SPL PATIENT PACKAGE INSERT SECTION.

Patient Package Insert. Patient InformationNOVOLIN(R) 70/30 (NO-voe-lin)(human insulin isophane suspension and human insulin injection)for subcutaneous useDo not share your Novolin 70/30 FlexPen or syringes with other people, even if the needle has been changed. You may give other people serious infection or get serious infection from them.What is Novolin70/30Novolin 70/30 is man-made insulin that is used to control high blood sugar in adults and children with diabetes mellitus. Who should not use Novolin 70/30Do not use Novolin 70/30 if you:oare having an episode of low blood sugar (hypoglycemia).ohave an allergy to human insulin isophane, human insulin or any of the ingredients in Novolin 70/30. See the end of this Patient Information leaflet for complete list of ingredients in Novolin 70/30.Before using Novolin 70/30, tell your healthcare provider about all of your medical conditions, including if you:ohave liver or kidney problems.otake other medicines, especially ones called TZDs (thiazolidinediones).ohave heart failure or other heart problems. If you have heart failure, it may get worse while you take TZDs with Novolin 70/30.oare pregnant or plan to become pregnant. Talk with your healthcare provider about the best way to control your blood sugar if you plan to become pregnant or while you are pregnant.oarebreastfeeding or plan to breastfeed. NOVOLIN 70/30 may pass into your breast milk. Talk with your healthcare provider about the best way to feed your baby while using NOVOLIN 70/30.Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines,vitamins, or herbal supplements.Before you start using Novolin 70/30, talk to your healthcare provider about low blood sugar and how tomanage it.How should use Novolin 70/30oRead the detailed Instructions for Use that comes with your Novolin 70/30.oUse Novolin 70/30 exactly as your healthcare provider tells you to. Your healthcare provider should tell you how much Novolin 70/30 to use and when to use it.oUse Novolin 70/30 about 30 minutes before eating meal.oKnow the type, strength, and amount of insulin you use. Do not change the type, or amount of insulin you use unless your healthcare provider tells you to. The amount of insulin and the best time for you to take your insulin may need to change if you use different types of insulin.oCheck your insulin label each time you give your injection to make sure you are using the correct insulin.oInject Novolin 70/30 under the skin (subcutaneously) in your stomach area, buttocks, upper legs (thighs) or upper arms. Do not inject Novolin 70/30 into your vein (intravenously) or muscle (intramuscularly) or use in an insulin infusion pump.oDo not mix Novolin 70/30 with any other insulins or liquids.oChange (rotate) your injection site within the area you choose with each dose to reduce your risk of getting lipodystrophy (pits in skin or thickened skin) and localized cutaneous amyloidosis (skin with lumps) at the injection sites.oDo not use the exact same spot for each injection.oDo not inject where the skin has pits, is thickened, or has lumps.oDo not inject where the skin is tender, bruised, scaly or hard, or into scars or damaged skin.oCheck your blood sugar levels. Ask your healthcare provider what your blood sugars should be and when you should check your blood sugar levels.Keep Novolin 70/30 and all medicines out of the reach of children.Your dose of Novolin 70/30 may need to change because of: ochange in level of physical activity or exercise, weight gain or loss, increased stress, illness, change in diet, or because of other medicines you take.What should avoid while using Novolin 70/30While using Novolin 70/30 do not: odrive or operate heavy machinery until you know how Novolin 70/30 affects you.odrink alcohol or use prescription or over-the-counter medicines that contain alcohol.What are the possible side effects of Novolin 70/30Novolin 70/30 may cause serious side effects that can lead to death, including:olow blood sugar (hypoglycemia). Signs and symptoms of low blood sugar may include:odizziness or lightheadedness, sweating, confusion, headache, blurred vision, slurred speech, shakiness, fast heartbeat, anxiety, irritability or mood changes, hunger. Your healthcare provider may prescribe glucagon emergency kit so that others can give you an injection if your blood sugar becomes too low (hypoglycemia) and you are unable to take sugar by mouth. osevere allergic reaction (whole body reaction). Get medical help right away if you have any of these signs or symptoms of severe allergic reaction: rash over your whole body, have trouble breathing, fast heartbeat, or sweating.olow potassium in your blood (hypokalemia).oheart failure. Taking certain diabetes pills called thiazolidinediones or TZDs with Novolin 70/30 may cause heart failure in some people. This can happen even if you have never had heart failure or heart problems before. If you already have heart failure it may get worse while you take TZDs with Novolin 70/30. Your healthcare provider should monitor you closely while you are taking TZDs with Novolin 70/30. Tell your healthcare provider if you have any new or worse symptoms of heart failure including:oshortness of breath, swelling of your ankles or feet, sudden weight gain.Treatment with TZDs and Novolin 70/30 may need to be adjusted or stopped by your healthcare provider if you have new or worse heart failure. Get emergency medical help if you have:osevere hypoglycemia needing hospitalization or emergency room care, and be sure to tell the hospital staff the units of Novolin 70/30 your healthcare provider has prescribed for you.otrouble breathing, shortness of breath, fast heartbeat, swelling of your face, tongue, or throat, sweating, extreme drowsiness, dizziness, confusion. The most common side effects of Novolin 70/30 include:olow blood sugar (hypoglycemia), allergic reactions including reactions at your injection site, skin thickening or pits at the injection site (lipodystrophy), weight gain, and swelling (edema) in hands or feet.These are not all of the possible side effects of Novolin 70/30. Call your doctor formedical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.General information about the safe and effective use of Novolin 70/30Medicines are sometimes prescribed for purposes other than those listed in Patient Information leaflet. Do not use Novolin 70/30 for condition for which it was not prescribed. Do not give Novolin 70/30 to other people, even if they have the same symptoms you have. It may harm them.This Patient Information leaflet summarizes the most important information about Novolin 70/30. If you would like more information, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about Novolin 70/30 that is written for healthcare providers. For more information, call 1-800-727-6500 or go to www.novonordisk-us.com.What are the ingredients in Novolin 70/30Active ingredient: 70% human insulin isophane and 30% human insulinInactive ingredients: glycerol,metacresol, zinc, phenol, disodium phosphate dihydrate, protamine sulfate, water for injection, hydrochloric acid and sodium hydroxide.Novolin(R), FlexPen(R) and Novo Nordisk(R) are registered trademarks of Novo Nordisk A/S.(C) 2005 2019 Novo NordiskManufactured by: Novo Nordisk A/SDK-2880 Bagsvaerd, DenmarkFor information about Novolin 70/30 contact:Novo Nordisk Inc.800 Scudders Mill RoadPlainsboro, New Jersey 085361-800-727-6500www.novonordisk-us.comThis Patient Information has been approved by the U.S. Food and Drug Administration. Revised: 11/2019Patient Instructions for UseNovolin(R) 70/30 10 mL multiple-dose vial (100 Units/mL, U-100)Before starting, gather all of the supplies that you will need to use for preparing and giving your insulin injection.Never re-use syringes and needles. How should use the Novolin 70/30 vial1.Check to make sure that you have the correct type of insulin.2.Look at the vial and the insulin. The insulin should be cloudy or milky suspension. The tamper-resistant cap should be in place before the first use. If the cap had been removed before your first use of the vial, or if the precipitate (the white deposit at the bottom of the vial) has become lumpy or granular in appearance or has formed deposit of solid particles on the wall of the vial, do not use it and call Novo Nordisk at 1-800-727-6500. 3.Wash your hands with soap and water. If you clean your injection site with an alcohol swab, let the injection site dry before you inject. Talk with your healthcare provider about how to rotate injection sites and how to give an injection. Novolin 70/30 can be injected under the skin (subcutaneously) of your stomach area, buttocks, upper legs (thighs), or upper arms. Change (rotate) your injection sites within the area you choose for each dose to reduce your risk of getting lipodystrophy (pits in skin or thickened skin) and localized cutaneous amyloidosis (skin with lumps) at the injection sites. Do not inject where the skin has pits, is thickened, or has lumps. Do not inject where the skin is tender, bruised, scaly or hard, or into scars or damaged skin.4.If you are using new vial, pull off the tamper-resistant cap. Wipe the rubber stopper with an alcohol swab. 5.Roll the vial gently 10 times in your hands to mix it. This procedure should be carried out with the vial in horizontal position. The rolling procedure must be repeated until the suspension appears uniformly white and cloudy. Shaking right before the dose is drawn into the syringe may cause bubbles or froth, which could cause you to draw up the wrong dose of insulin. 6.Pull back the plunger on the syringe until the black tip reaches the marking for the number of units you will inject. 7.Push the needle through the rubber stopper of the vial, and push the plunger all the way in to force air into the vial. 8.Turn the vial and syringe upside down and slowly pull the plunger back to few units beyond the correct dose. 9.If there are any air bubbles, tap the syringe gently with your finger to raise the air bubbles to the top. Then slowly push the plunger to the marking for your correct dose. This process should move any air bubbles present in the syringe back into the vial. 10.Check to make sure you have the right dose of Novolin 70/30 in the syringe. 11.Pull the syringe with needle out of the vials rubber stopper. 