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1. Important e Be careful not to drop Norditropin FlexPro pen or knock it against a hard surface If this happens you will need to repeat the airshot e Always make sure that a drop appears at the needle tip after completing your airshot Select your dose Use the dose selector on your Norditropin FlexPro pen to make sure you have the exact dose selected You can select up to 2 mg per dose G e Select or adjust the dose you need by turning the dose selector forwards or backwards until the right number of mg lines up with the pointer e When dialing back be careful not to press the dose button as liquid will come out e To guide you the dose selector Clicks differently when turned forwards backwards or past the number of mg that is left in the pen e When the pen has less than 2 mg the dose selector stops at the number of mg that is left in the pen How much growth hormone is left in the pen You can use the growth hormone scale to see how much growth hormone is left in the pen You can use the dose selector to see exactly how much growth hormone is left in the pen If the pen contains less than 2 mg turn the dose selector until it stops The figure that lines up with the pointer shows how many mg are left in the pen e You cannot set a dose higher than the number of mg left in the pen e f there is not enough Norditropin left in the pen to deliver your full dose use a new Norditropin FlexPro
2. Norditropin NordiFlex 10 mg 1 5 mL EITHER keep refrigerated 2 8 C 36 46 F for 4 weeks OR store not above 25 C 77 F for 3 weeks e When using a NordiFlex PenMate with a Norditropin NordiFlex 15 mg 1 5 mL keep refrigerated 2 8 C 36 46 F for 4 weeks e Do not freeze Norditropin MUST NOT BE INJECTED if the liquid is cloudy or contains particulate matter Use it only if it is clear and colorless e Keep NordiFlex PenMate and Norditropin NordiFlex in the supplied case whenever possible Inside the case you can also keep 3 extra NovoFine disposable needles Maintenance Guidelines for maintaining NordiFlex PenMate and Norditropin NordiFlex Be sure to e Clean the outside surface by wiping it with a soft cloth moistened with a mild detergent e Protect NordiFlex PenMate and Norditropin NordiFlex from dust dirt and direct sunlight when not in its case Make certain that you e Handle NordiFlex PenMate and Norditropin NordiFlex with care Do not drop it and avoid knocking it against hard surfaces e Do not soak NordiFlex PenMate and or Norditropin NordiFlex in alcohol wash or lubricate it Important Things to Know e Do not use Norditropin NordiFlex 30 mg 3 mL pens with the NordiFlex PenMate auto insertion accessory e Always screw Norditropin NordiFlex and NordiFlex PenMate tightly together e NordiFlex PenMate and Norditropin NordiFlex are not recommended for people who are bl
3. A comparison of HV between the two treatment groups during the first two years of treatment for the randomized subjects was 10 1 and 7 6 cm year with 0 066 mg kg day versus 8 55 and 6 7 cm year with 0 033 mg kg day for Year 1 and Year 2 respectively Age at start of treatment was a factor for change in height SDS national reference The younger the age at start of treatment the larger the change in height SDS Examination of gender subgroups did not identify differences in response to Norditropin Not all patients with Noonan syndrome have short stature some will achieve a normal adult height without treatment Therefore prior to initiating Norditropin for a patient with Noonan syndrome establish that the patient does have short stature 14 2 Short Stature in Children with Turner Syndrome Two randomized parallel group open label multicenter studies were conducted in the Netherlands to evaluate the efficacy and safety of Norditropin for the treatment of children with short stature associated with Turner syndrome Patients were treated to final height in both studies height velocity HV lt 2 cm year Changes in height were expressed as standard deviation scores SDS utilizing reference data for untreated Turner syndrome patients as well as the national Dutch population In Study 1 the primary study 68 euthyroid Caucasian patients stratified based on age and baseline height SDS were randomized in a 1 1 1 ratio to t
4. The safety and effectiveness of Norditropin in patients aged 65 and over has not been evaluated in clinical studies Elderly patients may be more sensitive to the action of somatropin and therefore may be more prone to develop adverse reactions A lower starting dose and smaller dose increments should be considered for older patients see Dosage and Administration 2 2 10 OVERDOSAGE Short Term short term overdosage could lead initially to hypoglycemia and subsequently to hyperglycemia Furthermore overdose with somatropin is likely to cause fluid retention Long Term Long term overdosage could result in signs and symptoms of gigantism and or acromegaly consistent with the known effects of excess growth hormone see Dosage and Administration 2 11 DESCRIPTION Norditropin is a polypeptide hormone of recombinant DNA origin The hormone is synthesized by a special strain of E coli bacteria that has been modified by the addition of a plasmid which carries the gene for human growth hormone Norditropin contains the identical sequence of 191 amino acids constituting the naturally occurring pituitary human growth hormone with a molecular weight of about 22 000 Daltons Norditropin cartridges are supplied as sterile solutions for Subcutaneous injection in ready to administer cartridges or prefilled pens with a volume of 1 5 mL or 3 mL Each Norditropin Cartridge contains the following see Table 2 Table 2 5mg 1
5. 2 8 C 36 46 F and used within 4 weeks OR stored for up to 3 weeks at not more than 25 C 77 F Discard unused portion 15 mg 1 5 mL green cartridges After a Norditropin cartridge 15 mg 1 5 mL has been inserted into its NordiPen delivery system NordiPen 15 it must be stored in the pen in the refrigerator 2 8 C 36 46 F and used within 4 weeks Discard unused portion after 4 weeks Table 10 Storage Options Before Use In use After 1st injection Storage Option 2 p 25 C 77 F 3 weeks p 2O F 3 weeks 36 46 F 4 weeks 36 46 F Until exp date 36 46 F 4 weeks 2 8 C 36 46 F 4 weeks 17 PATIENT COUNSELING INFORMATION See FDA approved patient labeling Patients being treated with Norditropin FlexPro or Norditropin NordiFlex prefilled pens or Norditropin Cartridges and or their parents should be informed about the potential risks and benefits associated with somatropin treatment in particular see Adverse Reactions 6 1 for a listing of the most serious and or most frequently observed adverse reactions associated with somatropin treatment in children and adults This information is intended to better educate patients and caregivers it is not a disclosure of all possible adverse or intended effects Patients and caregivers who will administer Norditropin FlexPro or Norditropin NordiFlex prefilled pens or Norditropin Cartridges should receive appr
6. In addition obese individuals are more likely to manifest adverse effects when treated with a weight based regimen In order to reach the defined treatment goal estrogen replete women may need higher doses than men Oral estrogen administration may increase the dose requirements in women 2 3 Preparation and Administration Noraitropin FlexPro 5 mg 1 5 mL 10 mg 1 5 mL and 15 mg 1 5 mL Instructions for delivering the dosage are provided in the PATIENT INFORMATION and INSTRUCTIONS FOR USE leaflets enclosed with the Norditropin FlexPro prefilled pen Norditropin NordiFlex 5 mg 1 5 mL 10 mg 1 5 mL 15 mg 1 5 mL and 30 mg 3 mL Instructions for delivering the dosage are provided in the PATIENT INFORMATION and INSTRUCTIONS FOR USE leaflets enclosed with the Norditropin NordiFlex prefilled pen Norditropin Cartridges must be administered using the NordiPen delivery systems Each cartridge size has a corresponding color coded pen which is graduated to deliver the appropriate dose based on the concentration of Norditropin in the cartridge Norditropin Cartridges 5 mg 1 5 mL and 15 mg 1 5 mL Each cartridge of Norditropin must be inserted into its corre sponding NordiPen delivery system Instructions for delivering the dosage are provided in the NordiPen INSTRUCTION booklet Parenteral drug products should always be inspected visually for particulate matter and discoloration prior to administration whenever solu
7. injection 30 mg 3 mL Prefilled Pen Your doctor will discuss with you the benefits and risks of Norditropin NordiFlex pronounced Nor dee tro pin Nor dee flex Read all of the information in this patient guide because it contains important information for you If you have further questions please ask your doctor or your pharmacist Norditropin NordiFlex has been prescribed for you and you must not pass it on to others What is the most important information should know about Norditropin NordiFlex Store Norditropin NordiFlex in a refrigerator before use Do not freeze it or expose it to heat For specific information on storage conditions please see the section How to store Norditropin NordiFlex Do not use Norditropin NordiFlex if the solution in the cartridge does not appear clear and colorless Check this by turning the pen upside down once or twice Norditropin NordiFlex is for use by one person only Do not use Norditropin NordiFlex if you need to make more than A air shots before the first injection Your doctor may measure your height weight and your ability to produce growth hormone before you are prescribed Norditropin NordiFlex Norditropin NordiFlex 30 mg 3 mL cannot be used with the NordiFlex PenMate auto insertion accessory What is Norditropin NordiFlex Norditropin is a clear and colorless solution It contains a human growth hormone called somatropin so ma tro pin made thro
8. of raised pressure in the brain contact your healthcare provider right away Norditropin may affect how other medicines work and other medicines may affect how Norditropin works so be sure to tell your healthcare provider about all the medicines you take including prescription and non prescrip tion medicines vitamins and herbal supplements Especially tell your healthcare provider if you take glucocorticoid medica tion thyroid hormone insulin or other medicine for diabetes medicines that are metabolized by the liver e g corti costeroids sex steroids anticonvulsants cyclosporine or oral estrogen replace ment medicine Mixed Sources Product group from well managed forests controlled sources and recycled wood or fiber ESC www fsc org Cert no SW COC 1996 Forest Stewardship Council norditropin somatropin rDNA origin injection norditropin somatropin rDNA origin injection PATIENT INFORMATION Norditropin Nor dee tro pin somatropin rDNA origin injection Read the Patient Information that comes with Norditropin before you start to take it and each time you get a refill There may be new information This leaflet does not take the place of talking with your healthcare provider about your medical condition or your treatment What is Norditropin Norditropin is a prescription medicine given by injection under the skin subcutaneous that contains human growth horm
9. pen to inject the remaining amount of your dose or contact your healthcare provider e Be sure to subtract the dose already received For example if your dose is 0 6 mg and you can only set the dose selector to 0 3 mg you should inject another 0 3 mg with a new Norditropin FlexPro pen Important e Never use the pen clicks to count the number of mg you select Only the display window and pointer will show the exact number e Never use the growth hormone scale to measure how much liquid to inject Only the display window and pointer will show the exact number Inject your dose Make sure that you receive your full dose by using the injection technique recommended by your healthcare provider This medicine is injected under your skin subcutaneous only H e Insert the needle into your skin as your healthcare provider has shown you e Press and hold the dose button to inject until the 0 in the display window lines up with the pointer As you do this you may hear or feel a firm click e f you remove your finger from the dose button before the 0 is in the display window the full dose has not been delivered Leave the needle in the skin and press and hold the dose button again until the 0 lines up with the pointer If 0 does not appear in the display window you did not receive the full dose Call 1 888 668 6444 for assistance e After the 0 in the display window lines up with th
10. you did not receive the full dose Call 1 888 668 6444 for assistance e After the 0 in the display window lines up with the pointer leave the needle under the skin for at least 6 seconds to make sure that you get your full dose You can let go of the dose button while you wait e Change the injection site using the injection procedure recommended by your healthcare provider Important e Always press the dose button to inject the dose Turning the dose selector will not inject the dose e Never touch the display window when you inject as this can block the injection e Remove the needle from your skin After that you may see a drop of liquid at the needle tip This is normal and does not affect the dose you received After the injection remove the needle right away and put the pen cap back on If the needle is not removed some liquid may come out of the Norditropin FlexPro Unscrew the needle and throw away the needle and any empty Norditropin FlexPro pen as directed by your healthcare provider A special sharps container such as a red biohazard container a hard plastic container such as an empty detergent bottle or a metal container such as an empty coffee can should be used The container should be sealed and disposed of properly e Caregivers should be most careful when handling used needles to avoid hurting themselves Care for your Norditropin FlexPro pen You must ta
11. 11BHSD 1 Consequently individuals with untreated GHD have relative increases in 11BHSD 1 and serum cortisol Introduction of somatropin treatment may result in inhibition of 11BHSD 1 and reduced serum cortisol concentrations As a consequence previously undiagnosed central secondary hypoadrenalism may be unmasked and glucocorticoid replacement may be required in patients treated with somatropin In addition patients treated with glucocorticoid replacement for previously diagnosed hypoadrenalism may require an increase in their maintenance or stress doses following initiation of somatropin treatment this may be especially true for patients treated with cortisone acetate and prednisone since conversion of these drugs to their biologically active metabolites is dependent on the activity of 11BHSD 1 7 2 Pharmacologic Glucocorticoid Therapy and Supraphysiologic Glucocorticoid Treatment Pharmacologic glucocorticoid therapy and supraphysiologic glucocorticoid treatment may attenuate the growth promoting effects of somatropin in children Therefore glucocorticoid replacement dosing should be carefully adjusted in children receiving concomitant somatropin and glucocorticoid treatments to avoid both hypoadrenalism and an inhibitory effect on growth 7 3 Cytochrome P450 Metabolized Drugs Limited published data indicate that somatropin treatment increases cytochrome P450 CYP450 mediated antipyrine clearance in man These data suggest that somatr
12. 5 mL A Norditropin NordiFlex 5 mg 1 5 mL prefilled pen orange is used to show the correct use of NordiFlex PenMate Norditropin NordiFlex is also available as a 10 mg 1 5 mL prefilled pen blue 15 mg 1 5 mL prefilled pen green and 30 mg 3 mL prefilled pen purple Do not use Norditropin NordiFlex 30 mg 3 mL pens with the NordiFlex PenMate auto insertion accessory Begin by reviewing the drawings of the parts of NordiFlex PenMate Norditropin NordiFlex prefilled pen and NovoFine disposable needle Important additional information is given below the instructions Read the text carefully and look at the drawings to make sure that you understand each step well Section 1 Assembling NordiFlex PenMate NOTE Do not use Norditropin NordiFlex 30 mg 3 mL pens with the NordiFlex PenMate auto insertion accessory 1 Remove NordiFlex PenMate cap 2 A Pull off the cap of Norditropin NordiFlex You will not need it with NordiFlex PenMate DO NOT use Norditropin NordiFlex if the liquid is cloudy or contains particles Use it only if it is clear and colorless Check this by turning Norditropin NordiFlex upside dawn anre nr twice and view the FOMNIGIG 4 Place a new NovoFine disposable needle onto Norditropin NordiFlex immediately before use Remove the protective tab off the needle and screw the needle tightly onto Norditropin NordiFlex prefilled pen NOTE Never place a NovoFine d
13. PenMate Check that Norditropin NordiFlex is intact NordiFlexPenMate Make sure that the cartridge is intact e g no cracks oe dropped or e Screw NordiFlex PenMate and Norditropin NordiFlex together as described in Section 1 e Screw on a new NovoFine disposable needle see Section 1 e Perform an air shot see Section 2 If you have any questions please call 1 888 NOVO 444 Date of Issue March 10 2009 Version 2 For assistance or further information write to Novo Nordisk Inc 100 College Road West
14. because of heart or stomach surgery trauma or serious breathing respiratory problems e high risk of death in children with Prader Willi syndrome who are severely obese or have breathing problems including Sleep apnea e return of tumor or cancerous growths e high blood sugar hyperglycemia e increase in pressure in the skull intracranial hypertension If you have headaches eye problems nausea or vomiting contact your healthcare provider right away e swollen hands and feet due to fluid retention e decrease in thyroid hormone levels Your healthcare provider will do blood tests to check your thyroid hormone levels e hip and knee pain or a limp in children slipped capital femoral epiphysis e worsening of curvature of the spine scoliosis e middle ear infection hearing problems or ear problems in patients with Turner syndrome e redness itching and tissue weakness in the area you inject e increase 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 Norditropin include e headaches e muscle pain e joint stiffness e high blood sugar hyperglycemia sugar in your urine glucosuria e swollen hands and feet due to fluid retention e redness and itching in the area you inject Talk to your healthcare provider if you have any side effect that bothers you or that does not go away These ar
