used to adjust the target concentrations of the corresponding components. 7. MARKETING AUTHORISATION HOLDER ALPHA PHARMACEUTICALS GmbH Hauptstraße 61 A D Wandlitz Germany 8. MARKETING AUTHORISATION NUMBER 9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 10. DATE OF REVISION OF THE TEXT Page 7