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1 YOUR GUIDE TO NOVOLOG MIX 70/30 FLEXPEN Take a closer look at NovoLog Mix 70/30 FlexPen novologmix70-30.com What should I consider while using NovoLog Mix 70/30 (70% insulin aspart protamine suspension 30% insulin aspart injection, [rdna origin])? Alcohol, including beer wine, may affect your blood sugar. Be careful when driving a car or operating machinery. You may have difficulty concentrating or reacting if you have low blood sugar. Talk to your health care provider if you often have low blood sugar or no warning signs of low blood sugar. What are the possible side effects of NovoLog Mix 70/30? Low blood sugar, including when too much is taken. Some symptoms include sweating, shakiness, confusion, headache. Severe low blood sugar can cause unconsciousness, seizures, death. Serious allergic reactions may occur. Get medical help right away, if you develop a rash over your whole body, have trouble breathing, a fast heartbeat, or sweating. Other side effects include low potassium in your blood, injection site reactions (like redness, swelling, itching), skin thickening or pits at the injection site, weight gain, swelling of your hs feet, if taken with thiazolidinediones (TZDs) possible heart failure, vision changes. Take a closer look at the difference of NovoLog Mix 70/30 FlexPen 70% insulin aspart protamine suspension 30% insulin aspart injection, (rdna origin) on pages 22-23, including updates related to thiazolidinediones (TZDs), enclosed Prescribing Information Patient Information. One study of people with type 2 diabetes found that NovoLog Mix 70/30 did a better job of reducing aftermeal (postprial) blood glucose levels than did human premix 70/30 insulin. A1C fasting blood glucose levels were similar in both groups. The importance of differences in high after-meal glucose levels between the groups studied as it relates to long-term complications of diabetes has not been established. If you need assistance with prescription drug costs, help may be available. Visit pparx.org or call PPA-NOW. Talk to your doctor about the importance of diet exercise in your treatment plan. on pages 22-23, including updates related to thiazolidinediones (TZDs), enclosed Prescribing Information Patient Information. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit fda.gov/medwatch or call FDA Cornerstones4Care, FlexPen, NovoFine, Novolin, NovoLog are registered trademarks of Novo Nordisk A/S Novo Nordisk Printed in the U.S.A September 2013

2 Introduction YOUR GUIDE TO NOVOLOG MIX 70/30 FLEXPEN (70% insulin aspart protamine suspension 30% insulin aspart injection, [rdna origin]) This guide will help you learn about NovoLog Mix 70/30 FlexPen how it can help you get to your blood sugar goal. Inside, you will find helpful information about different types of premixed insulins, the benefits of NovoLog Mix 70/30 FlexPen, ways to save get ongoing support. With this guide, you ll have the tools you need to help take control of your diabetes. INDICATIONS AND USAGE What is NovoLog Mix 70/30 (70% insulin aspart protamine suspension 30% insulin aspart injection, [rdna origin])? NovoLog Mix 70/30 is a man-made insulin used to control high blood sugar in adults with diabetes mellitus. It is not known if NovoLog Mix 70/30 is safe or effective in children. 2 on pages 22-23, including updates related to thiazolidinediones (TZDs), enclosed Prescribing Information Patient Information.

3 CONTENTS Introduction... 2 The NovoLog Mix 70/30 Difference... 4 Types of Premix Insulins... 5 About NovoLog Mix 70/ FlexPen Features...12 How to Use...14 Resources Support Important Safety Information IMPORTANT SAFETY INFORMATION Who should not use NovoLog Mix 70/30? Do not use NovoLog Mix 70/30 (70% insulin aspart protamine suspension 30% insulin aspart injection, [rdna origin]) if your blood sugar is too low (hypoglycemia) or you are allergic to any of its ingredients. 3

4 Benefits of NovoLog Mix 70/30 WHAT IS NOVOLOG MIX 70/30? NovoLog Mix 70/30 (70% insulin aspart protamine suspension 30% insulin aspart injection, [rdna origin]) is premixed insulin that works in 2 different ways. Types of premixed insulins Similar to fast-acting long-acting insulin, there are also 2 different types of premixed insulin, sometimes referred to as human analog. Human insulin Analog insulin Novolin 70/30 NovoLog Mix 70/30 70% has an extended action to control blood sugar in between meals up to 24 hours 30% acts fast to treat the spikes in sugar levels that happen when you eat NovoLog Mix 70/30 works in these 2 ways to help control blood sugar up to 24 hours in a medical study provided better mealtime coverage than human premixed insulin (ie, Novolin 70/30). NOVOLOG MIX 70/30 ALSO OFFERS F ewer episodes of major hypoglycemia (very Dosing flexibility 15 minutes before or after starting NovoLog Mix 70/30 is an analog insulin. That means it s a man-made medicine, it has some important benefits over regular human insulin (ie, Novolin 70/30). Insulin that is proven in studies to lower A1C NovoLog Mix 70/30 more closely mimics the body s natural release of insulin than human premixed insulin. low blood sugar) than human premixed insulin in a medical study a meal if you have type 2 diabetes NOVOLOG MIX 70/30 COMES IN A FLEXPEN A discreet, prefilled, dial-a-dose insulin pen that doesn t need refrigeration after first use. Once in use, NovoLog Mix 70/30 FlexPen must be kept at room temperature below 86 F for up to 14 days If you re not getting the blood sugar control you need from your human premixed insulin, talk to your doctor about NovoLog Mix 70/30 FlexPen to see if it s right for you. IMPORTANT SAFETY INFORMATION What should I tell my health care provider before taking NovoLog Mix 70/30? About all of your medical conditions, including liver, kidney, or heart problems. If you are pregnant, breastfeeding, or plan to do either. About all prescription nonprescription medicines you take, including supplements, as your dose may need to change. 4 on Safety pagesinformation 22-23, including updates Please see Important throughout related to thiazolidinediones (TZDs), enclosed on pages 22-23, enclosed Prescribing Information Patient Information. Prescribing Information Patient Information. 5

