SPL PATIENT PACKAGE INSERT SECTION.

PATIENT INFORMATION SOGROYA(R) (suh-GROY-uh)(somapacitan-beco) injection, for subcutaneous useWhat is SOGROYAoSOGROYA is prescription medicine that contains human growth hormone, the same growth hormone made by the human body.oSOGROYA is given by injection under the skin (subcutaneous) and is used to treat adults who do not make enough growth hormone. It is not known if SOGROYA is safe and effective in children.Do not use SOGROYA if:oyou have critical illness caused by certain types of heart or stomach surgery, trauma or breathing (respiratory) problems.oyou have cancer or other tumors.oyou are allergic to somapacitan-beco or any of the ingredients in SOGROYA. See the end of this Patient Information leaflet for complete list of ingredients in SOGROYA.oyour healthcare provider tells you that you have certain types of eye problems caused by diabetes (diabetic retinopathy).Before taking SOGROYA, tell your healthcare provider about all of your medical conditions, including if you:ohave had heart or stomach surgery, trauma or serious breathing (respiratory) problems.ohave had cancer or any tumor.ohave diabetes.ohave adrenal gland problems.oare taking replacement therapy with glucocorticoids.ohave thyroid gland problems.ohave liver problems.oare pregnant or plan to become pregnant. It is not known if SOGROYA will harm your unborn baby. Talk to your healthcare provider if you are pregnant or plan to become pregnant.oare breastfeeding or plan to breastfeed. It is not known if SOGROYA passes into your breast milk. You and your healthcare provider should decide if you will take SOGROYA while you breastfeed.Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. SOGROYA may affect how other medicines work, and other medicines may affect how SOGROYA works.How should use SOGROYAoRead the detailed Instructions for Use that come with SOGROYA.oSOGROYA comes in strengths: mg/1.5 mL (3.3 mg/mL) pen and 10 mg/1.5 mL (6.7 mg/mL) pen. Your healthcare provider will prescribe the dose that is right for you. oYour healthcare provider will show you how to inject SOGROYA.oUse SOGROYA exactly as your healthcare provider tells you to.oUse SOGROYA time each week.oIf you miss dose of SOGROYA, take the missed dose as soon as possible within days (72 hours) after the missed dose. If more than days (72 hours) have passed, skip the missed dose and take your next dose on the regularly scheduled day.oSOGROYA pens are for use by person only.oDo not share your SOGROYA pens and needles with another person, even if the needle has been changed. You may give another person an infection or get an infection from them.What are the possible side effects of SOGROYASOGROYA may cause serious side effects, including:ohigh risk of death in people who have critical illnesses because of heart or stomach surgery, trauma or serious breathing (respiratory) problems.oincreased risk of growth of cancer or tumor that is already present and increased risk of the return of cancer. Your healthcare provider will need to monitor you for return of cancer or tumor. Contact the healthcare provider if you start to have changes in moles, birthmarks, or the color of your skin. onew or worsening high blood sugar (hyperglycemia) or diabetes. Your blood sugar may need to be monitored during treatment with SOGROYA.oincrease in pressure in the skull (intracranial hypertension). If you have headaches, eye problems, nausea or vomiting, contact the healthcare provider.oserious allergic reactions. Get medical help right away if you have the following symptoms:oswelling of your face, lips, mouth, or tongueoskin rashes, redness, or swellingotrouble breathingodizziness or faintingowheezingofast heartbeat or pounding in your chestosevere itchingosweatingoyour body holding too much fluid (fluid retention) such as swelling in the hands and feet, pain in your joints or muscles or nerve problems that cause pain, burning or tingling in the hands, arms, legs and feet. Tell your healthcare provider if you have any of these signs or symptoms of fluid retention. odecrease in hormone called cortisol. The healthcare provider will do blood tests to check your cortisol levels. Tell your healthcare provider if you have darkening of the skin, severe fatigue, dizziness, weakness, or weight loss. odecrease in thyroid hormone levels. Decreased thyroid hormone levels may affect how well SOGROYA works. The healthcare provider will do blood tests to check your thyroid hormone levels.osevere and constant abdominal pain. This could be sign of pancreatitis. Tell your healthcare provider if you have any new abdominal pain. oloss of fat and tissue weakness in the area of skin you inject. Talk to your healthcare provider about rotating the areas where you inject SOGROYA.oincrease in phosphorus, alkaline phosphatase and parathyroid hormone levels in your blood. Your healthcare provider will do blood tests to check this.The most common side effects of SOGROYA include:oback painovomitingojoint painohigh blood pressureoindigestionoincrease in the level of an enzyme in your blood called creatine phosphokinaseosleep problemsoweight gainodizzinessolow red blood cells (anemia)oswelling of the tonsils (tonsillitis)These are not all the possible side effects of SOGROYA. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. You may also report side effects to Novo Nordisk at 1-888-668-6444. How should store SOGROYAoBefore you use SOGROYA pens for the first time: oStore your new, unused SOGROYA pen in refrigerator between 36oF to 46oF (2oC to 8oC).oStore your new, unused SOGROYA pen with the cap on and keep it in the original carton. oDo not freeze SOGROYA. oKeep SOGROYA away from direct heat and light.oDo not use SOGROYA that has been frozen or in temperatures warmer than 86oF (30oC).oDo not use SOGROYA after the expiration date printed on the carton and the pen.oAfter you use SOGROYA pens and there is still medicine left: oStore remaining SOGROYA in the refrigerator between 36oF to 46oF (2oC to 8oC) and use within weeks.oStore your in-use SOGROYA pen with the cap on and keep it in the original carton.oIf needed, unused and in-use SOGROYA pens can be stored out of the refrigerator. SOGROYA pens can be stored at room temperature no warmer than 77oF (25oC) for up to days (72 hours) and then returned to the refrigerator.Keep SOGROYA and all medicines out of the reach of children.General information about the safe and effective use of SOGROYA.Medicines are sometimes prescribed for purposes other than those listed in Patient Information leaflet. Do not use SOGROYA for condition for which it was not prescribed. Do not give SOGROYA to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or healthcare provider for information about SOGROYA that is written for health professionals. What are the ingredients in SOGROYAActive ingredient: somapacitan-becoInactive ingredients: histidine, mannitol, phenol, poloxamer 188, Water for Injection, and hydrochloric acid and sodium hydroxide (as needed)Manufactured by: Novo Nordisk Inc., Plainsboro, NJ 08536This Patient Information has been approved by the U.S. Food and Drug Administration.Revised: 10/2021Supplies you will need:oSOGROYA prefilled Penonew injection needle. SOGROYA prefilled Pen is designed to be used with all Novo Nordisk disposable needles up to length of mm.osharps disposal container. See Step for information on how to throw away (dispose of) used needles and Pens.oalcohol padogauze padHow to use your SOGROYA Pen5 steps you should follow for SOGROYA injection:Step 1: Prepare your SOGROYA Pen Step 2: Check the SOGROYA flow with each new PenStep 3: Select your doseStep 4: Inject your doseStep 5: After your injectionFor further information about your Pen see: Frequently Asked Questions and Important informationImportant informationPay special attention to these notes as they are important for safe use of the Pen.Additional informationSOGROYA is prefilled growth hormone Pen. It contains mg of somapacitan-beco and delivers doses from 0.025 mg to 2.0 mg, in increments of 0.025 mg. SOGROYA is for use under the skin only (subcutaneous) for injection time each week. Do not share your SOGROYA Pen and needles with another person. You may give another person an infection or get an infection from them.Do not use your Pen without proper training from your healthcare provider. Make sure that you are confident in giving an injection with the Pen before you start your treatment. If you are blind or have poor eyesight and cannot read the dose counter on the Pen, do not use this Pen without help. Get help from person with good eyesight who is trained to use the Pen.Step 1. Prepare your SOGROYA PenoWash your hands with soap and water.oCheck the name, strength, and colored label on your Pen to make sure that it contains SOGROYA in the right strength.oPull off the Pen cap.oTurn the Pen upside down or times to check that the SOGROYA in your Pen is clear to almost clear and colorless to slightly yellow (See Figure A). If SOGROYA looks cloudy or you see particles, do not use the Pen.oWhen you are ready to give your injection, get new disposable needle, and remove the paper tab.oPush the needle straight onto the Pen. Turn the needle clockwise until it is on tight (See Figure B). Make sure the right pen is used. Especially if you use more than one type of injection medicine. Using the wrong medicine could be harmful to your health.Always use new needle for each injection. This reduces the risk of contamination, infection, leakage of SOGROYA, and blocked needles leading to incorrect dosing.oPull off the outer needle cap and throw it away (dispose of) (See Figure C).oPull off the inner needle cap and throw it away (dispose of) (See Figure D). drop of SOGROYA may appear at the needle tip. This is normal, but you must still check the SOGROYA flow with each new Pen (See Step 2).Never use bent or damaged needle.Step 2. Check the SOGROYA flow with each new PenIf your Pen is already in use, go to Step 3.oBefore using new Pen, check the SOGROYA flow to make sure the growth hormone can flow through the Pen and needle.oTurn the dose selector clockwise marking on the dose counter to select 0.025 mg. You may hear faint click when you turn the dose selector (See Figure E).o1 marking on the dose counter equals 0.025 mg (See Figure F).oHold the Pen with the needle pointing up. Press and hold in the dose button until the dose counter returns to 0. The 0 must line up with the dose pointer (See Figure G).oCheck that drop of SOGROYA appears at the needle tip (See Figure H).If no SOGROYA appears, repeat Step up to times.If you still do not see drop of SOGROYA, change the needle: oCarefully remove the needle from the Pen by turning the needle counterclockwise. Place the needle in sharps disposal container immediately (See Step 5).oRepeat Step again.Do not use the Pen if drop of SOGROYA still does not appear after changing the needle and repeating Step 2. Call Novo Nordisk at 1-888-668-6444 for help.Step 3. Select your doseoTo start, check that the dose pointer is set at 0.oTurn the dose selector clockwise to select the dose you need (See Figure I). When you have selected your dose, you can go to Step 4.If there is not enough SOGROYA left to select full dose, see Frequently Asked Questions. The dose counter shows the dose in mg (See Figure and Figure K). Always use the dose counter to select the exact dose. Do not use the click sounds you hear when you turn the dose selector to select your dose. Only the dose pointer on the dose counter will show the exact dose selected. If you select the wrong dose, you can turn the dose selector clockwise or counterclockwise to the correct dose (See Figure L).The Pen clicks sound and feel differently when the dose selector is turned clockwise, counterclockwise, or if you forcefully move it past the number of mg left in the Pen.Step 4. Inject your doseoSelect the injection site.oSOGROYA can be injected under the skin (subcutaneously) of your stomach area (abdomen) or upper legs (thighs) as instructed by your healthcare provider (See Figure M). Change the injection site every week.oWipe the injection site with an alcohol pad and let the area dry.oInsert the needle into your skin as your healthcare provider has shown you (See Figure N).oMake sure you can see the dose counter. Do not cover it with your fingers. This could block the injection.oPress and hold down the dose button until the dose counter shows 0 (See Figure O). The 0 must line up with the dose pointer. You may then hear or feel click.oContinue to hold down the dose button with the needle in your skin. If 0 does not appear in the dose counter after continuously pressing the dose button, your needle may be blocked or damaged. See Frequently Asked Questions.oKeep holding down the dose button with the needle in your skin and slowly count to to make sure that the full dose has been delivered (See Figure P).oCarefully remove the needle from your skin (See Figure Q). If blood appears at the injection site, press lightly with gauze pad. Do not rub the area. You may see drop of SOGROYA at the needle tip after injecting. This is normal and does not affect your dose. Step 5. After your injectionoCarefully remove the needle from the Pen by turning the needle counterclockwise (See Figure R).oPlace the needle in an FDA-cleared sharps disposal container immediately to reduce the risk of needle stick (See Figure R). Always throw away (dispose of) the needle after each injection. For further information about safe sharps disposal, see Frequently Asked Questions.oPut the Pen cap on your Pen after each use to protect SOGROYA from direct light (See Figure S). See How should store my SOGROYA Pen.Do not try to put the needle cap back on. You may stick yourself with the needle. Always remove the needle from your Pen immediately after each injection. This reduces the risk of contamination, infection, leakage of SOGROYA, and blocked needles leading to incorrect dosing.How should store my SOGROYA PenBefore you use SOGROYA Pen for the first time: oStore your new, unused SOGROYA Pen in refrigerator between 36F to 46F (2C to 8C). oStore your new, unused SOGROYA Pen with the cap on and in the original carton.oDo not freeze SOGROYA. oWhen stored in the refrigerator, do not store the SOGROYA Pen directly next to the cooling element. oKeep SOGROYA away from direct heat and light.oDo not use SOGROYA if it has been frozen or in temperatures warmer than 86oF (30C). oDo not use SOGROYA after the expiration date printed on the carton and the Pen. After you use SOGROYA Pen and there is still medicine left:oStore remaining SOGROYA in the refrigerator between 36F to 46F (2C to 8C) and use within weeks.oStore your in-use SOGROYA Pen with the cap on and keep it in the original carton.Do not store SOGROYA Pen with the needle attached. If needed, unused and in-use SOGROYA pens can be stored out of the refrigerator. SOGROYA pens can be stored at room temperature no warmer than 77oF (25oC) for up to days (72 hours) and then returned to the refrigerator. Throw away (dispose of) SOGROYA if it has been stored above 77F (25C) for more than days (72 hours) or in temperatures warmer than 86F (30C).Always keep your SOGROYA Pen and needles out of reach of others, especially children.Frequently Asked QuestionsHow do see how much SOGROYA is left in my PenThe Pen scale shows you approximately how much SOGROYA is left in your Pen (See Figure T).To see how much SOGROYA is left in your Pen, use the dose counter:Turn the dose selector clockwise until the dose counter stops. The dose pointer will line up with the number of mg left in the Pen. You can select maximum dose of 2.0 mg. If the dose counter stops with the dose pointer lined up with 2, at least 2.0 mg are left in your Pen.If the dose counter stops with the dose pointer lined up with 1.7, only 1.7 mg are left in your Pen (See Figure U).What if need larger dose than what is left in my PenIt is not possible to select larger dose on the dose counter than the number of mg left in your Pen. If you need more SOGROYA than you have left in your Pen, you can use new Pen or split your dose between your current Pen and new Pen. Only split your dose if you have been trained or advised by your healthcare provider on how to do