NUTRYELT CONCENTRATE FOR SOLUTION FOR INFUSION - Summary of medicine characteristics

1. NAME OF THE MEDICINAL PRODUCT

NUTRYELT, concentrate for solution for infusion

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Composition of NUTRYELT expressed in quantities of salts per ampoule (10 ml) and per litre.

Content per ampoule of 10 ml

For a full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Concentrate for solution for infusion

Clear, limpid and slightly yellow solution.

Density              1.0

pH           2.6 to 3.2

Osmolality   60 to 100 mosm/kg

Osmolarity   60 to 100 mosm/l

4. CLINICAL PARTICULARS

4.1. Therapeutic indications

NUTRYELT is used as part of an intravenous nutrition regimen, to cover basal or moderately increased trace element requirements in parenteral nutrition.

NUTRYELT is indicated in adults only.

4.2. Posology and method of administration

Posology

For adults only.

The recommended daily dose in patients with basal to moderately increased requirements is one ampoule (10 ml) of NUTRYELT.

In cases of significantly increased trace element requirements (such as extensive burns, patients in severe hypercatabolic state due to major trauma) 2 ampoules (20 ml) of NUTRYELT may be given per day, and monitoring of serum trace element level is recommended.

In patients with renal, hepatic impairments or mild cholestasis the posology should be adapted (see section 4.4).

Paediatric population

NUTRYELT is contraindicated in children and adolescents (see section 4.3).

A specific paediatric product should be used for trace element supplementation in the paediatric population during parenteral nutrition.

Method of administration

NUTRYELT is not intended to be administered in its current presentation. It should be diluted according to the final desired osmolarity. The osmolarity value of the final preparation allows either administration through a peripheral vein, or only central venous catheter administration.

For incompatibilities and instructions for use see 6.2 and 6.6.

4.3. Contraindications

– Children and adolescents

– Pronounced cholestasis (serum bilirubin > 140 |imol/l)

– hypersensitivity to the active substances or to any of the excipients listed in section 6.1

– in cases of Wilson’s disease and hemochromatosis

if serum concentrations of any of the trace elements contained in NUTRYELT are elevated.

4.4. Special warnings and precautions for use

The solution should be used after an accurate control of the patient clinical and biological parameters. Blood manganese levels should be regularly monitored in case of prolonged artificial nutrition: dose reduction may be necessary or NUTRYELT infusion should be stopped if manganese levels rise into the potentially toxic range (please refer to appropriate reference ranges).

Particular attention must be paid when the product is given to patients with reduced biliary excretion, since it could interfere with the biliary elimination of manganese, copper and zinc, leading to accumulation and overdose.

NUTRYELT should be used with caution in patients with impaired renal function as excretion of some trace elements (selenium, fluoride, chromium, molybdenum and zinc) may be significantly decreased.

In patients with renal, hepatic impairments or mild cholestasis the posology should be adapted.

In patients undergoing medium to long-term parenteral nutrition, there is an increased occurence of iron, zinc and selenium deficiency. In such circumstances, when necessary, the dosage should be adapted with the use of an extra supply of solutions, which contain only these individual components.

For patients receiving repeated blood transfusions, a risk of iron overload can occur.

Parenterally administered iron preparations can cause hypersensitivity reactions including serious and potentially fatal anaphylactic/a­naphylactoid reactions. The risk is enhanced for patients with known allergies including drug allergies

Chromium deficiency leads to a decrease in glucose tolerance, which improves after chromium supplementation. As a consequence, in diabetic patients on insulin medication, relative overdose of insulin and consecutive hypoglycemia may occur. Therefore controls of the blood glucose levels are recommended and re-adjustment of the insulin doses may become necessary.

NUTRYELT should be given with caution in cases of manifest hyperthyroidism or sensitivity to iodine if other iodine containing medicinal products (e.g. iodine antiseptics) are administered concomitantly.

This product contains 0.052 mmol of sodium (1.2 mg) per dose, i.e. essentially “sodium free”. This product contains 0.001 mmol of potassium (0.039 mg) per dose, i.e. essentially “potassium-free”.

4.5. Interaction with other medicinal products and other forms of interaction

Combinations not recommended:

+ Iron salts (oral route):

Fainting or shock attributed to the rapid release of iron from its complex shape and transferrin saturation.

4.6. Fertility, pregnancy and lactation

Pregnancy

No safety data for NUTRYELT are available when it is administered during pregnancy. Therefore, NUTRYELT should not be used during pregnancy except after special consideration and if it is absolutely necessary.

Breast-feeding

No safety data for NUTRYELT are available when it is administered during lactation. Therefore, NUTRYELT should not be used during lactation except after special consideration and if it is absolutely necessary.