5 NOVOLOG MIX 70/30: 15 min Works fast NovoLog Mix 70/30 major hypos Human premixed insulin Recommended Up to 15 minutes before or after starting meals, to take it 30 minutes before meals It starts working In 30 minutes with type 2 diabetes In 10 to 20 minutes Had fewer cases of very low blood sugar In a medical study, people who took NovoLog Mix 70/30 had 73% fewer episodes of major hypoglycemia (very low blood sugar) compared with those taking human premixed insulin after 1 year. Goes almost anywhere without refrigeration Provides mealtime coverage The 30% in NovoLog Mix 70/30 acts fast to treat the spikes in sugar levels that happen when you eat. IMPORTANT SAFETY INFORMATION How should I take NovoLog Mix 70/30 (70% insulin aspart protamine suspension 30% insulin aspart injection, [rdna origin])? NovoLog Mix 70/30 starts acting fast. If you have type 1 diabetes, inject within 15 minutes before you eat a meal. If you have type 2 diabetes, inject within 15 minutes before or after starting your meal. Inject NovoLog Mix 70/30 under the skin of your stomach area, upper arms, buttocks, or thighs, but never into a vein or muscle. NovoLog Mix 70/30 FlexPen lasts up to 14 days at room temperature (below 86 F) without refrigeration, so it can be taken almost anywhere. NovoLog Mix 70/30 should not be refrigerated once in use. IMPORTANT SAFETY INFORMATION Do not mix NovoLog Mix 70/30 with other insulin products or use in an insulin pump. Do not change your dose or type of insulin unless you are told to by your health care provider. Do not share needles, insulin pens, or syringes. Check your blood sugar levels as directed by your health care provider. on Safety pagesinformation 22-23, including updates Please see Important throughout related to thiazolidinediones (TZDs), enclosed on pages 22-23, enclosed Prescribing Information Information. 6 Patient Prescribing Information Patient Information. 7

6 Blood sugar control up to 24 hours, including mealtimes 2-IN-1 CONTROL NovoLog Mix 70/30 (70% insulin aspart protamine suspension 30% insulin aspart injection, [rdna origin]) works in 2 ways to help control blood sugar. 2 ways Faster onset of action better coverage at mealtime than human premixed insulin in a medical study Extended action that can last up to 24 hours to control blood sugar between meals PROVEN TO LOWER A1C TO HELP YOU GET TO GOAL Your doctor may check your A1C a measure of your blood sugar levels over 2 to 3 months to determine how well your levels have been controlled over time. The American Diabetes Association recommends that an A1C of less than 7% is the goal. Make sure to talk to your doctor about the A1C goal you should be reaching. Studies have shown that NovoLog Mix 70/30 can help lower A1C help more people reach their treatment goals. <7% The ADA recommends an A1C goal of <7% Your A1C is directly affected by your blood sugar levels. Since they go up down together, it is important to keep your blood sugar under control to help reach your A1C treatment goal. A1C Levels IMPORTANT SAFETY INFORMATION What should I consider while using NovoLog Mix 70/30? Alcohol, including beer wine, may affect your blood sugar. Be careful when driving a car or operating machinery. You may have difficulty concentrating or reacting if you have low blood sugar. Talk to your health care provider if you often have low blood sugar or no warning signs of low blood sugar. 8 on Safety pagesinformation 22-23, including updates Please see Important throughout related to thiazolidinediones (TZDs), Information enclosed on pages 22-23, enclosed Prescribing Prescribing Information Patient Information. Patient Information. Average Blood Sugar 6% 126 mg/dl 7% 154 mg/dl 8% 183 mg/dl 9% 212 mg/dl 10% 240 mg/dl 11% 269 mg/dl 12% 298 mg/dl 9

7 FAST ACTING FOR MEALTIME CONTROL NovoLog Mix 70/30 (70% insulin aspart protamine suspension 30% insulin aspart injection, [rdna origin]) works fast to cover increases in blood sugar after meals, keeps working up to 24 hours. If you have type 2 diabetes, you can take NovoLog Mix 70/30 within 15 minutes before or after starting a meal; it begins to work in as little as 10 minutes. With human premixed insulin (ie, Novolin 70/30), it is recommended to wait 30 minutes before eating. LOW RATE OF HYPOGLYCEMIA major hypos Major hypoglycemia, or very low blood sugar, is a very serious side effect that can occur when taking insulin. It can cause passing out, seizures, or death. Symptoms of low blood sugar include the following: Sweating Dizziness or lightheadedness Trouble concentrating or confusion Blurred vision Shakiness Slurred speech Hunger Anxiety, irritability, Fast heartbeat Tingling of lips or mood changes Headache tongue If you have experienced very low blood sugar while on human premixed insulin, talk to your doctor about NovoLog Mix 70/30. In a medical study, people who took NovoLog Mix 70/30 had 73% fewer episodes of major hypoglycemia (very low blood sugar) compared with those taking human premixed insulin (ie, Novolin 70/30) after 1 year. 10 IMPORTANT SAFETY INFORMATION What are the possible side effects of NovoLog Mix 70/30? Low blood sugar, including when too much is taken. Some symptoms include sweating, shakiness, confusion, headache. Severe low blood sugar can cause unconsciousness, seizures, death. Serious allergic reactions may occur. Get medical help right away, if you develop a rash over your whole body, have trouble breathing, a fast heartbeat, or sweating. Other side effects include low potassium in your blood, injection site reactions (like redness, swelling, itching), skin thickening or pits at the injection site, weight gain, swelling of your hs feet, if taken with thiazolidinediones (TZDs) possible heart failure, vision changes. on Safety pagesinformation 22-23, including updates Please see Important throughout related to thiazolidinediones (TZDs), Information enclosed on pages 22-23, enclosed Prescribing Patient Information. Prescribing Information Patient Information. IMPORTANT SAFETY INFORMATION One study of people with type 2 diabetes found that NovoLog Mix 70/30 did a better job of reducing after-meal (postprial) blood glucose levels than did human premix 70/30 insulin. A1C fasting blood glucose levels were similar in both groups. The importance of differences in high after-meal glucose levels between the groups studied as it relates to long-term complications of diabetes has not been established. 11