15. for at least 6 seconds after injection with your thumb on the push button Keep the push button fully pushed in until after the needle has been removed from the skin After the injection check the dosage indicator window to make sure it shows zero 0 0 If zero does not appear you did not receive the full dose Call 1 888 NOVO 444 for assistance Note Always press the push button to inject the dose Turning the dosage selector will not inject the dose 5 Removing the NovoFine Disposable Needle H After the injection remove the needle without recapping and dispose of it in a puncture resistant container Used needles should be placed in sharps containers such as red biohazard containers hard plastic containers Such as detergent bottles or metal containers Such as an empty coffee can Such containers should be sealed and disposed of properly It is important that you use a new needle for each injection Healthcare professionals relatives and other caregivers should follow general precautionary measures for removal and disposal of needles to reduce the risk of unintended needle stick injuries When the cartridge is empty dispose of Norditropin NordiFlex without the needle attached 6 Maintenance Handle Norditropin NordiFlex with care Protect Norditropin NordiFlex from dust dirt and direct sunlight You can clean the outside of Norditropin NordiFlex by wiping it with a soft cloth moistened with water Do not
16. increase after treatment with somatropin Cell Growth It has been shown that the total number of skeletal muscle cells is markedly decreased in children with short stature lacking endogenous GH compared with normal children and that treatment with somatropin results in an increase in both the number and size of muscle cells Organ Growth Somatropin influences the size of internal organs and it also increases red cell mass Protein Metabolism Linear growth is facilitated in part by increased cellular protein synthesis This synthesis and growth are reflected by nitrogen retention which can be quantitated by observing the decline in urinary nitrogen excretion and blood urea nitrogen following the initiation of somatropin therapy Carbohydrate Metabolism Hypopituitary children sometimes experience fasting hypoglycemia that may be improved by treatment with somatropin In healthy subjects large doses of somatropin may impair glucose tolerance Although the precise mechanism of the diabetogenic effect of somatropin is not known it is attributed to blocking the action of insulin rather than blocking insulin secretion Insulin levels in serum actually increase as somatropin levels increase Administration of human growth hormone to normal adults and patients with growth hormone deficiency results in increases in mean serum fasting and postprandial insulin levels although mean values remain in the normal range In addition mean fastin
17. more frequently than in the placebo group These types of adverse events are thought to be related to the fluid accumulating effects of somatropin In general these adverse events were mild and transient in nature During the placebo controlled portion of this study approximately 5 of patients without preexisting diabetes mellitus treated with Norditropin were diagnosed with overt type 2 diabetes mellitus compared with none in the placebo group see Warnings and Precautions 5 4 and Adverse Reactions 6 1 Anti GH antibodies were not detected Of note the doses of Norditropin employed during this study completed in the mid 1990s were substantially larger than those currently recommended by the Growth Hormone Research Society and more than likely resulted in a greater than expected incidence of fluid retention and glucose intolerance related adverse events A similar incidence and pattern of adverse events were observed during the other three placebo controlled AO GHD trials and during the two placebo controlled CO GHD trials Table 1 Adverse Reactions with 5 Overall Incidence in Adult Onset Growth Hormone Deficient Patients Treated with Norditropin During a Six Month Placebo Controlled Clinical Trial faust eI a troenteritis Other Non Classifiable Disorders excludes accidental injury Increased sweating 4 8 1 2 a a a Placebo N Norditropin N a abnormal Laryngitis 3
18. of disease do not let anyone else use your Norditropin NordiFlex even if you attach a new needle e Keep the Norditropin NordiFlex out of the reach of children e Novo Nordisk is not responsible for harm due to using the Norditropin NordiFlex with products that are not recommended by Novo Nordisk 8 Customer Satisfaction Customer service and satisfaction are our top concerns If you have any questions about Norditropin NordiFlex prefilled pens please call Novo Nordisk Inc at 1 888 NOVO 444 Date of issue March 10 2009 Version 1 Norditropin Norditropin NordiFlex and NordiFlex PenMate are registered trademarks of Novo Nordisk Health Care AG Novo Nordisk and NovoFine are registered trademarks of Novo Nordisk A S US Patent Nos 6 235 004 6 004 297 5 849 704 and 6 582 404 For assistance or further information write to Novo Nordisk Inc 100 College Road West Princeton NJ 08540 USA 1 888 NOV0 444 norditropin us com Manufactured by Novo Nordisk A S O DK 2880 Bagsvaerd Denmark 2004 2009 Novo Nordisk Inc 138134 04 09 novo nordisk IMU Myg 1 0 TIL and to y o TIL PreMed pelo User Manual Please read this manual carefully before using NordiFlex PenMate Introduction NordiFlex PenMate is an auto insertion accessory designed to be used with Norditropin NordiFlex 5 mg 1 5 mL 10 mg 1 5 mL and 15 mg 1 5 mL prefilled pens NordiFlex PenMate helps you to insert the needle and t
19. of preexisting nevi 5 4 Impaired Glucose Tolerance and Diabetes Mellitus Treatment with somatropin may decrease insulin sensitivity particularly at higher doses in susceptible patients As a result previously undiagnosed impaired glucose tolerance and overt diabetes mellitus may be unmasked during somatropin treatment New onset type 2 Diabetes Mellitus has been reported in patients Therefore glucose levels should be monitored periodically in all patients treated with somatropin especially in those with risk factors for diabetes mellitus such as obesity Turner syndrome or a family history of diabetes mellitus Patients with preexisting type 1 or type 2 diabetes mellitus or impaired glucose tolerance should be monitored closely during somatropin therapy The doses of antihyperglycemic drugs i e insulin or oral injectable agents may require adjustment when somatropin therapy is instituted in these patients 5 5 Intracranial Hypertension Intracranial hypertension IH with papilledema visual changes headache nausea and or vomiting has been reported in a small number of patients treated with somatropin products Symptoms usually occurred within the first eight 8 weeks after the initiation of somatropin therapy In all reported cases IH associated signs and symptoms rapidly resolved after cessation of therapy or a reduction of the somatropin dose Funduscopic examination should be performed routinely before initiating treatm
20. something is wrong with it always screw on a new disposable needle and check the growth hormone flow airshot before you inject e Do not try to refill your disposable pen it is prefilled e Do not try to repair your pen or pull it apart e Do not expose your pen to dust dirt or any kind of liquid e Do not try to wash soak or lubricate your pen You may clean the Norditropin FlexPro pen with a mild detergent on a moistened cloth See section How do store Norditropin above for information about how to store your pen e Always keep your pen and needles out of reach of others especially children e Never share your needles and pen with anyone Date of Issue March 2 2010 Version 1 US Patent Nos 6 235 004 6 004 297 6 582 404 6 716 198 6 899 699 5 849 704 5 691 169 5 618 697 and other patents pending Norditropin FlexPro and Norditropin NordiFlex are registered trademarks of Novo Nordisk Health Care AG Novo Nordisk is a registered trademark of Novo Nordisk A S 2004 2010 Novo Nordisk Health Care AG Manufactured by O Novo Nordisk A S DK 2880 Bagsvaerd Denmark 140985 3 10 novo nordisk INSTRUCTIONS FOR USE Norditropin FlexPro somatropin rDNA origin injection 10 mg 1 5 mL blue Prefilled Pen Read these instructions before using your Norditropin FlexPro pen Norditropin FlexPro Growth Display Dose Dose Pencap hormone scale window Pointer selector bu
21. sure to tell your doctor about all of the medications you are taking especially if you are taking e a glucocorticoid medication for example hydrocortisone or cortisone acetate e thyroid hormone e insulin and or oral diabetes medicine e drugs metabolized by the liver for example corticosteroids sex Steroids anticonvulsants cyclosporine e oral estrogen replacement Adult height can be influenced if you are on Norditropin NordiFlex for growth failure and using glucocorticoids or thyroid hormone at the same time If you are treated with insulin and or oral diabetes medicine your insulin oral diabetes medicine dose may need to be adjusted What are the possible side effects of Norditropin NordiFlex The following side effects are usually mild and temporary e headaches e muscle pain e joint stiffness e high blood sugar hyperglycemia e sugar in your urine glucosuria e swollen hands and feet due to fluid retention e redness and itching in the area you inject If you experience any of these symptoms discuss this with your doctor In rare cases you may develop antibodies to growth hormone If you have symptoms of headaches eyesight problems nausea and or vomiting these may be symptoms of raised pressure in the brain Contact your doctor immediately Be sure to tell your doctor if you have any other side effects not mentioned here Special warnings In very rare cases children treated with growth ho
22. to become pregnant e are breast feeding or plan to breast feed It is not known if Norditropin passes into your breast milk You and your healthcare provider should decide if you will take Norditropin while you breast feed Tell your healthcare provider about all the medicines you take including prescription and non prescription medicines vitamins and herbal supplements Norditropin may affect how other medicines work and other medicines may affect how Norditropin works Especially tell your healthcare provider if you take e glucocorticoid medication e thyroid hormone e insulin or other medicine for diabetes e medicines that are metabolized by the liver e estrogen replacement medicines Ask your healthcare provider if you are not sure if any of your medicines are the kind listed above Keep a list of your medicines with you and show it to your healthcare provider and pharmacist when you get a new medicine How should I use Norditropin e Read the detailed Instructions for Use that come with Norditropin Your healthcare provider will show you how to inject Norditropin e Take Norditropin exactly as prescribed e Norditropin FlexPro pens NordiFlex pens and cartridges are for use by one person only e Novo Nordisk disposable needles are designed to be used with Norditropin for each injection e Always keep the pen cap closed on Norditropin when you are not using it e Norditropin comes in 3 do
23. who develops persistent severe abdominal pain 6 ADVERSE REACTIONS 6 1 Most Serious and or Most Frequently Observed Adverse Reactions This list presents the most serious and or most frequently observed adverse reactions during treatment with somatropin e DSudden death in pediatric patients with Prader Willi syndrome with risk factors including severe obesity history of upper airway obstruction or sleep apnea and unidentified respiratory infection see Contraindications 4 2 and Warnings and Precautions 5 2 e Intracranial tumors in particular meningiomas in teenagers young adults treated with radiation to the head as children for a first neoplasm and somatropin see Contraindications 4 3 and Warnings and Precautions 5 3 e abGlucose intolerance including impaired glucose tolerance impaired fasting glucose as well as overt diabetes mellitus see Warnings and Precautions 5 4 e Intracranial hypertension see Warnings and Precautions 5 5 e bSignificant diabetic retinopathy see Contraindications 4 4 e Slipped capital femoral epiphysis in pediatric patients see Warnings and Precautions 5 8 e Progression of preexisting scoliosis in pediatric patients see Warnings and Precautions 5 9 e aFluid retention manifested by edema arthralgia myalgia nerve compression syndromes including carpal tunnel syndrome paraesthesias see Warnings and Precautions 5 6 3 e aUnmasking of latent central hypothyroidism
24. with Noonan Syndrome Not all patients with Noonan syndrome have short stature some will achieve a normal adult height without treatment Therefore prior to initiating Norditropin for a patient with Noonan syndrome establish that the patient does have short stature A dosage of up to 0 066 mg kg day is recommended Pediatric Patients with Short Stature Associated with Turner Syndrome A dosage of up to 0 067 mg kg day is recommended Pediatric Patients with Short Stature Born Small for Gestational Age SGA with No Catch up Growth by Age 2 to 4 Years A dosage of up to 0 067 mg kg day is recommended Recent literature has recommended initial treatment with larger doses of somatropin e g 0 067 mg kg day especially in very short children i e HSDS lt 3 and or older pubertal children and that a reduction in dosage e g gradually towards 0 033 mg kg day should be considered if substantial catch up growth is observed during the first few years of therapy On the other hand in younger SGA children e g approximately lt 4 years who respond the best in general with less severe short stature i e baseline HSDS values between 2 and 3 consideration should be given to initiating treatment at a lower dose e g 0 033 mg kg day and titrating the dose as needed over time In all children clinicians should carefully monitor the growth response and adjust the rhGH dose as necessary 2 2 Dosing of Adult Patients Adult
25. you are a child with closed bone growth plates epiphyses e you are allergic to any of the ingredients in Norditropin see the end of this leaflet for a complete list of ingredients in Norditropin What should I tell my healthcare provider before start Norditropin Before you take Norditropin tell your healthcare provider if you e have diabetes e had cancer or any tumor e have any other medical condition e are pregnant or plan to become pregnant It is not known if Norditropin will harm your unborn baby Talk to your doctor if you are pregnant or plan to become pregnant e are breast feeding or plan to breast feed It is not known if Norditropin passes into your breast milk You and your healthcare provider should decide if you will take Norditropin while you breast feed Tell your healthcare provider about all the medicines you take including prescription and non prescription medicines vitamins and herbal supplements Norditropin may affect how other medicines work and other medicines may affect how Norditropin works Especially tell your healthcare provider if you take e glucocorticoid medication e thyroid hormone e insulin or other medicine for diabetes e medicines that are metabolized by the liver e estrogen replacement medicines Ask your healthcare provider if you are not sure if any of your medicines are the kind listed above Keep a list of your medicines with you and show it to your healthcare p
26. 0mg 15mg 30 mg Component 1 5mL 1 5mL 1 5 mL 3 mL 188 Water for up to up to up to up to Injection 1 5 mL 1 5 mL 1 5 mL 3 0 mL 12 CLINICAL PHARMACOLOGY 12 1 Mechanism of Action Somatropin as well as endogenous GH binds to a dimeric GH receptor in the cell membrane of target cells resulting in intracellular Signal transduction and a host of pharmacodynamic effects Some of these pharmacodynamic effects are primarily mediated by IGF I produced in the liver and also locally e g skeletal growth protein synthesis while others are primarily a consequence of the direct effects of somatropin e g lipolysis see Clinical Pharmacology 12 2 12 2 Pharmacodynamics Tissue Growth The primary and most intensively studied action of somatropin is the stimulation of linear growth This effect is demonstrated in children with GHD Skeletal Growth The measurable increase in bone length after administration of somatropin results from its effect on the cartilaginous growth areas of long bones Studies in vitro have shown that the incorporation of sulfate into proteoglycans is not due to a direct effect of somatropin but rather is mediated by the somatomedins or insulin like growth factors IGFs The somatomedins among them IGF I are polypeptide hormones which are synthesized in the liver kidney and various other tissues IGF I levels are low in the serum of hypopituitary dwarfs and hypophysectomized humans or animals and
27. 3 correspond to mean height gains of 4 5 9 1 and 9 4 cm after treatment with Doses A B and C respectively In each treatment group peak HV was observed during treatment Year 1 and then gradually decreased each year during Year 4 HV was less than the pre treatment HV However between Year 2 and Year 6 a greater HV was observed in the two dose escalation groups compared to the 0 045 mg kg day group Table 3 Final Height Related Results After Treatment of Patients with Turner Syndrome with Norditropin in a Randomized Dose Escalating Study Dose B up to 0 067 mg kg day n 15 n 12 n 46 Baseline height 105 12 108 12 7 107 11 7 1106 11 9 cm Final height 157 6 7 163 6 0 163 4 9 161 6 5 cm Number of patients reaching normal height height SDS gt 2 using National standard 10 53 12 80 10 83 32 70 Height SDS Turner standard Final 1 7 25 20 95 CI 1 4 2 0 2 1 2 8 2 1 2 91 Change from baseline 95 CI Height SDS National standard Final alz 1 2 95 CI 2 2 1 6 1 5 0 914 1 6 0 8 5 Change from baseline 95 CI Values are expressed as mean SD unless otherwise indicated SDS Standard deviation score 1Unadjusted raw means Adjusted least squares means based on an ANCOVA model including terms for treatment duration of treatment age at baseline bone age at baseline height SDS at baseline ag
