Addaven Injection

ADDAVEN is indicated as a trace element supplement to be used during total parenteral nutrition in adults.

Posology
Adults: The recommended daily dosage of ADDAVEN in adult patients with basic to moderately increased requirements is 10 mL (one ampoule), diluted as described under u201cMethod of administrationu201d. In patients with renal or hepatic impairment, or mild cholestasis, the dose should be adapted.

Method of administration
ADDAVEN must not be given undiluted. ADDAVEN is to be diluted in a parenteral nutrition solution/emulsion before being given as an intravenous infusion. Up to 20 mL ADDAVEN can be added aseptically to 1 000 mL Vamin 18 Electrolyte Free, glucose solution 55 mg/mL - 600 mg/mL in glass bottles or glucose solution 55 mg/mL - 500 mg/mL in plastic containers. The addition of ADDAVEN should be performed aseptically. Longer infusion periods are desirable, as this will minimise renal losses. The typical minimum infusion time when ADDAVEN is administered as part of parenteral nutrition is 8 hours. Chemical and physical in-use stability after dilution has been demonstrated for 24 hours at 25 u00b0C. Additions of other medicines should be avoided due to the risk of incompatibilities. From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage must not be longer than 24 hours at 2 - 8 u00b0C. ADDAVEN is for single use in one patient only. Discard any residue.

Compatibility
Only medicines and nutrition solutions where compatibility has been documented may be added to ADDAVEN. ADDAVEN is used as an additive to parenteral nutrition admixtures in compounded bags where data are available. Compatibility data are available for the addition of 10 mL ADDAVEN to the named branded products SMOFlipid, Intralipid 20 %, Aminoven 10 %, Vamin 18 Electrolyte Free, Dipeptiven, Soluvit Novum, Vitalipid Novum Adult and Glycophos in defined amounts, and generics of glucose and electrolytes in defined concentrations. 10 mL of ADDAVEN can also be added to the SmofKabiven range of products. NOTE: ADDAVEN should never be added directly to a lipid emulsion because of the destabilising effects of trace elements. It is recommended that the macronutrients (amino acid solution and glucose with or without lipid emulsion) are mixed first, before adding the ADDAVEN and any further additions, e.g. vitamins or electrolytes. Additions should be made aseptically.

Special populations
No specific data are available. See u201cPosologyu201d above.

• Hypersensitivity to the active substances or to any of the excipients of ADDAVEN listed in section 6.1.
• Conditions with total biliary obstruction.
• Wilsonu2019s disease, haemochromatosis.

To be used as intravenous infusion only. ADDAVEN must not be given undiluted. See section 4.2.

Parenterally administered iron or iodine preparations can cause hypersensitivity reactions on rare occasions, including serious and potentially fatal anaphylactic reactions. Patients should be clinically observed for signs and symptoms of hypersensitivity reactions. In case of hypersensitivity reactions, the infusion should be stopped immediately, and appropriate measures performed.

If iron is taken orally in parallel with infusion of ADDAVEN, the total intake of iron should be determined to ensure that there is no iron accumulation.

Peripheral infusion of ADDAVEN diluted in saline or glucose instead of a parenteral nutrition solution may result in local intolerability due to low pH. Osmolarity also needs to be considered. See section 4.2 u201cMethod of administrationu201d for dilution instructions.

ADDAVEN should be used with caution in patients with liver dysfunction (especially cholestasis). Liver dysfunction, including impaired biliary excretion, may interfere with excretion of trace elements from ADDAVEN, leading to a risk of accumulation.

ADDAVEN should be used with caution in patients with impaired renal function as excretion of some trace elements in urine may be significantly decreased. Monitoring of trace element levels, especially manganese, is recommended. If the treatment is continued for more than 4 weeks, checking of manganese levels in blood is required. If an individual patient has a markedly increased requirement for any of the trace elements, the regimen can be adjusted using separate supplements.

Laboratory and some animal studies indicate that vitamin B6 deficiency can increase the production of oxalate from xylitol. Adequate levels of vitamin B6 should be maintained.

Use in the elderly
Because of the increased likelihood of impaired renal or hepatic function or concomitant disorders and their treatment, ADDAVEN should be used with cautious monitoring in the elderly.

Paediatric use
ADDAVEN is not recommended for use in children.

Effects on laboratory tests
No effects on laboratory tests have been identified. ADDAVEN is administered as part of parenteral nutrition. No other additions should be made to solutions containing ADDAVEN unless compatibility is known.

No interactions with other medicines have been recorded. Molybdenum interacts with copper to form complexes that increase urinary elimination of copper. Amino acids, which are present in all total intravenous nutrition (IVN) mixtures, could complex with zinc and copper and the complex could be excreted in urine. However, amino acid loss in urine is usually small. Interactions of copper with ascorbic acid from vitamin supplementation of the parenteral nutrition mixture may occur, resulting in oxidative loss of ascorbic acid, which can be limited by use of oxygen impermeable bags.

Fertility
The potential effects of ADDAVEN on fertility and general reproductive performance have not been determined.

Pregnancy
Safety during pregnancy has not been established. Animal reproduction studies or clinical investigations during pregnancy have not been carried out with ADDAVEN.

Breastfeeding
The active substances in ADDAVEN are secreted in human milk and effects have been shown in breastfed newborns/infants of treated women. Safety during breastfeeding has not been established.

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

There have been no clinical trials of ADDAVEN. As a component of the parenteral nutrition administered, it would be extremely difficult to identify adverse reactions that could be attributed directly to ADDAVEN. Allergic reactions to iodine may occur following topical application. No adverse reactions are known to occur as a consequence of using the recommended intravenous iodide dosage levels. A minimum infusion time of 8 hours will minimise the risk of oxalosis associated with the infusion of xylitol (see Section 4.2 u201cPosology and method of administrationu201d).

System Organ Class Frequency Undesirable Effects
Nervous system disorders Frequency not known (1) Headache
Gastrointestinal disorders Frequency not known Nausea, vomiting
General disorders and administration s conditions Frequency not known Chills, pyrexia
(1) Post-marketing data. Frequency cannot be estimated from the available data

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Healthcare providers are asked to report any suspected adverse drug reactions to SAHPRA via the Med Safety APP (Medsafety X SAHPRA) and eReporting platform (who-umc.org) found on the SAHPRA website. Healthcare providers are asked to report any suspected adverse drug reactions to the Holder of the Certificate of Registration at the following email address: [email protected] and to the relevant medicines regulatory authority in the country where the product is marketed.

In case of a chronic overload of iron there is a risk of haemosiderosis, which in severe and rare cases can be treated by venesection. In overdose, side effects can be precipitated and/or be of increased severity (see section 4.8).