8 Insulin delivery that goes with you FLEXPEN : A DISCREET, PREFILLED, DIAL-A-DOSE INSULIN PEN NovoLog Mix 70/30 FlexPen (70% insulin aspart protamine suspension 30% insulin aspart injection, [rdna origin]) comes prefilled with NovoLog Mix 70/30 premixed insulin. It is ready to use in just a few steps,* you dial the exact dose of insulin you need. NovoLog Mix 70/30 FlexPen is about the size of a fountain pen fits neatly in your pocket or purse. And it lasts up to 14 days without refrigeration, so it can be taken almost anywhere. USED WITH THIN NOVOFINE 32G TIP NEEDLES Fits all insulin pens In a study, thinner needles caused less pain, NovoFine 32G Tip is the thinnest needle available in the United States Covered on most insurance plans GOES WHERE YOU GO WITHOUT REFRIGERATION Unopened NovoLog Mix 70/30 FlexPen is stored in the refrigerator. But once in use, you can keep it for up to 14 days at room temperature (below 86 F). That means it can be 12 DESIGNED FOR ACCURATE DOSING Prefilled with 300 units of NovoLog Mix 70/30 premixed insulin Capable of delivering from 1 to 60 units of insulin Dose can be adjusted in 1-unit increments Allows the resetting of a dose in the event of a misdial IMPORTANT SAFETY INFORMATION Do not share needles, insulin pens, or syringes. Stored with your other supplies. You can keep your NovoLog Mix 70/30 FlexPen in the same places you store the rest of your diabetes supplies, like your bedside table Taken almost anywhere. When you re on the go or traveling, you can take NovoLog Mix 70/30 FlexPen with you COVERED BY MOST HEALTH INSURANCE PLANS You can get NovoLog Mix 70/30 FlexPen for the same co-pay as vial syringe under most managed care plans. And one box of NovoLog Mix 70/30 FlexPen prefilled insulin pens contains 5 disposable pens for a total of 1500 units of NovoLog Mix 70/30 insulin. That s 50% more insulin than a vial! NovoFine needles are sold separately may require a prescription in some states. Needles FlexPen must not be shared. * Please see the enclosed Prescribing Information, which contains full Instructions For Use. Once in use, NovoLog Mix 70/30 FlexPen must be kept at room temperature below 86 F for up to 14 days. on pages 22-23, including updates related to thiazolidinediones (TZDs), enclosed Prescribing Information Patient Information. 13

9 Using your FlexPen YOUR DOSE Your doctor will tell you how much NovoLog Mix 70/30 (70% insulin aspart protamine suspension 30% insulin aspart injection, [rdna origin]) you should be taking how many times a day to take it. Different people have different needs, so you may not need to take the same amount of insulin as someone else. Your dose may be adjusted based on your blood sugar levels. When it is time to take your insulin, you can dial the exact dose of insulin you need inject it by pressing the button.* Before use: Unopened NovoLog Mix 70/30 FlexPen should be kept in the refrigerator within a temperature range of 36 F to 46 F (2 C to 8 C) Do not freeze NovoLog Mix 70/30 FlexPen or use if frozen Keep unopened NovoLog Mix 70/30 FlexPen in the carton to protect from the light YOUR INJECTION SITE NovoLog Mix 70/30 premixed insulin can be injected in: Thigh STORING YOUR NOVOLOG MIX 70/30 FLEXPEN Abdomen Once in use: NovoLog Mix 70/30 FlexPen should be kept at room temperature below 86 F (30 C) for up to 14 days Do not store the NovoLog Mix 70/30 FlexPen that you re using in the refrigerator Keep NovoLog Mix 70/30 FlexPen away from direct heat or light Be sure to throw away your used NovoLog Mix 70/30 FlexPen after 14 days, even if there s still insulin left in it Buttocks Upper Arm Make sure to change your injection site within the area you choose to use each time you inject. You should not inject into the exact same spot each time you take NovoLog Mix 70/30. This helps your body absorb insulin helps prevent skin changes, such as thickening or pitting. * Please see the enclosed Prescribing Information, which contains full Instructions For Use. 14 onsafety pagesinformation 22-23, including updates Please see Important throughout related to thiazolidinediones (TZDs), Information enclosed on pages 22-23, enclosed Prescribing Prescribing Information Patient Information. Patient Information. 15

10 Instructions for use NovoFine Needle NovoLog Mix 70/30 FlexPen Rubber stopper Pen cap Cartridge scale 12 units Dose display Pointer Pushbutton Dose selector Big outer needle cap Inner needle cap Needle Protective tab Glass ball Cartridge STEP 1: Preparing your NovoLog Mix 70/30 FlexPen (70% insulin aspart protamine suspension 30% insulin aspart injection, [rdna origin]) Wash your hs. Check the label to make sure that you are using the right type of insulin Pull off the pen cap roll the pen between your palms 10 times. Be sure to keep the pen horizontal Gently move the pen up down 10 times between positions 1 2 as shown. Keep rolling moving the pen until the liquid appears white cloudy Wipe the rubber stopper with an alcohol swab Before you inject, make sure there are at least 12 units left in the cartridge so that the remaining insulin can be evenly mixed Remove the protective tab from the needle screw it onto your FlexPen tightly Pull off the big outer needle cap then pull off the inner needle cap. Dispose of the inner needle cap right away Always use a new needle for each injection To reduce the risk of needle stick, never put the inner needle cap back on the needle 1 2 STEP 2: Giving the airshot before each injection Small amounts of air may collect in the cartridge during normal use. You need to avoid injecting air to ensure proper dosing. Turn the dose selector to 2 units Hold your FlexPen with the needle pointing up, tap the cartridge gently a few times. This moves the air bubbles to the top Press the push-button all the way in until the dose selector is back to 0. A drop of insulin should appear at the tip of the needle If no drop appears, change the needle repeat. If you still do not see a drop of insulin after 6 tries, do not use the FlexPen contact Novo Nordisk at units selected on Safety pagesinformation 22-23, including updates Please see Important throughout related to thiazolidinediones (TZDs), Information enclosed on pages 22-23, enclosed Prescribing Information. 16 Patient Prescribing Information Patient Information. 17

