Multrys

1 INDICATIONS AND USAGE Multrys is indicated in neonatal and pediatric patients weighing less than 10 kg as a source of zinc, copper, manganese, and selenium for parenteral nutrition when oral or enteral nutrition is not possible, insufficient, or contraindicated. Multrys is a combination of trace elements (zinc sulfate, cupric sulfate, manganese sulfate, and selenious acid) indicated in neonatal and pediatric patients weighing less than 10 kg as a source of zinc, copper, manganese, and selenium for parenteral nutrition when oral or enteral nutrition is not possible, insufficient, or contraindicated. ( 1 )

2 DOSAGE AND ADMINISTRATION Single-dose vial, for admixture use only. ( 2.1 ) See full prescribing information for information on preparation, administration and general dosing considerations. ( 2.1 , 2.2 , 2.3 , 2.4 ) Recommended Dosage Each mL of Multrys provides zinc 1,000 mcg, copper 60 mcg, manganese 3 mcg, and selenium 6 mcg. ( 2.5 ) Multrys is recommended only for pediatric patients who require supplementation with all four of the individual trace elements (i.e., zinc, copper, manganese, and selenium) to meet daily requirements. ( 2.5 ) Pediatric Patients 0.4 kg to 0.59 kg : The total recommended dosage of Multrys is 0.2 mL every other day .Daily supplementation of Zinc Sulfate, Cupric Chloride and Selenious Acid will be needed to meet daily requirements. ( 2.5 ) Pediatric Patients 0.6 kg to 10 kg : The recommended dosage of Multrys is 0.3 mL/kg/day rounded to the nearest 0.1 mL for up to a maximum of 1 mL per day. The recommended volume of Multrys to be added to parenteral nutrition ranges from 0.2 mL per day to 1 mL per day based on body weight. ( 2.5 ) Multrys is not recommended for patients who may require a lower dosage of one or more of the individual trace elements. ( 2.5 ) Monitor trace element concentrations in blood during long-term administration of parenteral nutrition. ( 2.5 ) 2.1 Important Administration Information Multrys is supplied as a single-dose vial for admixture use only. Prior to administration, Multrys must be transferred to a separate parenteral nutrition container and used as an admixture in parenteral nutrition solution. The final parenteral nutrition solution is for intravenous infusion into a central or peripheral vein. The choice of a central or peripheral venous route should depend on the osmolarity of the final infusate. Solutions with osmolarity of 900 mOsmol/L or greater must be infused through a central catheter [see Warnings and Precautions ( 5.2 )] . 2.2 Preparation and Administration Instructions Multrys is for admixture use only.Prior to administration, Multrys must be prepared and used as an admixture in parenteral nutrition solution. Add Multrys to the parenteral nutrition solution in a suitable work area such as a laminar flow hood (or an equivalent clean air compounding area).The key factor in the preparation is careful aseptic technique to avoid inadvertent touch contamination during mixing of solutions and addition of other nutrients. Inspect the parenteral nutrition solution containing Multrys for particulate matter before admixing, after admixing, and prior to administration. 2.3 Preparation Instructions for Admixing Using a Parenteral Nutrition Container Inspect Multrys single-dose vial for particulate matter. Transfer Multrys to the parenteral nutrition container after the admixture of amino acids, dextrose, lipid emulsion (if added), and electrolyte solutions is prepared. Because additives may be incompatible, evaluate all additions to the parenteral nutrition container for compatibility and stability of the resulting preparation.Consult with a pharmacist, if available.For introducing additives to the parenteral nutrition container, use aseptic technique. An interaction may occur between cupric ion and ascorbic acid; therefore, multivitamin additives should be added to the admixed parenteral nutrition solution shortly before infusion. Inspect the final parenteral nutrition solution containing Multrys to ensure that: Precipitates have not formed during mixing or addition of additives. The emulsion has not separated, if lipid emulsion has been added.Separation of the emulsion can be visibly identified by a yellowish streaking or the accumulation of yellowish droplets in the admixed emulsion. Discard if any precipitates are observed. Stability and Storage Single dose vial.Discard any unused portion. Penetrate vial closure only one time with a suitable sterile transfer device or dispensing set that allows measured dispensing of the contents. Transfer Multrys to the parenter…