12.Your doctor should tell you if you need to pinch the skin before inserting the needle. This can vary from patient to patient, so it is important to ask your doctor if you did not receive instructions on pinching the skin. Insert the needle into the skin. Press the plunger of the syringe to inject the insulin. When you are finished injecting the insulin, pull the needle out of your skin. You may see drop of Novolin 70/30 at the needle tip. This is normal and has no effect on the dose you just received. If you see blood after you take the needle out of your skin, press the injection site lightly with piece of gauze or an alcohol wipe. Do not rub the area. 13.After your injection, do not recap the needle. Place used syringes, needles and used insulin vials in disposable puncture-resistant sharps container, or some type of hard plastic or metal container with screw on cap such as detergent bottle or coffee can.14. Ask your healthcare provider about the right way to throw away used syringes and needles. There may be state or local laws about the right way to throw away used syringes and needles. Do not throw away used needles and syringes in household trash or recycle.How should store Novolin(R) 70/30oDo not freeze Novolin 70/30. Do not use Novolin 70/30 if it has been frozen. oKeep Novolin 70/30 away from heat or light.oAll unopened vials:oStore unopened Novolin 70/30 vials in the refrigerator at 36F to 46F (2C to 8C). oUnopened vials may be used until the expiration date printed on the label, if they have been stored in the refrigerator. oUnopened vials should be thrown away after 42 days, if they are stored at room temperature below 77F (25C).oAfter vials have been opened:oOpened Novolin 70/30vials can be stored at room temperature below 77F (25C). Do not refrigerate.oThrow away all opened Novolin 70/30vials after 42 days, even if they still have insulin left in them. Revised: 11/2019Instructions For UseNovolin(R) 70/30 FlexPen(R) (human insulin isophane suspension and human insulin injection)for subcutaneous useIntroductionPlease read the following instructions carefully before using your Novolin 70/30 FlexPen.Do not share your Novolin 70/30 FlexPen with other people, even if the needle has been changed. You may give other people serious infection, or get serious infection from them.Novolin 70/30 FlexPen is disposable dial-a-dose, single-patient-use, insulin pen. You can select doses from to 60 units in increments of unit. Novolin 70/30 FlexPen is designed to be used with NovoFine, NovoFine Plus or NovoTwist needles.People who are blind or have vision problems should not use Novolin 70/30 FlexPen without help from person trained to use Novolin 70/30 FlexPen.Getting readyMake sure you have the following texts:oNovolin 70/30 FlexPenoNew NovoFine, NovoFine Plus or NovoTwist needleoAlcohol swaboGauze padPreparing your Novolin 70/30 FlexPenWash your hands with soap and water. Before you start to prepare your injection, check the label to make sure that you are taking the right type of insulin. This is especially important if you take more than type of insulin. Novolin 70/30 should look white and cloudy after mixing.A. Let the insulin reach room temperature before you use it. This makes it easier to mix.Pull off the pen cap (see diagram A).B. Gently move the pen up and down twenty times between position and as shown, so the glass ball moves from one end of the cartridge to the other (see diagram B).Repeat moving the pen until the liquid appears white and cloudy. Do not use the pen if the liquid appears discolored or contains particles.For everyfollowing injection move the pen up and down between positions and at least ten times until the liquid appears white and cloudy.After mixing, complete all the following steps of the injection right away. If there is delay, the insulin will need to be mixed again.Wipe the rubber stopper with an alcohol swab.Before you inject, there must be at least 12 units of insulin left in the cartridge to make sure the remaining insulin is evenly mixed. If there are less than 12 units left in your Novolin 70/30 FlexPen, use new pen.Attaching the needleC. Remove the protective tab from disposable needle.Screw the needle tightly onto your Novolin 70/30 FlexPen. It is important that the needle is put on straight (see diagram C).Never place disposable needle on your Novolin 70/30 FlexPen until you are ready to take your injection.D. Pull off the big outer needle cap (see diagram D).E. Pull off the inner needle cap and dispose of it (see diagram E). Always use new needle for each injection to help ensure sterility and prevent blocked needles. Do not reuse or share your needles with other people. You may give other people serious infection, or get serious infection from them.Be careful not to bend or damage the needle before use.To reduce the risk of unexpected needle sticks, never put the inner needle cap back on the needle.Giving the airshot before each injection Before each injection small amounts of air may collect in the cartridge during normal use. To avoid injecting air and to make sure you take the right dose of insulin:F. Turn the dose selector to select units (see diagram F).G. Hold your Novolin 70/30 FlexPen with the needle pointing up. Tap the cartridge gently with your finger few times to make any air bubbles collect at the top of the cartridge (see diagram G).H. Keep the needle pointing upwards, press the push-button all the way in (see diagram H). The dose selector returns to 0.A drop of insulin should appear at the needle tip. If not, change the needle and repeat the procedure no more than times. If you do not see drop of insulin after times, do not use the Novolin 70/30 FlexPen and contact Novo Nordisk at 1-800-727-6500. small air bubble may remain at the needle tip, but it will not be injected.Selecting your doseCheck and make sure that the dose selector is set at 0.I. Turn the dose selector to the number of units you need to inject. The pointer should line up with your dose.The dose can be corrected either up or down by turning the dose selector in either direction until the correct dose lines up with the pointer (see diagram I). When turning the dose selector, be careful not to press the push-button as insulin will come out. You cannot select dose larger than the number of units left in the cartridge. You will hear click for every single unit dialed. Do not set the dose by counting the number of clicks you hear.Do not use the cartridge scale printed on the cartridge to measure your dose of insulin.Giving the injectionGive the injection exactly as shown to you by your healthcare provider. Your healthcare provider should tell you if you need to pinch the skin before injecting. Wipe the skin with an alcohol swab and let the area dry.Novolin 70/30 can be injected under the skin (subcutaneously) of your stomach area, buttocks, upper legs (thighs), or upper arms.For each injection, change (rotate) your injection site within the area of skin that you use. Change (rotate) your injection sites within the area you choose for each dose to reduce your risk of getting lipodystrophy (pits in skin or thickened skin) and localized cutaneous amyloidosis (skin with lumps) at the injection sites. Do not use the same injection site for each injection. Do not inject where the skin has pits, is thickened, or has lumps. Do not inject where the skin is tender, bruised, scaly or hard, or into scars or damaged skin. J. Insert the needle into your skin.Inject the dose by pressing the push-button all the way in until the lines up with the pointer (see diagram J). Be careful only to push the button when injecting.Turning the dose selector will not inject insulin.K. Keep the needle in the skin for at least seconds, and keep the push-button pressed all the way in until the needle has been pulled out from the skin (see diagram K). This will make sure that the full dose has been given. You may see drop of insulin at the needle tip. This is normal and has no effect on the dose you just received. If blood appears after you take the needle out of your skin, press the injection site lightly with gauze pad or an alcohol swab. Do not rub the area. After the injectionDo not recap the needle. Recapping can lead to needle stick injury. Remove the needle from the Novolin 70/30 FlexPen after each injection and dispose of it. This helps to prevent infection, leakage of insulin, and will help to make sure you inject the right dose of insulin.If you do not have sharps container, carefully slip the needle into the outer needle cap. Safely remove the needle and throw it away as soon as you can.oPut your used needles in FDA-cleared sharps disposal container right away after use. Do not throw away (dispose of) loose needles in your household trash. oIf you do not have FDA-cleared sharps disposal container, you may use household container that is:omade of heavy-duty plasticocan be closed with tight-fitting, puncture-resistant lid, without sharps being able to come outoupright and stable during useoleak-resistantoproperly labeled to warn of hazardous waste inside the containeroWhen your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used needles and syringes. For more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDAs website at: http://www.fda.gov/safesharpsdisposal. Do not dispose of your used sharps disposal container in your household trash unless your community guidelines permit this. Do not recycle your used sharps disposal container.oWhen there is not enough medicine left in your Novolin 70/30 FlexPen for your prescribed dose, the Novolin 70/30 FlexPen may be thrown away in your household trash after you have removed the needle. The Novolin 70/30 FlexPen prevents the cartridge from being completely emptied. It is designed to deliver 300 units.L. Put the pen cap on the Novolin 70/30 FlexPen and store the Novolin 70/30 FlexPen without the needle attached (see diagram L). Storing without the needle attached helps prevent leaking, blocking of the needle, and air from entering the Pen. How should store Novolin 70/30 FlexPenoDo not freeze Novolin 70/30. Do not use Novolin 70/30 if it has been frozen.oKeep Novolin 70/30 away from heat and light.oUntil first use:oStore unused Novolin 70/30 FlexPen in the refrigerator at 36F to 46F (2C to 8C).oUnused Novolin 70/30 FlexPen may be used until the expiration date printed on the label, if kept in the refrigerator at 36F to 46F (2C to 8C).oUnused Novolin 70/30 FlexPen stored at room temperature should be thrown away after 28 days.oIn-use:oStore the Novolin 70/30 FlexPen you are currently using out of the refrigerator at room temperature below 86F (30C) for up to 28 days.oThe Novolin 70/30 FlexPen you are using should be thrown away after 28 days, even if it still has insulin left in it.oStore the Novolin 70/30 FlexPen without the needle attached.MaintenanceFor the safe and proper use of your Novolin 70/30 FlexPen be sure to handle it with care. Avoid dropping your Novolin 70/30 FlexPen as it may damage it. If you are concerned that your Novolin 70/30 FlexPen is damaged, use new one. You can clean the outside of your Novolin 70/30 FlexPen by wiping it with damp cloth. Do not soak or wash your Novolin 70/30 FlexPen as it may damage it. Do not refill your Novolin 70/30 FlexPen.Remove the needle from Novolin 70/30 FlexPen after each injection. This helps to ensure sterility, prevent leakage of insulin, and will help to make sure you inject the right dose of insulin for future injections.Be careful when handling used needles to avoid needle sticks and transfer of infectious diseases.Keep your Novolin 70/30 FlexPen and needles out of the reach of children.Use Novolin 70/30 FlexPen as directed to treat your diabetes. Do not share your Novolin 70/30 FlexPen or needles with other people. You may give other people serious infection, or get serious infection from them. Always use new needle for each injection. Novo Nordisk is not responsible for harm due to using this insulin pen with products not recommended by Novo Nordisk. As precautionary measure, always carry spare insulin delivery device in case your Novolin 70/30 FlexPen is lost or damaged. Remember to keep the disposable Novolin 70/30 FlexPen with you. Do not leave it in car or other location where it can get too hot or too cold.This Instructions for Use has been approved by the U.S. Food and Drug Administration.Issued: 11/2019. oare having an episode of low blood sugar (hypoglycemia).. ohave an allergy to human insulin isophane, human insulin or any of the ingredients in Novolin 70/30. See the end of this Patient Information leaflet for complete list of ingredients in Novolin 70/30.. ohave liver or kidney problems.. otake other medicines, especially ones called TZDs (thiazolidinediones).. ohave heart failure or other heart problems. If you have heart failure, it may get worse while you take TZDs with Novolin 70/30.. oare pregnant or plan to become pregnant. Talk with your healthcare provider about the best way to control your blood sugar if you plan to become pregnant or while you are pregnant.. oarebreastfeeding or plan to breastfeed. NOVOLIN 70/30 may pass into your breast milk. Talk with your healthcare provider about the best way to feed your baby while using NOVOLIN 70/30.. oRead the detailed Instructions for Use that comes with your Novolin 70/30.. oUse Novolin 70/30 exactly as your healthcare provider