11 STEP 3: Selecting your dose STEP 5: After the injection The dose selector should be set at 0 Do not recap the needle to help Turn the dose selector to the number of units you need to inject. The pointer should line up with your dose Note that the dose can be corrected either up or down by turning the dose selector in either direction, right up until you are ready to inject Be careful not to press the push-button until you inject the needle You cannot select a dose larger than the number of units left in the cartridge 5 units selected units selected 24 prevent needle-stick injury Remove the needle from the FlexPen after each injection to prevent infection, insulin leakage, to ensure proper dosing Place the used needle any empty FlexPen in a sharps container or some type of hard plastic or metal container with a screw top. Check with your doctor about the right way to throw away the used needles Put the pen cap back on the FlexPen store it at room temperature without a needle attached Be sure to take the injection exactly as your doctor showed you. He or she may have specific instructions for how where to inject. Wipe the skin with an alcohol swab let the area dry. Insert the needle into your skin Press the push-button all the way in until the dose selector is back to 0. Turning the dose selector will not inject insulin Keep the needle in the skin for at least 6 seconds, keep the push-button pressed until the needle has been pulled out from the skin If blood appears, press the injection site lightly with an alcohol swab. Do not rub the area 4 6 STEP 4: Taking the injection 0 For more information about how to use maintain your NovoLog Mix 70/30 FlexPen (70% insulin aspart protamine suspension 30% insulin aspart injection, [rdna origin]), refer to the Prescribing Information Patient Information enclosed in the pocket of this. on Safety pagesinformation 22-23, including updates Please see Important throughout related to thiazolidinediones (TZDs), Information enclosed on pages 22-23, enclosed Prescribing Information. 18 Patient Prescribing Information Patient Information. 19

12 Resources Support It s time to get personal with your diabetes care. And NovoLogMix70/30Care gives you the tools to do it. When you sign up today for NovoLogMix70/30Care at Cornerstones4Care.com, you will get ongoing support, tips, tools to help you manage your type 2 diabetes. WAY TO SAVE NovoLog Mix 70/30 Instant Savings Card When you receive your NovoLog Mix 70/30 (70% insulin aspart protamine suspension 30% insulin aspart injection, [rdna origin]) prescription, sign up for your NovoLog Mix 70/30 Instant Savings Card at novologmix70-30.com. Bring the card prescription to your pharmacist for savings that last. Powerful tools to keep your diabetes management program on track Learn about our diabetes medicines delivery systems Key nutritional information on hundreds of foods PMS PMS Healthy eating doesn t have to be boring! Tasty, diabetes-friendly meals snacks Savings that last Pay no more than $25 per prescription for NovoLog Mix 70/30 FlexPen for up to 2 years.* You may be eligible for a FREE box of Novo Nordisk needles.* Needles are sold separately may require a prescription in some states. SUPPORT TO REACH YOUR GOALS There are several organizations you can look to if you seek guidance support when managing your diabetes. For more information, you can visit American Association of Diabetes Educators diabeteseducator.org Getting Support Support for helping you take the right actions make the right decisions can come from many sources, including family members, caregivers, a diabetes care team. Along with your doctor, a diabetes care team can include a pharmacist, an eye doctor, a foot doctor (podiatrist), a nurse educator, a registered dietician, a behavioral health professional. PMS PMS Visit Cornerstones4Care.com for more information. on Safety pagesinformation 22-23, including updates Please see Important throughout related to thiazolidinediones (TZDs), enclosed on pages 22-23, enclosed Prescribing Information Patient Information. Prescribing Information Patient Information. PMS 100- American Diabetes Association diabetes.org National Diabetes Education Program ndep.nih.gov Taking Control of Your Diabetes tcoyd.org PMS PMS PMS *Eligibility other restrictions apply. See novologmix70-30.com for details. 21

13 Indications Usage What is NovoLog Mix 70/30 (70% insulin aspart protamine suspension 30% insulin aspart injection, [rdna origin])? NovoLog Mix 70/30 is a man-made insulin used to control high blood sugar in adults with diabetes mellitus. It is not known if NovoLog Mix 70/30 is safe or effective in children. Important Safety Information Who should not use NovoLog Mix 70/30? Do not use NovoLog Mix 70/30 if your blood sugar is too low (hypoglycemia) or you are allergic to any of its ingredients. What should I tell my health care provider before taking NovoLog Mix 70/30? About all of your medical conditions, including liver, kidney, or heart problems. If you are pregnant, breastfeeding, or plan to do either. About all prescription nonprescription medicines you take, including supplements, as your dose may need to change. How should I take NovoLog Mix 70/30? NovoLog Mix 70/30 starts acting fast. If you have type 1 diabetes, inject within 15 minutes before you eat a meal. If you have type 2 diabetes, inject within 15 minutes before or after starting your meal. Inject NovoLog Mix 70/30 under the skin of your stomach area, upper arms, buttocks, or thighs, but never into a vein or muscle. Do not mix NovoLog Mix 70/30 with other insulin products or use in an insulin pump. Do not change your dose or type of insulin unless you are told to by your health care provider. Do not share needles, insulin pens, or syringes. Check your blood sugar levels as directed by your health care provider. Please see enclosed Prescribing Information Please Important Safety Information throughout onsee pages 22-23, enclosed Prescribing Information on pages Patient 22-23, Information. enclosed Prescribing Information Patient Information. Information. 22 Patient