28. 8 The adverse event pattern observed during the open label phase of the study was similar to the one presented above 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 Norditropin with the incidence of antibodies to other products may be misleading In the case of growth hormone antibodies with binding capacities lower than 2 mg mL have not been associated with growth attenuation In a very small number of patients treated with somatropin when binding capacity was greater than 2 mg mL interference with the growth response was observed In clinical trials GHD pediatric patients receiving Norditropin for up to 12 months were tested for induction of antibodies and 0 358 patients developed antibodies with binding capacities above 2 mg L Amongst these patients 165 had previously been treated with other somatropin formulations and 193 were previously untreated naive patients 6 3 Post Marketing Experience Because these adverse events are reported voluntarily from a population of uncerta
29. Children somatropin is contraindicated in patients with Prader Willi syndrome who are severely obese have a history of upper airway obstruction or sleep apnea or have severe respiratory impairment see Warnings and Precautions 5 2 There have been reports of sudden death when somatropin was used in such patients see Warnings and Precautions 5 2 Norditropin is not indicated for the treatment of pediatric patients who have growth failure due to genetically confirmed Prader Willi syndrome 4 3 Active Malignancy In general somatropin is contraindicated in the presence of active malignancy Any preexisting malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin Somatropin should be discontinued if there is evidence of recurrent activity Since GHD may be an early sign of the presence of a pituitary tumor or rarely other brain tumors the presence of such tumors should be ruled out prior to initiation of treatment Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor 4 4 Diabetic Retinopathy Somatropin is contraindicated in patients with active proliferative or severe non proliferative diabetic retinopathy 4 5 Closed Epiphyses Somatropin should not be used for growth promotion in pediatric patients with closed epiphyses 4 6 Hypersensitivity Norditropin is contraindicated in patients with a known hypersen
30. Growth Hormone Deficiency GHD Either of two approaches to Norditropin dosing may be followed a non weight based regimen or a weight based regimen Non weight based based on published consensus guidelines a Starting dose of approximately 0 2 mg day range 0 15 0 30 mg day may be used without consideration of body weight This dose can be increased gradually every 1 to 2 months by increments of approximately 0 1 0 2 mg day according to individual patient requirements based on the clinical response and serum insulin like growth factor IGF I concentrations The dose should be decreased as necessary on the basis of adverse events and or serum IGF I concentrations above the age and gender specific normal range Maintenance dosages vary considerably from person to person and between male and female patients Weight based based on the dosing regimen used in the original adult GHD registration trials the recommended dosage at the start of treatment is not more than 0 004 mg kg day The dose may be increased to not more than 0 016 mg kg day after approximately 6 weeks according to individual patient requirements Clinical response side effects and determination of age and gender adjusted serum IGF I concentrations should be used as guidance in dose titration A lower starting dose and smaller dose increments should be considered for older patients who are more prone to the adverse effects of somatropin than younger individuals
31. Letter for airport and airline security staff regarding the transport of medicine To Whom It May Concern patient s name is currently a patient in my care and is being treated with growth hormone injections This patient needs to inject growth hormone daily in order to maintain his her health This person parent or caregiver will therefore be carrying one or more of the following items 2 Norditropin FlexPro somatropin rDNA origin injection 5 mg 10 mg and or 15 mg per 1 5 mL delivery pen s Q Norditropin NordiFlex 30 mg per 3 mL delivery pen s 2 Disposable needles Q Biohazard container s for waste disposal It should also be noted that growth hormone medication is affected by extreme temperatures and therefore should not be Stored in checked luggage Please allow patient s name to pass through security and board his her flight with his her growth hormone and supplies For questions about Novo Nordisk products call 800 727 6500 Please contact my office if you have any patient specific questions Respecttully Doctor s signature Doctor s name Doctor s telephone number norditropin somatropin rDNA origin injection Needles may require a prescription in some states Please see full important safety information on following pages novo nordisk Please see accompanying Patient Prescribing Information Tips for traveling patients e Always carry this letter with you for airpo
32. TION CONTENTS 1 INDICATIONS AND USAGE 1 1 Pediatric Patients 1 2 Adult Patients 2 DOSAGE AND ADMINISTRATION 2 1 Dosing of Pediatric Patients 2 2 Dosing of Adult Patients 2 3 Preparation and Administration 3 DOSAGE FORMS AND STRENGTHS 4 CONTRAINDICATIONS 4 1 Acute Critical Illness 42 Prader Willi Syndrome in Children 4 3 Active Malignancy 44 Diabetic Retinopathy 45 Closed Epiphyses 46 Hypersensitivity 5 WARNINGS AND PRECAUTIONS 5 1 Acute Critical Illness 9 2 Prader Willi Syndrome in Children 9 3 Neoplasms 5 4 Impaired Glucose Tolerance and Diabetes Mellitus 5 0 Intracranial Hypertension color coded NordiPen delivery systems 2 3 e Injection sites should always be rotated to avoid lipoatrophy 2 3 DOSAGE FORMS AND STRENGTHS Norditropin is preloaded in the Norditropin FlexPro or Norditropin NordiFlex pens or cartridges for use with the corresponding NordiPens 3 e 5 mg 1 5 mL orange FlexPro and NordiFlex pens and cartridges e 10 mg 1 5 mL blue FlexPro and NordiFlex pens e 15 mg 1 5 mL green FlexPro and NordiFlex pens and cartridges e 30 mg 3 mL purple Norditropin NordiFlex pen only CONTRAINDICATIONS e Acute Critical Illness 4 1 5 1 e Children with Prader Willi syndrome who are severely obese or have severe respiratory impairment reports of sudden death 4 2 5 2 e Active Malignancy 4 3 e Active Proliferative or Severe Non Proliferative Diabetic Retino
33. ach injection Do not keep the needle screwed onto Norditropin NordiFlex when you are not using it Always keep the pen cap closed on Norditropin NordiFlex when you are not using it Never use Norditropin NordiFlex after the expiration date printed on the pen and on the carton 8 C 36 F INSTRUCTIONS FOR USE Norditropin NordiFlex Somatropin rDNA origin injection 30 mg 3 mL Prefilled Pen Using the disposable Norditropin NordiFlex 30 mg 3 mL Prefilled Pen Norditropin NordiFlex 30 mg 3 mL is a multi dose disposable prefilled pen with liquid growth hormone able to deliver doses from 0 1 to 6 0 mg The dose can be adjusted in increments of 0 1 mg Your doctor will determine the correct dose for you Norditropin NordiFlex prefilled pen is designed to be used with NovoFine disposable needles sold separately Norditropin NordiFlex prefilled pen is not recommended for people who are blind or have trouble seeing unless they have the help of a sighted individual trained to use Norditropin NordiFlex Please read these instructions carefully before using this pen Needle thread Dosage Push indicator window button Residual scale Pen cap window Residual scale Cartridge Dosage selector NovoFine needle Outer needle cap Inner needle cap Needle dg i 4 1 Preparing Norditropin NordiFlex 30 mg 3 mL for Injection A Pull off the pen cap and check if the growth hormone solution is clear and co
34. approximately 23 1 15 0 ng mL was reached at 150 min and a mean clearance rate of approximately 2 3 1 8 mL min kg or 139 105 mL min for hGH was observed Following infusion serum hGH levels had a biexponential decay with a terminal elimination half life 14 2 of approximately 21 1 5 1 min In a study conducted in 18 GHD adult patients where a SC dose of 0 024 mg kg or 3 U m2 was given in the thigh mean SD Cmax values of 13 8 45 8 and 17 1 10 0 ng mL were observed for the 4 and 8 mg Norditropin vials respectively at approximately 4 to 5 hr post dose The mean apparent terminal T 2 values were estimated to be approximately 7 to 10 hr However the absolute bioavailability for Norditropin after the SC route of administration is currently not known 13 NONCLINICAL TOXICOLOGY 13 1 Carcinogenesis Mutagenesis Impairment of Fertility Carcinogenicity mutagenicity and fertility studies have not been conducted with Norditropin 14 CLINICAL STUDIES 14 1 Short Stature in Children with Noonan Syndrome A prospective open label randomized parallel group trial with 21 children was conducted for 2 years to evaluate the efficacy and Safety of Norditropin treatment for short stature in children with Noonan syndrome An additional 6 children were not randomized but did follow the protocol After the initial two year trial children continued on Norditropin until final height Retrospective final height and adver
35. atory tract infection otitis externa gastroenteritis and eczema Otitis media adverse events in Study 1 were most frequent in the highest dose groups 86 4 in the 0 045 0 067 0 089 mg kg day group vs 78 3 in the 0 045 0 067 mg kg day group vs 69 6 in the 0 045 mg kg day group suggesting a possible dose response relationship Of note approximately 40 50 of these otitis media adverse events were designated as serious see Warnings and Precautions 5 10 No patients in either study developed clearcut overt diabetes mellitus however in Study 1 impaired fasting glucose at Month 48 was more frequent in patients in the 0 045 0 067 mg kg day group n 4 18 compared with the 0 045 mg kg day group n 1 20 Transient episodes of fasting blood sugars between 100 and 126 mg dL and on occasion exceeding 126 mg dL also occurred more often with larger doses of Norditropin in both studies see Warnings and Precautions 5 4 and Adverse Reactions 6 1 Three patients withdrew from the 2 high dose groups in Study 1 because of concern about excessive growth of hands or feet In addition in Study 1 exacerbation of preexisting scoliosis was designated a serious adverse reaction in two patients in the 0 045 mg kg day group see Warnings and Precautions 5 9 Clinical Trials in Children Born Small for Gestational Age SGA with No Catch up Growth by Age 2 4 Years Study 1 Long Term In a multi center randomized double blind stu
36. boys and girls combined both mean final height SDS Dose A 1 8 vs Dose B 1 3 and increase in height SDS from baseline to final height Dose A 1 4 vs Dose B 1 8 were significantly greater after treatment with Dose B 0 067 mg kg day A similar dose response was observed for the increase in height SDS from baseline to Year 2 Table 4 Overall mean height velocity at baseline was 5 4 cm y SD 1 2 n 29 Height velocity was greatest during the first year of Norditropin treatment and was significantly greater after treatment with Dose B mean 11 1 cm y SD 1 9 n 19 compared with Dose A mean 9 7 cm y SD 1 3 n 10 Table 4 Study 1 Results for Final Height SDS and Change from Baseline to Final Height in Height SDS Using National Standard After Long Term Treatment of SGA Children with Norditropin Raw Mean SD N Dose A Dose B 0 033 0 067 mg kg day mg kg day Baseline Height ka a Adjusted Eer mean standard error N and 95 confidence intervals Treatment Diff 0 4 0 2 0 7 p value 0 002 Height SDS Change from 1 4 0 1 26 Baseline at 1 1 1 6 Year 22 Height SDS Change from Baseline at Final Height Final Height SDS 1 4 0 2 19 0 9 1 8 Treatment Diff 0 5 Final Height SDS SAD 13 19 68 11 19 58 24 38 63 SDS Standard deviation score 1Adjusted least squares means based on an ANCOVA model including terms for treatment gender a
37. d to be used with Norditropin NordiFlex How much Norditropin should you take Your doctor will tell you how much Norditropin you should take In children it depends on the body weight General guidelines for dosages are shown below Children with growth failure caused by very low or no growth hormone 0 024 to 0 034 mg kg body weight 6 7 times a week Children with short stature and Noonan syndrome Up to 0 066 mg kg day Children with short stature and Turner syndrome Up to 0 067 mg kg day Children with short stature born small for gestational age SGA with no catch up growth by age 2 4 years Up to 0 067 mg kg day Adults Not more than 0 004 mg kg day at start of therapy Dosage may be increased as tolerated to not more than 0 016 mg kg day after approximately 6 weeks or Alternative dose for adults Approximately 0 2 mg day range 0 15 0 30 mg day at start of therapy Dosage can be increased gradually every 1 2 months by steps of approximately 0 1 0 2 mg day based on your doctor s recommendations If you forget to take a dose take the next dose as usual double your dose do not What should you do if you inject too much growth hormone using Norditropin NordiFlex If you inject too much growth hormone contact your doctor How long should you continue to take Norditropin Discuss with your doctor how long you should take Norditropin What should avoid while using Norditropin NordiFlex Be
38. dditional months During this period the reduction in waist hip ratio achieved during 16 HOW SUPPLIED STORAGE AND HANDLING Norditropin FlexPro prefilled pens somatropin rDNA Norditropin FlexPro is individually cartoned in 5 mg 1 5 mL 10 mg 1 5 mL or 15 mg 1 5 mL prefilled pens NDC 0169 7704 21 e Norditropin FlexPro 10 mg 1 5 mL blue e Norditropin FlexPro 15 mg 1 5 mL green NDC 0169 7708 21 origin injection 5 mg 1 5 mL 10 mg 1 5 mL 15 mg 1 5 mL and 30 mg 3 mL 10 mg 1 5 mL 15 mg 1 5 mL or 30 mg 3 mL prefilled pens e Norditropin NordiFlex 5 mg 1 5 mL orange e Norditropin NordiFlex 10 mg 1 5 mL blue NDC 0169 7705 11 NDC 0169 7708 11 e Norditropin NordiFlex 30 mg 3 mL purple Unused Norditropin NordiFlex and FlexPro prefilled pens must be stored at 2 8 C 36 46 F refrigerator Do not freeze Avoid Treatment difference mean 1 40 Analysis of the treatment difference on the change from baseline group Table 9 n Ms n 13 4 24 Norditropin also significantly reduced intraabdominal extra Forty four men were enrolled in an open label follow up study and the initial six months of treatment was maintained origin injection 5 mg 1 5 mL 10 mg 1 5 mL and 15 mg 1 5 mL e Norditropin FlexPro 5 mg 1 5 mL orange NDC 0169 7705 21 Norditropin NordiFlex prefilled pens somatropin rDNA Norditropin NordiFlex is individually cartoned in 5 mg 1 5 mL NDC 0169 7704 11 e Norditropin N
39. ditropin away from direct light e Do not use Norditropin that has been frozen or in temperatures warmer than 77 F 25 C e Do not use Norditropin after the expiration date printed on the carton and the pen or cartridge After the first injection e Norditropin FlexPro NordiFlex and cartridge 5 mg 1 5 mL orange either store in the refrigerator between 36 F to 46 F 2 C to 8 C and use within 4 weeks or keep for up to 3 weeks at no warmer than 77 F 25 C Throw away any unused medicine e Norditropin FlexPro and NordiFlex 10mg 1 5mL blue either store in the refrigerator between 36 F to 46 F 2 C to 8 C and use within 4 weeks or keep for up to 3 weeks at no warmer than 77 F 25 C Throw away any unused medicine e Norditropin FlexPro NordiFlex and cartridge 15 mg 1 5 mL green store in the refrigerator between 36 F to 46 F 2 C to 8 C and use within 4 weeks Throw away any unused medicine after 4 weeks e Norditropin NordiFlex pens 30 mg 3 mL purple store in the refrigerator between 36 F to 46 F 2 C to 8 C and use within 4 weeks Throw away any unused medicine after 4 weeks General Information about Norditropin Medicines are sometimes prescribed for purposes other than those listed in Patient Information Do not use Norditropin for a condition for which it was not prescribed Do not give Norditropin to other people e
40. dy 53 non GHD children with short stature born SGA with failure to catch up were treated with 2 doses of Norditropin 0 033 or 0 067 mg kg day to final height for up to 13 years mean duration of treatment 7 9 and 9 5 years for girls and boys respectively The most frequently reported adverse events were common childhood diseases including influenza like illness upper respiratory tract infection bronchitis gastroenteritis abdominal pain otitis media pharyngitis arthralgia and headache Adverse events possibly probably related to Norditropin were otitis media arthralgia headaches no confirmed diagnoses of benign intracranial hypertension gynecomastia and increased sweating One child treated with 0 067 mg kg day for 4 years was reported with disproportionate growth of the lower jaw and another child treated with 0 067 mg kg day developed a melanocytic nevus see Warnings and Precautions 5 3 There were no Clear cut reports of exacerbation of preexisting scoliosis or slipped capital femoral epiphysis No apparent differences between the treatment groups were observed In addition the timing of puberty was age appropriate in boys and girls in both treatment groups Therefore it can be concluded that no novel adverse events potentially related to treatment with Norditropin were reported in long term Study 1 Study 2 Short Term In a multi center randomized double blind parallel group study 98 Japanese non GHD childre