this. You may find it helpful to use calculator to plan the doses as instructed by your healthcare provider.Be very careful to calculate your split dose correctly so that you do not give the wrong dose. If you are not sure how to split your dose using Pens, then select and inject the dose you need with new Pen.What if no SOGROYA appears when check the flowA. Your needle may be blocked or damaged, if no SOGROYA appears at the needle tip. Remove the needle as described in Step and repeat Step and Step 2.B. Your Pen may be defective, if SOGROYA still does not appear after changing the needle. Do not use the Pen. Contact Novo Nordisk at 1-888-668-6444.What if 0 does not appear after completing my injectionThe needle may be blocked or damaged, and you have not received any SOGROYA, even though the dose counter has moved from the dose that you have set. Remove the needle as described in Step and repeat Step to Step 4.How should take care of my PenBe careful not to drop your Pen or knock it against hard surfaces. Do not expose your Pen to dust, dirt, liquid, or direct light. See How should store SOGROYA Do not try to refill your Pen, it is prefilled.What if drop my PenIf you drop your Pen or think that something is wrong with it, attach new disposable needle and check the SOGROYA flow before you inject (See Step and Step 2). Do not try to repair your Pen or pull it apart.How do clean my PenDo not wash, soak, or lubricate your Pen. If necessary, clean it with mild detergent on moistened cloth.Frequently Asked QuestionsHow do throw away (dispose of) used SOGROYA needles and PensPut your used needles and Pens in an FDA-cleared sharps disposal container right away after use. Do not throw away (dispose of) loose needles and Pens in your household trash. If you do not have an FDA-cleared sharps disposal container, you may use household container that is: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, and oproperly labeled to warn of hazardous waste inside the container.When 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 dispose of used needles and Pens. For more information about safe sharps disposal, and for specific information about safe 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. Important informationoCaregivers must be very careful when handling needles to reduce the risk of needle sticks and infection.PATENT Information: http://novonordisk-us.com/products/product-patents.htmlSOGROYA(R) is registered trademark of Novo Nordisk Health Care AG.Novo Nordisk(R) is registered trademark of Novo Nordisk A/S.(C) 2004-2021 Novo Nordisk Health Care AGFor further information contact:Novo Nordisk Inc.800 Scudders Mill Road Plainsboro, NJ 08536, USA 1-888-668-6444Sogroya.comManufactured by:Novo Nordisk Inc.Plainsboro, NJ 08536U.S. License No. 1261This Instructions for Use has been approved by the U.S. Food and Drug Administration.Issued: 10/2021Version: 1Supplies you will need:oSOGROYA prefilled Penonew injection needle. SOGROYA prefilled Pen is designed to be used with all Novo Nordisk disposable needles up to length of mm.osharps disposal container. See Step for information on how to throw away (dispose of) used needles and Pens.oalcohol padogauze padHow to use your SOGROYA Pen5 steps you should follow for SOGROYA injection:Step 1: Prepare your SOGROYA Pen Step 2: Check the SOGROYA flow with each new PenStep 3: Select your doseStep 4: Inject your doseStep 5: After your injectionFor further information about your Pen see: Frequently Asked Questions and Important information Important informationPay special attention to these notes as they are important for safe use of the Pen. Additional informationSOGROYA is prefilled growth hormone Pen. It contains 10 mg of somapacitan-beco and delivers doses from 0.05 mg to 4.0 mg, in increments of 0.05 mg. SOGROYA is for use under the skin only (subcutaneous) for injection time each week. Do not share your SOGROYA Pen and needles with another person. You may give another person an infection or get an infection from them.Do not use your Pen without proper training from your healthcare provider. Make sure that you are confident in giving an injection with the Pen before you start your treatment. If you are blind or have poor eyesight and cannot read the dose counter on the Pen, do not use this Pen without help. Get help from person with good eyesight who is trained to use the Pen.Step 1. Prepare your SOGROYA PenoWash your hands with soap and water.oCheck the name, strength, and colored label on your Pen to make sure that it contains SOGROYA in the right strength.oPull off the Pen cap.oTurn the Pen upside down or times to check that the SOGROYA in your Pen is clear to almost clear and colorless to slightly yellow (See Figure A). If SOGROYA looks cloudy or you see particles, do not use the Pen.oWhen you are ready to give your injection, get new disposable needle, and remove the paper tab.oPush the needle straight onto the Pen. Turn the needle clockwise until it is on tight (See Figure B).Make sure the right pen is used. Especially if you use more than one type of injection medicine. Using the wrong medicine could be harmful to your health.Always use new needle for each injection. This reduces the risk of contamination, infection, leakage of SOGROYA, and blocked needles leading to incorrect dosing.oPull off the outer needle cap and throw it away (dispose of) (See Figure C).oPull off the inner needle cap and throw it away (dispose of) (See Figure D). drop of SOGROYA may appear at the needle tip. This is normal, but you must still check the SOGROYA flow with each new Pen (See Step 2).Never use bent or damaged needle.Step 2. Check the SOGROYA flow with each new Pen If your Pen is already in use, go to Step 3.oBefore using new Pen, check the SOGROYA flow to make sure the growth hormone can flow through the Pen and needle.oTurn the dose selector clockwise marking on the dose counter to select 0.05 mg. You may hear faint click when you turn the dose selector (See Figure E).o1 marking on the dose counter equals 0.05 mg (See Figure F).oHold the Pen with the needle pointing up. Press and hold in the dose button until the dose counter returns to 0. The 0 must line up with the dose pointer (See Figure G).oCheck that drop of SOGROYA appears at the needle tip (See Figure H).If no SOGROYA appears, repeat Step up to times. If you still do not see drop of SOGROYA, change the needle: oCarefully remove the needle from the Pen by turning the needle counterclockwise. Place the needle in sharps disposal container immediately (See Step 5).oRepeat Step again.Do not use the Pen if drop of SOGROYA still does not appear after changing the needle and repeating Step 2. Call Novo Nordisk at 1-888-668-6444 for help.Step 3. Select your doseoTo start, check that the dose pointer is set at 0.oTurn the dose selector clockwise to select the dose you need (See Figure I). When you have selected your dose, you can go to Step 4. If there is not enough SOGROYA left to select full dose, see Frequently Asked Questions. The dose counter shows the dose in mg (See Figure and Figure K). Always use the dose counter to select the exact dose. Do not use the click sounds you hear when you turn the dose selector to select your dose. Only the dose pointer on the dose counter will show the exact dose selected. If you select the wrong dose, you can turn the dose selector clockwise or counterclockwise to the correct dose (See Figure L).The Pen clicks sound and feel differently when the dose selector is turned clockwise, counterclockwise, or if you forcefully move it past the number of mg left in the Pen.Step 4. Inject your doseoSelect the injection site.oSOGROYA can be injected under the skin (subcutaneously) of your stomach area (abdomen) or upper legs (thighs) as instructed by your healthcare provider (See Figure M). Change the injection site every week.oWipe the injection site with an alcohol pad and let the area dry.oInsert the needle into your skin as your healthcare provider has shown you (See Figure N). oMake sure you can see the dose counter. Do not cover it with your fingers. This could block the injection.oPress and hold down the dose button until the dose counter shows 0 (See Figure O). The 0 must line up with the dose pointer. You may then hear or feel click. oContinue to hold down the dose button with the needle in your skin. If 0 does not appear in the dose counter after continuously pressing the dose button, your needle may be blocked or damaged. See Frequently Asked Questions. oKeep holding down the dose button with the needle in your skin and slowly count to to make sure that the full dose has been delivered (See Figure P).oCarefully remove the needle from your skin (See Figure Q). If blood appears at the injection site, press lightly with gauze pad. Do not rub the area. You may see drop of SOGROYA at the needle tip after injecting. This is normal and does not affect your dose.Step 5. After your injectionoCarefully remove the needle from the Pen by turning the needle counterclockwise (See Figure R).oPlace the needle in an FDA-cleared sharps disposal container immediately to reduce the risk of needle stick (See Figure R). Always throw away (dispose of) the needle after each injection.For further information about safe sharps disposal, see Frequently Asked Questions. oPut the Pen cap on your Pen after each use to protect SOGROYA from direct light (See Figure S). See How should store my SOGROYA Pen.Do not try to put the needle cap back on. You may stick yourself with the needle.Always remove the needle from your Pen immediately after each injection. This reduces the risk of contamination, infection, leakage of SOGROYA, and blocked needles leading to incorrect dosing.How should store my SOGROYA PenBefore you use SOGROYA Pen for the first time: oStore your new, unused SOGROYA Pen in refrigerator between 36F to 46F (2C to 8C).oStore your new, unused SOGROYA Pen with the cap on and in the original carton. oDo not freeze SOGROYA. oWhen stored in the refrigerator, do not store the SOGROYA Pen directly next to the cooling element. oKeep SOGROYA away from direct heat and light.oDo not use SOGROYA if it has been frozen or in temperatures warmer than 86oF (30C).oDo not use SOGROYA after the expiration date printed on the carton and the Pen. After you use SOGROYA Pen and there is still medicine left:oStore remaining SOGROYA in the refrigerator between 36F to 46F (2C to 8C) and use within weeks.oStore your in-use SOGROYA Pen with the cap on and keep it in the original carton.Do not store SOGROYA Pen with the needle attached.If needed, unused and in-use SOGROYA pens can be stored out of the refrigerator. SOGROYA pens can be stored at room temperature no warmer than 77oF (25oC) for up to days (72 hours) and then returned to the refrigerator. Throw away (dispose of) SOGROYA if it has been stored above 77F (25C) for more than days (72 hours) or in temperatures warmer than 86F (30C).Always keep your SOGROYA Pen and needles out of reach of others, especially children.Frequently Asked QuestionsHow do see how much SOGROYA is left in my PenThe Pen scale shows you approximately how much SOGROYA is left in your Pen (See Figure T).To see how much SOGROYA is left in your Pen, use the dose counter:Turn the dose selector clockwise until the dose counter stops. The dose pointer will line up with the number of mg left in the Pen. You can select maximum dose of 4.0 mg. If the dose counter stops with the dose pointer lined up with 4, at least 4.0 mg are left in your Pen.If the dose counter stops with the dose pointer lined up with 2.8, only 2.8 mg are left in your Pen (See Figure U).What if need larger dose than what is left in my PenIt is not possible to select larger dose on the dose counter than the number of mg left in your Pen. If you need more SOGROYA than you have left in your Pen, you can use new Pen or split your dose between your current Pen and new Pen. Only split your dose if you have been trained or advised by your healthcare provider on how to do this. You may find it helpful to use calculator to plan the doses as instructed by your healthcare provider.Be very careful to calculate your split dose correctly so that you do not give the wrong dose. If you are not sure how to split your dose using Pens, then select and inject the dose you need with new Pen.What if no SOGROYA appears when check the flowA. Your needle may be blocked or damaged, if no SOGROYA appears at the needle tip. Remove the needle as described in Step and repeat Step and Step 2.B. Your Pen may be defective, if SOGROYA still does not appear after changing the needle. Do not use the Pen. Contact Novo Nordisk at 1-888-668-6444.What if 0 does not appear after completing my injectionThe needle may be blocked or damaged, and you have not received any SOGROYA, even though the dose counter has moved from the dose that you have set. Remove the needle as described in Step and repeat Step to Step 4.How should take care of my PenBe careful not to drop your Pen or knock it against hard surfaces. Do not expose your Pen to dust, dirt, liquid, or direct light. See How should store SOGROYA Do not try to refill your Pen, it is prefilled.What if drop my PenIf you drop your Pen or think that something is wrong with it, attach new disposable needle and check the SOGROYA flow before you inject (See Step and Step 2). Do not try to repair your Pen or pull it apart.How do clean my PenDo not wash, soak, or lubricate your Pen. If necessary, clean it with mild detergent on moistened cloth.Frequently Asked QuestionsHow do throw away (dispose of) used SOGROYA needles and PensPut your used needles and Pens in an FDA-cleared sharps disposal container right away after use. Do not throw away (dispose of) loose needles and Pens in your household trash. If you do not have an FDA-cleared sharps disposal container, you may use household container that is: 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, and oproperly labeled to warn of hazardous waste inside the container.When 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 dispose of used needles and Pens. For more information about safe sharps disposal, and for specific information about safe 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.Important informationoCaregivers must be very careful when handling needles to reduce the risk of needle sticks and infection.PATENT Information: http://novonordisk-us.com/products/product-patents.htmlSOGROYA(R) is registered trademark of Novo Nordisk Health Care AG.Novo Nordisk(R) is registered trademark of Novo Nordisk A/S.