14 HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use NovoLog Mix 70/30 safely effectively. See full prescribing information for NovoLog Mix 70/30. NovoLog Mix 70/30 (70% insulin aspart protamine suspension 30% insulin aspart injection, [rdna origin]) Suspension for subcutaneous injection Initial U.S. Approval: 2001 RECENT MAJOR CHANGES Warnings Precautions (5.8) 3/2013 INDICATIONS AND USAGE NovoLog Mix 70/30 is an insulin analog indicated to improve glycemic control in patients with diabetes mellitus. Important Limitations of Use: In premix insulins, such as NovoLog Mix 70/30, the proportions of rapid acting long acting insulins are fixed do not allow for basal versus prial dose adjustments (1). DOSAGE AND ADMINISTRATION Only for subcutaneous injection (2.1). Type 1 DM: dose within 15 minutes before meal initiation. Type 2 DM: dose within 15 minutes before or after starting a meal. Do not administer intravenously (2.1). Do not use in insulin infusion pumps (2.1). Must be resuspended immediately before use (2.2). DOSAGE FORMS AND STRENGTHS Each presentation contains 100 Units of insulin aspart per ml (U-100) (3) 10 ml vials 3 ml NovoLog Mix 70/30 FlexPen CONTRAINDICATIONS Do not use during episodes of hypoglycemia (4). Do not use in patients with hypersensitivity to NovoLog Mix 70/30 or one of its excipients (4). WARNINGS AND PRECAUTIONS NovoLog Mix 70/30 should not be mixed with any other insulin product (5.1). Hypoglycemia is the most common adverse effect of insulin therapy. Glucose monitoring is recommended for all patients with diabetes. Any change of insulin dose should be made cautiously only under medical supervision (5.1, 5.2). Insulin, particularly when given in settings of poor glycemic control, can cause hypokalemia. Use caution in patients predisposed to hypokalemia (5.3). Like all insulins, NovoLog Mix 70/30 requirements may be reduced in patients with renal impairment or hepatic impairment (5.4, 5.5). Severe, life-threatening, generalized allergy, including anaphylaxis, may occur with insulin products, including NovoLog Mix 70/30 (5.6). Fluid retention heart failure can occur with concomitant use of thiazolidinediones (TZDs), which are PPAR-gamma agonists, insulin, including NovoLog Mix 70/30 (5.8). ADVERSE REACTIONS Adverse reactions observed with insulin therapy include hypoglycemia, allergic reactions, local injection site reactions, lipodystrophy, rash pruritus (6). To report SUSPECTED ADVERSE REACTIONS, contact Novo Nordisk Inc. at or FDA at FDA-1088 or DRUG INTERACTIONS The following may increase the blood-glucose-lowering effect susceptibility to hypoglycemia: oral antidiabetic products, pramlintide, ACE inhibitors, disopyramide, fibrates, fluoxetine, monoamine oxidase (MAO) inhibitors, propoxyphene, salicylates, somatostatin analog (e.g. octreotide), sulfonamide antibiotics (7). The following may reduce the blood-glucose-lowering effect: corticosteroids, niacin, danazol, diuretics, sympathomimetic agents (e.g., epinephrine, salbutamol, terbutaline), isoniazid, phenothiazine derivatives, somatropin, thyroid hormones, estrogens, progestogens (e.g., in oral contraceptives), atypical antipsychotics (7). Beta-blockers, clonidine, lithium salts, alcohol may either potentiate or weaken the blood-glucose-lowering effect of insulin (7). Pentamidine may cause hypoglycemia, which may be followed by hyperglycemia (7). The signs of hypoglycemia may be reduced or absent in patients taking sympatholytic products such as beta-blockers, clonidine, guanethidine, reserpine (7). See 17 for PATIENT COUNSELING INFORMATION FDA-approved patient labeling. Revised: 3/2013 FULL PRESCRIBING INFORMATION: CONTENTS* 1 INDICATIONS AND USAGE 2 DOSAGE AND ADMINISTRATION 2.1 Dosing 2.2 Resuspension 3 DOSAGE FORMS AND STRENGTHS 4 CONTRAINDICATIONS 5 WARNINGS AND PRECAUTIONS 5.1 Administration 5.2 Hypoglycemia 5.3 Hypokalemia 5.4 Renal Impairment 5.5 Hepatic Impairment 5.6 Hypersensitivity Allergic Reactions 5.7 Antibody Production 5.8 Fluid retention heart failure with concomitant use of PPAR-gamma agonists 6 ADVERSE REACTIONS 7 DRUG INTERACTIONS 8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy 8.3 Nursing Mothers 8.4 Pediatric Use 8.5 Geriatric Use 10 OVERDOSAGE 11 DESCRIPTION 12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action 12.2 Pharmacodynamics 12.3 Pharmacokinetics 13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility 13.2 Animal Toxicology /or Pharmacology 14 CLINICAL STUDIES 14.1 NovoLog Mix 70/30 versus Novolin 70/ Combination Therapy: Insulin Oral Agents in Patients with Type 2 Diabetes 15 REFERENCES 16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied 16.2 Recommended Storage 17 PATIENT COUNSELING INFORMATION 17.1 Physician Instructions * Sections or subsections omitted from the full prescribing information are not listed. 1