Fertility

No data available.

4.7. Effects on ability to drive and use machines

None stated.

4.8. Undesirable effects

The following adverse reaction(s) have been reported during post-marketing experience of trace elements solutions. The frequency is not known (cannot be estimated from the available data).

Cases of hypersensitivity reactions including fatal anaphylactic reactions have been reported in patients receiving IV iron-containing products.

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:

United Kingdom

Yellow Card Scheme

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

4.9. Overdose

If overdose is suspected, treatment with NUTRYELT should be withdrawn. Overdose should be confirmed by appropriate laboratory tests.

5. PHARMACOLOGICAL PROPERTIES

5.1. Pharmacodynamic properties

Pharmacotherapeutic group: Electrolyte solutions

ATC code: B05XA31

NUTRYELT is a balanced solution composed of nine essential trace elements, which are necessary to maintain the metabolic equilibrium.

Trace elements are normally derived from a balanced diet, but the need increases in cases of insufficient supply or abnormal loss, hypercatabolism (surgery, major trauma, burns), and in cases of poor absorption (short bowel disease or Crohn’s disease).

The composition of NUTRYELT is based on current International recommendations regarding the requirements for trace elements

During artificial nutrition, the supply of trace elements is necessary because a deficiency of any one of them can generate important metabolic and clinical disturbances.

5.2. Pharmacokinetic properties

The various pathways of trace element metabolism can be summarised as follows:

– Blood transport by proteins: albumin (Mn, Cu, Zn, Se), transferrin (Fe, Cr), ceruloplasmin (Cu), selenomethionine (Se), or non-protein carriers (F, I, Mo).

– Storage involving specific proteins: ferritin (Fe), thyroid hormones (I), selenoproteins (Se), or non-specific proteins: metallothioneins (Cu, Zn, Mn, Mo) or fluoroapatite (F).

– Elimination: The cationic trace elements (Fe, Cu, Mn, Zn) are eliminated mainly through biliary excretion. The anionic trace elements (I, F) and some oxygenated forms of minerals (Mo, Se, Cr) are primarily excreted in the urine.

Elimination through the lungs and the skin is possible.

5.3. Preclinical safety data

Since trace element solutions for intravenous injection are well-known products that have been used for medical purposes for many decades, no preclinical studies have been specifically performed with NUTRYELT.

6. PHARMACEUTICAL PARTICULARS

6.1. List of excipients

– Hydrochloric acid (for pH adjustment)

– Water for Injections

6.2. Incompatibilities

– NUTRYELT must not be used as a vehicle for other drugs.

– NUTRYELT, as with other trace element solutions, cannot be added directly to inorganic phosphate (additive) solutions.

– Degradation of ascorbic acid in parenteral nutrition mix is accelerated by trace elements This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.

6.3. Shelf life 3 years.

After dilution, chemical and physical in-use stability has been demonstrated for 48 h at 25°C protected from light.

From a microbiological point of view, the product should be used immediately after dilution. 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

Do not freeze

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

6.5. Nature and contents of container

10 ml solution in polypropylene ampoule in pack sizes of 4, 10, 25 and 50.

Not all pack sizes may be marketed

6.6. Special precautions

Before use, check that the concentrate for solution for infusion is homogeneous and that the bottle is not damaged and is free of particles.

NUTRYELT is not intended to be administered in its current presentation. NUTRYELT must be diluted or mixed with gentle agitation during preparation under strict aseptic conditions, before infusion.

NUTRYELT must be diluted with respect to the final appropriate osmolarity. For example:

– 10 to 20 ml of NUTRYELT can be diluted in at least 250 ml of Sodium Chloride 0.9 %

solution for infusion,

– 10 to 20 ml of NUTRYELT can be diluted in at least 250 ml of Glucose 5% solution for

infusion

The pH after reconstitution of 20 ml of NUTRYELT with 250 ml Sodium chloride 0.9% will be 3.3, or 3.3–3.4 with Glucose 5%.

The reconstituted solution for infusion has to be visually inspected prior to use. Only clear solution without particles should be used.

Do not store partly used containers and discard all equipment after use.

The compatibility with solutions administered simultaneously via a common inlet cannula must be ensured.

7. MARKETING AUTHORISATION HOLDER

LABORATOIRE AGUETTANT

1 rue Alexander Fleming

69007 LYON

FRANCE

8. MARKETING AUTHORISATION NUMBER(S)

PL 14434/0022

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

23/07/2014

10. DATE OF REVISION OF THE TEXT

08/2019

11.

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Composition of NUTRYELT expressed in quantities of salts per ampoule (10 ml) and per litre.