5 WARNINGS AND PRECAUTIONS Pulmonary Embolism due to Pulmonary Vascular Precipitates : If signs of pulmonary distress occur, stop the infusion and initiate a medical evaluation. ( 5.1 ) Vein Damage and Thrombosis :Solutions with osmolarity of 900 mOsmol/L or more must be infused through a central catheter. ( 2.1 , 5.2 ) Neurologic Toxicity with Manganese :Monitor for clinical signs and symptoms of neurotoxicity, whole blood manganese concentrations, and liver function tests in patients receiving long-term Multrys.Discontinue Multrys and consider brain magnetic resonance imaging (MRI) if toxicity is suspected. ( 5.3 ) Hepatic Accumulation of Copper and Manganese :Assess for development of hepatic accumulation.Monitor concentrations of copper and manganese in patients with cholestasis or cirrhosis receiving Multrys long-term. ( 5.4 ) Aluminum Toxicity : Increased risk in patients with renal impairment, including preterm infants. ( 5.5 ) Monitoring and Laboratory Tests : Monitor zinc, copper, and selenium serum concentrations, whole blood manganese concentration, fluid and electrolyte status, serum osmolarity, blood glucose, liver and kidney function, blood count, and coagulation parameters. ( 5.6 , 2.4 ) Hypersensitivity Reactions with Zinc and Copper : If reactions occur, discontinue Multrys and initiate appropriate medical treatment. ( 5.7 ) 5.1 Pulmonary Embolism due to Pulmonary Vascular Precipitates Pulmonary vascular precipitates causing pulmonary vascular emboli and pulmonary distress have been reported in patients receiving parenteral nutrition. The cause of precipitate formation has not been determined in all cases; however, in some fatal cases, pulmonary emboli occurred as a result of calcium phosphate precipitates. Precipitation has occurred following passage through an in-line filter; in vivo precipitate formation may also have occurred. If signs of pulmonary distress occur, stop the parenteral nutrition infusion and initiate a medical evaluation. In addition to inspection of the solution [see Dosage and Administration ( 2.2 , 2.3 )] , the infusion set and catheter should also periodically be checked for precipitates. 5.2 Vein Damage and Thrombosis Multrys must be prepared and used as an admixture in parenteral nutrition solution. It is not for direct intravenous infusion. In addition, consider the osmolarity of the final parenteral nutrition solution in determining peripheral versus central administration. Solution with an osmolarity of 900 mOsmol/L or greater must be infused through a central catheter [see Dosage and Administration ( 2.1 )] . The infusion of hypertonic nutrient solution into a peripheral vein may result in vein irritation, vein damage, and/or thrombosis. The primary complication of peripheral access is venous thrombophlebitis, which manifests as pain, erythema, tenderness or a palpable cord. Remove the catheter as soon as possible, if thrombophlebitis develops. 5.3 Neurologic Toxicity with Manganese Pediatric patients on long-term parenteral nutrition receiving manganese at higher than recommended dosages and pediatric patients with cholestatic liver disease have experienced manganese accumulation in the basal ganglia. Some adult patients with brain MRI findings reportedly experienced neuropsychiatric symptoms, including changes in mood or memory, seizures and/or parkinsonian-like tremors, dysarthria, mask-face, and halting gait. Some pediatric patients experienced dystonic movements or seizures. Brain MRI findings and clinical symptoms have also been observed in patients who received manganese at or below the recommended dosage and with normal blood manganese concentrations. Regression of symptoms and brain MRI findings have occurred over weeks to months following discontinuation of manganese in most patients but have not always completely resolved. Monitor patients receiving long-term parenteral nutrition solutions containing Multrys for neurologic signs and symptoms and routinely monitor whole b…

4 CONTRAINDICATIONS Multrys is contraindicated in patients with hypersensitivity to zinc or copper [see Warnings and Precautions ( 5.7 )]. Hypersensitivity to zinc or copper ( 4, 5.7 )

6 ADVERSE REACTIONS The following adverse reactions were identified in clinical studies or post-marketing reports. Given that some of these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Adverse reactions with other components of parenteral nutrition solutions: Pulmonary embolism due to pulmonary vascular precipitates [see Warnings and Precautions ( 5.1 )] Vein damage and thrombosis [see Warnings and Precautions ( 5.2 )] Aluminum toxicity [see Warnings and Precautions ( 5.5 )] Adverse reactions with the use of trace elements administered parenterally or by other routes of administration: Neurologic toxicity with manganese [see Warnings and Precautions ( 5.3 )] Hepatic accumulation of copper and manganese [see Warnings and Precautions ( 5.4 )] Hypersensitivity reactions with zinc and copper [see Warnings and Precautions ( 5.7)] This section intentionally left blank. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact American Regent, Inc. at 1-800-734-9236 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .