This information is intended for use by health professionals
|L-LeucineL-IsoleucineL-Lysine (as hydrochloride salt)L-ValineL-PhenylalanineL-HistidineL-ThreonineL-MethionineL-TryptophanL-AlanineL-ArginineAmino acetic acidL-ProlineL-SerineL-Tyrosine||Ph. Eur.Ph. Eur.Ph. Eur.Ph. Eur.Ph. Eur.Ph. Eur.Ph. Eur.Ph. Eur.Ph. Eur.Ph. Eur.Ph. Eur.Ph. Eur.Ph. Eur.Ph. Eur.Ph. Eur.||0.730 w/v0.600% w/v0.580% w/v0.580% w/v0.560% w/v0.480% w/v0.420% w/v0.400% w/v0.180% w/v2.070% w/v1.150% w/v1.030% w/v0.680% w/v0.500% w/v0.040% w/v|
Paediatric populationIn children, the dosage of parenteral nutrition should be individually tailored to the amino acid, electrolyte and energy requirements of the patient. When used in neonates and children below 2 years, the solution (in containers and administration sets) should be protected from light exposure after admixture through administration (Section 4.4 and 6.6).
WARNINGSAnaphylactic/anaphylactoid reactions and other hypersensitivity/infusion reactions have been reported with Synthamin administered as a component of parenteral nutrition (see Section 4.8). The infusion must be stopped immediately if any signs or symptoms of a reaction develop. Pulmonary vascular precipitates causing pulmonary vascular emboli and pulmonary distress have been reported in patients receiving parenteral nutrition. In some cases, fatal outcomes have occurred. Excessive addition of calcium and phosphate increases the risk of the formation of calcium phosphate precipitates. Precipitates have been reported even in the absence of phosphate salt in the solution. Precipitation distal to the in-line filter and suspected in vivo precipitate formation has also been reported. Pulmonary vascular precipitates have also been reported with Synthamin (see Section 4.8). If signs of pulmonary distress occur, the infusion should be stopped and medical evaluation initiated. In addition to inspection of the solution, the infusion set and catheter should also periodically be checked for precipitates. Infection and sepsis may occur as a result of the use of intravenous catheters to administer parenteral formulations, poor maintenance of catheters or contaminated solutions. Immunosuppression and other factors such as hyperglycaemia, malnutrition and/or their underlying disease state may predispose patients to infectious complications. Careful symptomatic and laboratory monitoring for fever/chills, leukocytosis, technical complications with the access device, and hyperglycaemia can help recognize early infections.The occurrence of septic complications can be decreased with heightened emphasis on aseptic technique in catheter placement, maintenance, as well as aseptic technique in nutritional formula preparation. Refeeding severely undernourished patients may result in the refeeding syndrome that is characterized by the shift of potassium, phosphorus, and magnesium intracellularly as the patient becomes anabolic. Thiamine deficiency and fluid retention may also develop. Careful monitoring and slowly increasing nutrient intakes while avoiding overfeeding can prevent these complications. Hypertonic infusion solutions may cause irritation of the vein when administered into a peripheral vein (see Section 4.8).