Content per ampoule of 10 ml

NUTRYELT Molar composition (jimol /10 ml)

NUTRYELT Weight composition (pg /10 ml)

For a full list of excipients, see section 6.1.

12. 3 PHARMACEUTICAL FORM

Concentrate for solution for infusion

Clear, limpid and slightly yellow solution.

Density        1.0

pH            2.6 to 3.2

Osmolality    60 to 100 mosm/kg

Osmolarity    60 to 100 mosm/l

13. 4 CLINICAL PARTICULARS

13.1. 4.1Thera­peutic indications

NUTRYELT is used as part of an intravenous nutrition regimen, to cover basal or moderately increased trace element requirements in parenteral nutrition.

NUTRYELT is indicated in adults only.

13.2. 4.2Posology and method of administration

Posology

For adults only.

The recommended daily dose in patients with basal to moderately increased requirements is one ampoule (10 ml) of NUTRYELT.

In cases of significantly increased trace element requirements (such as extensive burns, patients in severe hypercatabolic state due to major trauma) 2 ampoules (20 ml) of NUTRYELT may be given per day, and monitoring of serum trace element level is recommended.

In patients with renal, hepatic impairments or mild cholestasis the posology should be adapted (see section 4.4).

Paediatric population

NUTRYELT is contraindicated in children and adolescents (see section 4.3).

A specific paediatric product should be used for trace element supplementation in the paediatric population during parenteral nutrition.

Method of administration

NUTRYELT is not intended to be administered in its current presentation. It should be diluted according to the final desired osmolarity. The osmolarity value of the final preparation allows either administration through a peripheral vein, or only central venous catheter administration.

For incompatibilities and instructions for use see 6.2 and 6.6.

13.3. 4.3Contra­indications

– Children and adolescents

– Pronounced cholestasis (serum bilirubin > 140 |imol/l)

– hypersensitivity to the active substances or to any of the excipients listed in section 6.1 – in cases of Wilson’s disease and hemochromatosis

– if serum concentrations of any of the trace elements contained in NUTRYELT are elevated.

13.4. 4.4Special warnings and precautions for use

The solution should be used after an accurate control of the patient clinical and biological parameters. Blood manganese levels should be regularly monitored in case of prolonged artificial nutrition: dose reduction may be necessary or NUTRYELT infusion should be stopped if manganese levels rise into the potentially toxic range (please refer to appropriate reference ranges).

Particular attention must be paid when the product is given to patients with reduced biliary excretion, since it could interfere with the biliary elimination of manganese, copper and zinc, leading to accumulation and overdose.

NUTRYELT should be used with caution in patients with impaired renal function as excretion of some trace elements (selenium, fluoride, chromium, molybdenum and zinc) may be significantly decreased.

In patients with renal, hepatic impairments or mild cholestasis the posology should be adapted.

In patients undergoing medium to long-term parenteral nutrition, there is an increased occurence of iron, zinc and selenium deficiency. In such circumstances, when necessary, the dosage should be adapted with the use of an extra supply of solutions, which contain only these individual components.

For patients receiving repeated blood transfusions, a risk of iron overload can occur.

Parenterally administered iron preparations can cause hypersensitivity reactions including serious and potentially fatal anaphylactic/a­naphylactoid reactions. The risk is enhanced for patients with known allergies including drug allergies.

Chromium deficiency leads to a decrease in glucose tolerance, which improves after chromium supplementation. As a consequence in diabetic patients on insulin medication, relative overdose of insulin and consecutive hypoglycemia may occur. Therefore controls of the blood glucose levels are recommended and re-adjustment of the insulin doses may become necessary.

NUTRYELT should be given with caution in cases of manifest hyperthyroidism or sensitivity to iodine if other iodine containing medicinal products (e.g. iodine antiseptics) are administered concomitantly.

This product contains 0.052 mmol of sodium (1.2 mg) per dose, i.e. essentially “sodium free”. This product contains 0.001 mmol of potassium (0.039 mg) per dose, i.e. essentially “potassium-free”.

13.5. 4.5Inte­raction with other medicinal products and other forms of interaction

Combinations not recommended:

+ Iron salts (oral route):

Fainting or shock attributed to the rapid release of iron from its complex shape and transferrin saturation.

13.6. 4.6Fertility, pregnancy and lactation

Pregnancy

No safety data for NUTRYELT are available when it is administered during pregnancy. Therefore, NUTRYELT should not be used during pregnancy except after special consideration and if it is absolutely necessary.

Breast-feeding

No safety data for NUTRYELT are available when it is administered during lactation.