tells you to. Your healthcare provider should tell you how much Novolin 70/30 to use and when to use it.. oUse Novolin 70/30 about 30 minutes before eating meal.. oKnow the type, strength, and amount of insulin you use. Do not change the type, or amount of insulin you use unless your healthcare provider tells you to. The amount of insulin and the best time for you to take your insulin may need to change if you use different types of insulin.. oCheck your insulin label each time you give your injection to make sure you are using the correct insulin.. oInject Novolin 70/30 under the skin (subcutaneously) in your stomach area, buttocks, upper legs (thighs) or upper arms. Do not inject Novolin 70/30 into your vein (intravenously) or muscle (intramuscularly) or use in an insulin infusion pump.. oDo not mix Novolin 70/30 with any other insulins or liquids.. oChange (rotate) your injection site within the area you choose with each dose to reduce your risk of getting lipodystrophy (pits in skin or thickened skin) and localized cutaneous amyloidosis (skin with lumps) at the injection sites.. oDo not use the exact same spot for each injection.. oDo not inject where the skin has pits, is thickened, or has lumps.. oDo not inject where the skin is tender, bruised, scaly or hard, or into scars or damaged skin.. oCheck your blood sugar levels. Ask your healthcare provider what your blood sugars should be and when you should check your blood sugar levels.. ochange in level of physical activity or exercise, weight gain or loss, increased stress, illness, change in diet, or because of other medicines you take.. odrive or operate heavy machinery until you know how Novolin 70/30 affects you.. odrink alcohol or use prescription or over-the-counter medicines that contain alcohol.. olow blood sugar (hypoglycemia). Signs and symptoms of low blood sugar may include:. odizziness or lightheadedness, sweating, confusion, headache, blurred vision, slurred speech, shakiness, fast heartbeat, anxiety, irritability or mood changes, hunger.. Your healthcare provider may prescribe glucagon emergency kit so that others can give you an injection if your blood sugar becomes too low (hypoglycemia) and you are unable to take sugar by mouth.. osevere allergic reaction (whole body reaction). Get medical help right away if you have any of these signs or symptoms of severe allergic reaction:. rash over your whole body, have trouble breathing, fast heartbeat, or sweating.. olow potassium in your blood (hypokalemia).. oheart failure. Taking certain diabetes pills called thiazolidinediones or TZDs with Novolin 70/30 may cause heart failure in some people. This can happen even if you have never had heart failure or heart problems before. If you already have heart failure it may get worse while you take TZDs with Novolin 70/30. Your healthcare provider should monitor you closely while you are taking TZDs with Novolin 70/30. Tell your healthcare provider if you have any new or worse symptoms of heart failure including:. oshortness of breath, swelling of your ankles or feet, sudden weight gain.. Get emergency medical help if you have:. osevere hypoglycemia needing hospitalization or emergency room care, and be sure to tell the hospital staff the units of Novolin 70/30 your healthcare provider has prescribed for you.. otrouble breathing, shortness of breath, fast heartbeat, swelling of your face, tongue, or throat, sweating, extreme drowsiness, dizziness, confusion.. The most common side effects of Novolin 70/30 include:. olow blood sugar (hypoglycemia), allergic reactions including reactions at your injection site, skin thickening or pits at the injection site (lipodystrophy), weight gain, and swelling (edema) in hands or feet.. 1.Check to make sure that you have the correct type of insulin.. 2.Look at the vial and the insulin. The insulin should be cloudy or milky suspension. The tamper-resistant cap should be in place before the first use. If the cap had been removed before your first use of the vial, or if the precipitate (the white deposit at the bottom of the vial) has become lumpy or granular in appearance or has formed deposit of solid particles on the wall of the vial, do not use it and call Novo Nordisk at 1-800-727-6500. 3.Wash your hands with soap and water. If you clean your injection site with an alcohol swab, let the injection site dry before you inject. Talk with your healthcare provider about how to rotate injection sites and how to give an injection. Novolin 70/30 can be injected under the skin (subcutaneously) of your stomach area, buttocks, upper legs (thighs), or upper arms. Change (rotate) your injection sites within the area you choose for each dose to reduce your risk of getting lipodystrophy (pits in skin or thickened skin) and localized cutaneous amyloidosis (skin with lumps) at the injection sites. Do not inject where the skin has pits, is thickened, or has lumps. Do not inject where the skin is tender, bruised, scaly or hard, or into scars or damaged skin.. 4.If you are using new vial, pull off the tamper-resistant cap. Wipe the rubber stopper with an alcohol swab. 5.Roll the vial gently 10 times in your hands to mix it. This procedure should be carried out with the vial in horizontal position. The rolling procedure must be repeated until the suspension appears uniformly white and cloudy. Shaking right before the dose is drawn into the syringe may cause bubbles or froth, which could cause you to draw up the wrong dose of insulin. 6.Pull back the plunger on the syringe until the black tip reaches the marking for the number of units you will inject. 7.Push the needle through the rubber stopper of the vial, and push the plunger all the way in to force air into the vial. 8.Turn the vial and syringe upside down and slowly pull the plunger back to few units beyond the correct dose. 9.If there are any air bubbles, tap the syringe gently with your finger to raise the air bubbles to the top. Then slowly push the plunger to the marking for your correct dose. This process should move any air bubbles present in the syringe back into the vial. 10.Check to make sure you have the right dose of Novolin 70/30 in the syringe. 11.Pull the syringe with needle out of the vials rubber stopper. 12.Your doctor should tell you if you need to pinch the skin before inserting the needle. This can vary from patient to patient, so it is important to ask your doctor if you did not receive instructions on pinching the skin. Insert the needle into the skin. Press the plunger of the syringe to inject the insulin. When you are finished injecting the insulin, pull the needle out of your skin. You may see drop of Novolin 70/30 at the needle tip. This is normal and has no effect on the dose you just received. If you see blood after you take the needle out of your skin, press the injection site lightly with piece of gauze or an alcohol wipe. Do not rub the area. 13.After your injection, do not recap the needle. Place used syringes, needles and used insulin vials in disposable puncture-resistant sharps container, or some type of hard plastic or metal container with screw on cap such as detergent bottle or coffee can.. 14. Ask your healthcare provider about the right way to throw away used syringes and needles. There may be state or local laws about the right way to throw away used syringes and needles. Do not throw away used needles and syringes in household trash or recycle.. oDo not freeze Novolin 70/30. Do not use Novolin 70/30 if it has been frozen. oKeep Novolin 70/30 away from heat or light.. oAll unopened vials:. oStore unopened Novolin 70/30 vials in the refrigerator at 36F to 46F (2C to 8C). oUnopened vials may be used until the expiration date printed on the label, if they have been stored in the refrigerator. oUnopened vials should be thrown away after 42 days, if they are stored at room temperature below 77F (25C).. oAfter vials have been opened:. oOpened Novolin 70/30vials can be stored at room temperature below 77F (25C). Do not refrigerate.. oThrow away all opened Novolin 70/30vials after 42 days, even if they still have insulin left in them. oNovolin 70/30 FlexPen. oNew NovoFine, NovoFine Plus or NovoTwist needle. oAlcohol swab. oGauze pad. Always use new needle for each injection to help ensure sterility and prevent blocked needles. Do not reuse or share your needles with other people. You may give other people serious infection, or get serious infection from them.. oPut your used needles in FDA-cleared sharps disposal container right away after use. Do not throw away (dispose of) loose needles in your household trash. oIf you do not have FDA-cleared sharps disposal container, you may use household container that is:omade of heavy-duty plasticocan be closed with tight-fitting, puncture-resistant lid, without sharps being able to come outoupright and stable during useoleak-resistantoproperly labeled to warn of hazardous waste inside the container. omade of heavy-duty plastic. ocan be closed with tight-fitting, puncture-resistant lid, without sharps being able to come out. oupright and stable during use. oleak-resistant. oproperly labeled to warn of hazardous waste inside the container. oWhen your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used needles and syringes. For more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDAs website at: http://www.fda.gov/safesharpsdisposal.. Do not dispose of your used sharps disposal container in your household trash unless your community guidelines permit this. Do not recycle your used sharps disposal container.. oWhen there is not enough medicine left in your Novolin 70/30 FlexPen for your prescribed dose, the Novolin 70/30 FlexPen may be thrown away in your household trash after you have removed the needle. The Novolin 70/30 FlexPen prevents the cartridge from being completely emptied. It is designed to deliver 300 units.. oDo not freeze Novolin 70/30. Do not use Novolin 70/30 if it has been frozen.. oKeep Novolin 70/30 away from heat and light.. oUntil first use:. oStore unused Novolin 70/30 FlexPen in the refrigerator at 36F to 46F (2C to 8C).. oUnused Novolin 70/30 FlexPen may be used until the expiration date printed on the label, if kept in the refrigerator at 36F to 46F (2C to 8C).. oUnused Novolin 70/30 FlexPen stored at room temperature should be thrown away after 28 days.. oIn-use:. oStore the Novolin 70/30 FlexPen you are currently using out of the refrigerator at room temperature below 86F (30C) for up to 28 days.. oThe Novolin 70/30 FlexPen you are using should be thrown away after 28 days, even if it still has insulin left in it.. oStore the Novolin 70/30 FlexPen without the needle attached.. Do not share your Novolin 70/30 FlexPen or needles with other people. You may give other people serious infection, or get serious infection from them. Novo Nordisk is not responsible for harm due to using this insulin pen with products not recommended by Novo Nordisk.. As precautionary measure, always carry spare insulin delivery device in case your Novolin 70/30 FlexPen is lost or damaged.. Remember to keep the disposable Novolin 70/30 FlexPen with you. Do not leave it in car or other location where it can get too hot or too cold.. Exclamation point. Novolin 70/30 FlexPen components. Needle components. Pull off the pen cap.. Move pen up and down.. Exclamation point.. Screw the needle on.. Pull off the big outer needle cap.. Pull off inner needle cap.. Exclamation point.. Exclamation point.. Exclamation point.. Turn the dose selector.. Tap the cartridge gently.. Press the push-button.. Turn the dose selector.. Exclamation point.. Inject the dose.. Keep the needle in the skin.. Put the pen cap on FlexPen.. Exclamation point.. Exclamation point.. Exclamation point.. Exclamation point.. Exclamation point.. Exclamation point.. Exclamation point.. Exclamation point.. Exclamation point.