(C) 2004-2021 Novo Nordisk Health Care AGFor further information contact:Novo Nordisk Inc.800 Scudders Mill RoadPlainsboro, NJ 08536, USA 1-888-668-6444Sogroya.comManufactured by:Novo Nordisk Inc.Plainsboro, NJ 08536U.S. License No. 1261This Instructions for Use has been approved by the U.S. Food and Drug Administration.Revised: 10/2021Version: 1. oSOGROYA is prescription medicine that contains human growth hormone, the same growth hormone made by the human body.. oSOGROYA is given by injection under the skin (subcutaneous) and is used to treat adults who do not make enough growth hormone.. It is not known if SOGROYA is safe and effective in children.. oyou have critical illness caused by certain types of heart or stomach surgery, trauma or breathing (respiratory) problems.. oyou have cancer or other tumors.. oyou are allergic to somapacitan-beco or any of the ingredients in SOGROYA. See the end of this Patient Information leaflet for complete list of ingredients in SOGROYA.. oyour healthcare provider tells you that you have certain types of eye problems caused by diabetes (diabetic retinopathy).. ohave had heart or stomach surgery, trauma or serious breathing (respiratory) problems.. ohave had cancer or any tumor.. ohave diabetes.. ohave adrenal gland problems.. oare taking replacement therapy with glucocorticoids.. ohave thyroid gland problems.. ohave liver problems.. oare pregnant or plan to become pregnant. It is not known if SOGROYA will harm your unborn baby. Talk to your healthcare provider if you are pregnant or plan to become pregnant.. oare breastfeeding or plan to breastfeed. It is not known if SOGROYA passes into your breast milk. You and your healthcare provider should decide if you will take SOGROYA while you breastfeed.. oRead the detailed Instructions for Use that come with SOGROYA.. oSOGROYA comes in strengths: mg/1.5 mL (3.3 mg/mL) pen and 10 mg/1.5 mL (6.7 mg/mL) pen. Your healthcare provider will prescribe the dose that is right for you. oYour healthcare provider will show you how to inject SOGROYA.. oUse SOGROYA exactly as your healthcare provider tells you to.. oUse SOGROYA time each week.. oIf you miss dose of SOGROYA, take the missed dose as soon as possible within days (72 hours) after the missed dose. If more than days (72 hours) have passed, skip the missed dose and take your next dose on the regularly scheduled day.. oSOGROYA pens are for use by person only.. oDo not share your SOGROYA pens and needles with another person, even if the needle has been changed. You may give another person an infection or get an infection from them.. ohigh risk of death in people who have critical illnesses because of heart or stomach surgery, trauma or serious breathing (respiratory) problems.. oincreased risk of growth of cancer or tumor that is already present and increased risk of the return of cancer. Your healthcare provider will need to monitor you for return of cancer or tumor. Contact the healthcare provider if you start to have changes in moles, birthmarks, or the color of your skin. onew or worsening high blood sugar (hyperglycemia) or diabetes. Your blood sugar may need to be monitored during treatment with SOGROYA.. oincrease in pressure in the skull (intracranial hypertension). If you have headaches, eye problems, nausea or vomiting, contact the healthcare provider.. oserious allergic reactions. Get medical help right away if you have the following symptoms:. oswelling of your face, lips, mouth, or tongue. oskin rashes, redness, or swelling. otrouble breathing. odizziness or fainting. owheezing. ofast heartbeat or pounding in your chest. osevere itching. osweating. oyour body holding too much fluid (fluid retention) such as swelling in the hands and feet, pain in your joints or muscles or nerve problems that cause pain, burning or tingling in the hands, arms, legs and feet. Tell your healthcare provider if you have any of these signs or symptoms of fluid retention. odecrease in hormone called cortisol. The healthcare provider will do blood tests to check your cortisol levels. Tell your healthcare provider if you have darkening of the skin, severe fatigue, dizziness, weakness, or weight loss. odecrease in thyroid hormone levels. Decreased thyroid hormone levels may affect how well SOGROYA works. The healthcare provider will do blood tests to check your thyroid hormone levels.. osevere and constant abdominal pain. This could be sign of pancreatitis. Tell your healthcare provider if you have any new abdominal pain. oloss of fat and tissue weakness in the area of skin you inject. Talk to your healthcare provider about rotating the areas where you inject SOGROYA.. oincrease in phosphorus, alkaline phosphatase and parathyroid hormone levels in your blood. Your healthcare provider will do blood tests to check this.. oback pain. ovomiting. ojoint pain. ohigh blood pressure. oindigestion. oincrease in the level of an enzyme in your blood called creatine phosphokinase. osleep problems. oweight gain. odizziness. olow red blood cells (anemia). oswelling of the tonsils (tonsillitis). oBefore you use SOGROYA pens for the first time: oStore your new, unused SOGROYA pen in refrigerator between 36oF to 46oF (2oC to 8oC).. oStore your new, unused SOGROYA pen with the cap on and keep it in the original carton. oDo not freeze SOGROYA. oKeep SOGROYA away from direct heat and light.. oDo not use SOGROYA that has been frozen or in temperatures warmer than 86oF (30oC).. oDo not use SOGROYA after the expiration date printed on the carton and the pen.. oAfter you use SOGROYA pens and there is still medicine left: oStore remaining SOGROYA in the refrigerator between 36oF to 46oF (2oC to 8oC) and use within weeks.oStore your in-use SOGROYA pen with the cap on and keep it in the original carton.. oStore remaining SOGROYA in the refrigerator between 36oF to 46oF (2oC to 8oC) and use within weeks.. oStore your in-use SOGROYA pen with the cap on and keep it in the original carton.. oIf needed, unused and in-use SOGROYA pens can be stored out of the refrigerator. SOGROYA pens can be stored at room temperature no warmer than 77oF (25oC) for up to days (72 hours) and then returned to the refrigerator.. oSOGROYA prefilled Pen. onew injection needle. SOGROYA prefilled Pen is designed to be used with all Novo Nordisk disposable needles up to length of mm.. osharps disposal container. See Step for information on how to throw away (dispose of) used needles and Pens.. oalcohol pad. ogauze pad. oWash your hands with soap and water.. oCheck the name, strength, and colored label on your Pen to make sure that it contains SOGROYA in the right strength.. oPull off the Pen cap.. oTurn the Pen upside down or times to check that the SOGROYA in your Pen is clear to almost clear and colorless to slightly yellow (See Figure A). If SOGROYA looks cloudy or you see particles, do not use the Pen.. oWhen you are ready to give your injection, get new disposable needle, and remove the paper tab.. oPush the needle straight onto the Pen. Turn the needle clockwise until it is on tight (See Figure B).. oPull off the outer needle cap and throw it away (dispose of) (See Figure C).. oPull off the inner needle cap and throw it away (dispose of) (See Figure D).. oBefore using new Pen, check the SOGROYA flow to make sure the growth hormone can flow through the Pen and needle.. oTurn the dose selector clockwise marking on the dose counter to select 0.025 mg. You may hear faint click when you turn the dose selector (See Figure E).. o1 marking on the dose counter equals 0.025 mg (See Figure F).. oHold the Pen with the needle pointing up. Press and hold in the dose button until the dose counter returns to 0. The 0 must line up with the dose pointer (See Figure G).. oCheck that drop of SOGROYA appears at the needle tip (See Figure H).. oCarefully remove the needle from the Pen by turning the needle counterclockwise. Place the needle in sharps disposal container immediately (See Step 5).. oRepeat Step again.. oTo start, check that the dose pointer is set at 0.. oTurn the dose selector clockwise to select the dose you need (See Figure I). When you have selected your dose, you can go to Step 4.. oSelect the injection site.. oSOGROYA can be injected under the skin (subcutaneously) of your stomach area (abdomen) or upper legs (thighs) as instructed by your healthcare provider (See Figure M). Change the injection site every week.. oWipe the injection site with an alcohol pad and let the area dry.. oInsert the needle into your skin as your healthcare provider has shown you (See Figure N).. oMake sure you can see the dose counter. Do not cover it with your fingers. This could block the injection.. oPress and hold down the dose button until the dose counter shows 0 (See Figure O). The 0 must line up with the dose pointer. You may then hear or feel click.. oContinue to hold down the dose button with the needle in your skin.. oKeep holding down the dose button with the needle in your skin and slowly count to to make sure that the full dose has been delivered (See Figure P).. oCarefully remove the needle from your skin (See Figure Q). If blood appears at the injection site, press lightly with gauze pad. Do not rub the area.. oCarefully remove the needle from the Pen by turning the needle counterclockwise (See Figure R).. oPlace the needle in an FDA-cleared sharps disposal container immediately to reduce the risk of needle stick (See Figure R).. oPut the Pen cap on your Pen after each use to protect SOGROYA from direct light (See Figure S). See How should store my SOGROYA Pen.. oStore your new, unused SOGROYA Pen in refrigerator between 36F to 46F (2C to 8C). oStore your new, unused SOGROYA Pen with the cap on and in the original carton.. oDo not freeze SOGROYA. oWhen stored in the refrigerator, do not store the SOGROYA Pen directly next to the cooling element. oKeep SOGROYA away from direct heat and light.. oDo not use SOGROYA if it has been frozen or in temperatures warmer than 86oF (30C). oDo not use SOGROYA after the expiration date printed on the carton and the Pen. oStore remaining SOGROYA in the refrigerator between 36F to 46F (2C to 8C) and use within weeks.. oStore your in-use SOGROYA Pen with the cap on and keep it in the original carton.. 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, and oproperly labeled to warn of hazardous waste inside the container.. oCaregivers must be very careful when handling needles to reduce the risk of needle sticks and infection.. oSOGROYA prefilled Pen. onew injection needle. SOGROYA prefilled Pen is designed to be used with all Novo Nordisk disposable needles up to length of mm.. osharps disposal container. See Step for information on how to throw away (dispose of) used needles and Pens.. oalcohol pad. ogauze pad. oWash your hands with soap and water.. oCheck the name, strength, and colored label on your Pen to make sure that it contains SOGROYA in the right strength.. oPull off the Pen cap.. oTurn the Pen upside down or times to check that the SOGROYA in your Pen is clear to almost clear and colorless to slightly yellow (See Figure A). If SOGROYA looks cloudy or you see particles, do not use the Pen.. oWhen you are ready to give your injection, get new disposable needle, and remove the paper tab.. oPush the needle straight onto the Pen. Turn the needle clockwise until it is on tight (See Figure B).. oPull off the outer needle cap and throw it away (dispose of) (See Figure C).. oPull off the inner needle cap and throw it away (dispose of) (See Figure D).. oBefore using new Pen, check the SOGROYA flow to make sure the growth hormone can flow through the Pen and needle.. oTurn the dose selector clockwise marking on the dose counter to select 0.05 mg. You may hear faint click when you turn the dose selector (See Figure E).. o1 marking on the dose counter equals 0.05 mg (See Figure F).. oHold the Pen with the needle pointing up. Press and hold in the dose button until the dose counter returns to 0. The 0 must line up with the dose pointer (See Figure G).. oCheck that drop of SOGROYA appears at the needle tip (See Figure H).. oCarefully remove the needle from the Pen by turning the needle counterclockwise. Place the needle in sharps disposal container immediately (See Step 5).. oRepeat Step again.. oTo start, check that the dose pointer is set at 0.. oTurn the dose selector clockwise to select the dose you need (See Figure I). When you have selected your dose, you can go to Step 4. oSelect the injection site.. oSOGROYA can be injected under the skin (subcutaneously) of your stomach area (abdomen) or upper legs (thighs) as instructed by your healthcare provider (See Figure M). Change the injection site every week.. oWipe the injection site with an alcohol pad and let the area dry.. oInsert the needle into your skin as your healthcare provider has shown you (See Figure N). oMake sure you can see the dose counter. Do not cover it with your fingers. This could block the injection.. oPress and hold down the dose button until the dose counter shows 0 (See Figure O). The 0 must line up with the dose pointer. You may then hear or feel click. oContinue to hold down the dose button with the needle in your skin.. oKeep holding down the dose button with the needle in your skin and slowly count to to make sure that the full dose has been delivered (See Figure P).. oCarefully remove the needle from your skin (See Figure Q). If blood appears at the injection site, press lightly with gauze pad. Do not rub the area.. oCarefully remove the needle from the Pen by turning the needle counterclockwise (See Figure R).. oPlace the needle in an FDA-cleared sharps disposal container immediately to reduce the risk of needle stick (See Figure R).. oPut the Pen cap on your Pen after each use to protect SOGROYA from direct light (See Figure S). See How should store my SOGROYA Pen.. oStore your new, unused SOGROYA Pen in refrigerator between 36F to 46F (2C to 8C).. oStore your new, unused SOGROYA Pen with the cap on and in the original carton. oDo not freeze SOGROYA. oWhen stored in the refrigerator, do not store the SOGROYA Pen directly next to the cooling element. oKeep SOGROYA away from direct heat and light.. oDo not use SOGROYA if it has been frozen or in temperatures warmer than 86oF (30C).. oDo not use SOGROYA after the expiration date printed on the carton and the Pen. oStore remaining SOGROYA in the refrigerator between 36F to 46F (2C to 8C) and use within weeks.. oStore your in-use SOGROYA Pen with the cap on and keep it in the original carton.. 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, and oproperly labeled to warn of hazardous waste inside the container.. oCaregivers must be very careful when handling needles to reduce the risk of needle sticks and infection.. Cover page for Sogroya mg Instructions for Use. Sogroya mg pen components. Sogroya mg pen cap. Needle components. Image of supplies needed. Important Information Symbol. Additional Information Symbol. Figure Pull off Pen cap.. Figure Push the needle straight onto the Pen.. Important information symbol. Important Information Symbol. Figure Pull off the outer needle cap.. Figure Pull off the inner needle cap.. Additional Information Symbol. Important Informational Symbol. Additional Information Symbol. Figure Turn the dose selector clockwise.. Figure 1 marking on the dose counter equals 0.025.. Figure Hold the Pen with the needle pointing up.. Figure Check that drop appears at the needle tip.. Additional Information Symbol. Figure Turn the dose selector clockwise.. Additional information symbol. Additional information symbol. Figure The dose counter shows the dose in mg.. Figure The dose counter shows the dose in mg.. Additional information symbol. Figure Turn the dose selector to the correct dose.. Figure Select the injection site.. Figure Insert the needle into your skin.. Figure Press and hold down the button.. Additional information symbol. Figure Slowly count to 6.. Figure Carefully remove the needle.. Additional information symbol. Figure Remove the needle from the Pen.. Additional information symbol. Figure Put the Pen cap on your Pen after each use.. Important information symbol. Important information symbol. Figure The Pen scale shows how much is left.. Figure Dose counter example of 1.7 mg left. Important information symbol. Image of back cover page.. Cover page for 10 mg Instructions for Use. Illustration of pen components. Illustration of pen cap.. Illustration of needle components.. Supplies you will need.. Important information symbol. Additional information symbol. Figure A: Turn pen upside down or times.. Figure B: Push the needle straight on.. Important information symbol.. Important information symbol. Fugure C: Pull off outer needle cap and dispose of it.. Figure D: Pull off inner needle cap and dispose of it.. Additional information symbol. Important information symbol. Additional information symbol. Figure E: Turn dose selector clockwise.. Figure F: Marking on dose counter equals 0.5 mg.. Figure G: Hold the Pen with the needle pointing up.. Figure H: Check that drop appears at the needle tip.. Additional information symbol. Figure I: Turn the dose selector clockwise.. Additional information symbol. Additional information symbol. Figure J: Example of 2.95 selected.. Figure K: Example of 1.5 mg selected.. Additional information symbol. Figure L: Turn the dose selector to correct wrong dose.. Figure injection sites. Figure N: insert the needle. Additional information symbol. Figure O: press and hold down the dose button. Figure P: Count slowly to 6.. Additional information symbol. Figure Q: remove the needle from your skin. Figure R: place the needle in sharps container. Additional information symbol. Figure S: Put the cap on your Pen.. Important information symbol. Important information symbol. Figure T: The Pen scale shows how much is left.. Figure U: Example of 2.8 mg left in Pen.. Important information symbol. Back cover page. Illustration of Sogroya Pen.

