HEALTH CARE PROVIDER LETTER SECTION.

IMPORTANT PRESCRIBING INFORMATION October 30, 2017Subject: Temporary importation of Glycophos to address drug shortage issuesDear Healthcare Professional, Due to the critical shortage of phosphate injection in the U.S. market, Fresenius Kabi USA, LLC (Fresenius Kabi USA) is coordinating with the U.S. Food and Drug Administration (FDA) to provide an alternative treatment option during this critical shortage period. Fresenius Kabi USA has initiated temporary importation of GlycophosTM 20 mL Injection Single Dose Plastic Vial into the U.S. market. This product is marketed in Europe, and is manufactured in the Fresenius Kabi Norway plant.At this time, no other entity except Fresenius Kabi USA is authorized by the FDA to import or distribute GlycophosTM 20 mL Injection Single Dose Plastic Vial in the U.S. FDA has not approved Fresenius Kabis GlycophosTM in the United States.Effective immediately, and during this temporary period, Fresenius Kabi USA will offer the following presentation of phosphate injection:Glycophos 20 mL Sterile Concentrate Single Dose Plastic VialChemical NameSodium Glycerophosphate Phosphate Concentration mMol per mL.Type of Phosphate OrganicSodium mEq per mL.Fill Volume 20 mL.Description Single Dose Plastic VialManufacturer Fresenius Kabi Norge A/SThe vial and carton labels will display the text used when marketing the product in English speaking countries. It is important to note that there are some key differences in the formulation and labeling between the current U.S. marketed phosphate injection products and Glycophos that you need to be aware of: Refer to the Glycophos package insert for full prescribing informationThis communication and product information is available on the Fresenius Kabi USA web site http://products.fresenius-kabi.us/product-323.html as well as on the FDA Drug Shortage web site. http://www.fda.gov/Drugs/DrugSafety/DrugShortages/default.htm.To report adverse events or quality problems experienced with the use of this product, call Fresenius Kabi USA Vigilance or Medical Affairs at 1-800-551-7176, Monday Friday, between the hours of a.m. and p.m. (CST), or e-mail adverse.events.USAfresenius-kabi.com or productcomplaint.USAfresenius-kabi.com. Fresenius Kabi USA CONTACT NUMBERS: Please use the following contact numbers as appropriate: Reason To Call DepartmentNumber ADE Reporting Vigilance Department 1-800-551-7176Clinical/Technical Info. Or Product Complaint Medical Affairs DepartmentProduct Availability Ordering Customer Service Department 1-888-386-1300 Adverse reactions or quality problems experienced with the use of this product may be reported to the FDAs MedWatch Adverse Event Reporting program either online, by regular mail or by fax. Complete and submit the report Online: www.fda.gov/medwatch/report.htmRegular Mail or Fax: Download form www.fda.gov/medwatch/getforms.htm or call 1-800-332-1088 to request reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178 (1-800-332-0178). Sincerely, Melanie Power-Burns Vice President, Quality and Compliance Key Differences between U.S. Marketed Phosphate Injection Products and Glycophos Current U.S. Marketed Inorganic Phosphate Injection, USPGlycophosWhat does this mean to you, as Healthcare ProfessionalIndications and contraindications: see package insertIndications and contraindications: see package insert Glycophos is indicated in adult patients and infants as supplement in intravenous nutrition to meet the requirements of phosphate.Glycophos is contraindicated in patients in state of dehydration or with hypernatremia, hyperphosphatemia, severe renal insufficiency or shock. Sodium Phosphates and Potassium Phosphates contain mMol of phosphate per mL.Glycophos contains mMol of phosphate per mL. Glycophos contains 20 mLs in each plastic vial for total concentration of 20 mMols of phosphate per vial.Glycophos must be diluted before administration. Sodium Phosphates and Potassium Phosphates are INORGANIC PHOSPHATE. Glycophos is an ORGANIC PHOSPHATE. Organic phosphates tend to be more calcium compatible1. This means: At higher concentrations, solutions of calcium and phosphate may exist together without precipitating into an insoluble salt complex.In high pH solutions (admixtures above pH 6.0), organic phosphate is less likely to precipitate. Barcode on container label No unit of use barcodeAny barcodes on Glycophos product will not be appropriately recognized by scanning systems used in the United States and should NOT be used. Institutions should manually input the product into their systems and to confirm that barcode systems do not provide incorrect information when the product is scanned. For questions regarding Glycophos in the United States, please contact Fresenius Kabi USA Medical Affairs at 1-800-551-7176 Option 4, Monday Friday, between the hours of a.m. and p.m. (CST), or e-mail nutrition.medinfo.USAfresenius-kabi.com. 1. Data on file. Comparison Table of U.S. Phosphate Injection Products to Glycophos Product Name Potassium Phosphates Sodium PhosphatesGlycophos Chemical Name Potassium Phosphate Sodium Phosphate Sodium GlycerophosphatePhosphate Concentration mMol per mL mMol per mL mMol per mLType of Phosphate Inorganic Inorganic OrganicSodium Does not contain mEq per mL mEq per mLPotassium 4.4 mEq per mL Does not contain Does not containFill Volume mL, 15 mL, 50 mL mL, 15 mL, 50 mL 20 mLDescription Single Dose Vial Single Dose Vial Single Dose Plastic VialCompanies Fresenius Kabi USA, Pfizer American Regent, Fresenius Kabi USA, Pfizer Fresenius Kabi Norge A/SPhosphate Label Product Comparison Table Complete and submit the report Online: www.fda.gov/medwatch/report.htm. Regular Mail or Fax: Download form www.fda.gov/medwatch/getforms.htm or call 1-800-332-1088 to request reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178 (1-800-332-0178).. At higher concentrations, solutions of calcium and phosphate may exist together without precipitating into an insoluble salt complex.. In high pH solutions (admixtures above pH 6.0), organic phosphate is less likely to precipitate.. market. comparison table.