ADVERSE REACTIONS SECTION.

6 ADVERSE REACTIONS The following adverse reactions are also discussed elsewhere in the labeling: oHypoglycemia [see Warnings and Precautions (5.3)]oMedication Errors [see Warnings and Precautions (5.4)]oHypersensitivity Reactions [see Warnings and Precautions (5.5)]oHypokalemia [see Warnings and Precautions (5.6)]Adverse Reactions from Clinical Studies or Postmarketing ReportsThe following additional adverse reactions have been identified during clinical studies or from postmarketing reports with use of NOVOLIN 70/30. 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 intensificationIntensification 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 reactionsSevere, life-threatening, generalized allergy, including anaphylaxis.HypoglycemiaHypoglycemia is the most commonly observed adverse reaction in NOVOLIN 70/30.HypokalemiaNOVOLIN 70/30 can cause shift in potassium from the extracellular to intracellular space, possibly leading to hypokalemia.Injection site reactionsNOVOLIN 70/30 can cause local injection site reactions including redness, swelling, or itching at the site of injection. These reactions usually resolve in few days to few weeks, but in some occasions, may require discontinuation. Localized reactions and generalized myalgias have been reported with the use of metacresol, which is an excipient in NOVOLIN 70/30. LipodystrophyAdministration of insulin subcutaneously, including NOVOLIN 70/30, has resulted in lipoatrophy (depression in the skin) or lipohypertrophy (enlargement or thickening of tissue) [see Dosage and Administration (2.1)] in some patients.Localized Cutaneous Amyloidosis Localized cutaneous amyloidosis at the injection site has occurred. Hyperglycemia has been reported with repeated insulin injections into areas of localized cutaneous amyloidosis; hypoglycemia has been reported with sudden change to an unaffected injection site.Medication ErrorsMedication errors in which other insulins have been accidentally substituted for NOVOLIN 70/30 have been identified during postapproval use.Peripheral edemaInsulins, including NOVOLIN 70/30, may cause sodium retention and edema, particularly if previously poor metabolic control is improved by intensified insulin therapy. Weight gainWeight gain can occur with insulin therapies, including NOVOLIN 70/30, and has been attributed to the anabolic effects of insulin and the decrease in glucosuria. ImmunogenicityAs with all therapeutic peptides, insulin administration may cause anti-insulin antibodies to form. The incidence of antibody formation with NOVOLIN 70/30 is unknown.. oHypoglycemia [see Warnings and Precautions (5.3)]. oMedication Errors [see Warnings and Precautions (5.4)]. oHypersensitivity Reactions [see Warnings and Precautions (5.5)]. oHypokalemia [see Warnings and Precautions (5.6)]. Adverse reactions observed with NOVOLIN 70/30 include hypoglycemia, allergic reactions, injection site reactions, lipodystrophy, weight gain and edema. (6)To report SUSPECTED ADVERSE REACTIONS, contact Novo Nordisk Inc. at 1-800-727-6500 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 Carcinogenicity and fertility studies were not performed in animals.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.

CLINICAL PHARMACOLOGY SECTION.

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action The primary activity of insulin, including NOVOLIN 70/30, 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 The time course of insulin action (i.e., glucose lowering) may vary considerably in different individuals or within the same individual. NOVOLIN 70/30 is an intermediate-acting insulin with up to 24 hours duration of action. When injected subcutaneously, the glucose-lowering effect of NOVOLIN 70/30 begins approximately 30 minutes post-dose.. 12.3 Pharmacokinetics The pharmacokinetics of NOVOLIN 70/30 have been established. The effects of gender, age, obesity, renal and hepatic impairment on the pharmacokinetics of NOVOLIN 70/30 have not been studied.

CONTRAINDICATIONS SECTION.

4 CONTRAINDICATIONS NOVOLIN 70/30 is contraindicated:oDuring episodes of hypoglycemia [see Warnings and Precautions (5.3)].oIn patients who have had hypersensitivity reactions to NOVOLIN 70/30 or any of its excipients [see Warnings and Precautions (5.5)].. oDuring episodes of hypoglycemia [see Warnings and Precautions (5.3)].. oIn patients who have had hypersensitivity reactions to NOVOLIN 70/30 or any of its excipients [see Warnings and Precautions (5.5)].. oDuring episodes of hypoglycemia (4)oHypersensitivity to NOVOLIN 70/30 or any of its excipients (4). oDuring episodes of hypoglycemia (4). oHypersensitivity to NOVOLIN 70/30 or any of its excipients (4).

DESCRIPTION SECTION.

11 DESCRIPTION NOVOLIN 70/30 (human insulin isophane suspension and human insulin injection) is mixture of 70% of human insulin isophane, an intermediate-acting human insulin, and 30% of human insulin, short-acting human insulin. Human insulins are produced by recombinant DNA technology, utilizing Saccharomyces cerevisiae (bakers yeast) as the production organism. NOVOLIN 70/30 has the empirical formula C257H383N65O77S6 and molecular weight of 5808.Figure 1: Structural formula of human insulinNOVOLIN 70/30 is sterile, white and cloudy suspension that contains human insulin isophane suspension (NPH) and human insulin injection (regular) for subcutaneous use, 100 units/mL, glycerol 16 mg/mL, metacresol 1.5 mg/mL, zinc approximately 20.5 mcg/mL (vial), zinc approximately 30.1 mcg/mL (FlexPen), phenol 0.65 mg/mL, disodium phosphate dihydrate 2.4 mg/mL, protamine sulfate approximately 0.25 mg/mL, and water for injection. The pH is adjusted to 7.1-7.5. Hydrochloric acid 2N and sodium hydroxide 2N are added to adjust pH.. Structural formula of human insulin.

DOSAGE & ADMINISTRATION SECTION.