15 NovoLog Mix 70/30 (70% insulin aspart protamine suspension 30% insulin aspart injection, [rdna origin]) 2 FULL PRESCRIBING INFORMATION 1 INDICATIONS AND USAGE NovoLog Mix 70/30 is an insulin analog indicated to improve glycemic control in patients with diabetes mellitus. Important Limitations of Use: In premix insulins, such as NovoLog Mix 70/30, the proportions of rapid acting long acting insulins are fixed do not allow for basal versus prial dose adjustments. 2 DOSAGE AND ADMINISTRATION 2.1 Dosing NovoLog Mix 70/30 is an insulin analog with an earlier onset intermediate duration of action in comparison to the basal human insulin premix. The addition of protamine to the rapid-acting aspart insulin analog (NovoLog ) results in insulin activity that is 30% shortacting 70% long-acting. NovoLog Mix 70/30 is typically dosed on a twice-daily basis (with each dose intended to cover 2 meals or a meal a snack). The dosage of NovoLog Mix 70/30 must be individualized. The written prescription for NovoLog Mix 70/30 should include the full name, to avoid confusion with NovoLog (insulin aspart) Novolin 70/30 (human premix). NovoLog Mix 70/30 should appear uniformly white cloudy. Do not use it if it looks clear or if it contains solid particles. NovoLog Mix 70/30 should not be used after the printed expiration date. NovoLog Mix 70/30 should be administered by subcutaneous injection in the abdominal region, buttocks, thigh, or upper arm. NovoLog Mix 70/30 has a faster onset of action than human insulin premix 70/30 should be dosed within 15 minutes before meal initiation for patients with type 1 diabetes. For patients with type 2 diabetes, dosing should occur within 15 minutes before or after meal initiation. Injection sites should be rotated within the same region to reduce the risk of lipodystrophy. As with all insulins, the duration of action may vary according to the dose, injection site, blood flow, temperature, level of physical activity. NovoLog Mix 70/30 should not be administered intravenously or used in insulin infusion pumps. Dose regimens of NovoLog Mix 70/30 will vary among patients should be determined by the health care professional familiar with the patient s recommended glucose treatment goals, metabolic needs, eating habits, other lifestyle variables. 2.2 Resuspension NovoLog Mix 70/30 is a suspension that must be visually inspected resuspended immediately before use. The NovoLog Mix 70/30 vial should be rolled gently in your hs in a horizontal position 10 times to mix it. The rolling procedure must be repeated until the suspension appears uniformly white cloudy. Inject immediately. Resuspension is easier when the insulin has reached room temperature. The NovoLog Mix 70/30 FlexPen should be rolled 10 times gently between your hs in a horizontal position. Thereafter, turn the NovoLog Mix 70/30 FlexPen upside down so that the glass ball moves from one end of the reservoir to the other. Do this at least 10 times. The rolling turning procedure must be repeated until the suspension appears uniformly white cloudy. Inject immediately. Before each subsequent injection, turn the disposable NovoLog Mix 70/30 FlexPen upside down so that the glass ball moves from one end of the reservoir to the other at least 10 times until the suspension appears uniformly white cloudy. Inject immediately. 3 DOSAGE FORMS AND STRENGTHS NovoLog Mix 70/30 is available in the following package sizes: each presentation contains 100 units of insulin aspart per ml (U-100). 10 ml vials 3 ml NovoLog Mix 70/30 FlexPen 4 CONTRAINDICATIONS NovoLog Mix 70/30 is contraindicated during episodes of hypoglycemia in patients with hypersensitivity to NovoLog Mix 70/30 or one of its excipients. 5 WARNINGS AND PRECAUTIONS 5.1 Administration The short long-acting components of insulin mixes, including NovoLog Mix 70/30, cannot be titrated independently. Because NovoLog Mix 70/30 has peak pharmacodynamic activity between 1-4 hours after injection, it should be administered within 15 minutes of meal initiation [see Clinical Pharmacology (12)]. The dose of insulin required to provide adequate glycemic control for one of the meals may result in hyper- or hypoglycemia for the other meal. The pharmacodynamic profile may also be inadequate for patients who require more frequent meals. NovoLog Mix 70/30 should not be mixed with any other insulin product. NovoLog Mix 70/30 should not be used intravenously. NovoLog Mix 70/30 should not be used in insulin infusion pumps. Glucose monitoring is recommended for all patients with diabetes. Any change of insulin dose should be made cautiously only under medical supervision. Changing from one insulin product to another or changing the insulin strength may result in the need for a change in dosage. Changes may also be necessary during illness, emotional stress, other physiologic stress in addition to changes in meals exercise. The pharmacokinetic pharmacodynamic profiles of all insulins may be altered by the site used for injection the degree of vascularization of the site. Smoking, temperature, exercise contribute to variations in blood flow insulin absorption. These other factors contribute to inter- intra-patient variability. Needles NovoLog Mix 70/30 FlexPen must not be shared. 