NUTRIFLEX PERI SOLUTION FOR INFUSION - summary of medicine characteristics

Summary of medicine characteristics - NUTRIFLEX PERI SOLUTION FOR INFUSION

SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Nutriflex peri 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		2.34 g	2.34 g		4.68 g	4.68 g
Leucine		3.13 g	3.13 g		6.26 g	6.26 g
Lysine hydrochloride (equivalent to lysine:)		2.84 g (2.27 g)	2.84 g (2.27 g)		5.68 g (4.54 g)	5.68 g (4.54 g)
Methionine		1.96 g	1.96 g		3.92 g	3.92 g
Phenylalanine		3.51 g	3.51 g		7.02 g	7.02 g
Threonine		1.82 g	1.82 g		3.64 g	3.64 g
Tryptophan		0.57 g	0.57 g		1.14 g	1.14 g
Valine		2.60 g	2.60 g		5.20 g	5.20 g
Arginine monoglutamate (equivalent to arginine:) (equivalent to glutamic acid:)		4.98 g (2.70 g) (2.28 g)	4.98 g (2.70 g) (2.28 g)		9.96 g (5.40 g) (4.56 g)	9.96 g (5.40 g) (4.56 g)
Histidine hydrochloride monohydrate (equivalent to histidine:)		1.69 g (1.25 g)	1.69 g (1.25 g)		3.38 g (2.50 g)	3.38 g (2.50 g)
Alanine		4.85 g	4.85 g		9.70 g	9.70 g
Aspartic acid		1.50 g	1.50 g		3.00 g	3.00 g
Glutamic acid		1.22 g	1.22 g		2.44 g	2.44 g
Glycine		1.65 g	1.65 g		3.30 g	3.30 g
Proline		3.40 g	3.40 g		6.80 g	6.80 g
Serine		3.00 g	3.00 g		6.00 g	6.00 g
Magnesium acetate tetrahydrate		0.86 g	0.86 g		1.72 g	1.72 g
Sodium acetate trihydrate		1.56 g	1.56 g		3.12 g	3.12 g
Potassium dihydrogen phosphate		0.78 g	0.78 g		1.56 g	1.56 g
Potassium hydroxide		0.52 g	0.52 g		1.04 g	1.04 g
Sodium hydroxide		0.50 g	0.50 g		1.00 g	1.00 g
Glucose monohydrate (equivalent to glucose:)	88.0 g (80.0 g)		88.0 g (80.0 g)	176.0 g (160.0 g)		176.0 g (160.0 g)
Sodium chloride	0.17 g		0.17 g	0.34 g		0.34 g
Calcium chloride dihydrate	0.37 g		0.37 g	0.74 g		0.74 g

Electrolytes:
Sodium	3.0 mmol	24.0 mmol	27.0 mmol	6.0 mmol	48.0 mmol	54.0 mmol
Potassium		15.0 mmol	15.0 mmol		30.0 mmol	30.0 mmol
Calcium	2.5 mmol		2.5 mmol	5.0 mmol		5.0 mmol
Magnesium		4.0 mmol	4.0 mmol		8.0 mmol	8.0 mmol
Chloride	8.0 mmol	23.6 mmol	31.6 mmol	16.0 mmol	47.2 mmol	63.2 mmol
Phosphate		5.7 mmol	5.7 mmol		11.4 mmol	11.4 mmol
Acetate		19.5 mmol	19.5 mmol		39.0 mmol	39.0 mmol

Amino acid content		40 g	40 g		80 g	80 g
Nitrogen content		5.7 g	5.7 g		11.4 g	11.4 g
Carbohydrate content	80 g		80 g	160 g		160 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)]	1340 (320)	2680 (640)
Total energy	[kJ (kcal)]	2010 (480)	4020 (960)
Osmolarity		900 mOsm/l	900 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.

Nutriflex peri is also indicated for peripheral administration in cases where a central venous catheter is contraindicated.

4.2 Posology and method of administration

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.