41. e disposable needles If you need the LOT number of your NordiFlex PenMate it is located as illustrated in the diagram on the first page Making your NordiFlex PenMate personal Between the outer cap and the inner cap you can place a drawing or picture to give your NordiFlex PenMate a personal look You can cut out the illustration placed on the page to the right or create the drawing yourself ED E e Screw on a new NovoFine disposable needle and perform one or more air shots until a drop of liquid appears at the needle tip see section 2 Norditropin NordiFlex may be damaged e Remove the NovoFine disposable needle carefully see Section 5 Unscrew Norditropin NordiFlex and replace it with a new Norditropin NordiFlex see Section 6 Attach a new NovoFine disposable needle and perform an air shot see Section 2 want to change the selected dose before e Turn the dosage selector forwards or backwards until the number of milligrams you need lines up with the dosage indicator injection You think the needle Make sure the needle caps are removed sa not entered the e Check that the needle is not bent skin e Check NordiFlex PenMate for damage that it is not broken or cracked and that it works normally This is normal Always press the push button to inject the dose Turning the dosage selector will not inject the dose I turn the dosage selector but Norditropin NordiFlex does
42. e at onset of puberty and mid parental target height SDS 39 0 005 vs Dose A 4p 0 006 vs Dose A p 0 008 vs Dose A In Study 2 a supportive study 19 euthyroid Caucasian patients with bone age lt 13 9 years were randomized to treatment with 0 067 mg kg day of Norditropin as a single subcutaneous dose in the evening or divided into two doses 1 3 morning and 2 3 evening All subjects were treated with concomitant ethinyl estradiol Overall at baseline mean age was 13 6 years mean height SDS National standard was 3 5 and mean HV during the previous year was 4 3 cm year Patients were treated for a mean of 3 6 years In that there were no significant differences between the two treatment groups for any linear growth variables the data from all patients were pooled Overall mean final height was 155 cm in the 17 children who attained final height Height SDS changed significantly from 3 5 at baseline to 2 4 at final height National standard and from 0 7 to 1 3 at final height Turner standard 14 3 Short Stature in Children Born Small for Gestational Age SGA with No Catch up Growth by Age 2 4 Years A multi center randomized double blind two arm study to final height Study 1 and a 2 year multi center randomized double blind parallel group study Study 2 were conducted to assess the efficacy and safety of Norditropin in children with short stature born SGA with no catch up growth Changes in height and height ve
43. e not all the possible side effects of Norditropin For more information ask your healthcare provider or pharmacist Call your healthcare provider for medical advice about side effects You may report side effects to FDA at 1 800 FDA 1088 1 800 332 1088 You may also report side effects to Novo Nordisk at 1 888 NOVO 444 1 888 668 6444 How do store Norditropin Unused Norditropin FlexPro and NordiFlex pens and cartridges e Keep in a refrigerator between 36 F to 46 F 2 C to 8 C e Do not freeze or expose Norditropin to heat e Keep Norditropin away from direct light e Do not use Norditropin that has been frozen or in temperatures warmer than 77 F 25 C e Do not use Norditropin after the expiration date printed on the carton and the pen or cartridge After the first injection e Norditropin FlexPro NordiFlex and cartridge 5 mg 1 5 mL orange either store in the refrigerator between 36 F to 46 F 2 C to 8 C and use within 4 weeks or keep for up to 3 weeks at no warmer than 77 F 25 C Throw away any unused medicine e Norditropin FlexPro and NordiFlex 10mg 1 5mL blue either store in the refrigerator between 36 F to 46 F 2 C to 8 C and use within 4 weeks or keep for up to 3 weeks at no warmer than 77 F 25 C Throw away any unused medicine e Norditropin FlexPro NordiFlex and cartridge 15 mg 1 5 mL green store in the refrige
44. e pointer leave the needle under the skin for at least 6 seconds to make sure that you get your full dose You can let go of the dose button while you wait e Change the injection site using the injection procedure recommended by your healthcare provider Important e Always press the dose button to inject the dose Turning the dose selector will not inject the dose e Never touch the display window when you inject as this can block the injection e Remove the needle from your skin After that you may see a drop of liquid at the needle tip This is normal and does not affect the dose you received After the injection remove the needle right away and put the pen cap back on If the needle is not removed some liquid may come out of the Norditropin FlexPro Unscrew the needle and throw away the needle and any empty Norditropin FlexPro pen as directed by your healthcare provider A special sharps container such as a red biohazard container a hard plastic container such as an empty detergent bottle or a metal container such as an empty coffee can should be used The container should be sealed and disposed of properly e Caregivers should be most careful when handling used needles to avoid hurting themselves Care for your Norditropin FlexPro pen You must take care of your Norditropin FlexPro pen e Do not drop your pen or knock it against hard surfaces If you do drop it or think that
45. e that you receive your full dose by checking the growth hormone flow performing an airshot before you select and inject your first dose from a new pen D Turn the dose selector to select 0 05 mg This is the smallest amount of medicine for a dose E e Hold the pen with the needle pointing up e Jap the top of the pen gently a few times to let any air bubbles rise to the top F e Press the dose button until the 0 in the display window lines up with the pointer and a drop of liquid appears at the needle tip e f no drop appears repeat steps D E and F up to 6 times e f no drop appears after these attempts change the needle and repeat steps D E and F one more time o lf a drop of liquid still does not appear call 1 888 668 6444 for help Important e Be careful not to drop Norditropin FlexPro pen or knock it against a hard surface If this happens you will need to repeat the airshot e Always make sure that a drop appears at the needle tip after completing your airshot Select your dose Use the dose selector on your Norditropin FlexPro pen to make sure you have the exact dose selected You can select up to 4 mg per dose G e Select or adjust the dose you need by turning the dose selector forwards or backwards until the right number of mg lines up with the pointer e When dialing back be careful not to press the dose button as liquid will come out e To gu
46. en with anyone Date of Issue March 2 2010 Version 1 US Patent Nos 6 235 004 6 004 297 6 582 404 6 716 198 6 899 699 5 849 704 5 691 169 5 618 697 and other patents pending Norditropin FlexPro and Norditropin NordiFlex are registered trademarks of Novo Nordisk Health Care AG Novo Nordisk is a registered trademark of Novo Nordisk A S 2004 2010 Novo Nordisk Health Care AG Manufactured by O Novo Nordisk A S DK 2880 Bagsvaerd Denmark 140984 3 10 novo nordisk INSTRUCTIONS FOR USE Norditropin FlexPro somatropin rDNA origin injection 15 mg 1 5 mL green Prefilled Pen Read these instructions before using your Norditropin FlexPro pen Norditropin FlexPro Growth Display Dose Dose Pencap hormone scale window Pointer selector button f era a Te l Needle thread Needle example Outer needle cap Norditropin FlexPro contains 15 mg human growth hormone solution and delivers doses from 0 1 mg to 8 mg in increments of 0 1 mg Norditropin FlexPro is made to be used with Novo Nordisk disposable needles Needles are not included with Norditropin FlexPro Prepare your Norditropin FlexPro pen A A e Pull off the pen cap e Check that the liquid in the pen is clear and colorless by tipping it upside down 1 or 2 times If the liquid looks unclear or cloudy do not use the pen e Wash hands well and dry them e Wipe the front stopper on t
47. enalism may require an increase in their maintenance doses 7 1 e Glucocorticoid Replacement Should be carefully adjusted 7 2 e Cytochrome P450 Metabolized Drugs Monitor carefully if used with somatropin 7 3 e Oral Estrogen Larger doses of somatropin may be required in women 7 4 e Insulin and or Oral Injectable Hypoglycemic Agents May require adjustment 7 5 See 17 for PATIENT COUNSELING INFORMATION Revised 5 2011 8 USEIN SPECIFIC POPULATIONS 8 1 Pregnancy 8 3 Nursing Mothers 8 5 Geriatric Use 10 OVERDOSAGE 11 DESCRIPTION 12 CLINICAL PHARMACOLOGY 12 1 Mechanism of Action 12 2 Pharmacodynamics 12 3 Pharmacokinetics 13 NONCLINICAL TOXICOLOGY 13 1 Carcinogenesis Mutagenesis Impairment of Fertility 14 CLINICAL STUDIES 14 1 Short Stature in Children with Noonan Syndrome 14 2 Short Stature in Children with Turner Syndrome 14 3 Short Stature in Children Born Small for Gestational Age SGA with No Catch up Growth by Age 2 4 Years 14 4 Adult Growth Hormone Deficiency GHD 16 HOW SUPPLIED STORAGE AND HANDLING 17 PATIENT COUNSELING INFORMATION Sections or subsections omitted from the full prescribing information are not listed FULL PRESCRIBING INFORMATION 1 INDICATIONS AND USAGE 1 1 Pediatric Patients Norditropin somatropin rDNA origin injection is indicated for the treatment of pediatric patients with growth failure due to inadequate secretion of endogenous growth hormone GH Nordit
48. ent with somatropin to exclude preexisting papilledema and periodically during the course of somatropin therapy If papilledema is observed by funduscopy during somatropin treatment treatment should be stopped If somatropin induced IH is diagnosed treatment with somatropin can be restarted at a lower dose after IH associated signs and symptoms have resolved Patients with Turner syndrome may be at increased risk for the development of IH 5 6 Fluid Retention Fluid retention during somatropin replacement therapy in adults may frequently occur Clinical manifestations of fluid retention are usually transient and dose dependent 5 7 Hypothyroidism Undiagnosed untreated hypothyroidism may prevent an optimal response to somatropin in particular the growth response in children Patients with Turner syndrome have an_ inherently increased risk of developing autoimmune thyroid disease and primary hypothyroidism In patients with GHD central secondary hypothyroidism may first become evident or worsen during somatropin treatment Therefore patients treated with somatropin should have periodic thyroid function tests and thyroid hormone replacement therapy should be initiated or appropriately adjusted when indicated In patients with hypopituitarism multiple hormone deficiencies standard hormonal replacement therapy should be monitored closely when somatropin therapy is administered 5 8 Slipped Capital Femoral Epiphysis in Pediatric Pati
49. ents Slipped capital femoral epiphysis may occur more frequently in patients with endocrine disorders including GHD and Turner syndrome or in patients undergoing rapid growth Any pediatric patient with the onset of a limp or complaints of hip or knee pain during somatropin therapy should be carefully evaluated 5 9 Progression of Preexisting Scoliosis in Pediatric Patients Progression of scoliosis can occur in patients who experience rapid growth Because somatropin increases growth rate patients with a history of scoliosis who are treated with somatropin should be monitored for progression of scoliosis However somatropin has not been shown to increase the occurrence of scoliosis Skeletal abnormalities including scoliosis are commonly seen in untreated patients with Turner syndrome and Noonan syndrome Scoliosis is also commonly seen in untreated patients with Prader Willi syndrome Physicians should be alert to these abnormalities which may manifest during somatropin therapy 5 10 Otitis Media and Cardiovascular Disorders in Turner Syndrome Patients with Turner syndrome should be evaluated carefully for otitis media and other ear disorders since these patients have an increased risk of ear and hearing disorders Somatropin treatment may increase the occurrence of otitis media in patients with Turner syndrome In addition patients with Turner syndrome should be monitored closely for cardiovascular disorders e g stroke aortic a
50. er randomized double blind placebo controlled parallel group dose finding six month clinical trial was conducted in 49 men with CO GHD comparing the effects of Norditropin and placebo on body composition Patients were randomized to placebo or one of three active treatment groups 0 008 0 016 and 0 024 6 months mean Treatment difference mean 95 confidence interval mg kg day Thirty three percent of the total dose to which each patient was randomized was administered during weeks 1 4 67 during weeks 5 8 and 100 for the remainder of the study The changes from baseline in LBM and percent TBF were measured by TBP after 6 months Treatment with Norditropin produced a significant p 0 0079 increase from baseline in LBM compared to placebo pooled data Table 8 Table 8 Lean Body Mass kg by TBP ei n 13 ae tropin n 36 48 18 48 90 ae a F at 6 months mean Treatment difference mean 95 confidence interval p value 2 06 0 70 6 months mean 95 confidence interval 0 39 2 41 p value p 0 0079 in percent TBF revealed a significant decrease p 0 0048 in the Norditropin treated groups pooled data compared to the placebo Table 9 Total Body Fat by i 34 55 34 07 ae a Sane at ae ae 7 11 1 37 p 0 0048 peritoneal and total abdominal fat volume waist hip ratio and LDL cholesterol and significantly increased serum osteocalcin treated with Norditropin for as long as 30 a
51. espiratory problems high risk of death in children with Prader Willi syndrome who are se verely obese or have breathing problems including sleep apnea return of tumor or cancerous growths high blood sugar hyperglycemia increase in pressure in the skull intracranial hypertension swollen hands and feet due to fluid retention decrease in thyroid hormone Please see accompanying Patient Prescribing Information Norditropin FlexPro and Norditropin NordiFlex are registered trademarks of Novo Nordisk Health Care AG O Novo Nordisk is a registered trademark of Novo Nordisk A S printed on recycled paper m novo nordisk 2011 Novo Nordisk Printed in the U S A 0611 00003428 1 July 2011 levels hip and knee pain or a limp in children slipped capital femoral epiphy sis worsening of pre existing curvature of the spine scoliosis middle ear infec tion hearing problems or ear problems in patients with Turner syndrome Patients with Noonan syndrome and Turner syndrome should be closely moni tored by their doctors as they are more likely to have congenital heart disease The most common side effects of Norditropin include headaches muscle pain joint stiffness high blood sugar hyperglycemia sugar in your urine glucosuria swollen hands and feet due to fluid retention and redness and itching in the area you inject If you have headaches eye problems nausea or vomiting these may be symptoms
52. essional After the injection check the dosage indicator window to make sure it shows zero 0 0 If zero does not appear you did not receive the full dose Call 1 888 NOVO 444 for assistance NOTE Always press the push button to inject the dose Turning the dosage selector will not inject the dose With Norditropin NordiFlex it is not possible to select a dose that is larger than the mg left in the cartridge If you need a dose more than the mg left in the cartridge you must spread your dose over two injections Follow the steps below To get the remaining part of your dose a Inject the dose left in the cartridge making a note of the number of mg you inject For example if your dose is 0 6 mg and you can only set the dose selector to 0 4 mg You will need to inject an additional 0 2 mg with a new Norditropin NordiFlex pen b Remove the NovoFine disposable needle from Norditropin NordiFlex see Section 5 c Remove the empty Norditropin NordiFlex see Section 6 d Insert a new Norditropin NordiFlex see Sections 1 and 6 e Attach a new NovoFine disposable needle see Section 1 f Perform an air shot see Section 2 g Dial the number of mg still needed to complete your dose h Give the injection Need Help Call 1 888 NOVO 444 Section 5 Removing the NovoFine Disposable Needle Remove the NovoFine Disposable Needle 1 Carefully replace the outer needle cap onto the needle immediately af
53. g National Standard After Short Term Treatment of SGA Children with Norditropin Raw Mean SD N No 0 033 0 067 Treatment mg kg day mg kg day Total 290I oO 20 0 29207 29 2036 15 35 34 84 Height SDS Baseline Height SDS Year 1 Height SDS 2 8 0 5 15 2 4 0 6 33 2 0 0 8 34 2 3 0 7 82 2 2 0 7 33 1 4 0 7 32 1 8 0 8 65 Adjusted least squares mean standard error N and 95 confidence intervals Height SDS Change from Baseline at 1 Year 1 0 033 vs No Treatment Treatment Diff 0 5 0 3 0 7 p lt 0 0001 0 067 vs No Treatment Treatment Diff 0 8 0 6 1 0 p lt 0 0001 0 067 vs 0 033 Treatment Diff 0 3 0 2 0 5 p value lt 0 0001 Height SDS Change from Baseline at 1 Year2 0 067 vs 0 033 Treatment Diff 0 6 0 5 0 8 p value lt 0 0001 SDS Standard deviation score Adjusted least squares means based on an ANCOVA model including terms for treatment gender age at baseline and height SDS at baseline All children remained prepubertal during the study 14 4 Adult Growth Hormone Deficiency GHD A total of six randomized double blind placebo controlled studies were performed Two representative studies one in adult onset AQ GHD patients and a second in childhood onset CO GHD patients are described below Study 1 A single center randomized double blind placebo con
