Insulin Aspart Protamine and Insulin Aspart Injectable Suspension Mix 70/30 HIGHLIGHTS OF PRESCRIBING INFORMATION • Insulin Aspart Protamine and Insulin Aspart Injectable Discontinue Insulin Aspart Protamine and Insulin Aspart These highlights do not include all the information Suspension Mix 70/30 is typically dosed twice-daily (with Injectable Suspension Mix 70/30, treat, and monitor, if needed to use Insulin Aspart Protamine and Insulin each dose intended to cover 2 meals or a meal and a snack) indicated (5.5). Aspart Injectable Suspension Mix 70/30 safely and (2.2). • Hypokalemia: May be life-threatening. Monitor potassium effectively. See full prescribing information for • Individualize dosage based on metabolic needs, blood levels in patients at risk of hypokalemia and treat if indicated Insulin Aspart Protamine and Insulin Aspart Injectable glucose monitoring results, glycemic control goal (2.2). (5.6). Suspension Mix 70/30. • Dosage adjustments may be needed with changes in physical • Fluid retention and heart failure with concomitant use of Insulin Aspart Protamine and Insulin Aspart Injectable activity, changes in meal patterns (i.e., macronutrient content thiazolidinediones (TZDs): Observe for signs and symptoms Suspension Mix 70/30, for subcutaneous use or timing of food intake), changes in renal or hepatic function of heart failure; consider dosage reduction or discontinuation Initial U.S. Approval: 2001 or during acute illness (2.2). if heart failure occurs (5.7). • Dosage adjustment may be needed when switching from ——— ADVERSE REACTIONS ——— ——— RECENT MAJOR CHANGES ——— another insulin to Insulin Aspart Protamine and Insulin Dosage and Administration (2.1) ----------------------- 11/2019 Aspart Injectable Suspension Mix 70/30 (2.2). Adverse reactions observed with insulin therapy include Warnings and Precautions (5.2) ------------------------ 11/2019 hypoglycemia, allergic reactions, local injection site reactions, ——— DOSAGE FORMS AND STRENGTHS ——— lipodystrophy, rash and pruritus (6). ——— INDICATIONS AND USAGE ——— Injectable suspension: 100 units per mL (U-100) of Insulin To report SUSPECTED ADVERSE REACTIONS, Insulin Aspart Protamine and Insulin Aspart Injectable Aspart Protamine and Insulin Aspart Injectable Suspension Mix contact Novo Nordisk Pharma, Inc. at 1-800-727-6500 Suspension Mix 70/30 is a mixture of insulin aspart protamine, 70/30, 70% insulin aspart protamine and 30% insulin aspart or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. an intermediate-acting human insulin analog, and insulin aspart, available as: ——— DRUG INTERACTIONS ——— a rapid-acting human insulin analog, indicated to improve • 10 mL multiple-dose vial (3) glycemic control in patients with diabetes mellitus. • Drugs that may increase the risk of hypoglycemia: • 3 mL single-patient-use Insulin Aspart Protamine and Insulin antidiabetic agents, ACE inhibitors, angiotensin II receptor Limitations of Use: ® Aspart Injectable Suspension Mix 70/30 FlexPen (3) blocking agents, disopyramide, fibrates, fluoxetine, • Not recommended for the treatment of diabetic ketoacidosis. ——— CONTRAINDICATIONS ——— monoamine oxidase inhibitors, pentoxifylline, pramlintide, • The proportions of rapid-acting and long-acting insulins • Do not use during episodes of hypoglycemia (4). propoxyphene, salicylates, somatostatin analog (e.g., are fixed and do not allow for basal versus prandial dose octreotide), and sulfonamide antibiotics (7). adjustments (1). • Do not use in patients with hypersensitivity to Insulin Aspart Protamine and Insulin Aspart Injectable Suspension Mix • Drugs that may decrease the blood glucose lowering effect: ——— DOSAGE AND ADMINISTRATION ——— 70/30 or one of its excipients (4). atypical antipsychotics, corticosteroids, danazol, diuretics, estrogens, glucagon, isoniazid, niacin, oral contraceptives, • Inject Insulin Aspart Protamine and Insulin Aspart Injectable phenothiazines, progestogens (e.g., in oral contraceptives), Suspension Mix 70/30 subcutaneously in the abdominal ——— WARNINGS AND PRECAUTIONS ——— protease inhibitors, somatropin, sympathomimetic agents region, buttocks, thigh, or upper arm (2.1). • Never share a Insulin Aspart Protamine and Insulin Aspart Injectable Suspension Mix 70/30 FlexPen® between (e.g., albuterol, epinephrine, terbutaline), and thyroid • Administer the dose within 15 minutes before meal initiation. hormones (7). For patients with type 2 diabetes, the dose may also be given patients, even if the needle is changed (5.1). • Hyperglycemia or hypoglycemia with changes in insulin • Drugs that may increase or decrease the blood glucose after meal initiation (2.1). lowering effect: alcohol, beta-blockers, clonidine, lithium • Rotate injection sites within the same region from one regimen: Make