Aminoplasmal 10% Solution for Infusion

Supply of amino acids for parenteral nutrition, when oral or enteral nutrition is impossible, insufficient or contraindicated. For adults, adolescents and children over 2 years of age.

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:

Maximum infusion rate:

Paediatric population

Newborn infants, infants and toddlers less than two years of age

Aminoplasmal 10% is contraindicated in newborn infants, infants and toddlers less than 2 years of age (see section 4.3).

Children and adolescents 2 to 18 years old

The dosages for the age groups 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 less than 3 years old:

1.0 - 2.5 g amino acids/kg body weight ≙ 10 - 25 ml/kg body weight

Daily dose for children 3 to 18 years old:

1.0 - 2.0 g amino acids/kg body weight ≙ 10 - 20 ml/kg body weight

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

Maximum infusion rate:

0.1 g amino acids/kg body weight/h ≙ 1.0 ml/kg body weight/h

In the case of amino acid requirements of 1.0 g/kg body weight/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.

Patients with renal/hepatic impairment

The doses should be adjusted individually in patients with mild and moderate hepatic or renal insufficiency (see also section 4.4). When given during dialysis amino acid losses into the dialysate have to be considered.

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.

● 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 or decompensated liver cirrhosis with hepatic encephalopathy (grades III and IV)

● Severe renal insufficiency in absence of renal replacement therapy

● Decompensated cardiac insufficiency

● Acute pulmonary oedema

● Disturbances of the electrolyte and fluid balance

The medicinal product must not be administered to newborn infants, infants and toddlers less than two years of age, because the amino acid composition does not properly meet the special requirements of this paediatric age group.

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.

Renal impairment

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.). Amino acid losses due to the dialysis procedure had to be taken into consideration when adjusting the dose.

Hepatic impairment

In patients with mild and moderate hepatic insufficiency or decompensated liver cirrhosis with hepatic encephalopathy (grades I and II), 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 non-protein energy supply, essential fatty acids, electrolytes, vitamins, fluids and trace elements must be administered together with amino acids.

None known

Pregnancy

There are no data from the use of Aminoplasmal 10% in pregnant women. No animal reproductive studies have been performed with Aminoplasmal 10%. The use of Aminoplasmal 10% may be considered during pregnancy, if necessary. Aminoplasmal 10% 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 10% no effects on the breastfed newborns/infants are anticipated.

Nevertheless, breast-feeding is not recommended for mothers on parenteral nutrition.

Fertility

No data available.

Not relevant.

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.

Undesirable effects are listed according to their frequencies as follows:

Immune system disorders

Not known: Allergic reactions

Gastrointestinal disorders

Uncommon: Nausea, vomiting

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 Yellowcard scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Symptoms of fluid overdose

Overdose or too high infusion rates may lead to hyperhydration, electrolyte imbalance and pulmonary oedema.

Symptoms of amino acid overdose

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

Treatment

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

Pharmacotherapeutic group: Blood substitutes and perfusion solutions, i.v. 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 non-protein energy supply (in the form of carbohydrates or fats) is necessary.

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.

No non-clinical studies have been performed with Aminoplasmal 10%. The amino acids and electrolytes contained in Aminoplasmal 10% are substances which occur naturally in the organism.

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

Acetylcysteine

Citric acid monohydrate (for pH-adjustment)

Water for injections

This medicinal product must not be mixed with other medicinal products for which compatibility has not been documented. See section 6.6.

Unopened

3 years

After first opening

The medicinal product should be used immediately.

After admixture of additives

Do not refrigerate

Chemical and physical in-use stability has been demonstrated for 24 hours at 25 ^oC. From a microbiological point of view, unless the method of opening and mixing precludes the risk of microbial contamination, the product should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of the user.

Do not store above 25 °C.

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

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.

Do not freeze.

For storage conditions after mixing with additives, see section 6.3.

Bottles of colourless glass (type II), sealed with halogen butyl rubber stoppers, containing 250 ml, 500 ml or 1000 ml of solution.

Pack sizes: 10 × 250 ml, 10 × 500 ml, 6 × 1000 ml

Not all pack sizes may be marketed.

No special requirements for disposal.

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

The solution should only be used if the closure of the container is not damaged and if the solution is clear colourless to faintly straw-coloured, practically free from visible particles.

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, electrolytes 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.

- Glucose: physicochemical stability has been demonstrated for 24 hours at room temperature up to a total quantity of 158 g/l of glucose in the mixture.

- Electrolytes: physicochemical stability has been demonstrated for 24 hours at room temperature up to a total quantity of 32 mmol/l of sodium, 16 mmol/l potassium and 2 mmol/l of magnesium in the mixture.

- Lipids: physicochemical stability has been demonstrated for 24 hours at room temperature up to a total quantity of 50 g/l of lipid emulsion in the mixture.

- Trace elements and vitamins: stability has been demonstrated for 24 hours at room temperature with commercially available multi-trace elements and multi-vitamins (e.g. Tracutil, Cernevit) up to the standard dosage recommended by the respective manufacturer of the micronutrient.