54. g and postprandial glucose and hemoglobin Ai levels remain in the normal range Lipid Metabolism somatropin stimulates intracellular lipolysis and administration of somatropin leads to an increase in plasma free fatty acids and triglycerides Untreated GHD is associated with increased body fat stores including increased abdominal visceral and subcutaneous adipose tissue Treatment of growth hormone deficient patients with somatropin results in a general reduction of fat stores and decreased serum levels of low density lipoprotein LDL cholesterol Mineral Metabolism Administration of somatropin results in an increase in total body potassium and phosphorus and to a lesser extent sodium This retention is thought to be the result of cell growth Serum levels of phosphate increase in children with GHD after somatropin therapy due to metabolic activity associated with bone growth Serum calcium levels are not altered Although calcium excretion in the urine is increased there is a simultaneous increase in calcium absorption from the intestine Negative calcium balance however may occasionally occur during somatropin treatment Connective Tissue Metabolism somatropin stimulates the synthesis of chondroitin sulfate and collagen and increases the urinary excretion of hydroxyproline 12 3 Pharmacokinetics A 180 min IV infusion of Norditropin 33 ng kg min was administered to 9 GHD patients A mean SD hGH steady state serum level of
55. g left in the pen e f there is not enough Norditropin left in the pen to deliver your full dose use a new Norditropin FlexPro pen to inject the remaining amount of your dose or contact your healthcare provider e Be sure to subtract the dose already received For example if your dose is 0 6 mg and you can only set the dose selector to 0 3 mg you should inject another 0 3 mg with a new Norditropin FlexPro pen Important e Never use the pen clicks to count the number of mg you select Only the display window and pointer will show the exact number e Never use the growth hormone scale to measure how much liquid to inject Only the display window and pointer will show the exact number Inject your dose Make sure that you receive your full dose by using the injection technique recommended by your healthcare provider This medicine is injected under your skin subcutaneous only H e Insert the needle into your skin as your healthcare provider has shown you e Press and hold the dose button to inject until the 0 in the display window lines up with the pointer As you do this you may hear or feel a firm click e f you remove your finger from the dose button before the 0 is in the display window the full dose has not been delivered Leave the needle in the skin and press and hold the dose button again until the 0 lines up with the pointer If 0 does not appear in the display window
56. g them through x ray scanners Indications And Usage Norditropin somatropin rDNA origin injection is used to treat children who have growth failure because of low or no growth hormone children who are short in stature and who have Noonan syndrome or Turner syndrome children who are short in stature because they were born small small for gestational age SGA and have not caught up in growth by age 2 to 4 years and adults who do not make enough growth hormone Important Safety Information Do not use Norditropin if you have a critical illness caused by certain types of heart or stomach surgery trauma or breathing respiratory problems you are a child with Prader Willi syndrome who is severely obese or has breath ing problems including sleep apnea you have cancer or other tumors your healthcare provider tells you that you have certain types of eye problems caused by diabetes you are a child with closed bone growth plates epiphyses or you are allergic to any of the ingredients in the medicine Before you take Norditropin tell your healthcare provider if you have diabe tes had cancer or any tumor have any other medical condition are pregnant or plan to become pregnant are breast feeding or plan to breast feed Norditropin can cause serious side effects including high risk of death in people who have critical illnesses because of heart or stomach surgery trauma or serious breathing r
57. ge at baseline bone age at baseline height SDS at baseline duration of treatment peak GH after stimulation and baseline IGF 1 Adjusted least squares means based on an ANCOVA model including terms for treatment gender age at baseline height SDS at baseline and pubertal status Study 2 In this study 84 randomized prepubertal non GHD Japanese children age 3 8 with short stature born SGA with no catch up growth were treated for 2 years with 0 033 or 0 067 mg kg day of Norditropin subcutaneously daily at bedtime or received no treatment for 1 year Additional inclusion criteria included birth length or weight SDS lt 2 or lt 10 percentile for gestational age height SDS for chronological age lt 2 and height velocity SDS for chronological age lt 0 within one year prior to Visit 1 Exclusion criteria included diabetes mellitus history or presence of active malignancy and serious co morbid conditions As seen in Table 5 for boys and girls combined there was a dose dependent increase in height SDS at Year 1 and Year 2 The increase in height SDS from baseline to Year 2 0 033 mg kg day 0 8 vs 0 067 mg kg day 1 4 was significantly greater after treatment with 0 067 mg kg day In addition the increase in height SDS at Year 1 was significantly greater in both active treatment groups compared to the untreated control group Table 5 Study 2 Results for Change from Baseline in Height SDS At Year 1 and Year 2 Usin
58. he needle thread with an alcohol swab Front Stopper Inner needle cap Needle Paper tab B e Jake a new disposable needle e Tear the paper tab off and screw the needle straight onto the pen e Make sure the needle is on tight e Never place a disposable needle on your Norditropin FlexPro pen until you are ready to give an injection C e Pull off the outer needle cap and inner needle cap and throw them both away e f you try to put the needle caps back on you may accidentally hurt yourself with the needle e A drop of liquid may appear at the needle tip This is normal Important e Always use a new needle for each injection This will help prevent contamination e Never bend or damage the needle Check the growth hormone flow airshot Make sure that you receive your full dose by checking the growth hormone flow performing an airshot before you select and inject your first dose from a new pen D Turn the dose selector to select 0 1 mg This is the smallest amount of medicine for a dose E e Hold the pen with the needle pointing up e Jap the top of the pen gently a few times to let any air bubbles rise to the top F e Press the dose button until the 0 in the display window lines up with the pointer and a drop of liquid appears at the needle tip e f no drop appears repeat steps D E and F up to 6 times e f no drop appears after these attempts cha
59. hree different Norditropin treatment regimens 0 045 mg kg day Dose A for the entire study 0 045 mg kg day for the first year and 0 067 mg kg day thereafter Dose B or 0 045 mg kg day for the first year 0 067 for the second year and 0 089 mg kg day thereafter Dose C Overall at baseline mean age was 6 5 years mean height SDS National standard was 2 7 and mean HV during the previous year was 6 5 cm year Patients also received estrogen therapy after age 12 and following four years of Norditropin treatment if they did not have spontaneous puberty Patients were treated for a mean of 8 4 years As seen in Table 3 overall mean final height was 161 cm in the 46 children who attained final height Seventy percent of these children reached a final height within the normal range height SDS gt 2 using the National standard A greater percentage of children in the two escalated dose groups reached normal final height The mean changes from baseline to final height in height SDS after treatment with Dose B and Dose C were significantly greater than the mean changes observed after treatment with Dose A utilizing both the National and Turner standards The mean changes from baseline to final height in height SDS Turner standard in Table 3 correspond to mean height gains of 9 4 14 1 and 14 4 cm after treatment with Doses A B and C respectively The mean changes from baseline to final height in height SDS National standard in Table
60. ide you the dose selector Clicks differently when turned forwards backwards or past the number of mg that is left in the pen e When the pen has less than 4 mg the dose selector stops at the number of mg that is left in the pen How much growth hormone is left in the pen You can use the growth hormone scale to see how much growth hormone is left in the pen You can use the dose selector to see exactly how much growth hormone is left in the pen If the pen contains less than 4 mg turn the dose selector until it stops The figure that lines up with the pointer shows how many mg are left in the pen e You cannot set a dose higher than the number of mg left in the pen e f there is not enough Norditropin left in the pen to deliver your full dose use a new Norditropin FlexPro pen to inject the remaining amount of your dose or contact your healthcare provider e Be sure to subtract the dose already received For example if your dose is 0 6 mg and you can only set the dose selector to 0 3 mg you should inject another 0 3 mg with a new Norditropin FlexPro pen Important e Never use the pen clicks to count the number of mg you select Only the display window and pointer will show the exact number e Never use the growth hormone scale to measure how much liquid to inject Only the display window and pointer will show the exact number Inject your dose Make sure that you receive your full dose by using the injec
61. ight away and put the pen cap back on If the needle is not removed some liquid may come out of the Norditropin FlexPro Unscrew the needle and throw away the needle and any empty Norditropin FlexPro pen as directed by your healthcare provider A special sharps container such as a red biohazard container a hard plastic container such as an empty detergent bottle or a metal container such as an empty coffee can should be used The container should be sealed and disposed of properly e Caregivers should be most careful when handling used needles to avoid hurting themselves Care for your Norditropin FlexPro pen You must take care of your Norditropin FlexPro pen e Do not drop your pen or knock it against hard surfaces If you do drop it or think that something is wrong with it always screw on a new disposable needle and check the growth hormone flow airshot before you inject e Do not try to refill your disposable pen it is prefilled e Do not try to repair your pen or pull it apart e Do not expose your pen to dust dirt or any kind of liquid e Do not try to wash soak or lubricate your pen You may clean the Norditropin FlexPro pen with a mild detergent on a moistened cloth See section How do store Norditropin above for information about how to store your pen e Always keep your pen and needles out of reach of others especially children e Never share your needles and p
62. in size it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure The adverse events reported during post marketing surveillance do not differ from those listed discussed above in sections 6 1 and 6 2 in children and adults Leukemia has been reported in a small number of GH deficient children treated with somatropin somatrem methionylated rhGH and GH of pituitary origin It is uncertain whether these cases of leukemia are related to GH therapy the pathology of GHD itself or other associated treatments such as radiation therapy On the basis of current evidence experts have not been able to conclude that GH therapy per se was responsible for these cases of leukemia The risk for children with GHD if any remains to be established see Contraindications 4 3 and Warnings and Precautions 5 3 The following additional adverse reactions have been observed during the appropriate use of somatropin headaches children and adults gynecomastia children and pancreatitis children and adults see Warnings and Precautions 5 14 New onset type 2 diabetes mellitus has been reported 4 7 DRUG INTERACTIONS 7 1 Inhibition of 118 Hydroxysteroid Dehydrogenase Type 1 11BHSD 1 The microsomal enzyme 116 hydroxysteroid dehydrogenase type 1 11BHSD 1 is required for conversion of cortisone to its active metabolite cortisol in hepatic and adipose tissue GH and somatropin inhibit
63. ind or who have trouble seeing unless they have the help of a sighted individual trained to use NordiFlex PenMate and Norditropin NordiFlex e f your NordiFlex PenMate becomes lost or damaged you can still use your Norditropin NordiFlex without NordiFlex PenMate e Keep Norditropin NordiFlex NordiFlex PenMate and NovoFine disposable needles out of the reach of children e With Norditropin NordiFlex it is not possible to select a dose larger than the number of mg left in the cartridge e When using a NordiFlex PenMate with a Norditropin NordiFlex 5 mg 1 5 mL or a Norditropin NordiFlex 10 mg 1 5 mL EITHER keep refrigerated 2 8 C 36 46 F for 4 weeks OR store not above 25 C 77 F for 3 weeks e When using a NordiFlex PenMate with a Norditropin NordiFlex 15 mg 1 5 mL keep refrigerated 2 8 C 36 46 F for 4 weeks Do not freeze e NordiFlex PenMate and Norditropin NordiFlex are designed for use with NovoFine disposable needles e Novo Nordisk is not responsible for harm due to using NordiFlex PenMate and Norditropin NordiFlex with products that are not recommended by Novo Nordisk Important Notes The following is a review of some important information about the use and care of your NordiFlex PenMate and Norditropin NordiFlex Before using a new Norditropin NordiFlex be certain to e Always perform an air shot with the NovoFine disposable needle pointing upward Be sure to e Rem
64. isposable needle on Norditropin NordiFlex until you are ready to give an injection If the NovoFine disposable needle is left on Norditropin NordiFlex some liquid may leak out NOTE NovoFine needles have an inner and outer cap that must be removed prior to injection NOTE Always use a new NovoFine disposable needle for each injection 5 Pull off the outer needle cap and keep it within reach 6 Carefully remove the inner needle cap and dispose of it properly NOTE To minimize the risks of unintended needle stick injuries never replace the inner needle cap once it has been removed Section 2 Performing an Air Shot small amounts of air may collect in the needle and cartridge To ensure proper dosing and to avoid injecting air you must perform an air shot before administering your first injection with a new Norditropin NordiFlex 1 Dial the dosage selector to the first line after 0 0 Each line between labeled dosages is 0 025 mg for a Norditropin NordiFlex 5 mg 1 5 mL 0 05 mg for a Norditropin NordiFlex 10 mg 1 5 mL and 0 075 mg for a Norditropin NordiFlex 15 mg 1 5 mL Hold NordiFlex PenMate with the NovoFine disposable needle pointing upwards and tap NordiFlex PenMate gently with your finger a few times to make any air bubbles rise to the top of the cartridge 3 Still holding NordiFlex PenMate with the needle up press the push button all the way in A drop of liquid sh
65. ke care of your Norditropin FlexPro pen e Do not drop your pen or knock it against hard surfaces If you do drop it or think that something is wrong with it always screw on a new disposable needle and check the growth hormone flow airshot before you inject e Do not try to refill your disposable pen it is prefilled e Do not try to repair your pen or pull it apart e Do not expose your pen to dust dirt or any kind of liquid e Do not try to wash soak or lubricate your pen You may clean the Norditropin FlexPro pen with a mild detergent on a moistened cloth See section How do store Norditropin above for information about how to store your pen e Always keep your pen and needles out of reach of others especially children e Never share your needles and pen with anyone Date of Issue March 2 2010 Version 1 US Patent Nos 6 235 004 6 004 297 6 582 404 6 716 198 6 899 699 5 849 704 5 691 169 5 618 697 and other patents pending Norditropin FlexPro and Norditropin NordiFlex are registered trademarks of Novo Nordisk Health Care AG Novo Nordisk is a registered trademark of Novo Nordisk A S 2004 2010 Novo Nordisk Health Care AG Manufactured by O Novo Nordisk A S DK 2880 Bagsvaerd Denmark 140983 3 10 novo nordisk norditropin norditlex somatropin rDNA origin injection 30 mg 3 mL Prefilled Pen PATIENT INFORMATION Norditropin NordiFlex Somatropin rDNA origin
66. locity were compared to a national reference population in both studies Study 1 The pivotal study included 53 38 male 15 female non GHD Dutch children 3 11 years of age with short stature born SGA with no catch up growth Catch up growth was defined as obtaining a height of 3 percentile within the first 2 years of life or at a later stage These prepubertal children needed to meet the following additional inclusion criteria birth length lt 3 percentile for gestational age and height velocity cm year for chronological age lt 50th percentile Exclusion criteria included chromosomal abnormalities signs of a syndrome except for Silver Russell syndrome serious chronic co morbid disease malignancy and previous rhGH therapy Norditropin was administered subcutaneously daily at bedtime at a dose of approximately 0 033 Dose A or 0 067 mg kg day Dose B for the entire treatment period Final height was defined as a height velocity below 2 cm year Treatment with Norditropin was continued to final height for up to 13 years Mean duration of treatment was 9 5 years boys and 7 9 years girls 38 out of 53 children 72 reached final height Sixty three percent 24 out of 38 of the children who reached final height were within the normal range of their healthy peers Dutch national reference For both doses combined actual mean final height was 171 SD 6 1 cm in boys and 159 SD 4 3 cm in girls As seen in Table 4 for
67. lorless by turning the Norditropin NordiFlex upside down once or twice and view the solution through the residual scale window DO NOT use Norditropin NordiFlex if the growth hormone solution is cloudy or contains particles Use it only if it is clear and colorless Wash hands well and dry completely Wipe the front rubber stopper on the needle thread with an alcohol swab B Place a new NovoFine disposable needle onto Norditropin NordiFlex immediately before use Remove the protective tab from the disposable needle and screw the needle tightly onto Norditropin NordiFlex Pull off the outer and inner needle caps Never place a disposable needle on your Norditropin NordiFlex until you are ready to give an injection Remove the needle immediately after use If the needle is not removed some liquid may be expelled from Norditropin NordiFlex Protective tab 2 Performing an Air Shot Do an air shot before small amounts of air may collect in the needle and cartridge To ensure proper dosing and to avoid injecting air you must perform an air shot before administering your first injection C Dial the dosage selector to 0 1 mg Each line between labeled dosages is 0 1 mg D Hold Norditropin NordiFlex with the needle pointing up tap the cartridge gently with your finger a few times to make any air bubbles rise to the top of the cartridge E Still holding Norditropin NordiFlex with the needle up press the p
