SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Aminoplasmal 15% solution for infusion

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

1000 ml of solution contains

Isoleucine	5.85 g
Leucine	11.40 g
Lysine monohydrate	8.93 g
(equivalent to lysine)	(7.95 g)
Methionine	5.70 g
Phenylalanine	5.70 g
Threonine	5.40 g
Tryptophan	2.10 g
Valine	7.20 g
Arginine	16.05 g
Histidine	5.25 g
Alanine	22.35 g
Glycine	19.20 g
Aspartic acid	7.95 g
Acetylcysteine	0.50 g
(equivalent to cysteine)	(0.37 g)
Glutamic acid	16.20 g
Proline	7.35 g
Serine	3.00 g
Tyrosine	0.50 g
Amino acid content	150 g/l
Nitrogen content	24 g/l

Excipient with known effect:

This medicinal product contains 5.3mmol sodium per 1000 ml. For the full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Solution for infusion

Clear, colourless or faintly straw-coloured aqueous solution

Energy [kJ/l (kcal/l)]    2505 (600)

Theoretical osmolarity [mOsm/l]    1290

Titration acidity (to pH 7.4) [mmolNaOH/l] approx. 31 pH 5.7 - 6.3

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

Supply of amino acids for parenteral nutrition, when oral or enteral nutrition is impossible, insufficient or contraindicated.

Posology and method of administration

Posology

The dosage has to be adjusted according to the individual need of amino acids and fluid, depending on the clinical condition of the patient (nutritional status and/or degree of nitrogen catabolism due to underlying disease).

Adults Daily dose:

6.7    - 13.3ml/kg body weight —1.0 - 2.0g amino acids/kg body weight

=469 - 931ml for a 70kg patient

Maximum infusion rate:

0.67ml/kg body weight/h    = 0. lg amino acids/kg body weight/h

=0 78m1/min for a 70kg patient

Paediatric population

Aminoplasmal 15% is contraindicated in children under 2 years old (see section 4.3).

The dosages for the age group stated below are average values for guidance. The exact dosage should be adjusted individually according to age, developmental stage and prevailing disease.

Daily dose for children 2 to 17 years old:

6.7    - 13.3ml/kg body weight —1.0 - 2.0g amino acids/kg body weight Critically ill children:

For critically ill patients the advisable amino acid intake may be higher (up to 3.0g amino acids/kg body weight per day).

Maximum infusion rate:

0.67ml/kg body weight /h    = 0. lg amino acids/kg body weight /h

Patients with renal/hepatic impairment

The doses should be adjusted individually in patients with hepatic or renal insufficiency (see also section 4.4). Aminoplasmal 15% is contraindicated in severe hepatic insufficiency and severe renal insufficiency (see section 4.3).

Duration of use

This solution can be administered as long as parenteral nutrition is indicated.

Method of administration Intravenous use.

For central venous infusion only.

4.3 Contraindications

•    Hypersensitivity to the active substances or to any of the excipients listed in section 6.1.

•    Inborn errors of amino acid metabolism

•    Severe circulation disorders with vital risk (e.g. shock)

•    Hypoxia

•    Metabolic acidosis

•    Severe hepatic insufficiency

•    Severe renal insufficiency without treatment with haemofiltration or haemodialysis

•    Decompensated cardiac insufficiency

•    Acute pulmonary oedema

•    Hyperhydration

The medicinal product must not be administered to neonates, infants, and children under 2 years old, because the nutrient ratios do not properly meet the special paediatric requirements.

4.4 Special warnings and precautions for use

The medicinal product should only be administered after careful benefit-risk assessment in the presence of disorders of amino acid metabolism of other origin than stated under section 4.3.

Care should be exercised in the administration of large volume infusion fluids to patients with cardiac insufficiency.

Caution should be exercised in patients with increased serum osmolarity.

Disturbances of fluid and electrolyte balance (e.g. hypotonic dehydration, hyponatraemia, hypokalaemia) should be corrected prior to the administration of parenteral nutrition.

Serum electrolytes, blood glucose, fluid balance, acid-base balance and renal function should be monitored regularly.

Monitoring should also include serum protein and liver function tests.

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.).

In patients with hepatic insufficiency, the dose must be carefully adjusted according to individual needs and severity of organ insufficiency.

Amino acid solutions are only one component of parenteral nutrition. For complete parenteral nutrition, substrates for energy supply, essential fatty acids, electrolytes, vitamins, fluids and trace elements must be administered together with amino acids.

This medicinal product contains 5.3mmol sodium per 1000ml. To be taken into consideration in patients on a controlled sodium diet.

4.5 Interaction with other medicinal products and other forms of interaction

None known

4.6 Fertility, pregnancy and lactation

Pregnancy

There are no data from the use of Aminoplasmal 15% in pregnant women. No animal reproductive studies have been performed Aminoplasmal 15% (see section 5.3). The use of Aminoplasmal 15% may be considered during pregnancy, if necessary. Aminoplasmal 15% should only be given to pregnant women after careful consideration.

