INFORMATION FOR PATIENTS SECTION.


17 PATIENT COUNSELING INFORMATION HypoglycemiaInform patients that hypoglycemia is the most common adverse reaction with insulin. Inform patients that their ability to concentrate and react may be impaired as result of hypoglycemia.Hypersensitivity ReactionsAdvise patients that hypersensitivity reactions have occurred with insulin human injection [see Warnings and Precautions (5.3)].

LACTATION SECTION.


8.2 Lactation Risk SummaryAvailable data from published literature suggest that exogenous human insulin products, including insulin human injection, are transferred into human milk. There are no adverse reactions reported in the breastfed infants in the literature. There are no data on the effects of exogenous human insulin products, including MYXREDLIN, on milk production. The developmental and health benefits of breastfeeding should be considered along with the mothers clinical need for MYXREDLIN and any potential adverse effects on the breastfed infant from MYXREDLIN or from the underlying maternal condition.

MECHANISM OF ACTION SECTION.


12.1 Mechanism of Action The primary activity of insulin, including MYXREDLIN is the regulation of glucose metabolism. Insulins lower blood glucose by stimulating peripheral glucose uptake, especially by skeletal muscle and fat, and by inhibiting hepatic glucose production. Insulin inhibits lipolysis and proteolysis, and enhances protein synthesis.

NONCLINICAL TOXICOLOGY SECTION.


13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Standard 2-year carcinogenicity studies in animals have not been performed to evaluate the carcinogenic potential of insulin human injection.Human insulin is not mutagenic in the following in vitro tests: The chromosomal aberration assay in human lymphocytes, the micronucleus assay in mouse polychromatic erythrocytes, and the mutation frequency assay in Chinese hamster cells.Standard reproduction and teratology studies in animals, including fertility assessments have not been conducted with insulin human injection.

OVERDOSAGE SECTION.


10 OVERDOSAGE Excess insulin administration may cause hypoglycemia and hypokalemia. More severe episodes with coma, seizure, or neurologic impairment can be treated with intramuscular or subcutaneous glucagon or intravenous glucose. Sustained monitoring may be necessary because hypoglycemia may recur after apparent clinical recovery. Hypokalemia must be corrected appropriately. [see Warnings and Precautions (5.2, 5.4)].

ADVERSE REACTIONS SECTION.


6 ADVERSE REACTIONS The following adverse reactions are also discussed elsewhere in the labeling:oHypoglycemia [see Warnings and Precautions (5.2)]oHypersensitivity Reactions [see Warnings and Precautions (5.3)]oHypokalemia [see Warnings and Precautions (5.4)]Adverse Reactions from Clinical Studies or Postmarketing Reports The following additional adverse reactions have been identified during clinical studies or from postmarketing reports with use of insulin human injection. Because some of these reactions are reported voluntarily from population of uncertain size, it is not always possible to reliably estimate their frequency or to establish causal relationship to drug exposure.Adverse reactions associated with insulin initiation and glucose control intensification Intensification or rapid improvement in glucose control has been associated with transitory, reversible ophthalmologic refraction disorder, worsening of diabetic retinopathy, and acute painful peripheral neuropathy. Over the long-term, improved glycemic control decreases the risk of diabetic retinopathy and neuropathy.Hypersensitivity reactions Severe, life-threatening, generalized allergy, including anaphylaxis.Hypoglycemia Hypoglycemia is the most commonly observed adverse reaction with MYXREDLIN.Hypokalemia MYXREDLIN can cause shift in potassium from the extracellular to intracellular space, possibly leading to hypokalemia.Peripheral edema Insulins, including MYXREDLIN, may cause sodium retention and edema, particularly if previously poor metabolic control is improved by intensified insulin therapy.Weight gain Weight gain can occur with insulin therapies, including MYXREDLIN, and has been attributed to the anabolic effects of insulin and the decrease in glucosuria.Immunogenicity As with all therapeutic peptides, insulin administration may cause anti-insulin antibodies to form. Increases in titers of anti-insulin antibodies that react with human insulin have been observed in patients treated with subcutaneous insulin human injection.. oHypoglycemia [see Warnings and Precautions (5.2)]. oHypersensitivity Reactions [see Warnings and Precautions (5.3)]. oHypokalemia [see Warnings and Precautions (5.4)]. Adverse reactions observed with insulin human injection include hypoglycemia, allergic reactions, weight gain and edema (6).To report SUSPECTED ADVERSE REACTIONS, contact Baxter Healthcare at 1-866-888-2472 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION.


13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Standard 2-year carcinogenicity studies in animals have not been performed to evaluate the carcinogenic potential of insulin human injection.Human insulin is not mutagenic in the following in vitro tests: The chromosomal aberration assay in human lymphocytes, the micronucleus assay in mouse polychromatic erythrocytes, and the mutation frequency assay in Chinese hamster cells.Standard reproduction and teratology studies in animals, including fertility assessments have not been conducted with insulin human injection.

CLINICAL PHARMACOLOGY SECTION.


12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action The primary activity of insulin, including MYXREDLIN is the regulation of glucose metabolism. Insulins lower blood glucose by stimulating peripheral glucose uptake, especially by skeletal muscle and fat, and by inhibiting hepatic glucose production. Insulin inhibits lipolysis and proteolysis, and enhances protein synthesis.. 12.2 Pharmacodynamics MYXREDLIN is short-acting insulin. The time course of insulin action (i.e., glucose lowering) may vary considerably in different individuals, within the same individual, and different doses. In double-blind, randomized, crossover, euglycemic glucose clamp study described below, the average onset of action, defined as start of intravenous glucose infusion during the clamp, was approximately 21 minutes after starting of the intravenous infusion administration. The glucose infusion rate gradually increased to maximum response of 13.7 mg/kg/min after hours of human insulin infusion.. 12.3 Pharmacokinetics In double-blind, randomized, crossover, euglycemic glucose clamp study, fifty eight healthy male subjects between 19 and 50 years of age received an intravenous infusion of either MYXREDLIN or another human insulin at milliUnit/kg/min for hours (0.36 units/kg total dose). On average, insulin concentrations of about 300 pM were attained approximately from 1.5 hours to hours after starting intravenous infusion of MYXREDLIN, followed by return to the baseline level 1.5 hours after stopping intravenous infusion.Metabolism and EliminationThe mean terminal half-life from concentration data after stopping the intravenous infusion was estimated to be 23.4 minutes in healthy volunteers.Specific PopulationThe effects of gender, age, obesity, renal and hepatic impairment on the pharmacodynamics and pharmacokinetics of insulin human injection have not been studied.

CONTRAINDICATIONS SECTION.


4 CONTRAINDICATIONS MYXREDLIN is contraindicated:oDuring episodes of hypoglycemiaoIn patients with hypersensitivity to insulin human or any of the excipients in MYXREDLIN. oDuring episodes of hypoglycemia. oIn patients with hypersensitivity to insulin human or any of the excipients in MYXREDLIN. oDuring episodes of hypoglycemia (4)oHypersensitivity to insulin human or any of the excipients in MYXREDLIN (4). oDuring episodes of hypoglycemia (4). oHypersensitivity to insulin human or any of the excipients in MYXREDLIN (4).

DESCRIPTION SECTION.


11 DESCRIPTION Insulin human is short-acting human insulin. It is polypeptide hormone and is produced by recombinant DNA technology, utilizing Pichia pastoris (a yeast) as the production organism. Insulin human is regular human insulin and has the empirical formula C257H383N65O77S6 and molecular weight of 5808.Figure 1: Structural formula of Insulin HumanMYXREDLIN (insulin human) in 0.9% sodium chloride injection for intravenous use is sterile, preservative-free, nonpyrogenic, clear, aqueous, and colorless solution supplied in 100 mL GALAXY single-dose container. MYXREDLIN contains 100 units of insulin human in 100 milliliters of 0.9% sodium chloride injection. Each milliliter of solution contains unit Insulin Human, USP; 0.412 mg Dibasic Sodium Phosphate Anhydrous, USP; 0.29 mg Monobasic Sodium Phosphate Monohydrate, USP; mg Sodium Chloride, USP; and Water for Injection, USP. The pH range is 6.5-7.2.. Structural Formula Insulin Human.

DOSAGE & ADMINISTRATION SECTION.


2 DOSAGE AND ADMINISTRATION oInspect MYXREDLIN visually before use. It should appear clear and colorless. Do not use MYXREDLIN if particulate matter or coloration is seen. (2.1)oAdminister MYXREDLIN intravenously ONLY under medical supervision with close monitoring of blood glucose and potassium levels.(2.1)oDo not add supplementary medication or additives. (2.1)oDo not use in series connections. (2.1)oDo not shake or freeze. Discard unused portion. (2.1)oIndividualize dose based on metabolic needs, blood glucose monitoring results, and glycemic control goal. (2.2)oDosage adjustments may be needed with changes in nutrition, renal, or hepatic function or during acute illness. (2.2). oInspect MYXREDLIN visually before use. It should appear clear and colorless. Do not use MYXREDLIN if particulate matter or coloration is seen. (2.1). oAdminister MYXREDLIN intravenously ONLY under medical supervision with close monitoring of blood glucose and potassium levels.(2.1). oDo not add supplementary medication or additives. (2.1). oDo not use in series connections. (2.1). oDo not shake or freeze. Discard unused portion. (2.1). oIndividualize dose based on metabolic needs, blood glucose monitoring results, and glycemic control goal. (2.2). oDosage adjustments may be needed with changes in nutrition, renal, or hepatic function or during acute illness. (2.2). 2.1 Important Administration Instructions oInspect MYXREDLIN visually before use. It should appear clear and colorless. Do not use MYXREDLIN if particulate matter or coloration is seen.oAdminister MYXREDLIN intravenously ONLY under medical supervision with close monitoring of blood glucose and potassium levels [see Warnings and Precautions (5.2, 5.4)].oDo not add supplementary medication or additives.oDo not use in series connections.oDo not shake. Do not freeze. Discard any unused portion.. oInspect MYXREDLIN visually before use. It should appear clear and colorless. Do not use MYXREDLIN if particulate matter or coloration is seen.. oAdminister MYXREDLIN intravenously ONLY under medical supervision with close monitoring of blood glucose and potassium levels [see Warnings and Precautions (5.2, 5.4)].. oDo not add supplementary medication or additives.. oDo not use in series connections.. oDo not shake. Do not freeze. Discard any unused portion.. 2.2 Dosage Information oIndividualize and adjust the dosage of MYXREDLIN based on the individuals metabolic needs, blood glucose monitoring results, and glycemic control goal.oDosage adjustments may be needed with changes in nutrition, changes in renal or hepatic function or during acute illness [see Warnings and Precautions (5.1, 5.2) and Use in Specific Populations (8.6, 8.7)].. oIndividualize and adjust the dosage of MYXREDLIN based on the individuals metabolic needs, blood glucose monitoring results, and glycemic control goal.. oDosage adjustments may be needed with changes in nutrition, changes in renal or hepatic function or during acute illness [see Warnings and Precautions (5.1, 5.2) and Use in Specific Populations (8.6, 8.7)].. 2.3 Dosage Adjustment due to Drug Interactions oDosage adjustment may be needed when MYXREDLIN is used concomitantly with certain drugs [see Drug Interactions (7)].. oDosage adjustment may be needed when MYXREDLIN is used concomitantly with certain drugs [see Drug Interactions (7)].

DOSAGE FORMS & STRENGTHS SECTION.


3 DOSAGE FORMS AND STRENGTHS Injection: 100 units insulin human in 100 mL of 0.9% sodium chloride (1 unit per mL) as clear, colorless solution in single-dose container.. Injection: 100 units insulin human in 100 mL of 0.9% sodium chloride (1 unit/mL) in single-dose container (3).

DRUG INTERACTIONS SECTION.


7 DRUG INTERACTIONS Table 1: Clinically Significant Drug Interactions with MYXREDLINDrugs that May Increase the Risk of HypoglycemiaDrugs:Antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, pramlintide, salicylates, somatostatin analog (e.g., octreotide), and sulfonamide antibiotics.Intervention:Dose adjustment and increased frequency of glucose monitoring may be required when MYXREDLIN is co-administered with these drugs.Drugs that May Decrease the Blood Glucose Lowering Effect of MYXREDLINDrugs:Atypical antipsychotics (e.g., olanzapine and clozapine), corticosteroids, danazol, diuretics, estrogens, glucagon, isoniazid, niacin, oral contraceptives, phenothiazines, progestogens (e.g., in oral contraceptives), protease inhibitors, somatropin, sympathomimetic agents (e.g., albuterol, epinephrine, terbutaline), and thyroid hormones.Intervention:Dose adjustment and increased frequency of glucose monitoring may be required when MYXREDLIN is co-administered with these drugs.Drugs that May Increase or Decrease the Blood Glucose Lowering Effect of MYXREDLINDrugs:Alcohol, beta-blockers, clonidine, and lithium salts. Pentamidine may cause hypoglycemia, which may sometimes be followed by hyperglycemia.Intervention:Dose adjustment and increased frequency of glucose monitoring may be required when MYXREDLIN is co-administered with these drugs.Drugs that May Blunt Signs and Symptoms of HypoglycemiaDrugs:Beta-blockers, clonidine, guanethidine, and reserpine.Intervention:Increased frequency of glucose monitoring may be required when MYXREDLIN is co-administered with these drugs.. oDrugs that may increase the risk of hypoglycemia: antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, pramlintide, salicylates, somatostatin analog (e.g., octreotide), and sulfonamide antibiotics. (7)oDrugs that may decrease the blood glucose lowering effect: atypical antipsychotics, corticosteroids, danazol, diuretics, estrogens, glucagon, isoniazid, niacin, oral contraceptives, phenothiazines, progestogens (e.g., in oral contraceptives), protease inhibitors, somatropin, sympathomimetic agents (e.g., albuterol, epinephrine, terbutaline), and thyroid hormones. (7)oDrugs that may increase or decrease the blood glucose lowering effect: Alcohol, beta-blockers, clonidine, lithium salts, and pentamidine. (7)oDrugs that may blunt the signs and symptoms of hypoglycemia: beta-blockers, clonidine, guanethidine, and reserpine. (7). oDrugs that may increase the risk of hypoglycemia: antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, pramlintide, salicylates, somatostatin analog (e.g., octreotide), and sulfonamide antibiotics. (7). oDrugs that may decrease the blood glucose lowering effect: atypical antipsychotics, corticosteroids, danazol, diuretics, estrogens, glucagon, isoniazid, niacin, oral contraceptives, phenothiazines, progestogens (e.g., in oral contraceptives), protease inhibitors, somatropin, sympathomimetic agents (e.g., albuterol, epinephrine, terbutaline), and thyroid hormones. (7). oDrugs that may increase or decrease the blood glucose lowering effect: Alcohol, beta-blockers, clonidine, lithium salts, and pentamidine. (7). oDrugs that may blunt the signs and symptoms of hypoglycemia: beta-blockers, clonidine, guanethidine, and reserpine. (7).

GERIATRIC USE SECTION.


8.5 Geriatric Use The effect of age on the pharmacokinetics and pharmacodynamics of insulin human injection has not been studied.Elderly patients using MYXREDLIN, may be at increased risk of hypoglycemia due to co-morbid disease [see Warnings and Precautions (5.2)].

HOW SUPPLIED SECTION.


16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied MYXREDLIN (insulin human) in 0.9% sodium chloride injection contains 100 units/100 mL (1 unit/mL) of insulin human in 0.9% sodium chloride and is clear, colorless solution available as: 100 mL single-dose GALAXY container, package of 12, NDC 0338-0126-12. 100 mL single-dose GALAXY container, package of 12, NDC 0338-0126-12. 16.2 Storage and Handling Store MYXREDLIN in the refrigerator (36F to 46F [2C to 8C]) in the original carton to protect from light. Do not use after the expiration date printed on the carton and container label.If needed, MYXREDLIN may be removed from the original carton and stored at room temperature up to 77F (25C) for up to 30 days. Once stored at room temperature, do not place back in the refrigerator. Discard MYXREDLIN after 30 days if stored at room temperature.Do not freeze and do not use MYXREDLIN if it has been frozen. Do not shake.

INDICATIONS & USAGE SECTION.


1 INDICATIONS AND USAGE MYXREDLIN is indicated to improve glycemic control in adults and pediatric patients with diabetes mellitus.. MYXREDLIN is short-acting human insulin indicated to improve glycemic control in adults and pediatric patients with diabetes mellitus (1).

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.


PACKAGE/LABEL PRINCIPAL DISPLAY PANEL NDC 0338-0126-12MYXREDLINInsulin Humanin 0.9% Sodium Chloride Injection100 units per 100 mL(1 unit mL)100 mL Single-Dose GALAXY containerDiscard unused portionFor Intravenous Infusion Only(REGULAR) Insulin HumanSterile NonpyrogenicCautions: Do not add supplemental medication or additives.Must not be used in series connections. Check for minute leaks andsolution clarity.Each mL contains: unit Insulin Human, USP; 0.412 mg Dibasic SodiumPhosphate Anhydrous, USP; 0.29 mg Monobasic Sodium PhosphateMonohydrate, USP; mg Sodium Chloride, USP; and Water for Injection,USP.Dosage: See prescribing information.Rx onlyStore refrigerated at 36F to 46F (2C to 8C) in the original carton toprotect from light. Do Not Shake. Do Not Freeze.If needed, may store at room temperature up to 77F (25C) up to30 days. Discard after 30 days if stored at room temperature.Baxter logoBaxter, Galaxy and Myxredlin are trademarks of Baxter International Inc.Baxter Healthcare CorporationDeerfield, IL 60015 USAU.S. License no. 0140Code 2G3322PL 2501 Plastic Product of USA07-34-00-0510NDC 0338-0126-12Code 2G3322MYXREDLINInsulin Humanin 0.9% Sodium Chloride Injection 100 units per 100 mL(1 unit mL)For Intravenous Infusion Only (REGULAR) Insulin HumanUSE CARTON TO PROTECT CONTENTSFROM LIGHT WHILE REFRIGERATEDRx Only1 Single-Dose Galaxy containerDiscard unused portionBaxter LogoFor Intravenous Infusion OnlyMYXREDLINInsulin Humanin 0.9% Sodium Chloride InjectionCONTAINS INSULIN HUMAN100 units per 100 mL(1 unit/mL)NDC 0338-0126-12MYXREDLINInsulin Humanin 0.9% Sodium Chloride Injection (1 unit/mL)UNVARNISHED AREA FOR ON-LINEPRINTING OF LOT AND EXPUPC-ABar CodePlacementSterile, NonpyrogenicEach mL contains: unit Insulin Human, USP; 0.412 mg Dibasic Sodium Phosphate Anhydrous,USP; 0.29 mg Monobasic Sodium Phosphate Monohydrate, USP; mg Sodium Chloride, USP;and Water for Injection, USP. No preservative.Dosage: For Intravenous Infusion Only. See prescribing information.Caution: Do not add supplemental medication or additives.Rx onlyStore refrigerated at 36F to 46F (2C to 8C) in the original carton to protect from light.Do Not Shake. Do Not Freeze.If needed, may store MYXREDLIN at room temperature up to 77F (25C) up to 30 days.Once stored at room temperature, do not place back in the refrigerator.Discard after 30 days if stored at room temperature.Discard 30 days after storing at room temperature. Discard After:(Month) (Day) (Year)(to be completed by dispensing pharmacist)Baxter, Galaxy and Myxredlin are registered trademarks of Baxter International Inc.Baxter Healthcare CorporationDeerfield, IL 60015 USAU.S. License no. 0140Product of USA 07-01-00-0251 MYXREDLINInsulin Humanin 0.9% Sodium Chloride Injection100 units per 100 mL (1 unit/mL)EXP: JUN 21LOT NC125840 Bar Code (01)50803380126120(17)210630(21)100000002582(10)NC125840Contains: 12 100 mL Single-Dose GALAXY ContainersNDC 0338-0126-12Code 2G3322Store refrigerated at 36F to 46F (2C to 8C) Do Not Shake. Do Not Freeze.If needed, may store at room temperature up to 77F (25C) up to 30 days.Once stored at room temperature, do not place back in the refrigerator.Discard after 30 days if stored at room temperature.Bar Code GTIN50303380126120SERIAL100000002582EXP210630LOTNC125840Rx OnlyBaxter LogoBaxter Healthcare CorporationDeerfield, IL 60015 USA07-06-00-0789G Representative Container lbl 0338-0126-12 panel of 2. Representative Container lbl 0338-0126-12 panel of 2. Representative Carton Label 0338-0126-12. Representative serialzied shipper label.

PEDIATRIC USE SECTION.


8.4 Pediatric Use MYXREDLIN is indicated to improve glycemic control in pediatric patients with diabetes mellitus.The dosage of MYXREDLIN must be individualized in pediatric patients based on metabolic needs and frequent monitoring of blood glucose to reduce the risk of hypoglycemia [see Dosage and Administration (2.2) and Warnings and Precautions (5.2)].

PHARMACODYNAMICS SECTION.


12.2 Pharmacodynamics MYXREDLIN is short-acting insulin. The time course of insulin action (i.e., glucose lowering) may vary considerably in different individuals, within the same individual, and different doses. In double-blind, randomized, crossover, euglycemic glucose clamp study described below, the average onset of action, defined as start of intravenous glucose infusion during the clamp, was approximately 21 minutes after starting of the intravenous infusion administration. The glucose infusion rate gradually increased to maximum response of 13.7 mg/kg/min after hours of human insulin infusion.

PHARMACOKINETICS SECTION.


12.3 Pharmacokinetics In double-blind, randomized, crossover, euglycemic glucose clamp study, fifty eight healthy male subjects between 19 and 50 years of age received an intravenous infusion of either MYXREDLIN or another human insulin at milliUnit/kg/min for hours (0.36 units/kg total dose). On average, insulin concentrations of about 300 pM were attained approximately from 1.5 hours to hours after starting intravenous infusion of MYXREDLIN, followed by return to the baseline level 1.5 hours after stopping intravenous infusion.Metabolism and EliminationThe mean terminal half-life from concentration data after stopping the intravenous infusion was estimated to be 23.4 minutes in healthy volunteers.Specific PopulationThe effects of gender, age, obesity, renal and hepatic impairment on the pharmacodynamics and pharmacokinetics of insulin human injection have not been studied.

PREGNANCY SECTION.


8.1 Pregnancy Risk SummaryAvailable data from published studies over decades have not established an association with human insulin use during pregnancy and major birth defects, miscarriage or adverse maternal or fetal outcomes (see Data). There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy (see Clinical Considerations). Animal reproduction studies were not performed.The estimated background risk of major birth defects is 6-10% in women with pre-gestational diabetes with HbA1c >7 and has been reported to be as high as 20-25% in women with HbA1c >10. The estimated background risk of miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.Clinical ConsiderationsDisease-associated maternal and/or embryo/fetal riskPoorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, preeclampsia, spontaneous abortions, preterm delivery, and delivery complications. Poorly controlled diabetes increases the fetal risk for major birth defects, stillbirth, and macrosomia-related morbidity.DataHuman DataWhile available studies cannot definitively establish the absence of risk, published data from retrospective studies, open-label, randomized, parallel studies and meta-analyses have not established an association with human insulin use during pregnancy and major birth defects, miscarriage, or adverse maternal or fetal outcomes. All available studies have methodological limitations including lack of blinding, unclear methods of randomization, and small sample size.

SPL UNCLASSIFIED SECTION.


2.1 Important Administration Instructions oInspect MYXREDLIN visually before use. It should appear clear and colorless. Do not use MYXREDLIN if particulate matter or coloration is seen.oAdminister MYXREDLIN intravenously ONLY under medical supervision with close monitoring of blood glucose and potassium levels [see Warnings and Precautions (5.2, 5.4)].oDo not add supplementary medication or additives.oDo not use in series connections.oDo not shake. Do not freeze. Discard any unused portion.. oInspect MYXREDLIN visually before use. It should appear clear and colorless. Do not use MYXREDLIN if particulate matter or coloration is seen.. oAdminister MYXREDLIN intravenously ONLY under medical supervision with close monitoring of blood glucose and potassium levels [see Warnings and Precautions (5.2, 5.4)].. oDo not add supplementary medication or additives.. oDo not use in series connections.. oDo not shake. Do not freeze. Discard any unused portion.