ABUSE SECTION.

9.2 Abuse Inappropriate use of SOGROYA may result in significant negative health consequences.

ADVERSE REACTIONS SECTION.

6 ADVERSE REACTIONS The following important adverse drug reactions are described elsewhere in the labeling:oIncreased mortality in patients with acute critical illness [see Warnings and Precautions (5.1)] oNeoplasms [see Warnings and Precautions (5.2)] oGlucose intolerance and diabetes mellitus [see Warnings and Precautions (5.3)] oIntracranial hypertension [see Warnings and Precautions (5.4)] oSevere hypersensitivity [see Warnings and Precautions (5.5)]oFluid retention [see Warnings and Precautions (5.6)] oHypoadrenalism [see Warnings and Precautions (5.7)] oHypothyroidism [see Warnings and Precautions (5.8)]oPancreatitis [see Warnings and Precautions (5.9)]oLipohypertrophy/Lipoatrophy [see Warnings and Precautions (5.10)]. oIncreased mortality in patients with acute critical illness [see Warnings and Precautions (5.1)] oNeoplasms [see Warnings and Precautions (5.2)] oGlucose intolerance and diabetes mellitus [see Warnings and Precautions (5.3)] oIntracranial hypertension [see Warnings and Precautions (5.4)] oSevere hypersensitivity [see Warnings and Precautions (5.5)]. oFluid retention [see Warnings and Precautions (5.6)] oHypoadrenalism [see Warnings and Precautions (5.7)] oHypothyroidism [see Warnings and Precautions (5.8)]. oPancreatitis [see Warnings and Precautions (5.9)]. oLipohypertrophy/Lipoatrophy [see Warnings and Precautions (5.10)]. Adverse reactions reported in >=2% of patients treated with SOGROYA are: back pain, arthralgia, dyspepsia, sleep disorder, dizziness, tonsillitis, peripheral edema, vomiting, adrenal insufficiency, hypertension, blood creatine phosphokinase increase, weight increase, anemia (6.1).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. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.SOGROYA was studied in adult patients with GHD in 35-week, placebo-controlled, double-blind trial with an active-control arm [see Clinical Studies (14)]. Adverse reactions occurring >2% with SOGROYA are presented in Table 1.Table 1: Adverse Reactions occurring >2% in Adults with GHD Treated with SOGROYA and More Frequently than in Placebo-Treated Patients for 34 WeeksPlacebo(N=61)SOGROYA(N=120)Adverse Reactions%%Back pain3.310Arthralgia1.66.7Dyspepsia3.35Sleep disorder1.64.2Dizziness1.64.2Tonsillitis1.63.3Peripheral edema1.63.3Vomiting1.63.3Adrenal insufficiency1.63.3Hypertension1.63.3Blood creatine phosphokinase increase03.3Weight increased03.3Anemia02.5 Included adverse reactions reported with at least 1% greater incidence in SOGROYA group compared to the placebo groupMore SOGROYA treated patients shifted from normal baseline levels to elevated phosphate and creatine phosphokinase levels at the end of the trial compared to the placebo group (17.5% vs 4.9% and 9.2% vs. 6.6%, respectively); these laboratory changes occurred intermittently, and were non-progressive.. 6.2 Immunogenicity As with all therapeutic proteins, there is potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to SOGROYA with the incidence of antibodies to other products may be misleading. No anti-somapacitan-beco antibodies were detected in the clinical trials in patients with GHD.

CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Long term studies in animals with somapacitan-beco to evaluate carcinogenic potential have not been conducted.Somapacitan-beco was not mutagenic or clastogenic in standard battery of genotoxicity tests (bacterial mutagenicity (Ames), human lymphocyte chromosome aberration, rat bone marrow micronucleus).In rat studies evaluating male and female fertility, somapacitan-beco was administered by subcutaneous injection at doses of 1, 2, and mg/kg twice weekly. Males were dosed from four weeks before pairing until termination and females were dosed beginning two weeks prior to mating through gestation day 7. No adverse effects were observed on male or female fertility in rats at doses up to mg/kg (29 times the MRHD, based on AUC).

CLINICAL PHARMACOLOGY SECTION.

12 CLINICAL PHARMACOLOGY . 12.1 Mechanism of Action Somapacitan-beco binds to dimeric GH receptor in the cell membrane of target cells resulting in intracellular signal transduction and host of pharmacodynamic effects. Some of these pharmacodynamic effects are primarily mediated by insulin-like growth factor (IGF-1) produced in the liver, while others are primarily consequence of the direct effects of somapacitan-beco.. 12.2 Pharmacodynamics IGF-1 was measured to assess the pharmacodynamic (PD) properties of somapacitan-beco. Somapacitan-beco normalizes the mean IGF-1 standard deviation score (SDS) level from baseline value below -2 to value within the reference range (-2 to +2) in treatment-naive adult patients with GHD [see Clinical Studies (14)]. In adult patients with GHD (n=26), somapacitan-beco induces less than dose proportional IGF-1 response at steady state. Maximum IGF-1 concentrations were observed within to days after dosing. Similar to the somapacitan-beco exposure time course, steady state IGF-1 response was reached after to weekly doses with limited cumulative IGF-1 response.. 12.3 Pharmacokinetics The pharmacokinetics (PK) of somapacitan-beco following subcutaneous administration have been investigated at clinically relevant doses (e.g., 0.01 to 0.32 mg/kg in healthy adults, and 0.02 to 0.12 mg/kg in adults with GHD).Overall, somapacitan-beco displays non-linear pharmacokinetics, however in the clinically relevant dose range of somapacitan-beco in adults with GHD, somapacitan-beco pharmacokinetics are approximately linear.AbsorptionIn adults with GHD, maximum concentration of somapacitan-beco is reached to 24 hours post dose. Steady state exposure is achieved following to weeks of once weekly administration of subcutaneous somapacitan-beco.DistributionSomapacitan-beco is extensively bound (>99%) to plasma proteins.Based on population PK analyses, the estimated volume of distribution (V/F) of somapacitan-beco in adult GHD patients is approximately 14.6 L. EliminationThe plasma elimination half-life of somapacitan-beco is approximately to days. Metabolism: Somapacitan-beco is metabolized via proteolytic cleavage of the linker sequence between the peptide backbone and albumin binder sidechain.Excretion: The primary excretion routes of somapacitan-beco-related material are via the urine and feces. Approximately 81% of the dose is excreted in the urine and approximately 13% is excreted in the feces. No intact somapacitan-beco is excreted indicating full breakdown of somapacitan-beco prior to excretion.Specific PopulationsBody weight: The exposure of somapacitan-beco decreases with increasing body weight. However, the somapacitan-beco dose range of 0.1 to mg/week provides adequate systemic exposure to reach target IGF-1 levels over the weight range of 34.5-150.5 kg evaluated in the clinical trials. Geriatric patients: Adult patients greater than 65 years of age and geriatric patients have higher exposure than younger subjects at the same somapacitan-beco dose [see Dosage and Administration (2.3) and Use in Specific Populations (8.5)].Female patients receiving estrogen: Female patients and in particular female patients on oral estrogen, have lower exposure than males at the same somapacitan-beco dose [see Dosage and Administration (2.3) and Drug Interactions (7)]. Hepatic impairment: somapacitan-beco dose of 0.08 mg/kg at steady state resulted in comparable somapacitan-beco exposure between patients with normal hepatic function and mild hepatic impairment (Child-Pugh A). However, higher exposure was observed in patients with moderate hepatic impairment (Child-Pugh B) (ratios to normal hepatic function were 4.69 and 3.52-fold increase for AUC0-168h and Cmax, respectively). Lower somapacitan-beco stimulated IGF-1 levels were observed in patients with mild and moderate hepatic impairment (ratios to normal hepatic function were 0.85 and 0.75, respectively) [see Dosage and Administration (2.3) and Use in Specific Populations (8.6)].Renal impairment: In general, somapacitan-beco exposure tended to increase with decreasing estimated glomerular filtration rate. somapacitan-beco dose of 0.08 mg/kg at steady state resulted in higher exposures in patients with renal impairment, that was most pronounced for patients with severe renal impairment and patients requiring hemodialysis (AUC0-168h ratios to normal renal function were 1.75 and 1.63, respectively). Higher IGF-1 AUC0-168h levels were also observed in patients with moderate and severe renal impairment and in patients requiring hemodialysis (ratios to normal renal function were 1.35, 1.40 and 1.24, respectively).

