Summary of medicine characteristics - NUTRIFLEX PLUS SOLUTION FOR INFUSION
1 NAME OF THE MEDICINAL PRODUCT
Nutriflex plus Solution for Infusion
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Amounts of active substances in both the 1000 ml and 2000 ml sizes of the product before and after mixing of the two chambers are given below.
| Composition | Before Lower Compartment 600 ml | Mixing Upper Compartment 400 ml | After Mixing 1000 ml | Before Lower Compartment 1200 ml | Mixing Upper Compartment 800 ml | After Mixing 2000 ml |
| Isoleucine | 2.82 g | 2.82 g | 5.64 g | 5.64 g | ||
| Leucine | 3.76 g | 3.76 g | 7.52 g | 7.52 g | ||
| Lysine hydrochloride (equivalent to lysine:) | 3.41 g (2.73 g) | 3.41 g (2.73 g) | 6.82 g (5.46 g) | 6.82 g (5.46 g) | ||
| Methionine | 2.35 g | 2.35 g | 4.70 g | 4.70 g | ||
| Phenylalanine | 4.21 g | 4.21 g | 8.42 g | 8.42 g | ||
| Threonine | 2.18 g | 2.18 g | 4.36 g | 4.36 g | ||
| Tryptophan | 0.68 g | 0.68 g | 1.36 g | 1.36 g | ||
| Valine | 3.12 g | 3.12 g | 6.24 g | 6.24 g | ||
| Arginine monoglutamate (equivalent to arginine:) (equivalent to glutamic acid:) | 5.98 g (3.24 g) (2.74 g) | 5.98 g (3.24 g) (2.74 g) | 11.96 g (6.48 g) (5.48 g) | 11.96 g (6.48 g) (5.48 g) | ||
| Histidine hydrochloride monohydrate (equivalent to histidine: ) | 2.03 g (1.50 g) | 2.03 g (1.50 g) | 4.06 g (3.00 g) | 4.06 g (3.00 g) | ||
| Alanine | 5.82 g | 5.82 g | 11.64 g | 11.64 g | ||
| Aspartic acid | 1.80 g | 1.80 g | 3.60 g | 3.60 g | ||
| Glutamic acid | 1.47 g | 1.47 g | 2.94 g | 2.94 g | ||
| Glycine | 1.98 g | 1.98 g | 3.96 g | 3.96 g | ||
| Proline | 4.08 g | 4.08 g | 8.16 g | 8.16 g | ||
| Serine | 3.60 g | 3.60 g | 7.20 g | 7.20 g | ||
| Magnesium acetate tetrahydrate | 1.23 g | 1.23 g | 2.46 g | 2.46 g | ||
| Sodium acetate trihydrate | 1.56 g | 1.56 g | 3.12 g | 3.12 g | ||
| Sodium dihydrogen phosphate dihydrate | 3.12 g | 3.12 g | 6.24 g | 6.24 g | ||
| Potassium hydroxide | 1.40 g | 1.40 g | 2.80 g | 2.80 g | ||
| Sodium hydroxide | 0.23 g | 0.23 g | 0.46 g | 0.46 g | ||
| Calcium chloride dihydrate | 0.53 g | 0.53 g | 1.06 g | 1.06 g | ||
| Glucose monohydrate (equivalent to glucose:) | 165.0 g (150.0 g) | 165.0 g (150.0 g) | 330.0 g (300.0 g) | 330.0 g (300.0 g) |
| Electrolytes: | ||||||
| Sodium | 37.2 mmol | 37.2 mmol | 74.4 mmol | 74.4 mmol | ||
| Potassium | 25.0 mmol | 25.0 mmol | 50.0 mmol | 50.0 mmol | ||
| Calcium | 3.6 mmol | 3.6 mmol | 7.2 mmol | 7.2 mmol | ||
| Magnesium | 5.7 mmol | 5.7 mmol | 11.4 mmol | 11.4 mmol | ||
| Chloride | 7.2 mmol | 28.3 mmol | 35.5 mmol | 14.4 mmol | 56.6 mmol | 71.0 mmol |
| Phosphate | 20.0 mmol | 20.0 mmol | 40.0 mmol | 40.0 mmol | ||
| Acetate | 22.9 mmol | 22.9 mmol | 45.8 mmol | 45.8 mmol |
I Amino acid content
48 g I 48 g II
96 g I 96 g
| Nitrogen content | 6.8 g | 6.8 g | 13.6 g | 13.6 g | ||
| Carbohydrate content | 150 g | 150 g | 300 g | 300 g |
Excipients
For a full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Solution for infusion
Infusion bag with two compartments
Amino acids and glucose solutions: clear, colourless or slightly yellowish aqueous solution
| 1000 ml | 2000 ml | |
| Non-protein energy [kJ (kcal)] | 2510 (600) | 5025(1200) |
| Total energy [kJ (kcal)] | 3310 (790) | 6615 (1580) |
| Osmolarity | 1400 mOsm/l | 1400 mOsm/l |
| pH | 4.8 – 6.0 | 4.8 – 6.0 |
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Supply of amino acids, energy, electrolytes and fluid in the parenteral nutrition of patients when oral or enteral nutrition is impossible, insufficient or contraindicated.