68. ls between 100 and 126 mg dL or with fasting blood glucose levels gt 126 mg dL Furthermore mean hemoglobin Ay levels tended to decrease during long term treatment in Study 1 and remained normal in Study 2 However in Study 1 4 children treated with 0 067 mg kg day of Norditropin and 2 children treated with 0 033 mg kg day of Norditropin shifted from normal fasting blood glucose levels at baseline to increased levels after 1 year of treatment 100 to 126 mg dL or gt 126 mg dL In addition small increases in mean fasting blood glucose and insulin levels within the normal reference range after 1 and 2 years of Norditropin treatment appeared to be dose dependent see Warnings and Precautions 5 4 and Adverse Reactions 6 1 In both Study 1 and Study 2 there was no acceleration of bone maturation A dose dependent increase in mean serum IGF I SDS levels within the reference range but including a substantial number of children with serum IGF 1 SDS gt 2 was observed after both long term Study 1 and short term Study 2 Norditropin treatment Clinical Trials in Adult GHD Patients Adverse events with an incidence of 5 occurring in patients with AO GHD during the 6 month placebo controlled portion of the largest of the six adult GHD Norditropin trials are presented in Table 1 Peripheral edema other types of edema arthralgia myalgia and paraesthesia were common in the Norditropin treated patients and reported much
69. n with short stature born SGA with failure to catch up were treated with 2 doses of Norditropin 0 033 or 0 067 mg kg day for 2 years or were untreated for 1 year The most frequently reported adverse events were common childhood diseases almost identical to those reported above for Study 1 Adverse events possibly probably related to Norditropin were otitis media arthralgia and impaired glucose tolerance No apparent differences between the treatment groups were observed However arthralgia and transiently impaired glucose tolerance were only reported in the 0 067 mg kg day treatment group Therefore it can also be concluded that no novel adverse events potentially related to treatment with rhGH were reported in short term Study 2 As with all protein drugs some patients may develop antibodies to the protein Eighteen of the 76 children 24 treated with Norditropin developed anti rhGH antibodies However these antibodies did not appear to be neutralizing in that the change from baseline in height SDS at Year 2 was similar in antibody positive and antibody negative children by treatment group In both Study 1 and Study 2 there were no clear cut cases of new onset diabetes mellitus no children treated for hyperglycemia and no adverse event withdrawals due to abnormalities in glucose tolerance In Study 2 after treatment with either dose of Norditropin for 2 years there were no children with consecutive fasting blood glucose leve
70. neurysm dissection hypertension as these patients are also at risk for these conditions 5 11 Confirmation of Childhood Onset Adult GHD Patients with epiphyseal closure who were treated with somatropin replacement therapy in childhood should be reevaluated according to the criteria in ndications and Usage 1 2 before continuation of somatropin therapy at the reduced dose level recommended for GH deficient adults 5 12 Local and Systemic Reactions When somatropin is administered subcutaneously at the same site over a long period of time tissue atrophy may result This can be avoided by rotating the injection site see Dosage and Administration 2 3 As with any protein local or systemic allergic reactions may occur Parents Patients should be informed that such reactions are possible and that prompt medical attention should be sought if allergic reactions occur 5 13 Laboratory Tests serum levels of inorganic phosphorus alkaline phosphatase parathyroid hormone PTH and IGF I may increase after somatropin therapy 5 14 Pancreatitis Cases of pancreatitis have been reported rarely in children and adults receiving somatropin treatment with some evidence supporting a greater risk in children compared with adults Published literature indicates that girls who have Turner syndrome may be at greater risk than other somatropin treated children Pancreatitis should be considered in any somatropin treated patient especially a child
71. nge the needle and repeat steps D E and F one more time o lf a drop of liquid still does not appear call 1 888 668 6444 for help Important e Be careful not to drop Norditropin FlexPro pen or knock it against a hard surface If this happens you will need to repeat the airshot e Always make sure that a drop appears at the needle tip after completing your airshot Select your dose Use the dose selector on your Norditropin FlexPro pen to make sure you have the exact dose selected You can select up to 8 mg per dose G e Select or adjust the dose you need by turning the dose selector forwards or backwards until the right number of mg lines up with the pointer e When dialing back be careful not to press the dose button as liquid will come out e To guide you the dose selector Clicks differently when turned forwards backwards or past the number of mg that is left in the pen e When the pen has less than 8 mg the dose selector stops at the number of mg that is left in the pen How much growth hormone is left in the pen You can use the growth hormone scale to see how much growth hormone is left in the pen You can use the dose selector to see exactly how much growth hormone is left in the pen If the pen contains less than 8 mg turn the dose selector until it stops The figure that lines up with the pointer shows how many mg are left in the pen e You cannot set a dose higher than the number of m
72. not release any liquid The push button stops during the injection before 0 0 lines up with the dosage indicator The needle may be blocked You did not receive the selected dose To complete your dose you must inject the remaining number of milligrams as described below e Check the dosage indicator window The number that lines up with the dosage indicator is the number of milligrams that you need to inject to complete your dose Make a note of this number e Turn the dosage selector until 0 0 lines up with the dosage indicator e Screw on a new needle and perform an air shot as described in Sections 1 and 2 e Select the number of milligrams you need to complete your dose This is the number that you made a note of Prepare NordiFlex PenMate as described in Section 3 Inject as described in section 4 When selecting a dose the dosage selector stops before have selected the required number of Either you are trying to select a dose larger than there is left in NordiFlex prefilled pen or you are trying to select a dose larger than the maximum dose for one injection e f you need a dose larger than the number of milligrams left in the cartridge follow the instructions in Section 4 milligrams e f you need a dose larger than the maximum dose for one injection you must spread the dose over two injections My Norditropin e Unscrew Norditropin NordiFlex and pull it gently out of NordiFlex NordiFlex and or my
73. ns 1 patients with multiple other pituitary hormone deficiencies due to organic disease and 2 patients with congenital genetic growth hormone deficiency 2 DOSAGE AND ADMINISTRATION For subcutaneous injection Therapy with Norditropin should be supervised by a physician who is experienced in the diagnosis and management of pediatric patients with short stature associated with GHD Noonan syndrome Turner syndrome or SGA and adult patients with either childhood onset or adult onset GHD 2 1 Dosing of Pediatric Patients General Pediatric Dosing Information The Norditropin dosage and administration schedule should be individualized based on the growth response of each patient Serum insulin like growth factor IGF I levels may be useful during dose titration Response to somatropin therapy in pediatric patients tends to decrease with time However in pediatric patients the failure to increase growth rate particularly during the first year of therapy indicates the need for close assessment of compliance and evaluation for other causes of growth failure such as hypothyroidism undernutrition advanced bone age and antibodies to recombinant human GH rhGH Treatment with Norditropin for short stature should be discontinued when the epiphyses are fused Pediatric Growth Hormone Deficiency GHD A dosage of 0 024 to 0 034 mg kg day 6 to 7 times a week is recommended Pediatric Patients with Short Stature Associated
74. o give injections easily and conveniently This manual includes everything you need to know about using NordiFlex PenMate Read it carefully before using NordiFlex PenMate for the first time NordiFlex PenMate is designed for use with e Norditropin NordiFlex somatropin rDNA origin injection 5 mg 1 5 mL 10 mg 1 5 mL and 15 mg 1 5 mL prefilled pens e NovoFine disposable needles Customer service and satisfaction are our top concern If you have any questions about NordiFlex PenMate or Norditropin NordiFlex prefilled pens please call Novo Nordisk Inc at 1 888 NOVO 444 Thank you for choosing NordiFlex PenMate See Important Things to Know and Important Notes NordiFlex PenMate PenMate LOT number Residual scale Blue insertion inside window button Norditropin NordiFlex Prefilled Pen 5 mg 1 5 mL Needle Residual scale Dosage indicator Push thread window window button Cap Cap a Cartridge Residual scale Dosage Dosage indicator selector NovoFine disposable needles Outer needle cap Inner needle cap Needle te b g NordiFlex PenMate is designed for use with NovoFine disposable needles and Norditropin NordiFlex 5 mg 1 5 mL 10 mg 1 5 mL and 15 mg 1 5 mL prefilled pens Protective tab How to use this manual This manual gives you step by step instructions for using NordiFlex PenMate in combination with Norditropin NordiFlex 5 mg 1 5 mL 10 mg 1 5 mL and 15 mg 1
75. obstruction including onset of or increased snoring and or new onset sleep apnea treatment should be interrupted All patients with Prader Willi syndrome treated with somatropin should also have effective weight control and be monitored for signs of respiratory infection which should be diagnosed as early as possible and treated aggressively see Contraindications 4 2 Norditropin is not indicated for the treatment of pediatric patients who have growth failure due to genetically confirmed Prader Willi syndrome 5 3 Neoplasms Patients with preexisting tumors or GHD secondary to an intracranial lesion should be monitored routinely for progression or recurrence of the underlying disease process In pediatric patients clinical literature has revealed no relationship between somatropin replacement therapy and central nervous system CNS tumor recurrence or new extracranial tumors However in childhood cancer survivors an increased risk of a second neoplasm has been reported in patients treated with somatropin after their first neoplasm Intracranial tumors in particular meningiomas in patients treated with radiation to the head for their first neoplasm were the most common of these second neoplasms In adults it is unknown whether there is any relationship between somatropin replacement therapy and CNS tumor recurrence Patients should be monitored carefully for potential malignant transformation of skin lesions i e increased growth
76. of Novo Nordisk A S For assistance or further information write to Novo Nordisk Inc 100 College Road West Princeton NJ 08540 USA 1 888 NOVO 444 1 888 668 6444 norditropin us com Manufactured by Novo Nordisk A S O DK 2880 Bagsvaerd Denmark 2004 2010 Novo Nordisk Health Care AG 143038 11 10 novo nordisk INSTRUCTIONS FOR USE Norditropin FlexPro somatropin rDNA origin injection 5 mg 1 5 mL orange Prefilled Pen Read these instructions before using your Norditropin FlexPro pen Norditropin FlexPro Growth Display Dose Dose Pencap hormone scale window Pointer selector button Needle thread Needle example Outer needle cap Norditropin FlexPro contains 5 mg human growth hormone solution and delivers doses from 0 025 mg to 2 mg in increments of 0 025 mg Norditropin FlexPro is made to be used with Novo Nordisk disposable needles Needles are not included with Norditropin FlexPro Prepare your Norditropin FlexPro pen A A e Pull off the pen cap e Check that the liquid in the pen is clear and colorless by tipping it upside down 1 or 2 times If the liquid looks unclear or cloudy do not use the pen e Wash hands well and dry them e Wipe the front stopper on the needle thread with an alcohol swab Front Stopper Inner needle cap Needle Paper tab B e Jake a new disposable needle e Tear the paper tab off and screw the needle s
77. on infections of childhood including upper respiratory infection gastroenteritis ear infection and influenza Cardiac disorders was the system organ class with the second most adverse events reported However congenital heart disease is an inherent component of Noonan syndrome and there was no evidence of somatropin induced ventricular hypertrophy or exacerbation of preexisting ventricular hypertrophy as judged by echocardiography during this study Children who had baseline cardiac disease judged to be significant enough to potentially affect growth were excluded from the study therefore the safety of Norditropin in children with Noonan syndrome and significant cardiac disease is not known Among children who received 0 033 mg kg day there was one adverse event of scoliosis among children who received 0 066 mg kg day there were four adverse events of scoliosis see Warnings and Precautions 5 9 Mean serum IGF I standard deviation score SDS levels did not exceed 1 in response to somatropin treatment The mean serum IGF I level was low at baseline and normalized during treatment Clinical Trials in Children with Turner Syndrome In two clinical studies wherein children with Turner syndrome were treated until final height with various doses of Norditropin as described in Clinical Studies 14 2 the most frequently reported adverse events were common childhood diseases including influenza like illness otitis media upper respir
78. one identical to the growth hormone produced in the human body used to treat e children who are not growing because of low or no growth hormone e children who are short in stature and who have Noonan syndrome or Turner syndrome e children who are short in stature because they were born small small for gestational age SGA and have not caught up in growth by age 2 to 4 years e adults who do not make enough growth hormone Who should not use Norditropin Do not use Norditropin if e you have a critical illness caused by certain types of heart or stomach surgery trauma or breathing respiratory problems e you are a child with Prader Willi syndrome who is severely obese or has breathing problems including sleep apnea e you have cancer or other tumors e your healthcare provider tells you that you have certain types of eye problems caused by diabetes e you are a child with closed bone growth plates epiphyses e you are allergic to any of the ingredients in Norditropin see the end of this leaflet for a complete list of ingredients in Norditropin What should I tell my healthcare provider before start Norditropin Before you take Norditropin tell your healthcare provider if you e have diabetes e had cancer or any tumor e have any other medical condition e are pregnant or plan to become pregnant It is not known if Norditropin will harm your unborn baby Talk to your doctor if you are pregnant or plan
79. opin administration may alter the clearance of compounds known to be metabolized by CYP450 liver enzymes e g corticosteroids sex steroids anticonvulsants cyclosporine Careful monitoring is advisable when somatropin is administered in combination with other drugs known to be metabolized by CYP450 liver enzymes However formal drug interaction studies have not been conducted 7 4 Oral Estrogen Because oral estrogens may reduce the serum IGF 1 response to somatropin treatment girls and women receiving oral estrogen replacement may require greater somatropin dosages see Dosage and Administration 2 2 7 5 Insulin and or Oral Injectable Hypoglycemic Agents In patients with diabetes mellitus requiring drug therapy the dose of insulin and or oral injectable agent may require adjustment when somatropin therapy is initiated see Warnings and Precautions 5 4 8 USE IN SPECIFIC POPULATIONS 8 1 Pregnancy Pregnancy Category C Animal reproduction studies have not been conducted with Norditropin It is not known whether Norditropin can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity Norditropin should be given to a pregnant woman only if clearly needed 8 3 Nursing Mothers It is not known whether Norditropin is excreted in human milk Because many drugs are excreted in human milk caution should be exercised when Norditropin is administered to a nursing woman 8 5 Geriatric Use