PRECAUTIONSMonitoring should be appropriate to the patient's clinical situation and condition, and should include determinations of water and electrolyte balance, serum osmolarity, acid/base balance, blood glucose, liver and kidney function. Metabolic complications may occur if the nutrient intake is not adapted to the patient's requirements, or the metabolic capacity of any given dietary component is not accurately assessed. Adverse metabolic effects may arise from administration of inadequate or excessive nutrients or from inappropriate composition of an admixture for a particular patient's needs. Amino acid solutions should be used with caution in patients with preexisting liver disease or liver insufficiency. Liver function parameters should be closely monitored in these patients, and they should be monitored for possible symptoms of hyperammonemia (see below). Patients on parenteral nutrition may experience hepatic complications (including cholestasis, hepatic steatosis, fibrosis and cirrhosis, possibly leading to hepatic failure, as well as cholecystitis and cholelithiasis) and should be monitored accordingly. The etiology of these disorders is thought to be multifactorial and may differ between patients. Patients developing abnormal laboratory parameters or other signs of hepatobiliary disorders should be assessed by a clinician knowledgeable in liver diseases in order to identify possible causative and contributory factors, and possible therapeutic and prophylactic interventions.Increase in blood ammonia levels and hyperammonemia may occur in patients receiving amino acid solutions. In some patients this may indicate the presence of a congenital disorder of amino acid metabolism (see Section 4.3) or hepatic insufficiency. Blood ammonia should be measured frequently in newborns and infants to detect hyperammonemia, which may indicate the presence of a congenital abnormality of amino acid metabolism. Depending on extent and etiology, hyperammonemia may require immediate intervention. Should symptoms of hyperammonemia develop, administration should be discontinued and the patient's clinical status reevaluated.Azotemia has been reported with parenteral administration of solutions containing amino acids, and may occur in particular in the presence of renal impairment. Use with caution in patients with pulmonary oedema or heart failure. Fluid status should be closely monitored. Use with caution in patients with renal insufficiency. Fluid and electrolyte status should be closely monitored in these patients. Severe water and electrolyte disorders, severe fluid overload states, and severe metabolic disorders should be corrected before starting the infusion. Mixtures containing amino acids may precipitate acute folate deficiency and folic acid should be administered daily.It is essential to provide an adequate source of non-protein energy concurrently if parenterally administered amino acids are to be retained by the body and utilised for protein synthesis. Concentrated glucose solutions are an effective source of such energy.The infusion of Synthamin with highly concentrated glucose solutions may result in hyperglycaemia, glycosuria and hyperosmolar syndrome. Blood and urine glucose should be monitored on a routine basis in patients receiving this treatment.
Paediatric useThere have been no studies performed by Baxter Healthcare Corporation in the paediatric population. See above regarding monitoring for hyperammonemia in paediatric patients. 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, Synthamin should be protected from ambient light until administration is completed (see sections 4.2, 6.3 and 6.6).
Geriatric useIn general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or drug therapy.
Tabulated list of adverse reactions
|System Organ Class||Preferred MedDRA Term||Frequency|
Immune system disorders
|Anaphylactic/anaphylactoid reactions* Hypersensitivity**||Not known Not known|
|Vascular disorders||Pulmonary vascular precipitate||Not known|
Reporting of suspected adverse reactionsReporting 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 reactions via the Yellow Card Scheme at: Website: www.mhra.gov.uk/yellowcard
|Water for InjectionsGlacial Acetic AcidSodium Acetate||Ph. Eur.Ph. Eur.Ph. Eur.||QS to 100%QS (for pH adjustment)QS (for pH adjustment)|
To openDo not remove from overpouch until ready to use. Remove the protective overpouch. Check bag for leaks.
If additions to the bag are madeAseptic conditions must be observed. Ensure stability and compatibility of additives. Prepare the injection site of the bag. Puncture the injection site and inject the additives using an injection needle or a reconstitution device.Mix content of the bag and the additives thoroughly. Inspect final solution for discoloration and particulate matter. Check bag for leaks. Ensure proper storage requirements of additives are followed.
Administration of the infusionDo not be administered simultaneously with, before or after an administration of blood through the same infusion equipment, because of the possibility of pseudo-agglutination. Do not connect bags in series in order to avoid air embolism due to possible residual air contained in the primary bag. For single use only. Discard all equipment after use. Discard any unused portion. Do not reconnect partially used bags.
When used in neonates and children below 2 years, protect from light exposure, until administration is completed. Exposure of Synthamin to ambient light, especially after admixture with trace elements and/ or vitamins, generates peroxides and other degradation products that can be reduced by protection from light exposure (see sections 4.2, 4.4 and 6.3).