4.2 Posology and method of administration
Posology
The dosage and infusion rate have to be adjusted individually according to the patients’ requirements and clinical status. If necessary, additional fluid, amino acid, glucose or lipid infusions may be given. In special clinical settings, e.g. haemodialysis, higher infusion rates may have to be applied.
Adults
The daily dose is:
Up to 40 ml per kg body weight per day, corresponding to:
– up to 1.92 g amino acids per kg body weight per day
– up to 6.0 g glucose per kg body weight per day
It is recommended that Nutriflex plus be administered continuously, if feasible.
The maximum infusion rate is:
Up to 1.7 ml per kg body weight per hour, corresponding to:
– up to 0.082 g amino acids per kg body weight per hour – up to 0.26 g glucose per kg body weight per hour.
For a patient weighing 70 kg the maximum infusion rate is 119 ml per hour, corresponding to 5.7 g of amino acids and 17.85 g of glucose per hour.
Paediatric patients
On account of its composition the product should not be administered to neonates, infants and children under 2 years of age.
No clinical studies with Nutriflex plus have been performed in the paediatric population so the information below can be considered as general guidance.
The exact dosage should be adjusted individually according to age, body weight, developmental stage, prevailing disease and ability to metabolise constituents of Nutriflex plus. The calorie supply should be adapted individually according to the energy requirements during the respective growth period, and any additional nutrition given orally or enterally. If necessary, additional glucose or lipid infusions may be given.
Posology in special conditions
If the oxidative metabolisation of glucose is impaired, which may be the case in the post-operative or post-traumatic phase or in the presence of hypoxia or organ failure, glucose intake should be limited to 2 – 4 g of glucose per kg body weight per day. The blood glucose level should not exceed 6.1 mmol/l (110 mg/100 ml).
Patients with renal/hepatic impairment
The doses should be adjusted individually in patients with hepatic or renal insufficiency (see also section 4.4). Nutriflex plus is contraindicated in severe hepatic insufficiency and severe renal insufficiency (see section 4.3).
Duration of use
The duration of treatment for the indications stated is not limited. During long-term administration of Nutriflex plus it is necessary to provide for appropriate supply of additional energy (preferably in the form of lipids), essential fatty acids, trace elements and vitamins.
Method of administration
Intravenous use. For central venous infusion only.
The solution should always be brought to room temperature prior to infusion.
4.3 Contraindications
– Known hypersensitivity to any of the ingredients
– Congenital abnormalities of amino acid metabolism
– Unstable metabolism (e.g. decompensated diabetes mellitus, metabolic acidosis, cellular hypoxia)
– Hyperglycaemia not responding to insulin doses of up to 6 units insulin/hour
– Pathologically elevated serum electrolyte values
– Intracranial or intraspinal haemorrhage
– Unstable circulatory status with vital threat (states of collapse and shock)
– Acidosis
– Severe hepatic insufficiency
– Severe renal insufficiency (oliguria or anuria) without renal replacement therapy
– Decompensated cardiac insufficiency.
On account of its composition the product should not be administered to neonates, infants and children under 2 years of age.
4.4 Special warnings and precautions for use
Caution should be exercised in cases of increased serum osmolarity.
As for all large-volume infusion solutions Nutriflex plus should be administered with caution to patients with impaired cardiac or renal function.
Care should be exercised in the administration of parenteral nutrition solutions containing amino acids to patients with altered amino acid metabolism.
Disturbances of fluid and electrolyte metabolism (e.g. hypotonic dehydration, hyponatraemia, hypokalaemia) should be corrected prior to the administration of Nutriflex plus.
