SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Aminoplasmal 5% solution for infusion

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

The solution for infusion contains:

Amino acids:	per 1 ml	per 250 ml	per 500 ml	per 1000 ml
Isoleucine	2.50 mg	0.63 g	1.25 g	2.50 g
Leucine	4.45 mg	1.11 g	2.23 g	4.45 g
Lysine hydrochloride	4.28 mg	1.07 g	2.14 g	4.28 g
(equivalent to lysine)	(3.43 mg)	(0.86 g)	(172 g)	(3.43 g)
Methionine	2.20 mg	0.55 g	1.10 g	2.20 g
Phenylalanine	2.35 mg	0.59 g	1.18 g	2.35 g
Threonine	2.10 mg	0.53 g	1.05 g	2.10 g
Tryptophan	0.80 mg	0.20 g	0.40 g	0.80 g
Valine	3.10 mg	0.78 g	1.55 g	3.10 g
Arginine	5.75 mg	1.44 g	2.88 g	5.75 g
Histidine	1.50 mg	0.38 g	0.75 g	1.50 g
Alanine	5.25 mg	1.31 g	2.63 g	5.25 g
Glycine	6.00 mg	1.50 g	3.00 g	6.00 g
Aspartic acid	2.80 mg	0.70 g	1.40 g	2.80 g
Glutamic acid	3.60 mg	0.90 g	1.80 g	3.60 g
Proline	2.75 mg	0.69 g	1.38 g	2.75 g
Serine	1.15 mg	0.29 g	0.58 g	1.15 g
Tyrosine	0.40 mg	0.10 g	0.20 g	0.40 g
Electrolytes:
Sodium acetate trihydrate	1.361 mg	0.340 g	0.681 g	1.361 g
Sodium chloride	0.964 mg	0.241 g	0.482 g	0.964 g
Sodium hydroxide	0.140 mg	0.035 g	0.070 g	0.140 g
Potassium acetate	2.453 mg	0.613 g	1.227 g	2.453 g
Magnesium chloride hexahydrate	0.508 mg	0.127 g	0.254 g	0.508 g
Disodium phosphate dodecahydrate	3.581 mg	0.895 g	1.791 g	3.581 g

Theoretical osmolarity:    592 mOsm/l

Titration acidity (to pH 7.4): approx. 17 mmol/l pH:    5.7 - 6.3

Sodium    50

Potassium    25

Magnesium    2.5

Acetate    35

Chloride    45

Phosphate    10

Citrate    2.0

For the full list of excipients, see section 6.1.

3    PHARMACEUTICAL FORM

Solution for infusion

Clear, colourless up to faintly straw-coloured solution

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

Supply of amino acids and a limited amount of electrolytes for parenteral nutrition, when oral or enteral nutrition is impossible, insufficient or contra-indicated. For adults, adolescents and children over 2 years of age.

In parenteral nutrition, amino acid infusions should always be combined with adequate calorie supply, e.g. in the form of carbohydrate infusions.

4.2    Posology and method of administration

Posology

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

Adults and adolescents from 14 to 17 years:

Average daily dose:

20 - 40 ml/kg body weight (BW) = 1.0 - 2.0 g amino acids/kg BW

= 1400 - 2800 ml for a 70 kg patient

Maximum daily dose:

40 ml/kg BW    = 2.0 g amino acids/kg BW

= 140 g amino acids for a 70 kg patient = 2800 ml for a 70 kg patient

Maximum infusion and drop rates, respectively:

2 ml/kg BW/h    = 0.1 g amino acids/kg BW/h

= 45 drops/min for a 70 kg patient = 2.34 ml/min for a 70 kg patient

Children and adolescents 2 to 13 years:

The dosages for this age group as 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 from 2 to 4 years:

30 ml/kg BW    = 1.5 g amino acids/kg BW

Daily dose for children from 5 to 13 years:

20 ml/kg BW    = 1.0 g amino acids/kg BW

Maximum infusion rate:

2 ml/kg BW/h    = 0.1 g amino acids/kg BW/h

In the case of amino acid requirements of 1 g/kg BW/day or more, particular attention should be paid to the limitations of fluid input. To avoid fluid overload, amino acid solutions with higher amino acid content may have to be used in such situations.

Duration of use

It can be administered as long as there is an indication for parenteral nutrition.

Method of administration

Intravenous use.

Aminoplasmal 5% is only one component of parenteral nutrition. In parenteral nutrition, amino acid supply must be combined with supply of calorie sources, essential fatty acids, electrolytes, vitamins, and trace elements.