80. opriate training and instruction on proper use from the physician or other suitably qualified health care professional A puncture resistant container for the disposal of used needles should be strongly recommended Patients and or parents should be thoroughly instructed in the importance of proper disposal and cautioned against any reuse of needles This information is intended to aid in the safe and effective administration of the medication If patients are prescribed Norditropin Cartridges to be inserted into color coded NordiPen delivery systems physicians should instruct patients to read the NordiPen INSTRUCTION booklet provided with the NordiPen delivery systems If patients are prescribed Norditropin FlexPro or Norditropin NordiFlex physicians should instruct patients to read the PATIENT INFORMATION and INSTRUCTIONS FOR USE leaflets provided with the Norditropin FlexPro and Norditropin NordiFlex prefilled pens Date of Issue May 25 2011 Version 14 Novo Nordisk is a registered trademark of Novo Nordisk A S Norditropin FlexPro NordiPer and Norditropin NordiFlex are registered trademarks of Novo Nordisk Health Care AG For information contact Novo Nordisk Inc 100 College Road West Princeton New Jersey 08540 USA 1 888 NOVO 444 1 888 668 6444 Manufactured by Novo Nordisk A S O DK 2880 Bagsvaerd Denmark 2002 2011 Novo Nordisk Health Care AG 132686 R6 June 2011 novo n
81. ordiFlex 15 mg 1 5 mL green NDC 0169 7703 11 direct light 5 mg 1 5 mL orange and 10 mg 1 5 mL blue prefilled pens After the initial injection a Norditropin FlexPro or Norditropin NordiFlex 5 mg 1 5 mL or 10 mg 1 5 mL prefilled pen may be EITHER stored in the refrigerator 2 8 C 36 46 F and used within 4 weeks OR stored for up to 3 weeks at not more than 25 C 77 F Discard unused portion 15 mg 1 5 mL green and 30 mg 3 mL purple prefilled pens After the initial injection a Norditropin FlexPro 15 mg 1 5 mL or Norditropin NordiFlex 15 mg 1 5 mL or 30 mg 3 mL prefilled pen must be stored in the refrigerator 2 8 C 36 46 F and used within 4 weeks Discard unused portion after 4 weeks Norditropin Cartridges somatropin rDNA origin injection 5 mg 1 5 mL and 15 mg 1 5 mL Norditropin is individually cartoned in 5 mg 1 5 mL or 15 mg 1 5 mL cartridges which must be administered using the corresponding color coded NordiPen delivery system e Norditropin Cartridges 5 mg 1 5 mL orange NDC 0169 7768 11 e Norditropin Cartridges 15 mg 1 5 mL green NDC 0169 7770 11 Unused Norditropin cartridges must be stored at 2 8 C 36 46 F refrigerator Do not freeze Avoid direct light 5 mg 1 5 mL orange cartridges After a Norditropin cartridge 5 mg 1 5 mL has been inserted into its NordiPen delivery system NordiPen 5 it may be EITHER stored in the pen in the refrigerator
82. ordisk norditropin somatropin rDNA origin injection PATIENT INFORMATION Norditropin Nor dee tro pin somatropin rDNA origin injection Read the Patient Information that comes with Norditropin before you start to take it and each time you get a refill There may be new information This leaflet does not take the place of talking with your healthcare provider about your medical condition or your treatment What is Norditropin Norditropin is a prescription medicine given by injection under the skin subcutaneous that contains human growth hormone identical to the growth hormone produced in the human body used to treat e children who are not growing because of low or no growth hormone e children who are short in stature and who have Noonan syndrome or Turner syndrome e children who are short in stature because they were born small small for gestational age SGA and have not caught up in growth by age 2 to 4 years e adults who do not make enough growth hormone Who should not use Norditropin Do not use Norditropin if e you have a critical illness caused by certain types of heart or stomach surgery trauma or breathing respiratory problems e you are a child with Prader Willi syndrome who is severely obese or has breathing problems including sleep apnea e you have cancer or other tumors e your healthcare provider tells you that you have certain types of eye problems caused by diabetes e
83. ould appear at the needle tip If not repeat steps 1 3 no more than 4 times If Norditropin NordiFlex or NordiFlex PenMate has been dropped or knocked against hard surfaces perform an air shot before your next injection lf a drop of liquid still does not appear or if you have any questions call 1 888 NOVO 444 for help NO Section 3 Preparing NordiFlex PenMate for Injection 1 P reparing NordiFlex PenMate To prepare NordiFlex PenMate grip both NordiFlex PenMate and Norditropin NordiFlex firmly and pull in opposite directions until you hear a click Now the needle is hidden in NordiFlex PenMate Section 4 Giving the Injection Setting the Dose Check that the dosage indicator on Norditropin NordiFlex is set at 0 0 1 Dial the number of mg you need to inject If you dial more than your dose the dose can be corrected up or down by turning the dosage selector in either direction When turning the dosage selector backwards be careful not to press the push button A ana lind a uanll anama nit Illaa tha daaanna indinantav nat It VVI yy LU UGIIVUL UIG UUOU To ensure that the full dose is injected keep the needle in the skin for at least 6 seconds after injection with your thumb on the push button Keep the push button fully pushed in until after the needle has been removed from the skin Vary the injection site using the injection procedure recommended by your healthcare prof
84. ove the NovoFine disposable needle immediately after each injection e Select your dose only by using the number in the dosage indicator window e Perform an air shot before injection if you dropped Norditropin NordiFlex or knocked it against a hard surface Make certain you e NEVER place a needle on Norditropin NordiFlex until you are ready to use it Remove the needle immediately after each injection If the NovoFine disposable needle is not removed some liquid may leak out of Norditropin NordiFlex e Do not use the clicking sound to set your dose e Avoid dropping Norditropin NordiFlex or knocking it against hard surfaces e DO NOT leave Norditropin NordiFlex in a car or other location where it can get too hot or too cold e Always have a spare Norditropin NordiFlex in order to avoid running out of this product e Do not use the same Norditropin NordiFlex for more than one person even if you attach a new NovoFine disposable needle for each injection This will prevent the spread of disease Each Norditropin NordiFlex is for single person use only Customer Satisfaction Customer service and satisfaction are our top concerns If you have any questions about NordiFlex PenMate or Norditropin NordiFlex prefilled pens please call Novo Nordisk Inc at 1 888 NOVO 444 Designed and intended for use with Norditropin NordiFlex 5 mg 1 5 mL 10 mg 1 5 mL and 15 mg 1 5 mL prefilled pens NordiFlex PenMate and NovoFin
85. pathy 4 4 e Children with closed epiphyses 4 5 e Known hypersensitivity to somatropin or excipients 4 6 WARNINGS AND PRECAUTIONS e Acute Critical Illness Potential benefit of treatment continuation should be weighed against the potential risk 5 1 e Prader Willi Syndrome in Children Evaluate for signs of upper airway obstruction and sleep apnea before initiation of treatment for GHD Discontinue treatment if these signs occur 5 2 e Neoplasm Monitor patients with preexisting tumors for progression or recurrence Increased risk of a second neoplasm in childhood cancer survivors treated with somatropin in particular meningiomas in patients treated with radiation to the head for their first neoplasm 5 3 e mpaired Glucose Tolerance and Diabetes Mellitus May be unmasked Periodically monitor glucose levels in all patients 9 6 Fluid Retention 5 7 Hypothyroidism 5 8 Slipped Capital Femoral Epiphysis in Pediatric Patients 5 9 Progression of Preexisting Scoliosis in Pediatric Patients 5 10 Otitis Media and Cardiovascular Disorders in Turner syndrome 5 11 Confirmation of Childhood Onset Adult GHD 5 12 Local and Systemic Reactions 5 13 Laboratory Tests 5 14 Pancreatitis 6 ADVERSE REACTIONS 6 1 Most Serious and or Most Frequently Observed Adverse Reactions 6 2 Clinical Trials Experience 6 3 Post Marketing Experience 7 DRUG INTERACTIONS 7 1 Inhibition of 118 Hydroxysteroid Dehydrogenase T
86. rator between 36 F to 46 F 2 C to 8 C and use within 4 weeks Throw away any unused medicine after 4 weeks e Norditropin NordiFlex pens 30 mg 3 mL purple store in the refrigerator between 36 F to 46 F 2 C to 8 C and use within 4 weeks Throw away any unused medicine after 4 weeks General Information about Norditropin Medicines are sometimes prescribed for purposes other than those listed in Patient Information Do not use Norditropin for a condition for which it was not prescribed Do not give Norditropin to other people even if they have the same symptoms that you have It may harm them This Patient Information summarizes the most important information about Norditropin If you would like more information talk with your healthcare provider You can ask your pharmacist or healthcare provider for information about Norditropin that is written for healthcare professionals What are the ingredients in Norditropin Active ingredient somatropin rDNA origin Inactive ingredients Histidine Poloxamer 188 Phenol Mannitol HCI NaQH as needed and Water for Injection Date of Issue March 2 2010 Version 7 US Patent Nos 6 235 004 6 004 297 6 582 404 6 716 198 6 899 699 5 849 704 5 691 169 5 618 697 and other patents pending Norditropin FlexPro and Norditropin NordiFlex are registered trademarks of Novo Nordisk Health Care AG Novo Nordisk is a registered trademark
87. rmone have experienced pain in the hip or knee or a limp These symptoms may be caused by a slippage of the growth plate in the hip slipped capital femoral epiphysis scoliosis curvature of the spine can occur in children who experience rapid growth Because growth hormone increases growth rate patients should be monitored for progression of scoliosis Thyroid function tests should be performed periodically Patients with Turner syndrome have an increased risk of ear or hearing disorders They should be carefully evaluated for middle ear infection otitis media and other ear disorders skin lesions should be checked carefully for any cancerous changes The following tumors have been reported in patients treated with growth hormone Leukemia in children relapse of brain tumors in children and adults However there is no evidence that growth hormone is responsible for causing these diseases Talk to your doctor if you think you have any of these conditions How to store Norditropin NordiFlex Store unused Norditropin NordiFlex in a refrigerator 2 C 46 F Do not freeze or expose it to heat Avoid direct light After the initial injection Norditropin NordiFlex 30 mg 3 mL must be kept in a refrigerator and used within 4 weeks Discard unused portion after 4 weeks Do not use Norditropin NordiFlex which has been frozen or exposed to temperatures higher than 25 C 77 F Always use a new NovoFine needle for e
88. ropin somatropin rDNA origin injection is indicated for the treatment of pediatric patients with short stature associated with Noonan syndrome Norditropin somatropin rDNA origin injection is indicated for the treatment of pediatric patients with short stature associated with Turner syndrome Norditropin somatropin rDNA origin injection is indicated for the treatment of pediatric patients with short stature born small for gestational age SGA with no catch up growth by age 2 to 4 years 1 2 Adult Patients Norditropin somatropin rDNA origin injection is indicated for the replacement of endogenous GH in adults with growth hormone deficiency GHD who meet either of the following two criteria e Adult Onset AQ Patients who have GHD either alone or associated with multiple hormone deficiencies hypopituitarism as a result of pituitary disease hypothalamic disease surgery radiation therapy or trauma or e Childhood Onset CQ Patients who were GH deficient during childhood as a result of congenital genetic acquired or idiopathic causes Patients who were treated with somatropin for GHD in childhood and whose epiphyses are closed should be reevaluated before continuation of somatropin therapy at the reduced dose level recommended for GHD adults According to current standards confirmation of the diagnosis of adult GHD in both groups involves an appropriate growth hormone provocative test with two exceptio
89. rovider will do blood tests to check your thyroid hormone levels e hip and knee pain or a limp in children slipped capital femoral epiphysis e worsening of curvature of the spine Scoliosis e middle ear infection hearing problems or ear problems in patients with Turner syndrome e redness itching and tissue weakness in the area you inject e increase 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 Norditropin include e headaches e muscle pain e joint stiffness e high blood sugar hyperglycemia e sugar in your urine glucosuria e swollen hands and feet due to fluid retention e redness and itching in the area you inject Talk to your healthcare provider if you have any side effect that bothers you or that does not go away These are not all the possible side effects of Norditropin For more information ask your healthcare provider or pharmacist Call your healthcare provider for medical advice about side effects You may report side effects to FDA at 1 800 FDA 1088 1 800 332 1088 You may also report side effects to Novo Nordisk at 1 888 NOVO 444 1 888 668 6444 How do store Norditropin Unused Norditropin FlexPro and NordiFlex pens and cartridges e Keep in a refrigerator between 36 F to 46 F 2 C to 8 C e Do not freeze or expose Norditropin to heat e Keep Nor
90. rovider and pharmacist when you get a new medicine How should use Norditropin e Read the detailed Instructions for Use that come with Norditropin Your healthcare provider will show you how to inject Norditropin e Take Norditropin exactly as prescribed e Norditropin FlexPro pens NordiFlex pens and cartridges are for use by one person only e Novo Nordisk disposable needles are designed to be used with Norditropin for each injection e Always keep the pen cap closed on Norditropin when you are not using it e Norditropin comes in 3 dose strengths for FlexPro prefilled color coded pens 4 dose strengths for NordiFlex prefilled color coded pens and 2 dose strengths for color coded cartridges e f you inject too much Norditropin call your healthcare provider e f you miss a dose take it as soon as you remember If it is almost time for your next dose skip the missed dose Just take the next dose at your regular time Do not take 2 doses at the same time unless your healthcare provider tells you to If you are not sure about your dosing call your healthcare provider e Throw away Norditropin when the cartridge is empty e Refer to the Instructions for Use about what to do if you have less than a full dose left in your pen What are the possible side effects of Norditropin Norditropin can cause serious side effects including e high risk of death in people who have critical illnesses
91. rt and security staff regarding the transportation of medications e Carry a letter signed by your doctor that specifies your health condition and states you or your caregiver are capable of administering the drug e Always carry your health insurance cards with you e Always carry with you the quantity of drugs and needles necessary for any possible treatments for the whole period of your trip e When traveling internationally your medication or needle may not be available on the market in many coun tries and many countries may not be able to supply the necessary medica tions or needles or may have limited supplies e Inform your doctor of any internation al trip you are undertaking and the country ies you will be visiting e Call ahead to your hotel or lodging to ensure availability of a refrigerator for medication in your sleeping room Many hotels will have them available at no charge if notified in advance e Always carry your treatment kit and drug with you as hand luggage Never check in your growth hormone medication e Do not hesitate to inform the flight crew and or airport and airline security staff if you feel it is necessary and explain clearly if asked anything about your healthcare e Please check TSA for full rules and regulations regarding traveling with medication e When carrying your medication and supplies in your carry on ask airport security to visually inspect them in stead of puttin
92. se event data were collected from 18 of the 21 subjects who were originally enrolled in the trial and the 6 who had followed the protocol without randomization Historical reference materials of height velocity and adult height analyses of Noonan patients served as the controls The twenty four 24 12 female 12 male children 3 14 years of age received either 0 033 mg kg day or 0 066 mg kg day of Norditropin subcutaneously which after the first 2 years was adjusted based on growth response In addition to a diagnosis of Noonan syndrome key inclusion criteria included bone age determination showing no significant acceleration prepubertal status height SDS lt 2 and HV SDS lt 1 during the 12 months pre treatment Exclusion criteria were previous or ongoing treatment with growth hormone anabolic Steroids or corticosteroids congenital heart disease or other serious disease perceived to possibly have major impact on growth FPG gt 6 7 mmol L gt 120 mg dL or growth hormone deficiency peak GH levels lt 10 ng mL Patients obtained a final height FH gain from baseline of 1 5 and 1 6 SDS estimated according to the national and the Noonan 5 reference respectively A height gain of 1 5 SDS national corresponds to a mean height gain of 9 9 cm in boys and 9 1 cm in girls at 18 years of age while a height gain of 1 6 SDS Noonan corresponds to a mean height gain of 11 5 cm in boys and 11 0 cm in girls at 18 years of age
93. se strengths for FlexPro prefilled color coded pens 4 dose strengths for NordiFlex prefilled color coded pens and 2 dose strengths for color coded cartridges e f you inject too much Norditropin call your healthcare provider e f you miss a dose take it as soon as you remember If it is almost time for your next dose skip the missed dose Just take the next dose at your regular time Do not take 2 doses at the same time unless your healthcare provider tells you to If you are not sure about your dosing call your healthcare provider e Throw away Norditropin when the cartridge is empty e Refer to the Instructions for Use about what to do if you have less than a full dose left in your pen What are the possible side effects of Norditropin Norditropin can cause serious side effects including e high risk of death in people who have critical illnesses because of heart or stomach surgery trauma or serious breathing respiratory problems e high risk of death in children with Prader Willi syndrome who are severely obese or have breathing problems including Sleep apnea e return of tumor or cancerous growths e high blood sugar hyperglycemia e increase in pressure in the skull intracranial hypertension If you have headaches eye problems nausea or vomiting contact your healthcare provider right away e swollen hands and feet due to fluid retention e decrease in thyroid hormone levels Your healthcare p