Solutions containing sodium salts should be used with caution in patients with sodium retention (see section 4.5).
In patients with renal insufficiency, the dose must be carefully adjusted according to individual needs, severity of organ insufficiency and the kind of instituted renal replacement therapy (haemodialysis, haemofiltration etc.).
Likewise in patients with insufficiencies of liver, adrenal glands, heart and lungs the dose must be carefully adjusted according to individual needs and the severity of organ insufficiency.
Too rapid infusion can lead to fluid overload with pathological serum electrolyte concentrations, hyperhydration and pulmonary oedema.
As with all solutions containing carbohydrates the administration of Nutriflex plus can lead to hyperglycaemia. The blood glucose level should be monitored. If there is hyperglycaemia the rate of infusion should be reduced or insulin should be administered.
To avoid occurrence of a re-feeding syndrome in malnourished or depleted patients (see section 4.8), parenteral nutrition should be built up gradually with great caution. Adequate substitution of potassium, magnesium and phosphate must be ensured.
Intravenous infusion of amino acids is accompanied by increased urinary excretion of the trace elements, especially copper and, in particular, zinc. This should be considered in the dosing of trace elements, especially during long-term intravenous nutrition.
Clinical monitoring should include fluid balance, serum electrolyte concentrations, acid-base balance, blood glucose, BUN. Hepatic function should be monitored as well. Frequency and kind of laboratory testing should be adapted to the overall condition of the patient.
Trace elements and vitamin levels should be assessed, particularly in the critically ill or those patients receiving prolonged nutrition, and supplementation may be required on an individual basis.
Substitution of additional energy in form of lipids may be necessary, as well an adequate supply of essential fatty acids, electrolytes, vitamins and trace elements. During long-term administration also blood cell counts and blood coagulation should be monitored carefully.
Abnormal results of liver function tests and cholestasis have been reported in some patients receiving total parenteral nutrition. However, this is generally related to overfeeding with glucose calories and to the administration of parenteral nutrition including lipid emulsions.
Nutriflex plus should not be given simultaneously with blood in the same infusion set due to the risk of pseudoagglutination.
As with all intravenous solutions strict aseptic precautions are necessary for the infusion of Nutriflex plus.
Nutriflex plus is a preparation of complex composition. If the product is mixed with other solutions or emulsions, compatibility must be ensured.
4.5 Interaction with other medicinal products and other forms of interaction
Corticosteroids and ACTH are associated with sodium and fluid retention.
Solutions containing potassium should be used with caution in patients receiving medicinal products that increase the serum potassium concentration, such as potassium sparing diuretics (triamterene, amiloride), ACE-inhibitors, cyclosporine and tacrolimus.
4.6 Fertility, pregnancy and lactation
Pregnancy
There are no or limited amount of data from the use of Nutriflex plus in pregnant women. Animal studies are insufficient with respect to reproductive toxicity (see section 5.3). Nutriflex plus should not be used during pregnancy unless the clinical condition of the woman requires treatment with parenteral nutrition.
Breast-feeding
Components/metabolites of Nutriflex plus are excreted in human milk, but at therapeutic doses no effects on the breastfed newborns/infants are anticipated.
Nevertheless, breast-feeding is not recommended for mothers on parenteral nutrition.
Fertility
No data available.
4.7 Effects on ability to drive and use machines
Not applicable
4.8 Undesirable effects
Undesirable effects with the components of Nutriflex plus are rare (> 1/10,000 to < 1/1,000) and usually related to inappropriate dosage and/or infusion rate. Those that do occur are usually reversible when therapy is discontinued.
Listing of undesirable effects
Undesirable effects are listed according to their frequencies as follows:
Very common (> 1/10)
Common (> 1/100 to < 1/10)
Uncommon (> 1/1,000 to < 1/100)
Rare (> 1/10,000 to < 1/1,000)
Very rare (< 1/10,000)
Not known (frequency cannot be estimated from the available data)
Metabolism and nutrition disorders
Not known: Parenteral nutrition in malnourished or depleted patients with full doses and infusion rates from the very beginning and without adequate substitution of potassium, magnesium and phosphate may lead to the re-feeding syndrome, characterised by hypokalaemia, hypophosphataemia and hypomagnesaemia. Clinical manifestations may develop within a few days of starting parenteral nutrition and may include haemolytic anaemia due to hypophosphataemia and somnolence. See also section 4.4.