Breast-feeding

Amino acids/metabolites are excreted in human milk, but at therapeutic doses of Aminoplasmal 15% 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 relevant

4.8 Undesirable effects

If used according to the directions given, undesirable effects are not to be expected.

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 Yellow Card Scheme at: www.mhra.gov.uk/yellowcard

4.9 Overdose

Symptoms

Overdose or too high infusion rates may lead to intolerance reactions manifesting in the form of nausea, vomiting, shivering, headache, metabolic acidosis and renal amino acid losses.

Treatment

If intolerance reactions occur, the amino acid infusion should be interrupted temporarily and resumed later on at a lower infusion rate.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Solutions for parenteral nutrition, amino acids ATC-Code: B05B A01

Mechanism of action

The aim of parenteral nutrition is the supply of all nutrients necessary for the growth, maintenance and regeneration of body tissues etc.

Amino acids are of special importance as they partly are essential for protein synthesis. Intravenously administered amino acids are incorporated in the respective intravascular and intracellular amino acid pools. Both endogenous and exogenous amino acids serve as substrate for the synthesis of functional and structural proteins.

To prevent the metabolisation of amino acids for energy production, and also to fuel the other energy-consuming processes in the organism, simultaneous energy supply (in the form of carbohydrates or fats) is necessary.

5.2 Pharmacokinetic properties

Absorption

Because this medicinal product is infused intravenously, the bio-availability of the amino acids contained in the solution is 100%.

Distribution

Amino acids are incorporated in a variety of proteins in different tissues of the body. In addition each amino acid is present as free amino acid in the blood and inside cells.

The composition of the amino acid solution is based upon the results of clinical investigations of the metabolism of intravenously administered amino acids. The quantities of the amino acids contained in the solution have been chosen so that a homogenous increase of the concentrations of all plasma amino acids is achieved. The physiological ratios of plasma amino acids, i.e. the amino acid homeostasis, are thus maintained during infusion of the medicinal product. Normal foetal growth and development depend on a continuous supply of amino acids from the mother to the foetus. The placenta is responsible for the transfer of amino acids between the two circulations.

Biotransformation

Amino acids that do not enter protein synthesis are metabolised as follows: The amino group is separated from the carbon skeleton by transamination. The carbon chain is either oxidised directly to CO2 or utilised as substrate for gluconeogenesis in the liver. The amino group is also metabolised in the liver to urea.

Elimination

Only minor amounts of amino acids are excreted unchanged in the urine.

5.3 Preclinical safety data

Non-clinical studies have not been performed with Aminoplasmal 15%. The amino acids contained in Aminoplasmal 15% are substances which occur naturally in the organism.

No toxic reactions are expected to occur as long as the indications, contraindications and dosage recommendations are duly observed.

6    PHARMACEUTICAL PARTICULARS

6.1    List of excipients

Sodium hydroxide

Citric acid monohydrate (for pH-adjustment)

Water for injections

6.2    Incompatibilities

This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.

6.3    Shelf life

Unopened 3 years

After first opening

The medicinal product should be used immediately.

After admixture of additives

Chemical and physical in-use stability after mixture with other components of parenteral nutrition has been demonstrated for 7 days at 2-8°C plus 2 days at 25°C. Detailed information on tested components (e.g. glucose, lipids, electrolytes, trace elements, vitamins) and shelf life can be provided on demand by the manufacturer.

From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user.

6.4    Special precautions for storage

Keep the bottles in the outer carton in order to protect from light.

Do not freeze.

Cool storage of the undiluted solution, below 15°C, may lead to formation of crystals, that can, however, be easily dissolved by gentle warming at 25°C until dissolution is complete. Shake container gently to ensure homogeneity.

6.5    Nature and contents of container

Bottles of colourless glass (type II), sealed with halogen butyl rubber stoppers, containing 500ml or 1000ml of solution.

Pack sizes: 1 ^x 500ml, 10 ^x 500ml, 1 ^x 1000ml, 6 ^x 1000ml Not all pack sizes may be marketed.

6.6    Special precautions for disposal

No special requirements for disposal.

Containers are for single use only. Discard container and any unused content after use.

Only to be used if the solution is clear and colourless or faintly straw-coloured and the bottle and its closure are undamaged.

Use a sterile giving set for administration.

Aminoplasmal 15% should only be mixed with other iv solutions, if compatibility has been proven in advance. Compatibility data for different additives (e.g. glucose, lipids, electrolytes, trace elements, vitamins) and the corresponding shelf-life of such admixtures can be provided on demand by the manufacturer.

It is essential that any admixture be prepared using strict aseptic techniques as this nutrient mixture supports microbial growth.

7 MARKETING AUTHORISATION HOLDER

B. Braun Melsungen AG Carl-Braun-StraBe 1 34212 Melsungen Germany

Postal address B. Braun Melsungen AG 34209 Melsungen Germany

Phone: +49-5661-71-0 Fax: +49-5661-71-4567

8    MARKETING AUTHORISATION NUMBER(S)

PL 03551/0137

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

01/04/2014

DATE OF REVISION OF THE TEXT

24/10/2014