2 DOSAGE AND ADMINISTRATION oSee Full Prescribing Information for important administration instructions. (2.1)oInject subcutaneously in abdominal wall, thigh, upper arm, or buttocks and rotate injection sites to reduce risk of lipodystrophy and localized cutaneous amyloidosis. (2.1)oIndividualize and adjust dosage based on metabolic needs, blood glucose monitoring results and glycemic control goal. (2.2)oInject NOVOLIN 70/30 subcutaneously approximately 30 minutes prior to start of meal. (2.2)oNOVOLIN 70/30 is typically dosed twice daily (with each dose intended to cover meals or meal and snack). (2.2). oSee Full Prescribing Information for important administration instructions. (2.1). oInject subcutaneously in abdominal wall, thigh, upper arm, or buttocks and rotate injection sites to reduce risk of lipodystrophy and localized cutaneous amyloidosis. (2.1). oIndividualize and adjust dosage based on metabolic needs, blood glucose monitoring results and glycemic control goal. (2.2). oInject NOVOLIN 70/30 subcutaneously approximately 30 minutes prior to start of meal. (2.2). oNOVOLIN 70/30 is typically dosed twice daily (with each dose intended to cover meals or meal and snack). (2.2). 2.1 Important Administration Instructions oAlways check insulin labels before administration [see Warnings and Precautions (5.4)].oNOVOLIN 70/30 is suspension that must be resuspended immediately before use. Resuspension is easier when the insulin has reached room temperature. oTo resuspend vial, roll the vial gently in your hands in horizontal position 10 times until the suspension appears uniformly white and cloudy. Inject immediately.oTo resuspend FlexPen, gently move the pen up and down 20 times so the glass ball moves from one end of the cartridge to the other until the suspension appears uniformly white and cloudy. Inject immediately.oInspect NOVOLIN 70/30 visually before use. Do not use NOVOLIN 70/30 if discoloration or particulate matter is seen. oAdminister NOVOLIN 70/30 by subcutaneous injection in the abdominal wall, thigh, upper arm, or buttocks. oRotate the injection site within the same region from one injection to the next to reduce the risk of lipodystrophy and localized cutaneous amyloidosis. Do not inject into areas of lipodystrophy or localized cutaneous amyloidosis [see Warnings and Precautions (5.2), Adverse Reactions (6)].oDuring changes to patients insulin regimen, increase the frequency of blood glucose monitoring [see Warnings and Precautions (5.2)].oDo not administer NOVOLIN 70/30 intravenously or intramuscularly and do not use in an insulin infusion pump. oDo not mix NOVOLIN 70/30 with any other insulins or diluents.. oAlways check insulin labels before administration [see Warnings and Precautions (5.4)].. oNOVOLIN 70/30 is suspension that must be resuspended immediately before use. Resuspension is easier when the insulin has reached room temperature. oTo resuspend vial, roll the vial gently in your hands in horizontal position 10 times until the suspension appears uniformly white and cloudy. Inject immediately.. oTo resuspend FlexPen, gently move the pen up and down 20 times so the glass ball moves from one end of the cartridge to the other until the suspension appears uniformly white and cloudy. Inject immediately.. oInspect NOVOLIN 70/30 visually before use. Do not use NOVOLIN 70/30 if discoloration or particulate matter is seen. oAdminister NOVOLIN 70/30 by subcutaneous injection in the abdominal wall, thigh, upper arm, or buttocks. oRotate the injection site within the same region from one injection to the next to reduce the risk of lipodystrophy and localized cutaneous amyloidosis. Do not inject into areas of lipodystrophy or localized cutaneous amyloidosis [see Warnings and Precautions (5.2), Adverse Reactions (6)].. oDuring changes to patients insulin regimen, increase the frequency of blood glucose monitoring [see Warnings and Precautions (5.2)].. oDo not administer NOVOLIN 70/30 intravenously or intramuscularly and do not use in an insulin infusion pump. oDo not mix NOVOLIN 70/30 with any other insulins or diluents.. 2.2 Dosage Information oIndividualize and adjust the dosage of NOVOLIN 70/30 based on the individuals metabolic needs, blood glucose monitoring results and glycemic control goal. oInject NOVOLIN 70/30 subcutaneously approximately 30 minutes before meal. oNOVOLIN 70/30 is typically dosed twice daily (with each dose intended to cover meals or meal and snack). oDosage adjustments may be needed with changes in physical activity, changes in meal patterns (i.e., macronutrient content or timing of food intake), changes in renal or hepatic function or during acute illness [see Warnings and Precautions (5.2, 5.3) and Use in Specific Populations (8.6, 8.7)]. oDosage adjustment may be needed when switching from another insulin to NOVOLIN 70/30 [see Warnings and Precautions (5.2)].. oIndividualize and adjust the dosage of NOVOLIN 70/30 based on the individuals metabolic needs, blood glucose monitoring results and glycemic control goal. oInject NOVOLIN 70/30 subcutaneously approximately 30 minutes before meal. oNOVOLIN 70/30 is typically dosed twice daily (with each dose intended to cover meals or meal and snack). oDosage adjustments may be needed with changes in physical activity, changes in meal patterns (i.e., macronutrient content or timing of food intake), changes in renal or hepatic function or during acute illness [see Warnings and Precautions (5.2, 5.3) and Use in Specific Populations (8.6, 8.7)]. oDosage adjustment may be needed when switching from another insulin to NOVOLIN 70/30 [see Warnings and Precautions (5.2)].. 2.3 Dosage Adjustment due to Drug Interactions oDosage adjustment may be needed when NOVOLIN 70/30 is co-administered with certain drugs [see Drug Interactions (7)].. oDosage adjustment may be needed when NOVOLIN 70/30 is co-administered with certain drugs [see Drug Interactions (7)].

DOSAGE FORMS & STRENGTHS SECTION.

3 DOSAGE FORMS AND STRENGTHS NOVOLIN 70/30 injectable suspension, 70% human insulin isophane and 30% human insulin, 100 units per mL (U-100), is white and cloudy suspension available as:o10 mL multiple-dose vialo3 mL single-patient-use NOVOLIN 70/30 FlexPen. o10 mL multiple-dose vial. o3 mL single-patient-use NOVOLIN 70/30 FlexPen. Injectable suspension: NOVOLIN 70/30 100 units per mL (U-100), 70% human insulin isophane and 30% human insulin, is available as:o10 mL multiple-dose vial (3)o3 mL single-patient-use NOVOLIN 70/30 FlexPen (3). o10 mL multiple-dose vial (3). o3 mL single-patient-use NOVOLIN 70/30 FlexPen (3).

DRUG INTERACTIONS SECTION.

7 DRUG INTERACTIONS Table 1: Clinically Significant Drug Interactions with NOVOLIN 70/30Drugs 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 antibioticsIntervention:Dose adjustment and increased frequency of glucose monitoring may be required when NOVOLIN 70/30 is co-administered with these drugs. Drugs that May Decrease the Blood Glucose Lowering Effect of NOVOLIN 70/30Drugs: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 NOVOLIN 70/30 is co-administered with these drugs.Drugs that May Increase or Decrease the Blood Glucose Lowering Effect ofNOVOLIN 70/30Drugs: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 NOVOLIN 70/30 is co-administered with these drugs.Drugs that May Blunt Signs and Symptoms of HypoglycemiaDrugs:Beta-blockers, clonidine, guanethidine, and reserpineIntervention:Increased frequency of glucose monitoring may be required when NOVOLIN 70/30 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 resperpine. (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 resperpine. (7).

GERIATRIC USE SECTION.

8.5 Geriatric Use The effect of age on the pharmacokinetics and pharmacodynamics of NOVOLIN 70/30 has not been studied. Elderly patients using insulin, including NOVOLIN 70/30, may be at increased risk of hypoglycemia due to co-morbid disease [see Warnings and Precautions (5.3)].

HOW SUPPLIED SECTION.

16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied NOVOLIN 70/30 injectable suspension is 70% human insulin isophane and 30% human insulin, 100 units per mL (U-100), white and cloudy suspension available as:10 mL multiple-dose vialNDC 0169-1837-11ReliOn(R) brandNDC 0169-1837-023 mL single-patient-use FlexPenNDC 0169-3007-15ReliOn(R) brandNDC 0169-3007-25NOVOLIN 70/30 FlexPen must never be shared between patients, even if the needle is changed. Patients using NOVOLIN 70/30 vials, must never share needles or syringes with another person. Always use new disposable syringe or needle for each injection to prevent contamination. 16.2 Storage and Handling Dispense in the original sealed carton with the enclosed Instructions for Use.Do not expose NOVOLIN 70/30 vials and NOVOLIN 70/30 FlexPen to excessive heat or light. Do not freeze. Do not use after the expiration date.Table 2: Storage Conditions and Expiration Dates for NOVOLIN 70/30Not In-use (Unopened)Refrigerated(36F 46F[2C 8C])Not In-use (Unopened)Room TemperatureIn-use (Opened)Room Temperature10 mL multiple-dose vialUntil expiration date42 daysbelow 77F (25C)42 daysbelow 77F (25 C)Do not refrigerate.3 mL single-patient-use FlexPenUntil expiration date28 daysbelow 86F (30C)28 daysbelow 86F (30C)Do not refrigerate.

