Omegaven

Each 100 mL of emulsion for infusion contains highly refined fish oil 10 g containing: Eicosapentaenoic acid (EPA) 1.25-2.82 g, docosahexaenoic acid (DHA) 1.44-3.09 g, dl-α-tocopherol (as antioxidant) 0.015-0.0296 g; glycerol 2.5 g; purified egg phosphatide 1.2 g.
Total Energy: 470 kJ/100 mL (112 kCal/100 mL); pH value: 7.5-8.7; titration acidity: <1 mmol HCl/L; osmolality: 308-376 mOsmol/kg.
Omegaven also contains the following excipients: Sodium oleate, sodium hydroxide and water for injections.

Pharmacotherapeutic Group: Emulsion for parenteral nutrition. ATC Code: B05BA.
Pharmacology: Pharmacodynamics: The long-chain omega-3 fatty acids in Omegaven are partly incorporated in plasma and tissue lipids. Docosahexaenoic acid is an important structural element in membrane phospholipids, while eicosapentaenoic acid is a precursor in the synthesis of a special class of eicosanoids (prostaglandins, thromboxanes, leukotrienes and other lipid mediators). Increased synthesis of these eicosapentaenoic acid-derived mediator substances may help promote antiaggregatory and anti-inflammatory effects, and is associated with immunomodulatory effects.
The glycerol contained in Omegaven is designed for use in energy production via glycolysis or is re-esterified together with free fatty acids in the liver to form triglycerides.
Omegaven also contains egg phospholipids, which are hydrolysed or incorporated into the cell membranes, where they are essential for the maintenance of membrane integrity.
Pharmacokinetics: The lipid particles infused with Omegaven are similar in size and elimination to physiological chylomicrons. In healthy male volunteers, a triglyceride half-life for Omegaven of 54 min has been calculated.

Parenteral nutrition supplementation with long chain omega-3-fatty acids, especially eicosapentaenoic acid and docosahexaenoic acid, when oral or enteral nutrition is impossible, insufficient or contraindicated.

Daily Dose: 1 mL up to maximum 2 mL/kg body weight (equivalent to fish oil 0.1 g up to maximum 0.2 g/kg body weight; equivalent to Omegaven 70 mL up to maximum 140 mL for a patient with a body weight of 70 kg).
Maximum Infusion Rate: The infusion rate should not exceed 0.5 mL/kg body weight/hr corresponding to  fish oil 0.05 g/kg body weight/hr.
The maximum infusion rate should be strictly adhered to, otherwise a severe increase in the serum triglyceride concentration can be observed.
Omegaven should be administered simultaneously with other fat emulsions. On the basis of a recommended total daily lipid intake of 1-2 g/kg body weight, the fish oil portion from Omegaven should constitute 10-20% of this intake.
Administration: For infusion via central or peripheral vein. Shake before use.
When Omegaven is to be administered with other infusion solutions (eg, amino acid or carbohydrate solutions) via a common infusion line (by-pass, y-tube), the compatibility of the solutions/emulsions used must be ensured.
Duration: The duration of administration should not exceed 4 weeks.

Overdose leading to fat overload syndrome may occur when the triglyceride level during lipid infusion rises >3 mmol/L, acutely, as a result of too rapid infusion rate or chronically at recommended rates of infusion in association with a change in the patient's clinical condition eg, renal function impairment or infection.
Overdosage may lead to side effects (see Adverse Reactions).
In these cases, the lipid infusion should be stopped or, if necessary, continued at a reduced dosage. The administration of fat also has to be stopped if a marked increase in blood glucose levels occur during infusion of Omegaven. A severe overdosage of Omegaven without simultaneous administration of a carbohydrate solution may lead to metabolic acidosis.

Severe haemorrhagic disorders.
Certain acute and life-threatening conditions eg, collapse and shock, recent cardiac infarction, stroke, embolism, undefined coma status.
Due to lack of experience, Omegaven should not be administered in patients with severe liver or renal insufficiency.
General Contraindications for Parenteral Nutrition: Hypokalaemia, hyperhydration, hypotonic dehydration, unstable metabolism, acidoses.
Omegaven should not be administered in patients known to be allergic to fish or egg protein.
Use in pregnancy & lactation: There is no evidence on the safety of Omegaven during pregnancy or breastfeeding. It should not be used during pregnancy and breastfeeding.
Use in children: Omegaven should not be used in premature infants, newborns, infants and children due to limited experience.