CLINICAL STUDIES SECTION.

14 CLINICAL STUDIES In 35-week, double-blind, placebo-controlled study, treatment-naive adult patients with GHD were randomized (2:1:2) and exposed to once-weekly SOGROYA 10 mg/1.5ml (n=120) or placebo (n=60) or daily somatropin product 10 mg/1.5ml (n=119) for 34-week treatment period. In this study, patients were 51.7% female and had mean age of 45.1 years. Most patients were 23 to 64 years old and most (69.7%) had adult onset GHD. The mean BMI was 27.4 kg/m2. Overall, 66.7% were White, 28.7% were Asian and 2.3% were Black or African American; 4.5% identified as Hispanic or Latino ethnicity. Treatment with SOGROYA demonstrated superiority compared to placebo in reduction in truncal fat percentage (%) as assessed by dual X-ray absorptiometry, with change of -1.06% for SOGROYA and +0.47% for placebo after 34 weeks (see Table 3). Patients treated with daily somatropin achieved change in truncal fat of -2.23% after 34 weeks.Table 3: Truncal Fat Results for weekly SOGROYA, weekly placebo and daily somatropin during the 34-week pivotal trialChange from baseline at 34 weeks Weekly PlaceboWeekly SOGROYA Daily Somatropin Number of subjects in FAS (N)61120119Truncal fat (baseline)36.939.1138.10Truncal fat %0.47-1.06-2.23Absolute Treatment Difference (%)[95% Confidence Interval]p-value-1.53[-2.68; -0.38]0.0090Abbreviations: FAS Full analysis set, = Number of subjects in FAS. Changes in truncal fat from baseline to 34 weeks were analyzed using an analysis of covariance model with treatment, GHD onset type, sex, region, diabetes mellitus status and sex by region by diabetes mellitus interaction as factors and baseline as covariate incorporating multiple imputation technique where missing week 34 values were imputed based on data from the placebo group. No formal statistical comparison between SOGROYA and daily somatropin was performed. After 34 weeks SOGROYA normalized the mean IGF-1 SDS level in treatment-naive adult patients with GHD with IGF-1 SDS of -0.17 in SOGROYA-treated patients compared to -2.62 in placebo-treated patients (see Table 4). The mean IGF-1 SDS levels in daily somatropin-treated patients was -2.53 at baseline and -0.23 at 34 weeks.Table 4: IGF-1 SDS for SOGROYA compared to placebo during the 34-week pivotal trialSOGROYAPlaceboNumber of subjects in FAS (N)12061IGF-1 SDS values at baseline, mean-2.54-2.64IGF-1 SDS value at week 34, mean-0.17-2.62Abbreviations: IGF-1 SDS: Insulin-like growth factor 1 standard deviation score, FAS full analysis set, = Number of patients in FAS. Baseline and end of main period (week 34) are observed means. Changes from baseline to the 35-weeks measurements were analysed using mixed-effect model for repeated measurements including treatment, GHD onset type, sex, region, diabetes mellitus and sex by region by diabetes mellitus interaction as factors and baseline as covariate, all nested within week as factor.

CONTRAINDICATIONS SECTION.

4 CONTRAINDICATIONS SOGROYA is contraindicated in patients with:oAcute critical illness after open-heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure because of the risk of increased mortality with use of pharmacologic doses of SOGROYA [see Warnings and Precautions (5.1)]. oActive malignancy [see Warnings and Precautions (5.2)].oHypersensitivity to SOGROYA or any of its excipients. Systemic hypersensitivity reactions have been reported postmarketing with other growth hormone products [see Warnings and Precautions (5.5)].oActive proliferative or severe non-proliferative diabetic retinopathy.. oAcute critical illness after open-heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure because of the risk of increased mortality with use of pharmacologic doses of SOGROYA [see Warnings and Precautions (5.1)]. oActive malignancy [see Warnings and Precautions (5.2)].. oHypersensitivity to SOGROYA or any of its excipients. Systemic hypersensitivity reactions have been reported postmarketing with other growth hormone products [see Warnings and Precautions (5.5)].. oActive proliferative or severe non-proliferative diabetic retinopathy.. oAcute critical illness (4)oActive malignancy (4)oHypersensitivity to somapacitan-beco or excipients (4)oActive proliferative or severe non-proliferative diabetic retinopathy (4). oAcute critical illness (4). oActive malignancy (4). oHypersensitivity to somapacitan-beco or excipients (4). oActive proliferative or severe non-proliferative diabetic retinopathy (4).

CONTROLLED SUBSTANCE SECTION.

9.1 Controlled Substance SOGROYA contains somapacitan-beco, which is not controlled substance.

DEPENDENCE SECTION.

9.3 Dependence SOGROYA is not associated with drug related withdrawal adverse reactions.

DESCRIPTION SECTION.

11 DESCRIPTION Somapacitan-beco is human growth hormone (hGH) analog with single substitution in the amino acid backbone (L101C) to which an albumin-binding moiety has been attached. The albumin-binding moiety (side-chain) consists of an albumin binder and hydrophilic spacer attached to position 101 of the protein. The protein part consists of 191 amino acids. Somapacitan-beco is produced in Escherichia coli by recombinant DNA technology. The molecular formula (including the albumin-binding moiety) is C1038H1609N273O319S9 and the molecular weight is 23305.10 g/mol, of which the albumin-binding moiety is 1191.39 g/mol.Structural Formula: SOGROYA (somapacitan-beco) injection is supplied as sterile, clear to slightly opalescent and colorless to slightly yellow solution for subcutaneous use in single-patient-use prefilled pen with deliverable volume of 1.5 mL.Each mL of SOGROYA mg/1.5 mL prefilled pen contains 3.3 mg of somapacitan-beco, histidine (0.68 mg), mannitol (44 mg), phenol (4 mg), poloxamer 188 (1 mg), and Water for Injection, USP. The pH is approximately 6.8. Hydrochloric acid and sodium hydroxide may be added to adjust the pH.Each mL of SOGROYA 10 mg/1.5 mL prefilled pen contains 6.7 mg of somapacitan-beco, histidine (0.68 mg), mannitol (44 mg), phenol (4 mg), poloxamer 188 (1 mg), and Water for Injection, USP. The pH is approximately 6.8. Hydrochloric acid and sodium hydroxide may be added to adjust the pH.. Image of molecule structure.

DOSAGE & ADMINISTRATION SECTION.

2 DOSAGE AND ADMINISTRATION . oAdminister by subcutaneous injection to the abdomen or thigh with regular rotation of injection sites to avoid lipohypertrophy/lipoatrophy (2.1).oAdminister the prescribed dose subcutaneously one time each week (2.2).oInitiate SOGROYA with dosage of 1.5 mg once weekly for treatment naive patients and patients switching from daily growth hormone (2.2).oIncrease the weekly dosage every to weeks by approximately 0.5 mg to 1.5 mg until the desired response has been achieved (2.2).oTitrate the dosage based on clinical response and serum insulin-like growth factor (IGF-1) concentrations (2.2).oThe maximum recommended dosage is mg once weekly. oSee the Full Prescribing Information for dosage recommendations in patients aged 65 years and older, patients with hepatic impairment, and women receiving oral estrogen (2.3).. oAdminister by subcutaneous injection to the abdomen or thigh with regular rotation of injection sites to avoid lipohypertrophy/lipoatrophy (2.1).. oAdminister the prescribed dose subcutaneously one time each week (2.2).. oInitiate SOGROYA with dosage of 1.5 mg once weekly for treatment naive patients and patients switching from daily growth hormone (2.2).. oIncrease the weekly dosage every to weeks by approximately 0.5 mg to 1.5 mg until the desired response has been achieved (2.2).. oTitrate the dosage based on clinical response and serum insulin-like growth factor (IGF-1) concentrations (2.2).. oThe maximum recommended dosage is mg once weekly. oSee the Full Prescribing Information for dosage recommendations in patients aged 65 years and older, patients with hepatic impairment, and women receiving oral estrogen (2.3).. 2.1 Administration and Use Instructions oTherapy with SOGROYA should be supervised by physician who is experienced in the diagnosis and management of patients with the conditions for which SOGROYA is indicated [see Indications and Usage (1)].oPerform fundoscopic examination before initiating treatment with SOGROYA to exclude preexisting papilledema, and periodically thereafter. If papilledema is identified, evaluate the etiology and treat the underlying cause before initiating therapy with SOGROYA [see Warnings and Precautions (5.4)].oAdminister SOGROYA by subcutaneous injection to the abdomen or thigh with regular rotation of injection sites to avoid lipohypertrophy.oInspect visually for particulate matter and discoloration. SOGROYA should be clear to slightly opalescent and colorless to slightly yellow solution. If the solution is cloudy or contains particulate matter do not use.oThe SOGROYA mg/1.5 mL (3.3 mg/mL) prefilled pen dials in 0.025 mg increments and delivers doses from 0.025 mg to mg. oThe SOGROYA 10 mg/1.5 mL (6.7 mg/mL) prefilled pen dials in 0.05 mg increments and delivers doses from 0.05 mg to mg.oInstructions for delivering the dosage are provided in the PATIENT INFORMATION and INSTRUCTIONS FOR USE leaflets enclosed with the SOGROYA prefilled pen.. oTherapy with SOGROYA should be supervised by physician who is experienced in the diagnosis and management of patients with the conditions for which SOGROYA is indicated [see Indications and Usage (1)].. oPerform fundoscopic examination before initiating treatment with SOGROYA to exclude preexisting papilledema, and periodically thereafter. If papilledema is identified, evaluate the etiology and treat the underlying cause before initiating therapy with SOGROYA [see Warnings and Precautions (5.4)].. oAdminister SOGROYA by subcutaneous injection to the abdomen or thigh with regular rotation of injection sites to avoid lipohypertrophy.. oInspect visually for particulate matter and discoloration. SOGROYA should be clear to slightly opalescent and colorless to slightly yellow solution. If the solution is cloudy or contains particulate matter do not use.. oThe SOGROYA mg/1.5 mL (3.3 mg/mL) prefilled pen dials in 0.025 mg increments and delivers doses from 0.025 mg to mg. oThe SOGROYA 10 mg/1.5 mL (6.7 mg/mL) prefilled pen dials in 0.05 mg increments and delivers doses from 0.05 mg to mg.. oInstructions for delivering the dosage are provided in the PATIENT INFORMATION and INSTRUCTIONS FOR USE leaflets enclosed with the SOGROYA prefilled pen.. 2.2 Recommended Dosage, Titration, and Monitoring oAdminister the prescribed dose subcutaneously one time each week (weekly).oInitiate SOGROYA with dosage of 1.5 mg once weekly for treatment naive patients and patients switching from daily growth hormone (somatropin).oIncrease the weekly dosage every to weeks by approximately 0.5 mg to 1.5 mg until the desired response is achieved.oTitrate the dosage based on clinical response and serum insulin-like growth factor (IGF-1) concentrations. Draw IGF-1 samples to days after the prior dose.oDecrease the dosage as necessary on the basis of adverse reactions and/or serum IGF-1 concentrations above the age- and sex-specific normal range.oThe maximum recommended dosage is mg once weekly.. oAdminister the prescribed dose subcutaneously one time each week (weekly).. oInitiate SOGROYA with dosage of 1.5 mg once weekly for treatment naive patients and patients switching from daily growth hormone (somatropin).. oIncrease the weekly dosage every to weeks by approximately 0.5 mg to 1.5 mg until the desired response is achieved.. oTitrate the dosage based on clinical response and serum insulin-like growth factor (IGF-1) concentrations. Draw IGF-1 samples to days after the prior dose.. oDecrease the dosage as necessary on the basis of adverse reactions and/or serum IGF-1 concentrations above the age- and sex-specific normal range.. oThe maximum recommended dosage is mg once weekly.. 2.3 Recommended Dosage and Titration for Specific Populations Patients Aged 65 Years and OlderInitiate SOGROYA with dosage of mg once weekly and use smaller dose increment increases when titrating the dosage [see Use in Specific Populations (8.5)]. See above for monitoring recommendations and the maximum recommended dosage of SOGROYA [see Dosage and Administration (2.2)]. Patients with Hepatic ImpairmentoSOGROYA is not recommended in patients with severe hepatic impairment. oFor patients with moderate hepatic impairment, initiate SOGROYA with dosage of mg once weekly and use smaller dose increment increases when titrating the dosage. See above for monitoring recommendations [see Dosage and Administration (2.2)]. The maximum recommended dosage is mg once weekly. oNo dosage adjustment is recommended for patients with mild hepatic impairment. Women Receiving Oral EstrogenInitiate SOGROYA with dosage of mg once weekly [see Drug Interactions (7)]. See above for titration and monitoring recommendations and the maximum recommended dosage of SOGROYA [see Dosage and Administration (2.2)]. oSOGROYA is not recommended in patients with severe hepatic impairment. oFor patients with moderate hepatic impairment, initiate SOGROYA with dosage of mg once weekly and use smaller dose increment increases when titrating the dosage. See above for monitoring recommendations [see Dosage and Administration (2.2)]. The maximum recommended dosage is mg once weekly. oNo dosage adjustment is recommended for patients with mild hepatic impairment. 2.4 Missed Doses oAdminister missed dose as soon as possible and not more than days after the missed dose (72 hours).oIf more than days have passed since the missed dose, skip the dose and administer the next dose on the regular dosing day.. oAdminister missed dose as soon as possible and not more than days after the missed dose (72 hours).. oIf more than days have passed since the missed dose, skip the dose and administer the next dose on the regular dosing day.