Therefore, NUTRYELT should not be used during lactation except after special consideration and if it is absolutely necessary.

Fertility

No data available.

13.7. 4.7Effects on ability to drive and use machines

None stated.

13.8. 4.8Unde­sirable effects

The following adverse reaction(s) have been reported during post-marketing experience of trace elements solutions. The frequency is not known (cannot be estimated from the available data).

Cases of hypersensitivity reactions including fatal anaphylactic reactions have been reported in patients receiving IV iron-containing products.

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:

United Kingdom

Yellow Card Scheme

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

13.9. 4.9Overdose

If overdose is suspected, treatment with NUTRYELT should be withdrawn. Overdose should be confirmed by appropriate laboratory tests.

14. 5 PHARMACOLOGICAL PROPERTIES

14.1. 5.1Phar­macodynamic properties

Pharmacotherapeutic group: Electrolyte solutions

ATC code: B05XA31

NUTRYELT is a balanced solution composed of nine essential trace elements, which are necessary to maintain the metabolic equilibrium.

Trace elements are normally derived from a balanced diet, but the need increases in cases of insufficient supply or abnormal loss, hypercatabolism (surgery, major trauma, burns), and in cases of poor absorption (short bowel disease or Crohn’s disease).

The composition of NUTRYELT is based on current International recommendations regarding the requirements for trace elements

During artificial nutrition, the supply of trace elements is necessary because a deficiency of any one of them can generate important metabolic and clinical disturbances.

14.2. 5.2Phar­macokinetic properties

The various pathways of trace element metabolism can be summarised as follows:

– Blood transport by proteins: albumin (Mn, Cu, Zn, Se), transferrin (Fe, Cr), ceruloplasmin (Cu), selenomethionine (Se), or non-protein carriers (F, I, Mo).

– Storage involving specific proteins: ferritin (Fe), thyroid hormones (I), selenoproteins (Se), or non-specific proteins: metallothioneins (Cu, Zn, Mn, Mo) or fluoroapatite (F).

– Elimination: The cationic trace elements (Fe, Cu, Mn, Zn) are eliminated mainly through biliary excretion. The anionic trace elements (I, F) and some oxygenated forms of minerals (Mo, Se, Cr) are primarily excreted in the urine.

Elimination through the lungs and the skin is possible.

14.3. 5.3Precli­nical safety data

Since trace element solutions for intravenous injection are well-known products that have been used for medical purposes for many decades, no preclinical studies have been specifically performed with NUTRYELT.

15. 6 PHARMACEUTICAL PARTICULARS

15.1. 6.1List of excipients

– Hydrochloric acid (for pH adjustment)

– Water for Injections

15.2. 6.2Incom­patibilities

– NUTRYELT must not be used as a vehicle for other drugs.

– NUTRYELT, as with other trace element solutions, cannot be added directly to inorganic phosphate (additive) solutions.

– Degradation of ascorbic acid in parenteral nutrition mix is accelerated by trace elements

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

15.3. 6.3Shelf life

3 years.

After dilution, chemical and physical in-use stability has been demonstrated for 48 h at 25°C protected from light.

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

15.4. 6.4Special precautions for storage

Do not freeze

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

21.5. Nature and contents of container

10 ml solution in polypropylene ampoule in pack sizes of 4, 10, 25 and 50.

Not all pack sizes may be marketed

21.6. 6.6Special precautions for disposal

Before use, check that the concentrate for solution for infusion is homogeneous and that the bottle is not damaged and is free of particles.

NUTRYELT is not intended to be administered in its current presentation. NUTRYELT must be diluted or mixed with gentle agitation during preparation under strict aseptic conditions, before infusion.

NUTRYELT must be diluted with respect to the final appropriate osmolarity. For example:

– 10 to 20 ml of NUTRYELT can be diluted in at least 250 ml of Sodium Chloride 0.9 %

solution for infusion,

– 10 to 20 ml of NUTRYELT can be diluted in at least 250 ml of Glucose 5% solution for

infusion

The pH after reconstitution of 20 ml of NUTRYELT with 250 ml Sodium chloride 0.9% will be 3.3 or 3.3–3.4 with Glucose 5%

The reconstituted solution for infusion has to be visually inspected prior to use. Only clear solution without particles should be used.

Do not store partly used containers and discard all equipment after use.

The compatibility with solutions administered simultaneously via a common inlet cannula must be ensured.

22. 7 MARKETING AUTHORISATION HOLDER

LABORATOIRE AGUETTANT

1 rue Alexander Fleming

69007 LYON

FRANCE

23. 8 MARKETING AUTHORISATION NUMBER(S)

PL 14434/0022

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

23/07/2014