changes to a patient’s insulin regimen (e.g., insulin strength, manufacturer, type, injection site or method salts, and pentamidine (7). injection to the next to reduce risk of lipodystrophy and • Drugs that may blunt the signs and symptoms of localized cutaneous amyloidosis (2.1). of administration) under close medical supervision with increased frequency of blood glucose monitoring (5.2). hypoglycemia: beta-blockers, clonidine, guanethidine, and • Inspect visually before use. Appearance should be uniformly reserpine (7). white and cloudy. Do not use it if it looks clear or if it • Hypoglycemia: May be life-threatening. Increase frequency contains solid particles (2.1). of glucose monitoring with changes to: insulin dosage, co-administered glucose lowering medications, meal See 17 for PATIENT COUNSELING INFORMATION and • Insulin Aspart Protamine and Insulin Aspart Injectable pattern, physical activity; and in patients with renal or FDA-approved patient labeling. Suspension Mix 70/30 must be resuspended immediately hepatic impairments and hypoglycemia unawareness (5.3). Revised: 10/2020 before use. Resuspension is easier when the insulin has reached room temperature (2.1). • Medication Errors: Accidental mix-ups between insulin products can occur. Instruct patients to check insulin labels • Do not administer intravenously or use in insulin infusion before injection (5.4). pumps (2.1). • Hypersensitivity reactions: Severe, life-threatening, generalized allergy, including anaphylaxis, may occur. FULL PRESCRIBING INFORMATION: CONTENTS* 6 ADVERSE REACTIONS 13 NONCLINICAL TOXICOLOGY 1 INDICATIONS AND USAGE 6.1 Clinical Trial Experience 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility 2 DOSAGE AND ADMINISTRATION 6.2 Immunogenicity 13.2 Animal Toxicology and/or Pharmacology 2.1 Important Administration Information 6.3 Postmarketing Experience 14 CLINICAL STUDIES 2.2 Dosage Information 7 DRUG INTERACTIONS 8 USE IN SPECIFIC POPULATIONS 14.1 Clinical Studies in Adult Patients with Type 1 and 2.3 Dosage Adjustment Due to Drug Interactions Type 2 Diabetes 3 DOSAGE FORMS AND STRENGTHS 8.1 Pregnancy 8.2 Lactation 14.2 Clinical Studies in Adult Patients with Type 2 4 CONTRAINDICATIONS Diabetes with Insulin and Oral Antidiabetic Agents 8.4 Pediatric Use 5 WARNINGS AND PRECAUTIONS 16 HOW SUPPLIED/STORAGE AND HANDLING 8.5 Geriatric Use 5.1 Never Share Insulin Aspart Protamine and Insulin 16.1 How Supplied ® 8.6 Renal Impairment Aspart Injectable Suspension Mix 70/30 FlexPen 16.2 Recommended Storage Between Patients 8.7 Hepatic Impairment 17 PATIENT COUNSELING INFORMATION 5.2 Hyperglycemia or Hypoglycemia with Changes in 10 OVERDOSAGE Insulin Regimen * Sections or subsections omitted from the full prescribing 11 DESCRIPTION information are not listed. 5.3 Hypoglycemia 12 CLINICAL PHARMACOLOGY 5.4 Hypoglycemia Due to Medication Errors 12.1 Mechanism of Action 5.5 Hypersensitivity and Allergic Reactions 12.2 Pharmacodynamics 5.6 Hypokalemia 12.3 Pharmacokinetics 5.7 Fluid Retention and Heart Failure with Concomitant Use of PPAR-gamma Agonists 1 Insulin Aspart Protamine and Insulin Aspart Injectable Suspension Mix 70/30 2 FULL PRESCRIBING INFORMATION 2.3 Dosage Adjustment Due to Drug Interactions Risk Mitigation Strategies for Hypoglycemia • Dosage adjustment may be needed when Insulin Aspart Patients and caregivers must be educated to recognize and 1 INDICATIONS AND USAGE Protamine and Insulin Aspart Injectable Suspension Mix manage hypoglycemia. Self-monitoring of blood glucose Insulin Aspart Protamine and Insulin Aspart Injectable 70/30 is co-administered with certain drugs [see Drug plays an essential role in the prevention and management of Suspension Mix 70/30 is a mixture of insulin aspart protamine Interactions (7)]. hypoglycemia; increased frequency of blood glucose monitoring and insulin aspart indicated to improve glycemic control in is recommended. In patients at higher risk for hypoglycemia patients with diabetes mellitus. 3 DOSAGE FORMS AND STRENGTHS and patients who have reduced symptomatic awareness of Limitations of Use: Injectable suspension: 100 units per mL (U-100) of Insulin Aspart hypoglycemia, increased frequency of blood glucose monitoring • Insulin Aspart Protamine and Insulin Aspart Injectable Protamine and Insulin Aspart Injectable Suspension Mix 70/30, is recommended. Suspension Mix 70/30 is not recommended for the treatment 70% insulin aspart protamine and 30% insulin aspart, is a white and cloudy suspension available as: 5.4 Hypoglycemia Due to Medication Errors of diabetic ketoacidosis. Accidental mix-ups between Insulin Aspart Protamine and • The proportions of rapid-acting and long-acting insulins • 10 mL multiple-dose vial Insulin Aspart Injectable Suspension Mix 70/30 and other in Insulin Aspart