5.2 Hypoglycemia Hypoglycemia is the most common adverse effect of insulin therapy, including NovoLog Mix 70/30. Severe hypoglycemia may lead to unconsciousness /or convulsions may result in temporary or permanent impairment of brain function or even death. Severe hypoglycemia requiring the assistance of another person /or parenteral glucose infusion or glucagon administration has been observed in clinical trials with insulin, including trials with NovoLog Mix 70/30. The timing of hypoglycemia may reflect the time-action profile of the insulin formulation [see Clinical Pharmacology (12)]. Other factors, such as changes in dietary intake (e.g., amount of food or timing of meals), injection site, exercise, concomitant medications may also alter the risk of hypoglycemia [see Drug Interactions (7)]. As with all insulins, use caution in patients with hypoglycemia unawareness in patients who may be predisposed to hypoglycemia (e.g. patients who are fasting or have erratic food intake). The patient s ability to concentrate react may be impaired as a result of hypoglycemia. This may present a risk in situations where these abilities are especially important, such as driving or operating machinery. Rapid changes in serum glucose levels may induce symptoms of hypoglycemia in persons with diabetes, regardless of the glucose value. Early warning symptoms of hypoglycemia may be different or less pronounced under certain conditions, such as long duration of diabetes, diabetic nerve disease, use of medications such as betablockers, or intensified diabetes control [see Drug Interactions (7)]. 5.3 Hypokalemia All insulin products, including NovoLog Mix 70/30, cause a shift in potassium from the extracellular to intracellular space, possibly leading to hypokalemia that, if left untreated, may cause respiratory paralysis, ventricular arrhythmia, death. Use caution in patients who may be at risk for hypokalemia (e.g. patients using potassium-lowering medications or patients taking medications sensitive to potassium concentrations). 5.4 Renal Impairment Clinical or pharmacology studies with NovoLog Mix 70/30 in diabetic patients with various degrees of renal impairment have not been conducted. As with other insulins, the requirements for NovoLog Mix 70/30 may be reduced in patients with renal impairment [see Clinical Pharmacology (12.3)]. 5.5 Hepatic Impairment Clinical or pharmacology studies with NovoLog Mix 70/30 in diabetic patients with various degrees of hepatic impairment have not been conducted. As with other insulins, the requirements for NovoLog Mix 70/30 may be reduced in patients with hepatic impairment [see Clinical Pharmacology (12.3)]. 5.6 Hypersensitivity Allergic Reactions Local Reactions - As with other insulin therapy, patients may experience reactions such as erythema, edema or pruritus at the site of NovoLog Mix 70/30 injection. These reactions usually resolve in a few days to a few weeks, but in some occasions, may require discontinuation of NovoLog Mix 70/30. In some instances, these reactions may be related to the insulin molecule, other components in the insulin preparation including protamine cresol, components in skin cleansing agents, or injection techniques. Localized reactions generalized myalgias have been reported with the use of cresol as an injectable excipient. Systemic Reactions - Less common, but potentially more serious, is generalized allergy to insulin, which may cause rash (including pruritus) over the whole body, shortness of breath, wheezing, reduction in blood pressure, rapid pulse, or sweating. Severe cases of generalized allergy, including anaphylactic reaction, may be life threatening. 5.7 Antibody Production Specific anti-insulin antibodies as well as cross-reacting anti-insulin antibodies were monitored in a 3-month, open-label comparator trial as well as in a long-term extension trial. Changes in cross-reactive antibodies were more common after NovoLog Mix 70/30 than with Novolin 70/30 but these changes did not correlate with change in HbA 1c or increase in insulin dose. The clinical significance of these antibodies has not been established. Antibodies did not increase further after long-term exposure (>6 months) to NovoLog Mix 70/ Fluid retention heart failure can occur with concomitant use of PPAR-gamma agonists Thiazolidinediones (TZDs), which are peroxisome proliferatoractivated 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 NovoLog Mix 70/30, a PPAR-gamma agonist should be observed for signs symptoms of heart failure. If heart failure develops, it should be managed according to current stards of care, discontinuation or dose reduction of the PPAR-gamma agonist must be considered. 6 ADVERSE REACTIONS Clinical Trial Experience Clinical trials are conducted under widely varying designs, therefore, the adverse reaction rates reported in one clinical trial may not be easily compared to those rates reported in another clinical trial, may not reflect the rates actually observed in clinical practice. Hypoglycemia Hypoglycemia is the most commonly observed adverse reaction in patients using insulin, including NovoLog Mix 70/30 [see Warnings Precautions (5.2)]. NovoLog Mix 70/30 should not be used during episodes of hypoglycemia [see Contraindications (4) Warnings Precautions (5)]. Insulin initiation glucose control intensification Intensification or rapid improvement in glucose control has been associated with transitory, reversible ophthalmologic refraction disorder, worsening of diabetic retinopathy, acute painful peripheral neuropathy. However, long-term glycemic control decreases the risk of diabetic retinopathy neuropathy. Lipodystrophy Long-term use of insulin, including NovoLog Mix 70/30, can cause lipodystrophy at the site of repeated insulin injections. Lipodystrophy includes lipohypertrophy (thickening of adipose tissue) lipoatrophy (thinning of adipose tissue), may affect insulin absorption. Rotate insulin injection sites within the same region to reduce the risk of lipodystrophy. Weight gain Weight gain can occur with some insulin therapies, including NovoLog Mix 70/30, has been attributed to the anabolic effects of insulin the decrease in glycosuria. Peripheral Edema Insulin may cause sodium retention edema, particularly if previously poor metabolic control is improved by intensified insulin therapy. Frequencies of adverse drug reactions The frequencies of adverse drug reactions during a clinical trial with NovoLog Mix 70/30 in patients with type 1 diabetes mellitus type 2 diabetes mellitus are listed in the tables below. The trial was a three-month, open-label trial in patients with Type 1 or Type 2 diabetes who were treated twice daily (before breakfast before supper) with NovoLog Mix 70/30.

