SYNTHAMIN

The solution is for administration by intravenous infusion through a central venous catheter with the tip located in the central vena cava. The total daily dose of the solution depends upon the patient’s metabolic requirement and clinical response.

The determination of nitrogen balance and accurate daily body weights, corrected for fluid balance, are probably the best means of assessing individual nitrogen requirements. In addition to meeting nitrogen needs, the rate of administration is governed, especially during the first few days of therapy, by the patient’s ability to tolerate glucose.

Daily intake of amino acids, electrolytes and glucose should be increased gradually to the maximum required dose as indicated by frequent determination of urine and blood sugar levels. 2g/kg of body weight for infants to 56g of protein per day for adults weighing 70kg.

75 megajoules (180kcal) per gram of nitrogen. In the initial treatment of severe trauma or in the presence of marked malnutrition, higher doses of amino acids with correspondingly larger quantities of carbohydrate will be necessary to promote adequate patient response to therapy.

The degree of negative nitrogen balance being treated is the primary consideration in determining replacement therapy. 2). Fat emulsion co-administration should be considered when prolonged parenteral nutrition is required in order to prevent essential fatty acid deficiency (EFAD).

2). The osmolarity of a specific infusion solution must be taken into account when peripheral administration is considered. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration.

The flow rate should be increased gradually during the first hour. The flow rate must be adjusted taking into account the dose being administered, the daily volume intake, and the duration of the infusion. Use of a final filter is recommended during administration of all parenteral nutrition solutions.

Paediatric population In children, the dosage of parenteral nutrition should be individually tailored to the amino acid, electrolyte and energy requirements of the patient. 6).

The following adverse reactions have been reported in the post-marketing experience.

Other adverse reactions reported with parenteral amino acid products include:

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 *Including: skin, gastrointestinal and severe circulatory (shock) and respiratory manifestations **Includes the following manifestations: Pyrexia, Chills, Hypotension, Hypertension, Anthralgia, Myalgia, Urticaria, Rash, Pruritus, Erythema, Headache.

Other adverse reactions reported with parenteral amino acid products include: • Azotemia, Hyperammonemia Adverse reactions reported with parenteral nutrition to which the amino acid component may play a causal or contributory role include: • Hepatic failure, Hepatic cirrhosis, Hepatic fibrosis, Cholestasis, Hepatic steatosis, Blood bilirubin increased, Hepatic enzyme increased; Cholecystitis, Cholelithiasis • Infusion site thrombophlebitis; Venous irritation (infusion site phlebitis, pain, erythema, warmth, swelling, induration).

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. uk/yellowcard

WARNINGS

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. 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. 8). PRECAUTIONS Monitoring 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. 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 re-evaluated. 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 use There 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 […]

Synthamin is contraindicated in patients with: • Known hypersensitivity to any of the active substances or excipients, or to components of the container • Congenital abnormality of amino acid metabolism Synthamin must not be administered to patients with clinically significant elevation of plasma concentrations of sodium, potassium, magnesium, and/or phosphorus.