STORAGE AND HANDLING SECTION.


16.2 Storage and Handling Store MYXREDLIN in the refrigerator (36F to 46F [2C to 8C]) in the original carton to protect from light. Do not use after the expiration date printed on the carton and container label.If needed, MYXREDLIN may be removed from the original carton and stored at room temperature up to 77F (25C) for up to 30 days. Once stored at room temperature, do not place back in the refrigerator. Discard MYXREDLIN after 30 days if stored at room temperature.Do not freeze and do not use MYXREDLIN if it has been frozen. Do not shake.

USE IN SPECIFIC POPULATIONS SECTION.


8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk SummaryAvailable data from published studies over decades have not established an association with human insulin use during pregnancy and major birth defects, miscarriage or adverse maternal or fetal outcomes (see Data). There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy (see Clinical Considerations). Animal reproduction studies were not performed.The estimated background risk of major birth defects is 6-10% in women with pre-gestational diabetes with HbA1c >7 and has been reported to be as high as 20-25% in women with HbA1c >10. The estimated background risk of miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.Clinical ConsiderationsDisease-associated maternal and/or embryo/fetal riskPoorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, preeclampsia, spontaneous abortions, preterm delivery, and delivery complications. Poorly controlled diabetes increases the fetal risk for major birth defects, stillbirth, and macrosomia-related morbidity.DataHuman DataWhile available studies cannot definitively establish the absence of risk, published data from retrospective studies, open-label, randomized, parallel studies and meta-analyses have not established an association with human insulin use during pregnancy and major birth defects, miscarriage, or adverse maternal or fetal outcomes. All available studies have methodological limitations including lack of blinding, unclear methods of randomization, and small sample size.. 8.2 Lactation Risk SummaryAvailable data from published literature suggest that exogenous human insulin products, including insulin human injection, are transferred into human milk. There are no adverse reactions reported in the breastfed infants in the literature. There are no data on the effects of exogenous human insulin products, including MYXREDLIN, on milk production. The developmental and health benefits of breastfeeding should be considered along with the mothers clinical need for MYXREDLIN and any potential adverse effects on the breastfed infant from MYXREDLIN or from the underlying maternal condition.. 8.4 Pediatric Use MYXREDLIN is indicated to improve glycemic control in pediatric patients with diabetes mellitus.The dosage of MYXREDLIN must be individualized in pediatric patients based on metabolic needs and frequent monitoring of blood glucose to reduce the risk of hypoglycemia [see Dosage and Administration (2.2) and Warnings and Precautions (5.2)].. 8.5 Geriatric Use The effect of age on the pharmacokinetics and pharmacodynamics of insulin human injection has not been studied.Elderly patients using MYXREDLIN, may be at increased risk of hypoglycemia due to co-morbid disease [see Warnings and Precautions (5.2)].. 8.6 Renal Impairment The effect of renal impairment on the pharmacokinetics and pharmacodynamics of MYXREDLIN has not been studied. Patients with renal impairment are at increased risk of hypoglycemia and may require more frequent MYXREDLIN dose adjustment and more frequent blood glucose monitoring [see Warnings and Precautions (5.2) ].. 8.7 Hepatic Impairment The effect of hepatic impairment on the pharmacokinetics and pharmacodynamics of MYXREDLIN has not been studied. Patients with hepatic impairment are at increased risk of hypoglycemia and may require more frequent MYXREDLIN dose adjustment and more frequent blood glucose monitoring [see Warnings and Precautions (5.2)].

WARNINGS AND PRECAUTIONS SECTION.