Posology

Adults

The daily dose is:

Up to 40 ml per kg body weight per day, corresponding to

– up to 1.6 g amino acids per kg body weight per day

– up to 3.2 g glucose per kg body weight per day

It is recommended that Nutriflex peri be administered continuously, if feasible.

The maximum infusion rate is:

Up to 2.0 ml per kg body weight per hour, corresponding to

– up to 0.08 g amino acids per kg body weight per hour

– up to 0.16 g glucose per kg body weight per hour

For a patient weighing 70 kg this corresponds to an infusion rate of 140 ml per hour. The amount of amino acids administered is then 5.6 g per hour and of glucose 11.2 g 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 peri 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 peri. 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.

Patients with renal/hepatic impairment

The doses should be adjusted individually in patients with hepatic or renal insufficiency (see also section 4.4). Nutriflex peri is contraindicated in severe hepatic insufficiency and severe renal insufficiency (see section 4.3).

Duration of use

Nutriflex peri should only be administered via a peripheral vein for a maximum of 10 days. When administered via central venous access, the duration of treatment for the indications stated is not limited. During long-term administration of Nutriflex peri 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. Suitable for infusion via peripheral veins.

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 peri 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 peri.

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.

As with all solutions containing carbohydrates the administration of Nutriflex peri 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.

Too rapid infusion can lead to fluid overload with pathological serum electrolyte concentrations, hyperhydration and pulmonary oedema.

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 peri 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 peri.

Nutriflex peri is a preparation of complex composition. If the product is mixed with other solutions or emulsions, compatibility must be ensured.

When Nutriflex peri is administered peripherally the state of the veins should be taken into account. It is recommended to change the site of venous access regularly. See section 4.8.

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 peri in pregnant women. Animal studies are insufficient with respect to reproductive toxicity (see section 5.3). Nutriflex peri should not be used during pregnancy unless the clinical condition of the woman requires treatment with parenteral nutrition.

Breast-feeding

Components/metabolites of Nutriflex peri 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 systemic effects with the components of Nutriflex peri 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 Common Uncommon Rare

Very rare Not known

(> 1/10)

(> 1/100 to < 1/10)

(> 1/1,000 to < 1/100)

(> 1/10,000 to < 1/1,000)

(< 1/10,000)

(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.

General disorders and administration site conditions

Not known:

After a few days, vein irritation, phlebitis or thrombophlebitis may occur.

Undesirable effects 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 peri, 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

Symptoms 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 peri 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 nonessential amino acids.

5.3 Preclinical safety data

Preclinical studies have not been performed with Nutriflex peri.

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 life

Unopened

2 years

After first opening the container

The product should be administered immediately after connecting to infusion set. Partially used containers must not be stored for later use.

After mixing of the contents

Ideally after mixing the two solutions, Nutriflex peri 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 peri 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

No special requirements are needed for disposal of container, overwrap and oxygen absorber.

The design of the dual chamber bag permits aseptic mixing of amino acids, glucose and optional fat in the lower chamber. The addition of further electrolytes is possible if required.

Immediately before use the internal peel seam between the two compartments must be opened allowing the respective contents to be aseptically mixed.

Remove the bag from its protective bag and proceed as follows:

– Open out the bag and lay on a solid surface

– Open the peel seam by using pressure with both hands

– Briefly mix the contents of the bag together

An additive port is provided for admixing of supplements to Nutriflex peri.

Only mixtures of known compatibility should be prepared. Information on compatibility of specified mixtures is available from the manufacturer.

When admixing other solutions or fat emulsions to Nutriflex peri, aseptic precautions must be strictly observed. Fat emulsions can be easily admixed by means of a special transfer set.

After infusion, any remaining solution should never be stored for later use. Only completely clear solutions from undamaged containers are to be used.

7 MARKETING AUTHORISATION HOLDER

B. Braun Melsungen AG

Carl-Braun-StraBe 1

34212 Melsungen

Germany

Postal address

B. Braun Melsungen AG 34209 Melsungen