TRACUTIL S dilute perf 5Amp/10ml

The concentrate for solution for perfusion contains:

Ferrous chloride .............................................................................................................................695,80 micrograms

Zinc chloride .............................................................................................................................681,50 micrograms

Manganese chloride ...............................................................................................................197,90 micrograms

Copper chloride ..........................................................................................................................204,60 micrograms

Chromium chloride ...........................................................................................................................5,30 micrograms

Sodium selenite pentahydrate ....................................................................................................7,89 micrograms

Sodium molybdate dihydrate .......................................................................................................2,42 micrograms

Potassium iodide ........................................................................................................................16,60 micrograms

Sodium fluoride ........................................................................................................................126,00 micrograms

For 1 ml.

Excipient with known effect :

Each ampoule of 10 ml contains 147 micromoles (or 3,4 mg) of sodium.

TRACUTIL is used as a source of trace elements during parenteral nutrition in adults.

Reserved for adults.

Dosage

The recommended daily dosage is 10 ml (1 ampoule) for patients with standard requirements.

For patients with moderately increased requirements, the daily dose may go up to 20 ml (2 ampoules), while monitoring serum trace element concentrations.

In case of significant increase in trace element requirements (extensive burns, polytrauma, severe hypercatabolism), higher doses may be necessary.

Paediatric population

TRACUTIL is contraindicated in newborns, infants and children (see section Contraindications).

TRACUTIL is not recommended in adolescents (see section Warnings and precautions).

Patients with renal and hepatic impairment

For patients with impaired renal and/or hepatic function, doses must be determined on a case-by-case basis. For these patients, lower doses may be necessary.

Method of administration

TRACUTIL is a concentrated solution of trace elements, which must only be administered intravenously after dilution in at least 250 ml of a compatible infusion solution, for example:

-          a glucose solution (at 5 % or 10 %),

-          an electrolyte solution (for example: sodium chloride at 0,9 %, Ringer's solution).

Compatibility must be tested before mixing with other infusion solutions.

The infusion duration of the ready-to-use mixture must not be less than 6 hours and must not be prolonged beyond 24 hours.

Administration may be continued for the duration of parenteral nutrition.

For incompatibilities and instructions for use, see sections Incompatibilities and Disposal and handling.

Remarks

Diarrhoea may lead to an increase in intestinal losses of zinc. In this case, serum concentrations must be monitored.

Deficiencies in given trace elements must be corrected by specific supplementation.

• Hypersensitivity to the active substances or to any of the excipients mentioned in section Composition.
• Pronounced cholestasis (serum bilirubin > 140 mmol/l and increase in gamma-glutamyltransferase and alkaline phosphatases).
• Wilson's disease and iron storage disorders (for example haemosiderosis or haemochromatosis).
• TRACUTIL is contraindicated in newborns, infants and children because its composition is inappropriate for this age group.

The blood manganese level must be monitored regularly in case of prolonged parenteral nutrition. In case of manganese accumulation, proceed to a dose reduction or discontinuation of the TRACUTIL infusion.

TRACUTIL must be used with caution in case of impaired hepatic function, as this may disrupt the biliary elimination of manganese, copper and zinc, leading to accumulation and overdose.

This trace element solution must be used with caution in case of impaired renal function, as the excretion of certain trace elements (selenium, fluoride, chromium, molybdenum and zinc) may be significantly decreased.

To prevent iron overdose, which is particularly a risk in case of hepatic impairment or in patients receiving blood transfusions, serum ferritin concentrations must be monitored at regular intervals.

In patients receiving parenteral nutrition of medium to long duration, the risk of zinc and selenium deficiency is increased. In such cases, especially in the presence of hypercatabolism, for example after major trauma, major surgery, burns, etc..., if necessary, the dosage must be adapted and an additional supply of these elements provided.

TRACUTIL should be administered with caution in cases of confirmed hyperthyroidism or sensitivity to iodine if other iodine-based medicines (for example iodinated antiseptics) are administered concomitantly.

A chromium deficiency leads to a decrease in glucose tolerance, which improves after chromium supplementation. Thus, in diabetic patients on insulin, a relative insulin overdose followed by hypoglycaemia may be observed; therefore, blood glucose monitoring is recommended. Adjustment of the insulin dosage may become necessary.

Paediatric population :

TRACUTIL is not recommended in adolescents due to the absence of specific studies.

This medicine contains less than 1 mmol of sodium (23 mg) per 10 ml dose; that is to say that it is considered without sodium.

For information on compatibilities/incompatibilities, see sections Incompatibilities. and Disposal and handling.