DOSAGE FORMS & STRENGTHS SECTION.

3 DOSAGE FORMS AND STRENGTHS SOGROYA is clear to slightly opalescent and colorless to slightly yellow solution available as follows:oInjection: mg/1.5 mL (3.3 mg/mL) in single-patient-use prefilled pen (teal)oInjection: 10 mg/1.5 mL (6.7 mg/mL) in single-patient-use prefilled pen (yellow). oInjection: mg/1.5 mL (3.3 mg/mL) in single-patient-use prefilled pen (teal). oInjection: 10 mg/1.5 mL (6.7 mg/mL) in single-patient-use prefilled pen (yellow). Injection: mg/1.5 mL (3.3 mg/mL) or 10 mg/1.5 mL (6.7 mg/mL) in single-patient-use prefilled pen (3):. Injection: mg/1.5 mL (3.3 mg/mL) or 10 mg/1.5 mL (6.7 mg/mL) in single-patient-use prefilled pen (3):.

DRUG ABUSE AND DEPENDENCE SECTION.

9 DRUG ABUSE AND DEPENDENCE . 9.1 Controlled Substance SOGROYA contains somapacitan-beco, which is not controlled substance.. 9.2 Abuse Inappropriate use of SOGROYA may result in significant negative health consequences.. 9.3 Dependence SOGROYA is not associated with drug related withdrawal adverse reactions.

DRUG INTERACTIONS SECTION.

7 DRUG INTERACTIONS Table includes list of drugs with clinically important drug interactions when administered concomitantly with SOGROYA and instructions for preventing or managing them.Table 2: Clinically Important Drug Interactions with SOGROYA Replacement Glucocorticoid Treatment Clinical Impact:Microsomal enzyme 11-hydroxysteroid dehydrogenase type (11HSD-1) is required for conversion of cortisone to its active metabolite, cortisol, in hepatic and adipose tissue. GH inhibits 11HSD-1. Consequently, individuals with untreated GH deficiency have relative increases in 11HSD-1 and serum cortisol. Initiation of SOGROYA may result in inhibition of 11HSD-1 and reduced serum cortisol concentrations. Intervention:Patients treated with glucocorticoid replacement for hypoadrenalism may require an increase in their maintenance or stress doses following initiation of SOGROYA [see Warnings and Precautions 5.7 )]. Examples:Cortisone acetate and prednisone may be affected more than others because conversion of these drugs to their biologically active metabolites is dependent on the activity of 11HSD-1.Cytochrome P450-Metabolized DrugsClinical Impact:Limited published data indicate that GH treatment increases cytochrome P450 (CP450)-mediated antipyrine clearance. SOGROYA may alter the clearance of compounds known to be metabolized by CP450 liver enzymes.Intervention:Careful monitoring is advisable when SOGROYA is administered in combination with drugs metabolized by CP450 liver enzymes.Oral EstrogenClinical Impact:Oral estrogens may reduce the serum IGF-1 response to SOGROYA. Intervention:Patients receiving oral estrogen replacement may require higher SOGROYA dosages [see Dosage and Administration (2.3)].Insulin and/or Other Hypoglycemic AgentsClinical Impact:Treatment with SOGROYA may decrease insulin sensitivity, particularly at higher doses. Intervention:Patients with diabetes mellitus may require adjustment of their doses of insulin and/or other hypoglycemic agents [see Warnings and Precautions 5.3 )]. oReplacement Glucocorticoid Treatment: Patients treated with glucocorticoid for hypoadrenalism may require an increase in their maintenance or stress doses following initiation of SOGROYA (7).oCytochrome P450-Metabolized Drugs: SOGROYA may alter the clearance. Monitor carefully if used with SOGROYA (7).oOral Estrogen: Larger doses of SOGROYA may be required (7).oInsulin and/or Other Hypoglycemic Agents: Dose adjustment of insulin or hypoglycemic agent may be required (5.3, 7).. oReplacement Glucocorticoid Treatment: Patients treated with glucocorticoid for hypoadrenalism may require an increase in their maintenance or stress doses following initiation of SOGROYA (7).. oCytochrome P450-Metabolized Drugs: SOGROYA may alter the clearance. Monitor carefully if used with SOGROYA (7).. oOral Estrogen: Larger doses of SOGROYA may be required (7).. oInsulin and/or Other Hypoglycemic Agents: Dose adjustment of insulin or hypoglycemic agent may be required (5.3, 7).

GERIATRIC USE SECTION.

8.5 Geriatric Use In clinical studies total of 52 (15.6%) of the 333 SOGROYA-treated patients were 65 years or older and (0.9%) were 75 years or older [see Clinical Studies (14)]. Subjects older than 65 years appeared to have higher exposure than younger subjects at the same dose level. Elderly patients may be more sensitive to the action of somapacitan-beco, and therefore may be at increased risk for adverse reactions. Initiate SOGROYA with dose of mg once weekly and use smaller increments when increasing the dose [see Dosage and Administration (2.3)].

HOW SUPPLIED SECTION.

16 HOW SUPPLIED/STORAGE AND HANDLING How SuppliedSOGROYA (somapacitan-beco) injection is clear to slightly opalescent and colorless to slightly yellow solution available as one 1.5 mL single-patient-use prefilled pen per carton:oSOGROYA mg/1.5 mL (3.3 mg/mL) pen (teal) NDC 0169-2035-11oSOGROYA 10 mg/1.5 mL (6.7 mg/mL) pen (yellow) NDC 0169-2030-11Storage and HandlingBefore and during use: Store in refrigerator at 36F to 46F (2C to 8C) with the cap on and in the original carton to protect from light. Do not freeze. Do not use SOGROYA if it has been frozen. Discard prefilled pen if kept above 86F (30C). Avoid direct or excessive heat. Avoid sunlight.Write the date of first use in the space provided on the carton.Always remove and safely discard the needle after each injection and store the SOGROYA prefilled pen without an injection needle attached. Always use new needle for each injection to prevent contamination.Table 5: Storage conditions for SOGROYABefore first use (unopened)After first use (opened)Refrigerated36F to 46F(2C to 8C)Room Temperatureup to 77F (25C)Refrigerated36F to 46F(2C to 8C)Room Temperatureup to 77F (25C)SOGROYA Until expiration dateMaximum 72 hours (3 days)up to weeksMaximum 72 hours (3 days)The total time allowed at room temperature (up to 77F [25C]) is 72 hours (3 days) regardless of whether the product is in-use (opened) or before first use (unopened). Must discard if kept above 86F (30C).. oSOGROYA mg/1.5 mL (3.3 mg/mL) pen (teal) NDC 0169-2035-11. oSOGROYA 10 mg/1.5 mL (6.7 mg/mL) pen (yellow) NDC 0169-2030-11.

INDICATIONS & USAGE SECTION.

1 INDICATIONS AND USAGE SOGROYA is indicated for the replacement of endogenous growth hormone (GH) in adults with growth hormone deficiency (GHD). SOGROYA is human growth hormone analog indicated for replacement of endogenous growth hormone in adults with growth hormone deficiency (1).. SOGROYA is human growth hormone analog indicated for replacement of endogenous growth hormone in adults with growth hormone deficiency (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).oNeoplasms Advise patients to report marked changes in skin pigmentation or changes in the appearance of pre-existing nevi.oFluid Retention Advise patients that fluid retention during SOGROYA replacement therapy may frequently occur. Inform patients of the clinical manifestations of fluid retention (e.g. edema, arthralgia, myalgia, nerve compression syndromes including carpal tunnel syndrome/paresthesia) and to report to their healthcare provider any of these signs or symptoms occur during treatment with SOGROYA.oPancreatitis Advise patients that pancreatitis may develop and to report to their healthcare provider any new onset abdominal pain. oHypoadrenalism Advise patients who have or who are at risk for corticotropin deficiency that hypoadrenalism may develop and to report to their healthcare provider if they experience hyperpigmentation, extreme fatigue, dizziness, weakness, or weight loss.oHypothyroidism Advise patients/caregivers that undiagnosed/untreated hypothyroidism may prevent an optimal response to SOGROYA. Advise patients/caregivers they may require periodic thyroid function tests.oIntracranial Hypertension Advise patients to report to their healthcare provider any visual changes, headache, and nausea and/or vomiting.oHypersensitivity Reactions Advise patients that serious systemic hypersensitivity reactions (anaphylaxis and angioedema) are possible and that prompt medical attention should be sought if an allergic reaction occurs.oGlucose Intolerance/ Diabetes Mellitus Advise patients that new onset pre- /diabetes mellitus or exacerbation of preexisting diabetes mellitus can occur and monitoring of blood glucose during treatment with SOGROYA may be needed.oLipohypertrophy/ Lipoatrophy Advise patients that lipohypertrophy or lipoatrophy can occur if SOGROYA is administered subcutaneously at the same site over long period of time. Advise patients to rotate injection sites when administering SOGROYA to reduce this risk.Novo Nordisk(R) is registered trademark of Novo Nordisk A/S.SOGROYA(R) is registered trademark of Novo Nordisk Health Care AG. (C) 2002-2021 Novo Nordisk Health Care AGPATENT INFORMATION: http://novonordisk-us.com/products/product-patents.htmlFor information contact:Novo Nordisk Inc.800 Scudders Mill RoadPlainsboro, New Jersey 085361-888-668-6444Manufactured by:Novo Nordisk Inc.Plainsboro, NJ 08536U.S. License No. 1261. oNeoplasms Advise patients to report marked changes in skin pigmentation or changes in the appearance of pre-existing nevi.. oFluid Retention Advise patients that fluid retention during SOGROYA replacement therapy may frequently occur. Inform patients of the clinical manifestations of fluid retention (e.g. edema, arthralgia, myalgia, nerve compression syndromes including carpal tunnel syndrome/paresthesia) and to report to their healthcare provider any of these signs or symptoms occur during treatment with SOGROYA.. oPancreatitis Advise patients that pancreatitis may develop and to report to their healthcare provider any new onset abdominal pain. oHypoadrenalism Advise patients who have or who are at risk for corticotropin deficiency that hypoadrenalism may develop and to report to their healthcare provider if they experience hyperpigmentation, extreme fatigue, dizziness, weakness, or weight loss.. oHypothyroidism Advise patients/caregivers that undiagnosed/untreated hypothyroidism may prevent an optimal response to SOGROYA. Advise patients/caregivers they may require periodic thyroid function tests.. oIntracranial Hypertension Advise patients to report to their healthcare provider any visual changes, headache, and nausea and/or vomiting.. oHypersensitivity Reactions Advise patients that serious systemic hypersensitivity reactions (anaphylaxis and angioedema) are possible and that prompt medical attention should be sought if an allergic reaction occurs.. oGlucose Intolerance/ Diabetes Mellitus Advise patients that new onset pre- /diabetes mellitus or exacerbation of preexisting diabetes mellitus can occur and monitoring of blood glucose during treatment with SOGROYA may be needed.. oLipohypertrophy/ Lipoatrophy Advise patients that lipohypertrophy or lipoatrophy can occur if SOGROYA is administered subcutaneously at the same site over long period of time. Advise patients to rotate injection sites when administering SOGROYA to reduce this risk.