SPL MEDGUIDE SECTION.

1. QUALITATIVE AND QUANTITATIVE COMPOSITION ml of Glycophos containsActive ingredient Quantity Sodium glycerophosphate pentahydrate 306.1 mgCorresponds to 216 mg sodium glycerophosphate The active ingredient in ml of Glycophos correspond toPhosphate mmolSodium mmolFor excipients, see 5.1PRODUCT PROPERTIESo Osmolality: 2760 mosm/kg watero pH: 7.42. PHARMACEUTICAL FORM Concentrate for solution for infusion.3. CLINICAL PARTICULARS 3.1 Therapeutic indicationsGlycophos is indicated in adult patients and infants as supplement in intravenous nutrition to meet the requirements of phosphate.3.2 Posology and method of administrationGlycophos must not be given undiluted.Adults:The recommended dosage is individual. The recommended daily dosage of phosphate during intravenous nutrition would normally be 10-20 mmol. This can be met by using 10-20 ml of Glycophos added to the infusion solution or to the admixture for which compatibility has been proved.Infants:The recommended dosage is individual. The recommended dose for infants and neonates is 1.0-1.5 mmol/Kg body weight/day.3.3 Contra-indicationsGlycophos should not be given to patients in state of dehydration or with hypernatraemia, hyperphosphataemia, severe renal insufficiency or shock.3.4 Special warnings and special precautions for useGlycophos should be used with caution in patients with impaired renal function. The phosphate status of all patients should be monitored regularly.Glycophos must not be given undiluted.3.5 Interaction with other medicaments and other forms of interactionNo interactions with other drugs have been observed, but moderate fall in serum phosphate can be seen during carbohydrate infusions.3.6 Pregnancy and lactationAnimal reproduction studies or clinical investigations during pregnancy have not been carried out with Glycophos. However, the requirements of phosphate in pregnant woman are slightly increased compared to non-pregnant women. No adverse events are to be expected when Glycophos is administered during pregnancy.3.7 Effects on ability to drive and use machinesNo effects on the ability to drive and use machines are to be expected.3.8 Undesirable effectsNo adverse effects related to glycerophosphate have been reported.3.9 OverdoseNo adverse effects of an overdose have been reported. Most patients in need of intravenous nutrition have an increased capacity to handle glycerophosphate. See also 3.3 Contra-indications.4. PHARMACOLOGICAL PROPERTIES4.1 Pharmacodynamic propertiesGlycerophosphate is metabolic intermediate in fat metabolism and any pharmacodynamic effects other than maintaining the normal metabolic pathways are unlikely.4.2 Pharmacokinetic propertiesTo become available it is necessary for the phosphate group to be hydrolysed from the glycerophosphate molecule. The hydrolysis occurs maximally at plasma concentration of >0.7 mmol/l. Assuming that all hydrolysis of glycerophosphate takes place in plasma, about 12-15 mmol of sodium glycerophosphate will be hydrolysed each day in individuals with normal serum alkaline phosphatase.No pharmacokinetical data is available for infants, however with the recommended dosage hyperphosphataemia is unlikely.4.3 Preclinical safety dataPreclinical safety studies on Glycophos demonstrated good tolerance.5. PHARMACEUTICAL PARTICULARS 5.1 List of excipientsHydrochloric acidWater for Injections 5.2 IncompatibilitiesGlycophos may only be added to or mixed with other medicinal products for which compatibility has been documented. See 5.6.5.3 Shelf life3 years5.4 Special precautions for storageDo not store above 25C. Do not freeze.5.5 Nature and contents of containerPolypropylene vial. Pack size: 10 20 ml5.6 Instructions for use/handlingGlycophos must not be given undiluted.CompatibilityAdditions should be made aseptically.Up to 120 ml of Glycophos and 48 mmol of calcium (as CaCl2) can be added to 1000 ml Vamin Glucose, Vamin Electrolyte Free, Vamin 14, Vamin 14 Electrolyte Free, Vamin 18 Electrolyte Free and Vaminolact. Up to 10 ml of Glycophos and 10 mmol of calcium (as CaCl2) can be added to 1000 ml Glucose 50 mg/ml.Up to 20 ml of Glycophos and 20 mmol of calcium (as CaCl2) can be added to 1000 ml Glucose 200 mg/ml.Up to 60 mmol of Glycophos and 24 mmol of calcium (as CaCl2) can be added to 1000 ml Glucose 500 mg/ml.Infusion timeThe infusion time should not be less than hours.StabilityWhen additions are made to an infusion solution, the infusion should be completed within 24 hours from preparation to prevent microbiological contamination. The left over contents of opened bottles/vials/ampoules should be discarded and not kept for later use.