Omegaven should be given with caution to patients with an impaired lipid metabolism and uncontrolled diabetes mellitus.
The serum triglyceride level should be monitored daily. Monitoring of blood glucose profiles, acid base metabolism, serum electrolytes, fluid balance, blood count and bleeding time in patients treated with anticoagulants must be carried out regularly. The serum triglyceride concentration should not exceed 3 mmol/L during the infusion of fat emulsions.
Effects on the Ability to Drive or Operate Machinery: Not applicable.

There is no evidence on the safety of Omegaven during pregnancy or breastfeeding. It should not be used during pregnancy and breastfeeding.

The infusion of Omegaven can lead to a prolonged bleeding time and an inhibited platelet aggregation. In rare cases, patients may experience a fishy taste.
Adverse Reactions Observed During the Administration of Fat Emulsions: Slight increase in body temperature; heat and/or cold sensations; chills; flush or cyanosis; lack appetite, nausea, vomiting; dyspnoea; headache, pain in the chest, back and loins, bone pain; priapism (in very rare cases); increase or decrease in blood pressure; anaphylactic reactions (eg, erythema).
Possible signs of metabolic overload must be observed. The cause may be genetic (individually different metabolisms) and with respect to different previous illnesses with varying rapidity and following different  doses, but has been observed mainly with the use of cottonseed oil emulsions.
Metabolic Overload Might Give the Following Symptoms: Hepatomegaly with or without icterus; a change or reduction of some coagulation parameters (eg, bleeding time, coagulation time, prothrombin time, platelet count); splenomegaly; anaemia, leukopenia, thrombocytopenia; bleedings and tendency to bleed; pathological liver function tests; fever; hyperlipidaemia; headache, stomach pains, fatigue; hyperglycemia.
Should these adverse reactions occur or should the triglyceride level during lipid infusion rise >3 mmol/L, the lipid infusion should be stopped or, if necessary, continued at a reduced dosage.

The infusion of Omegaven can cause prolonged bleeding time and an inhibited platelet aggregation. Therefore, Omegaven should be administered with caution to patients requiring anticoagulant therapy even with regard to a possible reduction of anticoagulants.
Incompatibilities: Incompatibilities may occur through the addition of polyvalent cations eg, calcium, especially when combined with heparin.

Instructions for Use, Handling and Disposal: Containers should be shaken before use.
Use only if the emulsion is homogenous and the container is undamaged.
Non-phthalate-containing equipment should be used for administration wherever possible.
Any portions of contents as well as mixtures remaining after use should be discarded.
Omegaven may be aseptically mixed with fat emulsions as well as fat-soluble vitamins. When simultaneously administered with other fat emulsions admixed or diluted before administration, the fish oil portion from Omegaven should constitute 10-20% of the total daily lipid intake.

Do not store above 25°C. Do not freeze.
Shelf-Life: 18 months.
Shelf-Life After Dilution or Reconstitution According to Directions: Chemical and physical in-use stability of mixtures containing Omegaven has been demonstrated for 24 hrs at 25°C. From a microbiological point of view, mixtures with fat emulsions containing fat-soluble vitamins should be used immediately. If not used immediately, in-use storage time and conditions prior to use are the responsibility of the user. Only if compounding has taken place in controlled and validated aseptic conditions can storage conditions be based on the manufacturers stability data.
From a microbiological point of view, mixtures compounded in uncontrolled and unvalidated conditions should normally be used within 24 hrs, including the infusion time.
Shelf-Life After Opening the Container: Omegaven should be used with sterile transfer equipment immediately after opening. To be used immediately after breaking the vial seal.

Parenteral Nutritional Products

C10AX06 - omega-3-triglycerides incl. other esters and acids ; Belongs to the class of other lipid modifying agents.

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