ADDNUTRIV

1 Dosing Considerations  In patients with renal or hepatic impairment or mild cholestasis, the dose should be adapted.  In general, longer infusion periods are desirable, as this may minimize renal losses. The typical infusion time for parenteral nutrition is 8 hours.

2 Recommended Dose and Dosage Adjustment Adults: The recommended daily dosage of Addnutriv, in adult patients with basal to moderately increased requirements, is 10 mL (one ampoule).

Pediatrics:

Health Canada has not authorized an indication for pediatric use. 3 Administration Addnutriv must not be given undiluted. Addnutriv should be diluted in a parenteral nutrition solution / emulsion before given as an intravenous infusion.

4 Reconstitution and Mixing Guidelines Aseptic addition of Addnutriv, Trace Elements for Injection, to the amino acid or dextrose component of a parenteral nutrition solution under a laminar flow hood conditions is recommended. Addnutriv may only be added to medications and parenteral nutrition solutions for which compatibility has been shown.

Addnutriv is used as an additive to parenteral nutrition admixtures in compounded bags where data are available. e. SmofKabiven®, Intralipid® 20% and SMOFlipid®), dextrose and electrolytes in prescribed concentrations. Mixing Guidelines Admixtures should be prepared in bags suitable for parenteral nutrition compounding according to a defined mixing sequence.

Addnutriv should never be added directly to a lipid emulsion because of the destabilizing effects of trace elements. When adding Addnutriv to SmofKabiven®, a three-chamber bag, it is recommended that the macronutrients from each chamber (amino acid solution, dextrose solution and lipid emulsion) are mixed first (bag activation), before adding Addnutriv and any other additives.

Any other additions to the bag should be evaluated by a pharmacist for compatibility. Questions about compatibility may be directed to Fresenius Kabi Canada. When compounding admixtures, from individual macronutrients and micronutrients, in empty suitable bags, the admixing sequence below may be followed: 1.

Add Addnutriv and electrolytes (except phosphate solution) to the amino acid solution, mixing well between additions 2. Add phosphate to the dextrose solution 3. Add the above two solutions to the bag and mix well 4. Add vitamins to the lipid emulsion (SMOFlipid 20% or Intralipid 20%) 5.

1 Adverse Reaction Overview Adverse reaction information is based on post-marketing experiences. 2 Post-Market Adverse Reactions Adverse drug reactions with trace elements, administered in combination with parenteral nutrition products, have been reported, and may have been caused by any component of the parenteral nutrition.

0000001) than the lowest “very rare” frequency of < 1 / 10 000.

Table 2:

Serious ADRs by preferred term reported for trace elements SOC Preferred ADR term Cardiac disorders Cardiac arrest Arrhythmia Palpitations Tachycardia Gastrointestinal disorders Diarrhea Nausea Vomiting General disorders and administration site conditions Administration site reaction Chest pain Chest discomfort Chills Death Malaise (Hyper-) Pyrexia Infusion site phlebitis Injection site pain, Pain Swelling (Peripheral) swelling Asthenia Hepatobiliary disorders Hepatic function abnormal Jaundice Hepatic failure Addnutriv – Product Monograph Page 8 of 18 SOC Preferred ADR term Immune system disorders Hypersensitivity Anaphylactic shock Infections and infestations Abdominal sepsis Candida infection Vascular device infection Infective pulmonary exacerbation of cystic fibrosis Dysentery Infection Pneumonia Sepsis Urinary tract infection Injury, poisoning and procedural complications Hip fracture Product administration error Product dose omission Exposure during pregnancy Product prescribing error Medication error Product use in unapproved indication Investigations Blood pressure increased Body temperature increased General physical condition abnormal Liver function test abnormal Oxygen saturation decreased Blood potassium increased Renal function test abnormal Urine output decreased Hyperglycemia Hypernatraemia Hyponatraemia Refeeding syndrome Hypovitaminosis Musculoskeletal and connective tissue disorders Back pain Muscle spasms Myalgia Muscle twitching Nervous system disorders Cerebral infarction Dysgeusia Headache Paraesthesia Seizure Poor quality sleep Tremor Loss of consciousness Pregnancy, puerperium and perinatal conditions Abortion spontaneous Psychiatric disorders Nervousness Renal and urinary disorders Renal impairment Addnutriv – Product Monograph Page 9 of 18 SOC Preferred ADR term Respiratory, thoracic and mediastinal disorders Acute pulmonary oedema Dyspnea Respiratory failure Skin and subcutaneous tissue disorders Cold sweat Erythema Pruritus Rash Hyperhidrosis Urticaria Vascular disorders Embolism Flushing Hypotension Thrombophlebitis Thrombosis

General 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 should be taken. Parenterally administered iron or iodine preparations can cause hypersensitivity reactions on rare occasions, including serious and potentially fatal anaphylactic reactions.

If iron is taken orally in parallel with the administration of Addnutriv, the total intake of iron should be determined to ensure that there is no iron accumulation. If the treatment is continued for more than 4 weeks, checking of manganese levels in blood is required.

Hepatic/Biliary/Pancreatic Addnutriv should be used with caution in patients with impaired biliary function in whom the excretion of trace elements may be significantly decreased. Addnutriv should be used with caution in patients with biochemical or clinical evidence of liver dysfunction (especially cholestasis).

Liver dysfunction, including impaired biliary excretion, may interfere with excretion of trace elements, leading to a risk of accumulation . Renal Addnutriv should be used with caution in patients with impaired renal function in whom the excretion of trace elements may be significantly decreased.

1 Pregnant Women Animal reproduction studies or clinical investigations during pregnancy have not been carried out with Addnutriv. The requirements of trace elements in a pregnant woman are slightly increased compared to non-pregnant women.

There is no sufficient data available on use of Addnutriv in pregnant women. Healthcare professionals should carefully consider the potential risks and benefits for each pregnant patient before prescribing Addnutriv. 2 Breast-feeding It is unknown to what extent Addnutriv is excreted in human milk.

Because many drugs are excreted in human milk precaution should be exercised. Healthcare professionals should carefully consider the potential risks and benefits for each case before prescribing the product. 3 Pediatrics No data are available to Health Canada; therefore, Health Canada has not authorized an indication for pediatric use.

Addnutriv, Trace Elements for Injection, is contraindicated in patients who are hypersensitive to this product or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. For a complete listing, see Dosage Forms, Strengths, Composition and Packaging.

Addnutriv is also contraindicated in:  Conditions with total biliary obstruction.  Wilson’s disease, hemochromatosis.