Additrace® concentrate for solution for infusion – Summary of Product Characteristics (SmPC) for healthcare professionals

1. NAME OF THE MEDICINAL PRODUCT

Additrace^® concentrate for solution for infusion

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each ampoule contains 10ml of concentrate.

Each 1ml of Additrace concentrate contains;

Chromic chloride 6 H2O 5.33 microgram Copper chloride 2 H2O 340 microgram Ferric chloride 6 H2O 540 microgram Manganese chloride 4 H2O 99 microgram Potassium iodide 16.6 microgram Sodium fluoride 210 microgram Sodium molybdate 2 H2O 4.85 microgram Sodium selenite anhydrous 6.90 microgram Zinc chloride 1.36 milligram

The active ingredients in 1 ml of Additrace correspond to:

Cr ³⁺ 0.02 micromol

Cu ²⁺ 2 micromol

Fe ³⁺ 2 micromol

Mn ²⁺ 0.5 micromol

I ^- 0.1 micromol

F ^- 5 micromol

Mo ⁶⁺ 0.02 micromol

Se ⁴⁺ 0.04 micromol

Zn ²⁺ 10 micromol

The content of sodium and potassium correspond to;

Sodium 118 microgram 5.12 micromol Potassium 3.9 microgram 0.1 micromol

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Concentrate for solution for infusion.

A clear, almost colourless, sterile solution.

• Osmolality: approx. 3100 mosm/kg water
• pH: 2.3 – 2.8

4. CLINICAL PARTICULARS

4.1 Therapeutic Indications

Additrace is used as part of a complete intravenous nutrition regimen providing a source of trace elements for adults and children over 40kg.

4.2 Posology and method of administration

Posology

Adults

One 10ml ampoule of Additrace is added to either 500ml or 1000ml of one of the following solutions:

Vamin 9 Glucose, Vamin 14, Vamin 14 Electrolyte-Free, Vamin 18 Electrolyte-Free, Glucose 5%-50%.

Where higher amounts of trace elements are considered necessary, two ampoules of Additrace may be added to 1000ml of solution.

Elderly

No adjustment of the adult dosage is required.

Paediatric Population

Additrace is contraindicated in infants and children under 40kg body-weight. For infants and children under 40kg, the trace-element solution Peditrace^® should be used.

Method of administration

Intravenous infusion after dilution.

Additrace must not be given undiluted. For instructions on dilution of the medicinal product before administration, see section 6.6.

4.3 Contraindications

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

4.4 Special warnings and precautions for use

Care should be taken in the administration of Additrace to patients with impaired liver function (especially cholestasis). Manganese toxicity is more likely to occur in patients with impaired liver function and cholestasis as manganese is almost entirely dependent on the biliary route for excretion. Manganese blood levels and liver function should be monitored regularly (monthly) in such patients. Additrace should be stopped if manganese levels rise to the potentially toxic range. (Please refer to appropriate reference ranges for the testing laboratory.)

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

4.5 Interaction with other medicinal products and other forms of interaction

None known.

4.6 Fertility, pregnancy and lactation

Additrace is a solution of trace elements indicated as a supplement in total parenteral nutrition (TPN) regimens and contains the elements: Fe3+, Zn2+, Mn2+, Cu2+, Cr3+, Se4+, Mo6+, F-, I- in amounts not exceeding the recommended daily requirements where these exist. No hazard is expected if used in pregnancy at the recommended dosage.

No animal studies have been performed. There are, however, published reports on safe and successful use of trace elements as part of a TPN regimen during pregnancy in the human.

4.7 Effects on ability to drive and use machines

Additrace has no or negligible influence on the ability to drive and use machines.

4.8 Undesirable effects.

There have been no reported undesirable effects observed during the administration of Additrace

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

In general, overdosage with Additrace is extremely unlikely as the quantity of trace elements per ampoule lies well below known toxic levels of administration.

Chronic overdosage may very rarely occur secondary to an unsuspected idiosyncratic deficiency in metabolism or excretion of a trace element. In this case, signs, such as nail dystrophy and insidious onset of symptoms secondary to haematological changes or tissue deposition, may be observed. Diagnosis would be confirmed by biochemical or haematological tests and treatment with Additrace should be withdrawn.

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: concentrate for solution for infusion.

ATC code: B05X A31

Additrace is a mixture of trace elements in amounts normally absorbed from the oral diet and should have no pharmacodynamic effect besides maintaining or repleting the nutritional status.

5.2 Pharmacokinetic properties

When infused intravenously, the trace elements in Additrace are handled in a similar way to trace elements from an oral diet. Individual trace elements will be taken up by tissues to different extents, depending on the requirements within each tissue to maintain or restore the concentration of each element for the metabolic requirements of that tissue.

Copper and manganese are normally excreted via the bile, whereas selenium, zinc and chromium (especially in patients receiving intravenous nutrition) are mainly excreted via the urine.

The main route of molybdenum excretion is the urine, although small amounts are excreted in the bile.

Iron is eliminated in small amounts by superficial loss and desquamation of gut cells. Premenopausal women can lose 30-150 mg of iron in the monthly blood loss. Iron excretion follows all kinds of bleedings.

5.3. Preclinical Safety Data

There are no pre-clinical data of relevance to the prescriber, which are additional to that already included in other sections of this Summary of Product Characteristics.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Xylitol,

Hydrochloric acid 1 M (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 dilution: The addition of Additace should be performed aseptically immediately before the start of the infusion and should be used within 24 hours (Chemical and physical in-use stability after dilution has been demonstrated for 24 hours at 25°C). If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2-8°C, unless mixing has taken place in controlled and validated aseptic conditions. See section 4.2.

6.4 Special precautions for storage

Store below 25°C. Do not freeze.

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

For storage conditions after dilution of the medicinal product, see section 6.3.

6.5 Nature and contents of container

Polypropylene ampoules, 10ml: Packs of 20

Clear glass ampoules, 10ml: Packs of 10

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

Additrace must not be given undiluted.

The addition of Additrace should be performed aseptically, immediately before the start of infusion and the solution should be used within 24 hours.

Data on compatibility of Additrace with various admixtures are available on request.

The following admixtures are compatible with Additrace and should be used within 24 hours of mixing:

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

7 MARKETING AUTHORISATION HOLDER

Fresenius Kabi Limited

Cestrian Court

Eastgate Way, Manor Park

Runcorn

Cheshire

UK

WA7 1NT

8. MARKETING AUTHORISATION NUMBER

PL 08828/0102

9. DATE OF FIRST AUTHORISATION/RENEWAL OF

AUTHORISATION

Date of first authorisation: 31 May 1999 Date of latest renewal: 03 February 2009

10 DATE OF REVISION OF THE TEXT

06/05/2016