Pregnancy

There are no data or there are limited data on the use of TRACUTIL in pregnant women. There have been no reproductive and developmental toxicity studies in animals with TRACUTIL (see section Preclinical safety). TRACUTIL should not be used during pregnancy unless the clinical condition of the woman requires treatment with TRACUTIL.

Breastfeeding

It is not known whether the active substances/metabolites of TRACUTIL are excreted in breast milk. Thus, TRACUTIL should not be used during pregnancy and breastfeeding except after thorough examination of the expected benefit for the mother and the potential risks for the child.

Fertility

No data available.

Immune system disorders:

Frequency not known (cannot be estimated from the available data):

-       Anaphylactic reactions to parenterally administered iron, which may lead to death.

-       Iodine may also cause allergic reactions.

Reporting of suspected adverse reactions

Reporting of suspected adverse reactions after authorisation of the medicinal product is important. It allows continuous monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reaction via the national reporting system: Agence nationale de sécurité du médicament et des produits de santé (ANSM) and network of Regional Pharmacovigilance Centres. Website: www.ansm.sante.fr.

An overdose with TRACUTIL is extremely unlikely because the amount of trace elements per ampoule is well below toxic levels. If an overdose is suspected, treatment with TRACUTIL should be discontinued. An overdose must be confirmed by appropriate laboratory tests.

Pharmacotherapeutic group: B05X : Additives for intravenous solutions.

Pharmacodynamic effects

TRACUTIL is a balanced solution composed of the 9 trace elements commonly considered essential. They are necessary to maintain the metabolic balance of the body.

The pharmacodynamic and pharmacokinetic properties of the ingredients are similar to those of the substances present in the natural state.

During artificial nutrition, the supply of trace elements is necessary because deficiencies can generate significant metabolic and clinical disorders.

Trace elements are normally supplied by a balanced diet, but requirements are increased in cases of hypercatabolism (for example related to surgery, polytrauma, burns), insufficient intake or abnormal losses and in cases of malabsorption (short bowel syndrome or Crohn's disease).

The composition of TRACUTIL follows the current international recommendations on trace element requirements.

Elimination of trace elements occurs via different routes.

Iron is eliminated via the faeces and, to a lesser extent, in the urine.

Zinc is excreted mainly via the faeces, and renal excretion is low.

Manganese is excreted mainly via the bile into the intestines and is partially reabsorbed by the intestines (enterohepatic circulation). The main route of excretion is via the faeces; urinary elimination or via sweat is insignificant.

The main route of elimination of copper is biliary, whereas only small quantities are eliminated, through the intestinal wall into the lumen, or through the urine.

Chromium and molybdenum are essentially excreted by the kidneys, and the remainder is eliminated by the intestines. Molybdenum is also excreted by the bile and recycled by the enterohepatic circulation.

Elimination of selenium occurs via the faeces or urine, depending on the form in which it is present.

Fluoride and iodine have mainly renal excretion.

No preclinical studies on pharmacological safety, repeated-dose toxicity, genotoxicity, carcinogenic potential and reproductive toxicity have been performed with TRACUTIL.

As TRACUTIL is indicated as replacement therapy, the risk of toxic effects is considered low for normal clinical use.

The product must not be mixed with alkaline solutions with marked buffering capacity, for example sodium bicarbonate solutions.

Do not mix with lipid emulsions.

Degradation of vitamin C in infusion solutions is accelerated in the presence of trace elements.

TRACUTIL cannot be mixed directly with solutions of inorganic phosphate (additive).

It is not possible to present complete information on incompatibilities in this chapter.

Please contact the marketing authorisation holder for more information.

This product must not be mixed with any medicinal product except those mentioned in section Disposal and handling.

Shelf life in the closed container:

5 years.

Shelf life after dilution:

Physicochemical stability has been demonstrated for 24 hours at 25°C.

However, from a microbiological point of view, the product must be used immediately. If not used immediately, the storage times and conditions prior to use are the sole responsibility of the user and must not exceed 24 hours at a temperature between 2°C and 8°C, unless reconstitution/dilution has been performed under duly controlled and validated aseptic conditions.

This medicinal product does not require any special storage precautions.

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

TRACUTIL may be diluted in at least 250 mL of glucose solution at 5 %, 10 %, 20 %, 40 % or 50 %, electrolyte solution for example sodium chloride at 0,9 % or Ringer's solution.

Mixing with the diluent solution must be performed under strict aseptic conditions.

TRACUTIL must not be used as a diluent for other medicinal products.

Compatibility with solutions administered simultaneously via the same tubing must be ensured.

The solution must be administered within a maximum of 24 hours.

The product must be visually inspected for particles, any damage to the ampoule and any visible signs of deterioration before dilution and administration.

Any solution in which such defects are observed must be discarded.

Any unused medicinal product or waste must be disposed of in accordance with current regulations.