16 NovoLog Mix 70/30 (70% insulin aspart protamine suspension 30% insulin aspart injection, [rdna origin]) 3 Table 1: Treatment-Emergent Adverse Events in Patients with Type 1 diabetes mellitus (Adverse events with frequency 5% are included.) NovoLog Mix 70/30 (N=55) Novolin 70/30 (N=49) Preferred Term N % N % Hypoglycemia Headache Influenza-like symptoms Dyspepsia Back pain Diarrhea Pharyngitis Rhinitis Skeletal pain Upper respiratory tract infection Table 2: Treatment-Emergent Adverse Events in Patients with Type 2 diabetes mellitus (Adverse events with frequency 5% are included.) NovoLog Mix 70/30 (N=85) Novolin 70/30 (N=102) Preferred Term N % N % Hypoglycemia Upper respiratory tract infection Headache Diarrhea Neuropathy Pharyngitis Abdominal pain Rhinitis Postmarketing Data Additional adverse reactions have been identified during post-approval use of NovoLog Mix 70/30. Because these adverse reactions are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency. They include medication errors in which other insulins have been accidentally substituted for NovoLog Mix 70/30 [see Patient Counseling Information (17)]. 7 DRUG INTERACTIONS A number of substances affect glucose metabolism may require insulin dose adjustment particularly close monitoring. The following are examples of substances that may increase the blood-glucose-lowering effect susceptibility to hypoglycemia: oral antidiabetic products, pramlintide, ACE inhibitors, disopyramide, fibrates, fluoxetine, monoamine oxidase (MAO) inhibitors, propoxyphene, salicylates, somatostatin analog (e.g. octreotide), sulfonamide antibiotics. The following are examples of substances that may reduce the blood-glucose-lowering effect: corticosteroids, niacin, danazol, diuretics, sympathomimetic agents (e.g., epinephrine, salbutamol, terbutaline), isoniazid, phenothiazine derivatives, somatropin, thyroid hormones, estrogens, progestogens (e.g., in oral contraceptives), atypical antipsychotics. Beta-blockers, clonidine, lithium salts, alcohol may either potentiate or weaken the blood-glucose-lowering effect of insulin. Pentamidine may cause hypoglycemia, which may sometimes be followed by hyperglycemia. The signs of hypoglycemia may be reduced or absent in patients taking sympatholytic products such as beta-blockers, clonidine, guanethidine, reserpine. 8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Pregnancy Category B. All pregnancies have a background risk of birth defects, loss, or other adverse outcome regardless of drug exposure. This background risk is increased in pregnancies complicated by hyperglycemia may be decreased with good metabolic control. It is essential for patients with diabetes or history of gestational diabetes to maintain good metabolic control before conception throughout pregnancy. Insulin requirements may decrease during the first trimester, generally increase during the second third trimesters, rapidly decline after delivery. Careful monitoring of glucose control is essential in such patients. An open-label, romized study compared the safety efficacy of NovoLog (the rapid-acting component of NovoLog Mix 70/30) versus human insulin in the treatment of pregnant women with Type 1 diabetes (322 exposed pregnancies (NovoLog: 157, human insulin: 165)). Two-thirds of the enrolled patients were already pregnant when they entered the study. Since only one-third of the patients enrolled before conception, the study was not large enough to evaluate the risk of congenital malformations. Mean HbA 1c of ~ 6% was observed in both groups during pregnancy, there was no significant difference in the incidence of maternal hypoglycemia. Animal reproduction studies have not been conducted with NovoLog Mix 70/30. However, subcutaneous reproduction teratology studies have been performed with NovoLog (the rapid-acting component of NovoLog Mix 70/30) regular human insulin in rats rabbits. In these studies, NovoLog was given to female rats before mating, during mating, throughout pregnancy, to rabbits during organogenesis. The effects of NovoLog did not differ from those observed with subcutaneous regular human insulin. NovoLog, like human insulin, caused pre- post-implantation losses visceral/skeletal abnormalities in rats at a dose of 200 U/ kg/day (approximately 32-times the human subcutaneous dose of 1.0 U/kg/day, based on U/body surface area), in rabbits at a dose of 10 U/kg/day (approximately three times the human subcutaneous dose of 1.0 U/kg/day, based on U/body surface area). The effects are probably secondary to maternal hypoglycemia at high doses. No significant effects were observed in rats at a dose of 50 U/kg/day rabbits at a dose of 3 U/kg/day. These doses are approximately 8 times the human subcutaneous dose of 1.0 U/kg/day for rats equal to the human subcutaneous dose of 1.0 U/kg/day for rabbits based on U/ body surface area. Female patients should be advised to discuss with their physician if they intend to, or if they become pregnant. There are no adequate well-controlled studies of the use of NovoLog Mix 70/30 in pregnant women. 8.3 Nursing Mothers It is unknown whether insulin aspart is excreted in human milk as occurs with human insulin. There are no adequate well-controlled studies of the use of NovoLog Mix 70/30 or NovoLog in lactating women. Women with diabetes who are lactating may require adjustments of their insulin doses. 8.4 Pediatric Use Safety effectiveness of NovoLog Mix 70/30 have not been established in pediatric patients. 8.5 Geriatric Use Clinical studies of NovoLog Mix 70/30 did not include sufficient numbers of patients aged 65 over to determine whether they respond differently than younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range reflecting the greater frequency of decreased hepatic, renal, or cardiac function, of concomitant disease or other drug therapy in this population. 10 OVERDOSAGE Hypoglycemia may occur as a result of an excess of insulin relative to food intake, energy expenditure, or both. Mild episodes of hypoglycemia usually can be treated with oral glucose. Adjustments in drug dosage, meal patterns, or exercise, may be needed. More severe episodes with coma, seizure, or neurologic impairment may be treated with intramuscular/subcutaneous glucagon or concentrated intravenous glucose. Sustained carbohydrate intake observation may be necessary because hypoglycemia may recur after apparent clinical recovery. 11 DESCRIPTION NovoLog Mix 70/30 (70% insulin aspart protamine suspension 30% insulin aspart injection, [rdna origin]) is a human insulin analog suspension containing 70% insulin aspart protamine crystals 30% soluble insulin aspart. NovoLog Mix 70/30 is a blood-glucoselowering agent with an earlier onset an intermediate duration of action. Insulin aspart is homologous with regular human insulin with the exception of a single substitution of the amino acid proline by aspartic acid in position B28, is produced by recombinant DNA technology utilizing Saccharomyces cerevisiae (baker s yeast). Insulin aspart (NovoLog ) has the empirical formula C 256 H 381 N 65 O 79 S 6 a molecular weight of Da. A-chain S S Cys Gly Ile Val Glu Gln Cys Thr Ser Ile Cys Ser Leu Tyr Gln Leu Glu Asn Tyr Cys Asn S S S B-chain Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Tyr Leu Val Cys Gly Glu Arg Gly Phe Phe Tyr Thr Asp Lys Thr Figure 1. Structural formula of insulin aspart NovoLog Mix 70/30 is a uniform, white, sterile suspension that contains insulin aspart 100 Units/mL. Inactive ingredients are glycerol 16.0 mg/ml, phenol 1.50 mg/ml, metacresol 1.72 mg/ml, zinc 19.6 μg/ml, disodium hydrogen phosphate dihydrate 1.25 mg/ml, sodium chloride mg/ml, protamine sulfate 0.32 mg/ml. NovoLog Mix 70/30 has a ph of Hydrochloric acid or sodium hydroxide may be added to adjust ph. 12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action The primary activity of NovoLog Mix 70/30 is the regulation of glucose metabolism. Insulins, including NovoLog Mix 70/30, bind to the insulin receptors on muscle, liver fat cells lower blood glucose by facilitating the cellular uptake of glucose simultaneously inhibiting the output of glucose from the liver Pharmacodynamics The two euglycemic clamp studies described below [see Clinical Pharmacology (12.3)] assessed glucose utilization after dosing of healthy volunteers. NovoLog Mix 70/30 has an earlier onset of action than human premix 70/30 in studies of normal volunteers patients with diabetes. The onset of action is between minutes for NovoLog Mix 70/30 compared to 30 minutes for Novolin 70/30. The mean ± SD time to peak activity for NovoLog Mix 70/30 is 2.4 hr ± 0.8 hr compared to 4.2 hr ± 0.4 hr for Novolin 70/30. The duration of action may be as long as 24 hours (see Figure 2). Glucose Infusion Rate (mg/kg min) Time (hours) S NovoLog Mix 70/30 Novolin 70/30 Figure 2. Pharmacodynamic Activity Profile of NovoLog Mix 70/30 Novolin 70/30 in healthy subjects Pharmacokinetics The single substitution of the amino acid proline with aspartic acid at position B28 in insulin aspart (NovoLog ) reduces the molecule s tendency to form hexamers as observed with regular human insulin. The rapid absorption characteristics of NovoLog are maintained by NovoLog Mix 70/30. The insulin aspart in the soluble component of NovoLog Mix 70/30 is absorbed more rapidly from the subcutaneous layer than regular human insulin. The remaining 70% is in crystalline form as insulin aspart protamine which has a prolonged absorption profile after subcutaneous injection. Bioavailability Absorption - The relative bioavailability of NovoLog Mix 70/30 compared to NovoLog Novolin 70/30 indicates that the insulins are absorbed to similar extent. In euglycemic clamp studies in healthy volunteers (n=23) after dosing with NovoLog Mix 70/30 (0.2 U/kg), a mean maximum serum concentration (C max ) of 23.4 ± 5.3 mu/l was reached after 60 minutes. The mean half-life (t 1/2 ) of Asp Pro