4.3    Contraindications

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

•    Congenital abnormalities of amino acid metabolism

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

•    Hypoxia

•    Metabolic acidosis

•    Advanced liver disease

•    Severe renal insufficiency without access to haemofiltration or haemodialysis

•    High and pathological plasma concentration of one of the electrolytes included in the product

•    Children under 2 years of age because the nutrient ratios do not properly meet the special paediatric requirements

•    General contraindications of infusion therapy:

-    uncompensated cardiac insufficiency

-    acute pulmonary oedema

-    hyperhydration

4.4    Special warnings and precautions for use

Aminoplasmal 5% 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.

In patients with liver or renal insufficiency, the dose must be adjusted according to individual requirements.

Caution should be exercised in patients with increased serum osmolarity.

Electrolyte and fluid imbalances such as hypotonic dehydration and hyponatraemia should be corrected by adequate supply of fluid and electrolytes prior to parenteral nutrition.

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

Monitoring should also include serum protein and liver function tests.

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

Aminoplasmal 5% is applicable as part of a total parenteral nutrition regimen in combination with adequate amounts of energy supplements (carbohydrate solutions, fat emulsions), vitamins, trace elements and electrolytes.

If Aminoplasmal 5% is administered in combination with other nutrient solutions, the possibility of peripheral venous infusion depends on the osmolarity of the resulting mixture.

The site of infusion should be checked daily for signs of inflammation or infection.

4.5    Interaction with other medicinal products and other forms of interaction

None known

4.6    Fertility, pregnancy and lactation

Studies in pregnant or breast-feeding women have not been conducted with this medicinal product. There are no pre-clinical data regarding the administration of Aminoplasmal 5% during pregnancy. Aminoplasmal 5% should therefore be

administered with caution during pregnancy and lactation and only if deemed clearly indicated after assessment of its benefits and possible risks.

4.7    Effects on ability to drive and use machines

Not applicable

4.8    Undesirable effects

Undesirable effects that, however, are not specifically related to the product but to parenteral nutrition in general may occur, especially at the beginning of parenteral nutrition.

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)

Immune system disorders Not known: Allergic reactions

Gastrointestinal disorders

Uncommon: Nausea, vomiting

General disorders and administration site conditions

Uncommon: Headache, shivering, fever

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 via the MHRA 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 shivering, nausea, vomiting, 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

5.1    Pharmacodynamic properties

Pharmacotherapeutic group: Blood substitutes and perfusion solutions, i.v. solutions, solutions for parenteral nutrition, ATC code B05BA10.

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 carbohydrate or fat) is necessary.

Electrolytes administered with parenteral nutrition help to maintain the serum levels necessary for the physiological processes of the cell, for which tightly regulated electrolyte levels are prerequisite. In addition to this, combination of these electrolytes with amino acids is advantageous, as the homeostasis of each both, amino acids and electrolytes, is interdependent.

5.2    Pharmacokinetic properties

Because Aminoplasmal 5% is infused intravenously, the bio-availability of the amino acids and electrolytes contained in the solution is 100%.

The composition of Aminoplasmal 5% is based upon the results of clinical investigations of the metabolism of intravenously administered amino acids. The quantities of the amino acids contained in Aminoplasmal 5% have been chosen so that a homogenous increase of the concentrations of all plasma amino acids is achieved. The physiological relations of plasma amino acids, i. e. the amino acid homeostasis is thus maintained during infusion of Aminoplasmal 5%.

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

5.3    Preclinical safety data

Preclinical studies have not been performed with this medicinal product.

Aminoplasmal 5% only contains amino acids and electrolytes that are substrates of human metabolism.

Therefore, 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

Acetylcysteine

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

Shelf life in the unopened container 3 years

Shelf life after first opening the container

The medicinal product should be used immediately.

Shelf life after mixing with other components

From the microbiological point of view, mixtures should be administered immediately after preparation. If not administered immediately, storage times and conditions of mixtures prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 °C - 8 °C, unless mixing has taken place under controlled and validated aseptic conditions.

6.4    Special precautions for storage

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

Do not freeze.

Cool storage of the 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 chlorobutyl-rubber stoppers.

Contents: 250 ml, available in packs of 10 bottles 500 ml, available in packs of 10 bottles 1000 ml, available in packs of 6 bottles

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 any unused contents remaining after the end of the infusion.

The solution should only be used if the closure of the container is not damaged and if the solution is clear.

Use a sterile giving set for administration.

If in the setting of complete parenteral nutrition it is necessary to add other nutrients such as carbohydrates, lipids, vitamins and trace elements to this medicinal product, admixing must be performed under strict aseptic conditions. Mix well after admixture of any additive. Pay special attention to compatibility.

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:    +49-5661-4567

8    MARKETING AUTHORISATION NUMBER(S)

PL 03551/0103

DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

22/10/2009 10 DATE OF REVISION OF THE TEXT

September/2014