Gastrointestinal disorders
Not known: Nausea or vomiting
Renal and urinary disorders
Not known: In the event of a rapid infusion osmotically induced polyuria might occur as a result of the high osmolarity.
If these side effects occur the infusion should be discontinued or, if appropriate, the infusion should be continued at a slower rate.
Undesirable effect after abruptly stopping administration
Not known: Abrupt discontinuation of high glucose infusion rates during parenteral nutrition may lead to hypoglycaemia, especially in children less than 3 years of age and in patients with disturbed glucose metabolism. When stopping administration of Nutriflex plus, it is recommended to taper the rate of infusion gradually.
Abnormal results of liver function tests and cholestasis have been reported in some patients receiving parenteral nutrition, particularly in those receiving lipid emulsions.
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 reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.
4.9 Overdose
4.9 OverdoseSymptoms of fluid and electrolyte overdose:
Hypertonic hyperhydration, electrolyte imbalances and pulmonary oedema.
Symptoms of amino acid overdose:
Renal amino acid losses with consecutive amino acid imbalances, metabolic acidosis, nausea, vomiting and shivering.
Symptoms of glucose overdose:
Hyperglycaemia, glucosuria, dehydration, hyperosmolality, hyperglycaemic -hyperosmolar coma.
Treatment
Immediate stop of infusion is indicated for overdose.
Further therapeutic measures depend on the particular symptoms and their severity. In severe cases peritoneal dialysis or haemodialysis should be used. When infusion is recommenced after the symptoms have declined it is recommended that the infusion rate be raised gradually with monitoring at frequent intervals.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Solutions for parenteral nutrition, combinations
ATC code: B05B A10
Parenteral nutrition must supply the body with all the components necessary for growth and tissue regeneration. The amino acids play a prominent role, being the building blocks for protein synthesis. However, in order to ensure optimal utilisation of the amino acids the administration of an energy source is required. This can be fulfilled partly in the form of carbohydrates. As glucose can be employed directly, it is the carbohydrate of choice. Additional energy, is ideally supplemented in the form of fat. Electrolytes are administered for the maintenance of metabolic and physiological functions.
5.2 Pharmacokinetic properties
Following intravenous infusion, the constituents of Nutriflex plus are immediately available for metabolism. Electrolytes are available in sufficient amounts to sustain the numerous biological processes that they are required for.
A portion of the amino acids is used for protein synthesis, the rest being broken down as follows: the amino groups are separated by transamination and the carbon moiety is either oxidised to CO2 in the citric acid cycle or utilised in the liver as a substrate for gluconeogenesis. The amino groups resulting from protein breakdown in muscle tissue are transported to the liver, where they are used to synthesise urea or non-essential amino acids.
Glucose is metabolized to CO2 and H2O. Some Glucose is utilized for lipid synthesis.
5.3 Preclinical safety data
5.3 Preclinical safety dataPreclinical studies have not been performed with Nutriflex plus.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Citric acid monohydrate
Water for injections
6.2 Incompatibilities
No additive or other component should be added to the medicinal product unless compatibility has been proven in advance. See also section 6.6.
6.3 Shelf lifeUnopened
2 years
The product should be administered immediately after connecting to infusion set. Partially used containers must not be stored for later use.
Ideally after mixing the two solutions, Nutriflex Plus should be administered immediately but it can in special circumstances be stored for up to 7 days at room temperature and up to 14 days if stored in a refrigerator (including administration time).
6.4 Special precautions for storage
Do not store above 25°C.
Keep bag in the outer carton in order to protect from light.
6.5 Nature and contents of container
Flexible plastic bag made of a dual-layer film consisting of polyamide (external layer) and polypropylene (internal layer). The container is divided into two compartments, separated by an internal peel seam, of either 400 ml and 600 ml or 800 ml and 1200 ml. Opening the peel seam results in an aseptic mixing of the two solutions.
Each bag is packed in a protective plastic bag.
Nutriflex Plus is supplied in two-chamber plastic bags containing:
– 1000 ml (400 ml of amino acids solution + 600 ml of glucose solution)
– 2000 ml (800 ml of amino acids solution + 1200 ml of glucose solution)
Pack sizes: 5 × 1000 ml, 5 × 2000 ml
Not all pack sizes may be marketed.
6.6 Special precautions for disposal
7 MARKETING AUTHORISATION HOLDER
8 MARKETING AUTHORISATION NUMBER(S)
PL 03551/0023
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THEAUTHORISATION
01/11/1995