LACTATION SECTION.

8.2 Lactation Risk SummaryThere is no information on the presence of somapacitan-beco in human milk, the effects on the breastfed infant, or the effects on milk production. Somapacitan-beco-related material was secreted into milk of lactating rats. When substance is present in animal milk, it is likely that the substance will be present in human milk. Available published data describing administration of short-acting recombinant growth hormone (rhGH) to lactating women for days reported that short-acting rhGH did not increase the normal breastmilk concentration of growth hormone and no adverse effects were reported in breastfed infants. The developmental and health benefits of breastfeeding should be considered along with the mothers clinical need for SOGROYA and any potential adverse effects on the breastfed infant from SOGROYA or from the underlying maternal condition.

MECHANISM OF ACTION SECTION.

12.1 Mechanism of Action Somapacitan-beco binds to dimeric GH receptor in the cell membrane of target cells resulting in intracellular signal transduction and host of pharmacodynamic effects. Some of these pharmacodynamic effects are primarily mediated by insulin-like growth factor (IGF-1) produced in the liver, while others are primarily consequence of the direct effects of somapacitan-beco.

NONCLINICAL TOXICOLOGY SECTION.

13 NONCLINICAL TOXICOLOGY . 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Long term studies in animals with somapacitan-beco to evaluate carcinogenic potential have not been conducted.Somapacitan-beco was not mutagenic or clastogenic in standard battery of genotoxicity tests (bacterial mutagenicity (Ames), human lymphocyte chromosome aberration, rat bone marrow micronucleus).In rat studies evaluating male and female fertility, somapacitan-beco was administered by subcutaneous injection at doses of 1, 2, and mg/kg twice weekly. Males were dosed from four weeks before pairing until termination and females were dosed beginning two weeks prior to mating through gestation day 7. No adverse effects were observed on male or female fertility in rats at doses up to mg/kg (29 times the MRHD, based on AUC).

OVERDOSAGE SECTION.

10 OVERDOSAGE Acute overdosage could lead initially to hypoglycemia and subsequently to hyperglycemia. Overdose with SOGROYA is likely to cause fluid retention. Long-term overdosage could result in signs and symptoms of gigantism and/or acromegaly consistent with the known effects of excess endogenous growth hormone.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.

PRINCIPAL DISPLAY PANEL 5 mg Sogroya(R) mg penNDC 0169-2035-11 (somapacitan-beco) injection List: 2035115 mg 1.5 mL (3.3 mg/mL) Prefilled PenFor subcutaneous Use Only1x1.5 mL single-patient use prefilled penDials in 0.025 mg increments and contains mg totalRx onlyonce weekly. Sogroya(R) mg penNDC 0169-2035-11. (somapacitan-beco) injection List: 203511. Image of mg carton.

PEDIATRIC USE SECTION.

8.4 Pediatric Use The safety and effectiveness of SOGROYA have not been established in pediatric patients. Risks in pediatric patients associated with growth hormone use include:oSudden death in pediatric patients with Prader-Willi SyndromeoIncreased risk of second neoplasm in pediatric cancer survivors treated with radiation to the brain and/or headoSlipped capital femoral epiphysisoProgression of preexisting scoliosisoPancreatitis. oSudden death in pediatric patients with Prader-Willi Syndrome. oIncreased risk of second neoplasm in pediatric cancer survivors treated with radiation to the brain and/or head. oSlipped capital femoral epiphysis. oProgression of preexisting scoliosis. oPancreatitis.

PHARMACODYNAMICS SECTION.

12.2 Pharmacodynamics IGF-1 was measured to assess the pharmacodynamic (PD) properties of somapacitan-beco. Somapacitan-beco normalizes the mean IGF-1 standard deviation score (SDS) level from baseline value below -2 to value within the reference range (-2 to +2) in treatment-naive adult patients with GHD [see Clinical Studies (14)]. In adult patients with GHD (n=26), somapacitan-beco induces less than dose proportional IGF-1 response at steady state. Maximum IGF-1 concentrations were observed within to days after dosing. Similar to the somapacitan-beco exposure time course, steady state IGF-1 response was reached after to weekly doses with limited cumulative IGF-1 response.

PHARMACOKINETICS SECTION.

12.3 Pharmacokinetics The pharmacokinetics (PK) of somapacitan-beco following subcutaneous administration have been investigated at clinically relevant doses (e.g., 0.01 to 0.32 mg/kg in healthy adults, and 0.02 to 0.12 mg/kg in adults with GHD).Overall, somapacitan-beco displays non-linear pharmacokinetics, however in the clinically relevant dose range of somapacitan-beco in adults with GHD, somapacitan-beco pharmacokinetics are approximately linear.AbsorptionIn adults with GHD, maximum concentration of somapacitan-beco is reached to 24 hours post dose. Steady state exposure is achieved following to weeks of once weekly administration of subcutaneous somapacitan-beco.DistributionSomapacitan-beco is extensively bound (>99%) to plasma proteins.Based on population PK analyses, the estimated volume of distribution (V/F) of somapacitan-beco in adult GHD patients is approximately 14.6 L. EliminationThe plasma elimination half-life of somapacitan-beco is approximately to days. Metabolism: Somapacitan-beco is metabolized via proteolytic cleavage of the linker sequence between the peptide backbone and albumin binder sidechain.Excretion: The primary excretion routes of somapacitan-beco-related material are via the urine and feces. Approximately 81% of the dose is excreted in the urine and approximately 13% is excreted in the feces. No intact somapacitan-beco is excreted indicating full breakdown of somapacitan-beco prior to excretion.Specific PopulationsBody weight: The exposure of somapacitan-beco decreases with increasing body weight. However, the somapacitan-beco dose range of 0.1 to mg/week provides adequate systemic exposure to reach target IGF-1 levels over the weight range of 34.5-150.5 kg evaluated in the clinical trials. Geriatric patients: Adult patients greater than 65 years of age and geriatric patients have higher exposure than younger subjects at the same somapacitan-beco dose [see Dosage and Administration (2.3) and Use in Specific Populations (8.5)].Female patients receiving estrogen: Female patients and in particular female patients on oral estrogen, have lower exposure than males at the same somapacitan-beco dose [see Dosage and Administration (2.3) and Drug Interactions (7)]. Hepatic impairment: somapacitan-beco dose of 0.08 mg/kg at steady state resulted in comparable somapacitan-beco exposure between patients with normal hepatic function and mild hepatic impairment (Child-Pugh A). However, higher exposure was observed in patients with moderate hepatic impairment (Child-Pugh B) (ratios to normal hepatic function were 4.69 and 3.52-fold increase for AUC0-168h and Cmax, respectively). Lower somapacitan-beco stimulated IGF-1 levels were observed in patients with mild and moderate hepatic impairment (ratios to normal hepatic function were 0.85 and 0.75, respectively) [see Dosage and Administration (2.3) and Use in Specific Populations (8.6)].Renal impairment: In general, somapacitan-beco exposure tended to increase with decreasing estimated glomerular filtration rate. somapacitan-beco dose of 0.08 mg/kg at steady state resulted in higher exposures in patients with renal impairment, that was most pronounced for patients with severe renal impairment and patients requiring hemodialysis (AUC0-168h ratios to normal renal function were 1.75 and 1.63, respectively). Higher IGF-1 AUC0-168h levels were also observed in patients with moderate and severe renal impairment and in patients requiring hemodialysis (ratios to normal renal function were 1.35, 1.40 and 1.24, respectively).

PREGNANCY SECTION.

8.1 Pregnancy Risk SummaryThere are no available data on SOGROYA use in pregnant women; however, published studies with short-acting recombinant growth hormone (rhGH) use in pregnant women over several decades have not identified any drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal reproduction studies, subcutaneously administered somapacitan-beco was not teratogenic in rats or rabbits during organogenesis at doses approximately 12 times the clinical exposure at the maximum recommended human dose (MRHD) of mg/week. No adverse developmental outcomes were observed in pre- and post-natal development study with administration of somapacitan-beco to pregnant rats from organogenesis through lactation at approximately 275 times the clinical exposure at the MRHD (see Data).The estimated background risk of birth defects and 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. DataAnimal DataIn an embryo-fetal development study in rats, somapacitan-beco was administered by subcutaneous injection at doses of 2, 6, and 18 mg/kg/day during the period of organogenesis from gestation day to 17. Fetal viability and development were not affected at doses up to mg/kg/day (31 times the MRHD, based on AUC). Transient, fetal skeletal variations (short/bent/thickened long bones) were observed at 18 mg/kg/day (261 times the MRHD, based on AUC). In an embryo-fetal development study in rabbits, somapacitan-beco was administered by subcutaneous injection at doses of 1, 3, and mg/kg every two days during the period of organogenesis from gestation day to 18. Fetal viability and development were not adversely affected at somapacitan-beco dose of mg/kg/every two days (12 times the MRHD, based on AUC). Reduced fetal growth was observed at doses >=3 mg/kg/every two days (>=130 times the MRHD, based on C12h).In pre- and post-natal development study in pregnant rats, somapacitan-beco was administered by subcutaneous injection at doses of 4, 9, and 18 mg/kg twice week from gestation day through lactation day 18. No adverse developmental effects were observed in the offspring at doses up to mg/kg (275 times the MRHD, based on AUC). Increased incidence of renal pelvic dilatation was observed on post-natal day 21 at 18 mg/kg (630 times the MRHD, based on AUC), but was not observed in the adult F1 generation.

RECENT MAJOR CHANGES SECTION.

Dosage and Administration (2.1) 10/2021.

SPL UNCLASSIFIED SECTION.

2.1 Administration and Use Instructions oTherapy with SOGROYA should be supervised by physician who is experienced in the diagnosis and management of patients with the conditions for which SOGROYA is indicated [see Indications and Usage (1)].oPerform fundoscopic examination before initiating treatment with SOGROYA to exclude preexisting papilledema, and periodically thereafter. If papilledema is identified, evaluate the etiology and treat the underlying cause before initiating therapy with SOGROYA [see Warnings and Precautions (5.4)].oAdminister SOGROYA by subcutaneous injection to the abdomen or thigh with regular rotation of injection sites to avoid lipohypertrophy.oInspect visually for particulate matter and discoloration. SOGROYA should be clear to slightly opalescent and colorless to slightly yellow solution. If the solution is cloudy or contains particulate matter do not use.oThe SOGROYA mg/1.5 mL (3.3 mg/mL) prefilled pen dials in 0.025 mg increments and delivers doses from 0.025 mg to mg. oThe SOGROYA 10 mg/1.5 mL (6.7 mg/mL) prefilled pen dials in 0.05 mg increments and delivers doses from 0.05 mg to mg.oInstructions for delivering the dosage are provided in the PATIENT INFORMATION and INSTRUCTIONS FOR USE leaflets enclosed with the SOGROYA prefilled pen.. oTherapy with SOGROYA should be supervised by physician who is experienced in the diagnosis and management of patients with the conditions for which SOGROYA is indicated [see Indications and Usage (1)].. oPerform fundoscopic examination before initiating treatment with SOGROYA to exclude preexisting papilledema, and periodically thereafter. If papilledema is identified, evaluate the etiology and treat the underlying cause before initiating therapy with SOGROYA [see Warnings and Precautions (5.4)].. oAdminister SOGROYA by subcutaneous injection to the abdomen or thigh with regular rotation of injection sites to avoid lipohypertrophy.. oInspect visually for particulate matter and discoloration. SOGROYA should be clear to slightly opalescent and colorless to slightly yellow solution. If the solution is cloudy or contains particulate matter do not use.. oThe SOGROYA mg/1.5 mL (3.3 mg/mL) prefilled pen dials in 0.025 mg increments and delivers doses from 0.025 mg to mg. oThe SOGROYA 10 mg/1.5 mL (6.7 mg/mL) prefilled pen dials in 0.05 mg increments and delivers doses from 0.05 mg to mg.. oInstructions for delivering the dosage are provided in the PATIENT INFORMATION and INSTRUCTIONS FOR USE leaflets enclosed with the SOGROYA prefilled pen.