INDICATIONS & USAGE SECTION.

1 INDICATIONS AND USAGE NOVOLIN 70/30 is indicated to improve glycemic control in adults and pediatric patients with diabetes mellitus.Limitations of Use:In NOVOLIN 70/30, the proportions of short-acting and intermediate-acting insulins are fixed and do not allow for basal versus prandial dose adjustments.. NOVOLIN 70/30 is mixture of human insulin isophane, an intermediate-acting human insulin, and human insulin, short-acting human insulin, indicated to improve glycemic control in adults and pediatric patients with diabetes mellitus. (1).

INFORMATION FOR PATIENTS SECTION.

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use).Never Share NOVOLIN 70/30 FlexPen or Syringe between PatientsAdvise patients using NOVOLIN 70/30 vials or NOVOLIN 70/30 FlexPen not to share needles, syringes, or FlexPen with another person. Sharing poses risk for transmission of blood-borne pathogens [see Warnings and Precautions (5.1)].Hyperglycemia or Hypoglycemia Inform patients that hypoglycemia is the most common adverse reaction with insulin. Instruct patients on self-management procedures including glucose monitoring, proper injection technique, and management of hypoglycemia and hyperglycemia, especially at initiation of NOVOLIN 70/30 therapy. Instruct patients on handling of special situations such as intercurrent conditions (illness, stress, or emotional disturbances), an inadequate or skipped insulin dose, inadvertent administration of an increased insulin dose, inadequate food intake, and skipped meals. Instruct patients on the management of hypoglycemia [see Warnings and Precautions (5.3)].Inform patients that their ability to concentrate and react may be impaired as result of hypoglycemia. Advise patients who have frequent hypoglycemia or reduced or absent warning signs of hypoglycemia to use caution when driving or operating machinery.Advise patients that changes in insulin regimen can predispose to hyperglycemia or hypoglycemia and that changes in insulin regimen should be made under close medical supervision [see Warnings and Precautions (5.2)].Hypoglycemia due to Medication ErrorsInstruct patients to always check the insulin label before each injection to avoid mix-ups between insulin products [see Warnings and Precautions (5.4)].Hypersensitivity Reactions Advise patients that hypersensitivity reactions have occurred with NOVOLIN 70/30. Inform patients on the symptoms of hypersensitivity reactions and to seek medical attention if they occur [see Warnings and Precautions (5.5)]. Novolin(R), FlexPen(R) and Novo Nordisk(R) are registered trademarks of Novo Nordisk A/S.ReliOn(R) is registered trademark of Wal-Mart Stores, Inc. and is used under license by Novo Nordisk Inc.Patent Information: http://novonordisk-us.com/patients/products/product-patents.html(C) 2019 Novo NordiskManufactured by: Novo Nordisk A/S DK-2880 Bagsvaerd, DenmarkReliOn(R) brand manufactured by:Novo Nordisk A/S DK-2880 Bagsvaerd, DenmarkFor Wal-Mart Stores Inc.For information about NOVOLIN 70/30 contact: Novo Nordisk Inc. 800 Scudders Mill RoadPlainsboro, New Jersey 08536www.novonordisk-us.com1-800-727-6500.

MECHANISM OF ACTION SECTION.

12.1 Mechanism of Action The primary activity of insulin, including NOVOLIN 70/30, 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 Carcinogenicity and fertility studies were not performed in animals.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.

OVERDOSAGE SECTION.

10 OVERDOSAGE Excess insulin administration may cause hypoglycemia and hypokalemia. 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 can be treated with intramuscular or subcutaneous glucagon or intravenous glucose. Sustained carbohydrate intake and observation may be necessary because hypoglycemia may recur after apparent clinical recovery. Hypokalemia must be corrected appropriately [see Warnings and Precautions (5.3, 5.6)].

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.

PRINCIPAL DISPLAY PANEL 10 mL Vial NDC 0169-1837-11 Novolin(R) 70/30 (human insulin isophane suspension andhuman insulin injection)100 units/mL 10 mL multi-dose vialNovo Nordisk(R) Novolin 70/30 vial carton image.

PEDIATRIC USE SECTION.

8.4 Pediatric Use NOVOLIN 70/30 is indicated to improve glycemic control in pediatric patients with diabetes mellitus.The dosage of NOVOLIN 70/30 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 (5.3)].

PHARMACODYNAMICS SECTION.

12.2 Pharmacodynamics The time course of insulin action (i.e., glucose lowering) may vary considerably in different individuals or within the same individual. NOVOLIN 70/30 is an intermediate-acting insulin with up to 24 hours duration of action. When injected subcutaneously, the glucose-lowering effect of NOVOLIN 70/30 begins approximately 30 minutes post-dose.

PHARMACOKINETICS SECTION.

12.3 Pharmacokinetics The pharmacokinetics of NOVOLIN 70/30 have been established. The effects of gender, age, obesity, renal and hepatic impairment on the pharmacokinetics of NOVOLIN 70/30 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 Considerations Disease-associated maternal and/or embryo/fetal riskPoorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, pre-eclampsia, 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.

RECENT MAJOR CHANGES SECTION.

Dosage and Administration (2.1)....................................11/2019Warnings and Precautions (5.2)......................................11/2019.

SPL UNCLASSIFIED SECTION.

2.1 Important Administration Instructions oAlways check insulin labels before administration [see Warnings and Precautions (5.4)].oNOVOLIN 70/30 is suspension that must be resuspended immediately before use. Resuspension is easier when the insulin has reached room temperature. oTo resuspend vial, roll the vial gently in your hands in horizontal position 10 times until the suspension appears uniformly white and cloudy. Inject immediately.oTo resuspend FlexPen, gently move the pen up and down 20 times so the glass ball moves from one end of the cartridge to the other until the suspension appears uniformly white and cloudy. Inject immediately.oInspect NOVOLIN 70/30 visually before use. Do not use NOVOLIN 70/30 if discoloration or particulate matter is seen. oAdminister NOVOLIN 70/30 by subcutaneous injection in the abdominal wall, thigh, upper arm, or buttocks. oRotate the injection site within the same region from one injection to the next to reduce the risk of lipodystrophy and localized cutaneous amyloidosis. Do not inject into areas of lipodystrophy or localized cutaneous amyloidosis [see Warnings and Precautions (5.2), Adverse Reactions (6)].oDuring changes to patients insulin regimen, increase the frequency of blood glucose monitoring [see Warnings and Precautions (5.2)].oDo not administer NOVOLIN 70/30 intravenously or intramuscularly and do not use in an insulin infusion pump. oDo not mix NOVOLIN 70/30 with any other insulins or diluents.. oAlways check insulin labels before administration [see Warnings and Precautions (5.4)].. oNOVOLIN 70/30 is suspension that must be resuspended immediately before use. Resuspension is easier when the insulin has reached room temperature. oTo resuspend vial, roll the vial gently in your hands in horizontal position 10 times until the suspension appears uniformly white and cloudy. Inject immediately.. oTo resuspend FlexPen, gently move the pen up and down 20 times so the glass ball moves from one end of the cartridge to the other until the suspension appears uniformly white and cloudy. Inject immediately.. oInspect NOVOLIN 70/30 visually before use. Do not use NOVOLIN 70/30 if discoloration or particulate matter is seen. oAdminister NOVOLIN 70/30 by subcutaneous injection in the abdominal wall, thigh, upper arm, or buttocks. oRotate the injection site within the same region from one injection to the next to reduce the risk of lipodystrophy and localized cutaneous amyloidosis. Do not inject into areas of lipodystrophy or localized cutaneous amyloidosis [see Warnings and Precautions (5.2), Adverse Reactions (6)].. oDuring changes to patients insulin regimen, increase the frequency of blood glucose monitoring [see Warnings and Precautions (5.2)].. oDo not administer NOVOLIN 70/30 intravenously or intramuscularly and do not use in an insulin infusion pump. oDo not mix NOVOLIN 70/30 with any other insulins or diluents.

