Allergic Reactions / Hypersensitivity Reactions
Anaphylactic/anaphylactoid reactions and other hypersensitivity/infusion reactions have been reported with amino acid solutions 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.
Precipitates in Patients Receiving Parenteral Nutrition
Pulmonary vascular precipitates 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.
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.
Infectious complications
Infection and sepsis may occur as a result of intravenous catheters used 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 Syndrome in Patients Receiving Parenteral Nutrition
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 solutions
Hypertonic infusion solutions may cause irritation of the vein, vein damage, and thrombosis when administered into a peripheral vein (see section 4.8).
In view of its osmolality, Primene 10% should not be infused alone into a peripheral vein.
General Monitoring
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 levels, blood ammonia levels, and liver and kidney function.
Metabolic Effects
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.
Hepatic function
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.
Amino acid solutions should be used with caution in patients with pre-existing liver disease or liver insufficiency.
Liver function parameters should be closely monitored in these patients, and they should be monitored for possible symptoms of hyperammonaemia.
Increase in blood ammonia levels and hyperammonaemia 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 hyperammonaemia.
Depending on extent and etiology, hyperammonaemia may require immediate intervention.
Renal effects
Azotaemia 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 renal insufficiency (with e.g., uraemia). Nitrogen tolerance may be altered and dosage may have to be adjusted. Fluid and electrolyte status should be closely monitored in these patients.
Additional precautions
• Light exposure of solutions for intravenous parenteral nutrition, especially after admixture with trace elements and/or vitamins, may have adverse effects on clinical outcomes in neonates, due to the generation of peroxides and other degradation products. When used in neonates and children below 2 years of age, Primene should be protected from ambient light until administration is completed (see sections 4.2, 6.3, and 6.6).
• Infusion site reactions have occurred with the use of parenteral nutrition. They include infusion site thrombophlebitis and venous irritation, as well as severe reactions (with, e.g., necrosis and blistering) when associated with extravasation. See section 4.8. Patients should be monitored accordingly.
• Severe water and electrolyte disorders, severe fluid overload states, and severe metabolic disorders should be corrected before starting the infusion.
• Use with caution in patients with pulmonary oedema or heart failure. Fluid status should be closely monitored.