USE IN SPECIFIC POPULATIONS SECTION.

8 USE IN SPECIFIC POPULATIONS . 8.1 Pregnancy Risk SummaryThere are no available data on SOGROYA use in pregnant women; however, published studies with short-acting recombinant growth hormone (rhGH) use in pregnant women over several decades have not identified any drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal reproduction studies, subcutaneously administered somapacitan-beco was not teratogenic in rats or rabbits during organogenesis at doses approximately 12 times the clinical exposure at the maximum recommended human dose (MRHD) of mg/week. No adverse developmental outcomes were observed in pre- and post-natal development study with administration of somapacitan-beco to pregnant rats from organogenesis through lactation at approximately 275 times the clinical exposure at the MRHD (see Data).The estimated background risk of birth defects and 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. DataAnimal DataIn an embryo-fetal development study in rats, somapacitan-beco was administered by subcutaneous injection at doses of 2, 6, and 18 mg/kg/day during the period of organogenesis from gestation day to 17. Fetal viability and development were not affected at doses up to mg/kg/day (31 times the MRHD, based on AUC). Transient, fetal skeletal variations (short/bent/thickened long bones) were observed at 18 mg/kg/day (261 times the MRHD, based on AUC). In an embryo-fetal development study in rabbits, somapacitan-beco was administered by subcutaneous injection at doses of 1, 3, and mg/kg every two days during the period of organogenesis from gestation day to 18. Fetal viability and development were not adversely affected at somapacitan-beco dose of mg/kg/every two days (12 times the MRHD, based on AUC). Reduced fetal growth was observed at doses >=3 mg/kg/every two days (>=130 times the MRHD, based on C12h).In pre- and post-natal development study in pregnant rats, somapacitan-beco was administered by subcutaneous injection at doses of 4, 9, and 18 mg/kg twice week from gestation day through lactation day 18. No adverse developmental effects were observed in the offspring at doses up to mg/kg (275 times the MRHD, based on AUC). Increased incidence of renal pelvic dilatation was observed on post-natal day 21 at 18 mg/kg (630 times the MRHD, based on AUC), but was not observed in the adult F1 generation.. 8.2 Lactation Risk SummaryThere is no information on the presence of somapacitan-beco in human milk, the effects on the breastfed infant, or the effects on milk production. Somapacitan-beco-related material was secreted into milk of lactating rats. When substance is present in animal milk, it is likely that the substance will be present in human milk. Available published data describing administration of short-acting recombinant growth hormone (rhGH) to lactating women for days reported that short-acting rhGH did not increase the normal breastmilk concentration of growth hormone and no adverse effects were reported in breastfed infants. The developmental and health benefits of breastfeeding should be considered along with the mothers clinical need for SOGROYA and any potential adverse effects on the breastfed infant from SOGROYA or from the underlying maternal condition.. 8.4 Pediatric Use The safety and effectiveness of SOGROYA have not been established in pediatric patients. Risks in pediatric patients associated with growth hormone use include:oSudden death in pediatric patients with Prader-Willi SyndromeoIncreased risk of second neoplasm in pediatric cancer survivors treated with radiation to the brain and/or headoSlipped capital femoral epiphysisoProgression of preexisting scoliosisoPancreatitis. oSudden death in pediatric patients with Prader-Willi Syndrome. oIncreased risk of second neoplasm in pediatric cancer survivors treated with radiation to the brain and/or head. oSlipped capital femoral epiphysis. oProgression of preexisting scoliosis. oPancreatitis. 8.5 Geriatric Use In clinical studies total of 52 (15.6%) of the 333 SOGROYA-treated patients were 65 years or older and (0.9%) were 75 years or older [see Clinical Studies (14)]. Subjects older than 65 years appeared to have higher exposure than younger subjects at the same dose level. Elderly patients may be more sensitive to the action of somapacitan-beco, and therefore may be at increased risk for adverse reactions. Initiate SOGROYA with dose of mg once weekly and use smaller increments when increasing the dose [see Dosage and Administration (2.3)]. 8.6 Hepatic Impairment No specific dose adjustment of SOGROYA is required for patients with mild hepatic impairment. Higher somapacitan-beco exposure was observed in patients with moderate hepatic impairment. In patients with moderate hepatic impairment, initiate SOGROYA with dose of mg once weekly and use smaller increments when increasing the dose. The maximum dose should not exceed mg once weekly. Somapacitan-beco was not studied in patients with severe hepatic impairment. Therefore, use of SOGROYA is not recommended in patients with severe hepatic impairment [see Dosage and Administration (2.3) and Clinical Pharmacology (12.3)].

WARNINGS AND PRECAUTIONS SECTION.

5 WARNINGS AND PRECAUTIONS . oIncreased Risk of Neoplasm: There are risks of malignancy progression in patients with active malignancy and of malignant changes of preexisting nevi. Monitor patients with preexisting tumors for progression or recurrence (5.2).oGlucose Intolerance and Diabetes Mellitus: SOGROYA may decrease insulin sensitivity, particularly at higher doses. Monitor glucose levels periodically in all patients receiving SOGROYA, especially in patients with existing diabetes mellitus or at risk for its development (5.3).oIntracranial Hypertension (IH): Has been reported usually within weeks of initiation. Perform fundoscopic examinations prior to initiation and periodically thereafter. If papilledema is identified prior to initiation, evaluate the etiology and treat the underlying cause before initiating. If papilledema occurs with SOGROYA, stop treatment (5.4).oHypersensitivity: Serious hypersensitivity reactions may occur. In the event of an allergic reaction, seek prompt medical attention (5.5).oFluid Retention: May occur in adults and may be dose dependent (5.6).oHypoadrenalism: Monitor patients for reduced serum cortisol levels and/or need for glucocorticoid dose increases in those with known hypoadrenalism (5.7).oHypothyroidism: Monitor thyroid function periodically as hypothyroidism may occur or worsen after initiation of SOGROYA (5.8).oPancreatitis: Has been reported; consider pancreatitis in patients with persistent severe abdominal pain (5.9).oLipohypertrophy/lipoatrophy: May occur if SOGROYA administered in the same location over long period of time. Rotate injection sites on regular basis (5.10).. oIncreased Risk of Neoplasm: There are risks of malignancy progression in patients with active malignancy and of malignant changes of preexisting nevi. Monitor patients with preexisting tumors for progression or recurrence (5.2).. oGlucose Intolerance and Diabetes Mellitus: SOGROYA may decrease insulin sensitivity, particularly at higher doses. Monitor glucose levels periodically in all patients receiving SOGROYA, especially in patients with existing diabetes mellitus or at risk for its development (5.3).. oIntracranial Hypertension (IH): Has been reported usually within weeks of initiation. Perform fundoscopic examinations prior to initiation and periodically thereafter. If papilledema is identified prior to initiation, evaluate the etiology and treat the underlying cause before initiating. If papilledema occurs with SOGROYA, stop treatment (5.4).. oHypersensitivity: Serious hypersensitivity reactions may occur. In the event of an allergic reaction, seek prompt medical attention (5.5).. oFluid Retention: May occur in adults and may be dose dependent (5.6).. oHypoadrenalism: Monitor patients for reduced serum cortisol levels and/or need for glucocorticoid dose increases in those with known hypoadrenalism (5.7).. oHypothyroidism: Monitor thyroid function periodically as hypothyroidism may occur or worsen after initiation of SOGROYA (5.8).. oPancreatitis: Has been reported; consider pancreatitis in patients with persistent severe abdominal pain (5.9).. oLipohypertrophy/lipoatrophy: May occur if SOGROYA administered in the same location over long period of time. Rotate injection sites on regular basis (5.10).. 5.1 Increased Mortality in Patients with Acute Critical Illness Increased mortality has been reported after treatment with pharmacologic amounts of growth hormone products in patients with acute critical illness due to complications following open-heart surgery, abdominal surgery and multiple accidental trauma, as well as patients with acute respiratory failure [see Contraindications (4)]. Two placebo-controlled clinical trials in non-growth hormone deficient adult patients (n=522) with these conditions in intensive care units revealed significant increase in mortality (42% vs. 19%) among somatropin-treated patients (doses 5.3-8 mg/day) compared to those receiving placebo. The safety of continuing SOGROYA treatment in patients receiving replacement doses for approved indications who concurrently develop these illnesses has not been established. SOGROYA is not indicated for the treatment of non-GH deficient adults.. 5.2 Increased Risk of Neoplasms Active MalignancyThere is an increased risk of malignancy progression with growth hormone treatment in patients with active malignancy [See Contraindications (4)]. Any preexisting malignancy should be inactive, and its treatment complete prior to instituting therapy with SOGROYA. Discontinue SOGROYA if there is evidence of recurrent activity.New Skin Malignancy during TreatmentThere is potential risk of malignant changes of preexisting nevi. Monitor all patients receiving SOGROYA carefully for increased growth, or potential malignant changes, of preexisting nevi. Advise patients to report changes in skin pigmentation or changes in the appearance of pre-existing nevi.. 5.3 Glucose Intolerance and Diabetes Mellitus Treatment with growth hormone products may decrease insulin sensitivity, particularly at higher doses. New onset type diabetes mellitus has been reported in patients taking growth hormone products. Patients with undiagnosed pre-diabetes and diabetes mellitus may experience worsened glycemic control and become symptomatic. Monitor glucose levels periodically in all patients receiving SOGROYA, especially in those with risk factors for diabetes mellitus, such as obesity, or family history of diabetes mellitus. Patients with preexisting type or type diabetes mellitus or pre-diabetes should be monitored closely. The doses of antidiabetic agents may require adjustment when SOGROYA is initiated. 5.4 Intracranial Hypertension Intracranial hypertension with papilledema, visual changes, headache, nausea, and/or vomiting has been reported in patients treated with growth hormone products. Symptoms usually occurred within the first eight (8) weeks after the initiation of growth hormone therapy. In all reported cases, intracranial hypertension-associated signs and symptoms rapidly resolved after cessation of therapy or reduction of the growth hormone dose. Perform fundoscopic examination before initiating treatment with SOGROYA to exclude preexisting papilledema and periodically thereafter. If papilledema is identified prior to initiation, evaluate the etiology and treat the underlying cause before initiating SOGROYA. If papilledema is observed by fundoscopy during SOGROYA treatment, treatment should be stopped. If intracranial hypertension is diagnosed, treatment with SOGROYA can be restarted at lower dose after intracranial hypertension-associated signs and symptoms have resolved.. 5.5 Severe Hypersensitivity Serious systemic hypersensitivity reactions including anaphylactic reactions and angioedema have been reported postmarketing with use of growth hormone products. Patients should be informed that such reactions are possible, and that prompt medical attention should be sought if an allergic reaction occurs [see Contraindications (4)]. 5.6 Fluid Retention Fluid retention during SOGROYA replacement therapy may occur. Clinical manifestations of fluid retention (e.g. edema and nerve compression syndromes including carpal tunnel syndrome/paresthesia) are usually transient and dose dependent. 5.7 Hypoadrenalism Patients receiving growth hormone therapy who have or are at risk for corticotropin deficiency may be at risk for reduced serum cortisol levels and/or unmasking of central (secondary) hypoadrenalism. In addition, patients treated with glucocorticoid replacement for previously diagnosed hypoadrenalism may require an increase in their maintenance or stress doses following initiation of SOGROYA treatment. Monitor patients with known hypoadrenalism for reduced serum cortisol levels and/or need for glucocorticoid dose increases [see Drug Interactions (7)]. 5.8 Hypothyroidism Undiagnosed/untreated hypothyroidism may prevent an optimal response to SOGROYA. In patients with GH deficiency, central (secondary) hypothyroidism may first become evident or worsen during treatment with growth hormone therapy. Therefore, patients should have periodic thyroid function tests and thyroid hormone replacement therapy should be initiated or appropriately adjusted when indicated.. 5.9 Pancreatitis Cases of pancreatitis have been reported in patients receiving growth hormone products. Pancreatitis should be considered in patients who develop persistent severe abdominal pain.. 5.10 Lipohypertrophy/Lipoatrophy When SOGROYA is administered subcutaneously at the same site over long period of time, tissue lipohypertrophy or lipoatrophy may result. Rotate injection sites when administering SOGROYA to reduce this risk [see Dosage and Administration (2.1)]. 5.11 Laboratory Tests Serum levels of inorganic phosphorus, alkaline phosphatase, and parathyroid hormone may increase after somatropin therapy.