5 WARNINGS AND PRECAUTIONS oHyper- or Hypoglycemia with Changes in Insulin Regimen: Carry out under close medical supervision and increase frequency of blood glucose monitoring. (5.1)oHypoglycemia: May be life-threatening. Factors which may increase the risk include changes in nutrition and co-administered medication and patients with renal or hepatic impairment. Increased frequency of blood glucose monitoring is recommended in patients at increased risk. (5.2)oHypersensitivity Reactions: Severe, life-threatening, generalized allergy, including anaphylaxis, can occur. Discontinue MYXREDLIN, monitor, and treat if indicated. (5.3)oHypokalemia: May be life-threatening. Monitor potassium levels and treat if indicated. (5.4)oFluid Retention and Heart Failure with Concomitant Use of Thiazolidinediones (TZDs): Observe for signs and symptoms of heart failure; consider dosage reduction or discontinuation if heart failure occurs. (5.5). oHyper- or Hypoglycemia with Changes in Insulin Regimen: Carry out under close medical supervision and increase frequency of blood glucose monitoring. (5.1). oHypoglycemia: May be life-threatening. Factors which may increase the risk include changes in nutrition and co-administered medication and patients with renal or hepatic impairment. Increased frequency of blood glucose monitoring is recommended in patients at increased risk. (5.2). oHypersensitivity Reactions: Severe, life-threatening, generalized allergy, including anaphylaxis, can occur. Discontinue MYXREDLIN, monitor, and treat if indicated. (5.3). oHypokalemia: May be life-threatening. Monitor potassium levels and treat if indicated. (5.4). oFluid Retention and Heart Failure with Concomitant Use of Thiazolidinediones (TZDs): Observe for signs and symptoms of heart failure; consider dosage reduction or discontinuation if heart failure occurs. (5.5). 5.1 Hyperglycemia or Hypoglycemia with Changes in Insulin Regimen Changes in insulin strength, manufacturer, type, or method of administration may affect glycemic control and predispose to hypoglycemia [see Warnings and Precautions (5.2)] or hyperglycemia. These changes should be made cautiously and under close medical supervision and the frequency of blood glucose monitoring should be increased.. 5.2 Hypoglycemia Hypoglycemia is the most common adverse reaction of all insulins, including MYXREDLIN. Severe hypoglycemia can cause seizures, may lead to unconsciousness, may be life threatening or cause death. Hypoglycemia can impair concentration ability and reaction time.Hypoglycemia can happen suddenly and symptoms may differ in each individual and change over time in the same individual. Symptomatic awareness of hypoglycemia may be less pronounced in patients with longstanding diabetes, in patients with diabetic nerve disease, in patients using medications that block the sympathetic nervous system (e.g., beta-blockers) [see Drug Interactions (7)], or in patients who experience recurrent hypoglycemia.Risk Factors for Hypoglycemia Factors which may increase the risk of hypoglycemia include changes in nutrition and co-administered medication [see Drug Interactions (7)]. Patients with renal or hepatic impairment may be at higher risk of hypoglycemia [see Use in Specific Populations (8.6, 8.7)].Risk Mitigation Strategies for HypoglycemiaPatients and caregivers must be educated to recognize hypoglycemia. In patients at higher risk for hypoglycemia and patients who have reduced symptomatic awareness of hypoglycemia, increased frequency of blood glucose monitoring is recommended.. 5.3 Hypersensitivity and Allergic Reactions Severe, life-threatening, generalized allergy, including anaphylaxis, can occur with MYXREDLIN. Generalized allergy to insulin may manifest as whole body rash (including pruritus), dyspnea, wheezing, hypotension, tachycardia, or diaphoresis. If hypersensitivity reactions occur, discontinue MYXREDLIN; treat per standard of care and monitor until symptoms and signs resolve. MYXREDLIN is contraindicated in patients who have had hypersensitivity reactions to insulin human or any of the excipients in MYXREDLIN [see Contraindications (4)].. 5.4 Hypokalemia All insulins, including MYXREDLIN, cause shift in potassium from the extracellular to intracellular space, possibly leading to hypokalemia. Untreated hypokalemia may cause respiratory paralysis, ventricular arrhythmia, and death. Monitor potassium levels and treat if indicated.. 5.5 Fluid Retention and Heart Failure with Concomitant Use of PPAR-gamma agonists Thiazolidinediones (TZDs), which are peroxisome proliferator-activated receptor (PPAR)-gamma agonists, can cause dose-related fluid retention, particularly when used in combination with insulin. Fluid retention may lead to or exacerbate heart failure. Patients treated with insulin, including MYXREDLIN, and PPAR-gamma agonist should be observed for signs and symptoms of heart failure. If heart failure develops, it should be managed according to current standards of care, and discontinuation or dose reduction of the PPAR-gamma agonist must be considered.