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 Considerations Disease-associated maternal and/or embryo/fetal riskPoorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, pre-eclampsia, 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 suggests that exogenous human insulin products, including NOVOLIN 70/30, 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 NOVOLIN 70/30, on milk production. The developmental and health benefits of breastfeeding should be considered along with the mothers clinical need for NOVOLIN 70/30, and any potential adverse effects on the breastfed infant from NOVOLIN 70/30, or from the underlying maternal condition.. 8.4 Pediatric Use NOVOLIN 70/30 is indicated to improve glycemic control in pediatric patients with diabetes mellitus.The dosage of NOVOLIN 70/30 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 (5.3)]. 8.5 Geriatric Use The effect of age on the pharmacokinetics and pharmacodynamics of NOVOLIN 70/30 has not been studied. Elderly patients using insulin, including NOVOLIN 70/30, may be at increased risk of hypoglycemia due to co-morbid disease [see Warnings and Precautions (5.3)]. 8.6 Renal Impairment The effect of renal impairment on the pharmacokinetics and pharmacodynamics of NOVOLIN 70/30 has not been studied. Patients with renal impairment are at increased risk of hypoglycemia and may require more frequent NOVOLIN 70/30 dose adjustment and more frequent blood glucose monitoring [see Warnings and Precautions (5.3)].. 8.7 Hepatic Impairment The effect of hepatic impairment on the pharmacokinetics and pharmacodynamics of NOVOLIN 70/30 has not been studied. Patients with hepatic impairment are at increased risk of hypoglycemia and may require more frequent NOVOLIN 70/30 dose adjustment and more frequent blood glucose monitoring [see Warnings and Precautions (5.3)].

WARNINGS AND PRECAUTIONS SECTION.

5 WARNINGS AND PRECAUTIONS oNever share NOVOLIN 70/30 FlexPen or syringe between patients, even if the needle is changed. (5.1)oHyperglycemia or Hypoglycemia with Changes in Insulin Regimen: Make changes to patients insulin regimen (e.g., insulin strength, manufacturer, type, injection site or method of administration) under close medical supervision with increased frequency of blood glucose monitoring. (5.2)oHypoglycemia: May be life-threatening. Increase frequency of blood glucose monitoring with changes to: insulin dosage, co-administered glucose lowering medications, meal pattern, physical activity; in patients with renal or hepatic impairment; and in patients with hypoglycemia unawareness. (5.3)oHypoglycemia Due to Medication Errors: Accidental mix-ups between insulin products can occur. Instruct patients to check insulin labels before injection. (5.4)oHypersensitivity Reactions: Severe, life-threatening, generalized allergy, including anaphylaxis, can occur. Discontinue NOVOLIN 70/30, monitor, and treat if indicated. (5.5)oHypokalemia: May be life-threatening. Monitor potassium levels in patients at risk for hypokalemia and treat if indicated. (5.6)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. (5.7). oNever share NOVOLIN 70/30 FlexPen or syringe between patients, even if the needle is changed. (5.1). oHyperglycemia or Hypoglycemia with Changes in Insulin Regimen: Make changes to patients insulin regimen (e.g., insulin strength, manufacturer, type, injection site or method of administration) under close medical supervision with increased frequency of blood glucose monitoring. (5.2). oHypoglycemia: May be life-threatening. Increase frequency of blood glucose monitoring with changes to: insulin dosage, co-administered glucose lowering medications, meal pattern, physical activity; in patients with renal or hepatic impairment; and in patients with hypoglycemia unawareness. (5.3). oHypoglycemia Due to Medication Errors: Accidental mix-ups between insulin products can occur. Instruct patients to check insulin labels before injection. (5.4). oHypersensitivity Reactions: Severe, life-threatening, generalized allergy, including anaphylaxis, can occur. Discontinue NOVOLIN 70/30, monitor, and treat if indicated. (5.5). oHypokalemia: May be life-threatening. Monitor potassium levels in patients at risk for hypokalemia and treat if indicated. (5.6). 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. (5.7). 5.1 Never Share NOVOLIN 70/30 FlexPen or Syringe between Patients NOVOLIN 70/30 FlexPen must never be shared between patients, even if the needle is changed. Patients using NOVOLIN 70/30 vials must never share needles or syringes with another person. Sharing poses risk for transmission of blood-borne pathogens.. 5.2 Hyperglycemia or Hypoglycemia with Changes in Insulin Regimen Changes in an insulin regimen (e.g., insulin strength, manufacturer, type, injection site or method of administration) may affect glycemic control and predispose to hypoglycemia [see Warnings and Precautions (5.3)] or hyperglycemia. Repeated insulin injections into areas of lipodystrophy or localized cutaneous amyloidosis have been reported to result in hyperglycemia; and sudden change in the injection site (to an unaffected area) has been reported to result in hypoglycemia [see Adverse Reactions (6)].Make any changes to patients insulin regimen under close medical supervision with increased frequency of blood glucose monitoring. Advise patients who have repeatedly injected into areas of lipodystrophy or localized cutaneous amyloidosis to change the injection site to unaffected areas and closely monitor for hypoglycemia. For patients with type diabetes, dosage adjustments of concomitant anti-diabetic products may be needed.. 5.3 Hypoglycemia Hypoglycemia is the most common adverse reaction of all insulin therapies, including NOVOLIN 70/30. Severe hypoglycemia can cause seizures, may lead to unconsciousness may be life threatening or cause death. Hypoglycemia can impair concentration ability and reaction time; this may place an individual and others at risk in situations where these abilities are important (e.g., driving or operating other machinery).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 HypoglycemiaThe risk of hypoglycemia after an injection is related to the duration of action of the insulin and, in general, is highest when the glucose lowering effect of the insulin is maximal. As with all insulin preparations, the time course of glucose lowering effect of NOVOLIN 70/30 may vary in different individuals or at different times in the same individual and depends on many conditions, including the area of injection as well as the injection site blood supply and temperature. Other factors which may increase the risk of hypoglycemia include changes in meal pattern (e.g., macronutrient content or timing of meals), changes in level of physical activity, or changes to 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 Hypoglycemia Patients and caregivers must be educated to recognize and manage hypoglycemia. Self-monitoring of blood glucose plays an essential role in the prevention and management of 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.. 5.4 Hypoglycemia Due to Medication Errors Accidental mix-ups between NOVOLIN 70/30 and other insulin products have been reported. To avoid medication errors between NOVOLIN 70/30 and other insulins, instruct patients to always check the insulin label before each injection. 5.5 Hypersensitivity and Allergic Reactions Severe, life-threatening, generalized allergy, including anaphylaxis can occur with NOVOLIN 70/30. Generalized allergy to insulin may manifest as whole body rash (including pruritus), dyspnea, wheezing, hypotension, tachycardia, or diaphoresis. If hypersensitivity reactions occur, discontinue NOVOLIN 70/30; treat per standard of care and monitor until symptoms and signs resolve. NOVOLIN 70/30 is contraindicated in patients who have had hypersensitivity reactions to NOVOLIN 70/30 or its excipients [see Contraindications (4)]. 5.6 Hypokalemia All insulins, including NOVOLIN 70/30, 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 in patients at risk for hypokalemia if indicated (e.g., patients using potassium-lowering medications, patients taking medications sensitive to serum potassium concentration).. 5.7 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 NOVOLIN 70/30, 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.