94. see Warnings and Precautions 5 7 e alnjection site reactions rashes and lipoatrophy as well as rare generalized hypersensitivity reactions see Warnings and Precautions 5 12 e Pancreatitis see Warnings and Precautions 5 14 6 2 Clinical Trials Experience Because clinical trials are conducted under varying conditions adverse reaction rates observed during the clinical trials performed with one somatropin formulation cannot always be directly compared to the rates observed during the clinical trials performed with a second somatropin formulation and may not reflect the adverse reaction rates observed in practice Clinical Trials in Children with Noonan Syndrome Norditropin was studied in a two year prospective randomized parallel dose group trial in 21 children 3 14 years old with Noonan syndrome Doses were 0 033 and 0 066 mg kg day After the initial two year randomized trial children continued Norditropin treatment until final height was achieved randomized dose groups were not maintained Final height and adverse event data were later collected retrospectively from 18 children total follow up was 11 years An additional 6 children were not randomized but followed the protocol and are included in this assessment of adverse events Based on the mean dose per treatment group no significant difference in the incidence of adverse events was seen between the two groups The most frequent adverse events were the comm
95. sitivity to somatropin or any of its excipients Localized reactions are the most common hypersensitivity reactions 5 WARNINGS AND PRECAUTIONS 5 1 Acute Critical Illness Increased mortality in patients with acute critical illness due to complications following open heart surgery abdominal surgery or multiple accidental trauma or those with acute respiratory failure has been reported after treatment with pharmacologic amounts of somatropin see Contrainadications 4 1 The safety of continuing somatropin treatment in patients receiving replacement doses for approved indications who concurrently develop these illnesses has not been established Therefore the potential benefit of treatment continuation with somatropin in patients experiencing acute critical illnesses should be weighed against the potential risk 5 2 Prader Willi Syndrome in Children There have been reports of fatalities after initiating therapy with somatropin in pediatric patients with Prader Willi syndrome who had one or more of the following risk factors severe obesity history of upper airway obstruction or sleep apnea or unidentified respiratory infection Male patients with one or more of these factors may be at greater risk than females Patients with Prader Willi syndrome should be evaluated for signs of upper airway obstruction and sleep apnea before initiation of treatment with somatropin If during treatment with somatropin patients show signs of upper airway
96. soak Norditropin NordiFlex in alcohol wash or lubricate it 7 Important Things to Know e Norditropin NordiFlex 30 mg 3 mL cannot be used with the NordiFlex PenMate auto insertion accessory e Store unused Norditropin NordiFlex pens in a refrigerator 2 C 8 C 36 F 46 F After the initial injection keep Norditropin NordiFlex 30 mg 3 mL refrigerated and use within 4 weeks e Remember to perform an air shot before starting a new Norditropin NordiFlex or before the injection if you dropped or knocked the pen against a hard surface See diagrams C D and E e f you need to perform more than 4 air shots before the first use of Norditropin NordiFlex to get a droplet of liquid at the needle tip DO NOT use Norditropin NordiFlex Call 1 888 NOVO 444 for help e Jake care not to drop Norditropin NordiFlex or knock it against a hard surface e DO NOT leave Norditropin NordiFlex in a car or other location where it can get too hot or too cold e Always have a spare Norditropin NordiFlex disposable pen in order to avoid running out of this product e Norditropin NordiFlex is designed to be used with NovoFine disposable needles e NEVER place a needle on Norditropin NordiFlex until you are ready to use it Remove the needle right after use without recapping e Dispose of used needles properly so people will not be harmed e Dispose of used Norditropin NordiFlex without the needle attached e To avoid spread
97. ter the injection Follow the instructions you received for removal and disposal of needles to reduce the risk of needle stick injuries Hold NordiFlex PenMate firmly while you unscrew the NovoFine disposable needle Place the NovoFine disposable needle in a puncture resistant disposal container Used needles should be placed in sharps containers such as red biohazard containers hard plastic containers such as detergent bottles or metal containers such as an empty coffee can Such containers should be sealed and disposed of properly 2 Replace NordiFlex PenMate cap NOTE The NovoFine disposable needle must be removed immediately after each injection If the NovoFine disposable needle is not removed some liquid may leak out of Norditropin cartridge It is important that you use a new needle for each injection Healthcare professionals relatives and other caregivers should follow general precautionary measures for removal and disposal of needles to reduce the risk of unintended needle stick injuries 0 Section 6 Replacing an Empty Norditropin NordiFlex You will need to remove Norditropin NordiFlex prefilled pen when it is empty 1 When Norditropin NordiFlex is empty turn Norditropin NordiFlex counterclockwise until you feel a click and gently pull it out of NordiFlex PenMate Dispose of Norditronin NordiFlex nronerlv QAINUTUIUTU MITE INUTUTE TUN UO TTY Pe IC Ut a
98. tion and container permit Norditropin MUST NOT BE INJECTED if the solution is cloudy or contains particulate matter Use it only if it is clear and colorless Injection sites should always be rotated to avoid lipoatrophy 3 DOSAGE FORMS AND STRENGTHS Norditropin is available preloaded in the Norditropin FlexPro or Norditropin NordiFlex pens or in cartridges for use with the corresponding NordiPens e 5 mg 1 5 mL orange Norditropin FlexPro and Norditropin NordiFlex prefilled pens and cartridges e 10 mg 1 5 mL blue Norditropin FlexPro and Norditropin 2 NordiFlex prefilled pens e 15 mg 1 5 mL green Norditropin FlexPro and Norditropin NordiFlex prefilled pens and cartridges e 30 mg 3 mL purple Norditropin NordiFlex prefilled pen only 4 CONTRAINDICATIONS 4 1 Acute Critical Illness Treatment with pharmacologic amounts of somatropin is contraindicated in patients with acute critical illness due to complications following open heart surgery abdominal surgery or multiple accidental trauma or those with acute respiratory failure Two placebo controlled clinical trials in non growth hormone deficient adult patients n 522 with these conditions in intensive care units revealed a significant increase in mortality 41 9 vs 19 3 among somatropin treated patients doses 5 3 8 mg day compared to those receiving placebo see Warnings and Precautions 5 1 4 2 Prader Willi Syndrome in
99. tion for Norditropin Cartridges Norditropin Cartridges somatropin rDNA origin injection for subcutaneous use Initial U S Approval 1987 RECENT MAJOR CHANGES e Warnings and Precautions Pancreatitis 5 14 12 2010 e Warnings and Precautions Impaired Glucose Tolerance and Diabetes Mellitus 5 4 3 2011 INDICATIONS AND USAGE Norditropin is a recombinant human growth hormone indicated for o Pediatric Treatment of children with growth failure due to growth hormone deficiency GHD short stature associated with Noonan syndrome short stature associated with Turner syndrome and short stature born SGA with no catch up growth by age 2 to 4 years 1 1 e Adult Treatment of adults with either adult onset or childhood onset GHD 1 2 DOSAGE AND ADMINISTRATION Norditropin should be administered subcutaneously 2 o Pediatric GHD 0 024 to 0 034 mg kg day 6 to 7 times a week 2 1 e Noonan Syndrome Up to 0 066 mg kg day 2 1 e Turner Syndrome Up to 0 067 mg kg day 2 1 e SGA Up to 0 067 mg kg day 2 1 e Adult GHD 0 004 mg kg day to be increased as tolerated to not more than 0 016 mg kg day after approximately 6 weeks or a Starting dose of approximately 0 2 mg day range 0 15 to 0 30 mg day increased gradually every 1 to 2 months by increments of approximately 0 1 to 0 2 mg day 2 2 e Norditropin cartridges must be used with their corresponding FULL PRESCRIBING INFORMA
100. tion technique recommended by your healthcare provider This medicine is injected under your skin subcutaneous only H e Insert the needle into your skin as your healthcare provider has shown you e Press and hold the dose button to inject until the 0 in the display window lines up with the pointer As you do this you may hear or feel a firm click e f you remove your finger from the dose button before the 0 is in the display window the full dose has not been delivered Leave the needle in the skin and press and hold the dose button again until the 0 lines up with the pointer If 0 does not appear in the display window you did not receive the full dose Call 1 888 668 6444 for assistance e After the 0 in the display window lines up with the pointer leave the needle under the skin for at least 6 seconds to make sure that you get your full dose You can let go of the dose button while you wait e Change the injection site using the injection procedure recommended by your healthcare provider Important e Always press the dose button to inject the dose Turning the dose selector will not inject the dose e Never touch the display window when you inject as this can block the injection e Remove the needle from your skin After that you may see a drop of liquid at the needle tip This is normal and does not affect the dose you received After the injection remove the needle r
101. traight onto the pen e Make sure the needle is on tight e Never place a disposable needle on your Norditropin FlexPro pen until you are ready to give an injection C e Pull off the outer needle cap and inner needle cap and throw them both away e f you try to put the needle caps back on you may accidentally hurt yourself with the needle e A drop of liquid may appear at the needle tip This is normal Important e Always use a new needle for each injection This will help prevent contamination e Never bend or damage the needle Check the growth hormone flow airshot Make sure that you receive your full dose by checking the growth hormone flow performing an airshot before you select and inject your first dose from a new pen D Turn the dose selector to select 0 025 mg This is the smallest amount of medicine for a dose lla gp amp iT 0 025 mg selected E e Hold the pen with the needle pointing up e Jap the top of the pen gently a few times to let any air bubbles rise to the top F e Press the dose button until the 0 in the display window lines up with the pointer and a drop of liquid appears at the needle tip e f no drop appears repeat steps D E and F up to 6 times e f no drop appears after these attempts change the needle and repeat steps D E and F one more time o lf a drop of liquid still does not appear call 1 888 668 6444 for help
102. trolled parallel group six month clinical trial was conducted in 31 adults with AO GHD comparing the effects of Norditropin somatropin rDNA origin for injection and placebo on body composition Patients in the active treatment arm were treated with Norditropin 0 017 mg kg day not to exceed 1 33 mg day The changes from baseline in lean body mass LBM and percent total body fat TBF were measured by total body potassium TBP after 6 months Treatment with Norditropin produced a significant p 0 0028 increase from baseline in LBM compared to placebo Table 6 Table 6 Lean Body Mass kg by TBP Norditropin hen n 16 n 15 5027 S ae a Sane at 6 months mean Treatment difference mean 1 74 95 confidence interval 0 65 2 83 p value p 0 0028 Analysis of the treatment difference on the change from baseline in percent TBF revealed a significant decrease p 0 0004 in the Norditropin treated group compared to the placebo group Table 7 Table 7 Total Body Fat by TBP fae n 16 we tropin 44 74 42 26 n 15 ma a ane at 4 14 7 18 2 30 p value p 0 0004 Fifteen 48 4 of the 31 randomized patients were male The adjusted mean treatment differences on the increase in LBM and decrease in percent TBF from baseline were larger in males compared to females Norditropin also significantly increased serum osteocalcin a marker of osteoblastic activity Study 2 A single cent
103. tton come a i Needle thread Needle example Outer needle cap Norditropin FlexPro contains 10 mg human growth hormone solution and delivers doses from 0 05 mg to 4 mg in increments of 0 05 mg Norditropin FlexPro is made to be used with Novo Nordisk disposable needles Needles are not included with Norditropin FlexPro Prepare your Norditropin FlexPro pen A A e Pull off the pen cap e Check that the liquid in the pen is clear and colorless by tipping it upside down 1 or 2 times If the liquid looks unclear or cloudy do not use the pen e Wash hands well and dry them e Wipe the front stopper on the needle thread with an alcohol swab Front Stopper Inner needle cap Needle Paper tab B e Jake a new disposable needle e Tear the paper tab off and screw the needle straight onto the pen e Make sure the needle is on tight e Never place a disposable needle on your Norditropin FlexPro pen until you are ready to give an injection C e Pull off the outer needle cap and inner needle cap and throw them both away e f you try to put the needle caps back on you may accidentally hurt yourself with the needle e A drop of liquid may appear at the needle tip This is normal Important e Always use a new needle for each injection This will help prevent contamination e Never bend or damage the needle Check the growth hormone flow airshot Make sur
104. ugh biotechnology It is identical to the growth hormone produced in the human body Norditropin is used to treat the following e children with growth failure caused by very low or no production of growth hormone e short stature in children with Noonan syndrome e short stature in children with Turner syndrome e Children with short stature born small for gestational age SGA with no catch up growth by age 2 4 years e adults who do not make sufficient growth hormone Norditropin is injected using Norditropin NordiFlex a multi dose disposable 1 5 mL or 3 mL prefilled pen Norditropin NordiFlex contains several doses of growth hormone solution A dose is injected under the skin in the evening 6 times a week or daily Norditropin NordiFlex is available in several delivery pens sizes and as Outlined in the table below Concentration Throw away Norditropin NordiFlex when the cartridge is empty Medicines are sometimes prescribed for purposes other than those listed in a patient guide You should ask your doctor about any concerns and refer to the prescriber information for additional information What does Norditropin NordiFlex contain The cartridge in Norditropin NordiFlex contains human growth hormone The cartridge also contains other ingredients Histidine Poloxamer 188 Phenol Mannitol and Water for Injection Who should not use Norditropin NordiFlex Do not use Norditropin NordiFlex if you ha
105. ush button all the way in A drop of liquid should appear at the needle tip If not repeat the above steps no more than 4 times If a drop of liquid still does not appear call 1 888 NOVO 444 for help 3 Setting the Dose F Check that the dose selector is set at 0 0 Dial the number of mg milligram that you need to inject If you dial more than your dose the dose can be changed up or down by turning the dose selector in either direction When dialing back be careful not to press the push button as liquid will come out Use dosage indicator NOT the clicking sound as a guide for selecting the dose The numbers on the residual scale can be used to estimate the mg left in the cartridge DO NOT use these numbers to measure the dose You cannot set a dose higher than the number of mg left in the cartridge Use a new Norditropin NordiFlex pen to inject the remaining amount of your dose Be sure to remember the dose already received with the first dose For example if your dose is 0 6 mg and you can only set the dose selector to 0 3 mg You will need to inject an additional 0 3 mg with a new Norditropin NordiFlex pen 4 Giving the Injection Use the injection technique recommended by your healthcare professional G This product is for subcutaneous use only Insert the needle under the skin and press the push button as far as it goes to deliver the dose To ensure that the full dose is injected keep the needle in the skin
106. ve any of the following conditions e child with closed epiphyses closed bone growth plates e child with Prader Willi syndrome who is also severely obese or has significant respiratory impairment e allergic to phenol or any other ingredients in the medicine e had a kidney transplant e pregnant e breast feeding e active cancer or other forms of tumor e acute critical illness due to certain types of heart or abdomen surgery trauma or acute respiratory failure What should you consider if you are pregnant or breast feeding If you become pregnant while you are using Norditropin NordiFlex you are recommended to stop the treatment and discuss this with your doctor You are recommended not to use Norditropin NordiFlex while you are breast feeding because growth hormone might pass into your milk Be sure to tell your doctor if you e have diabetes mellitus e had cancer or other forms of tumor e are pregnant planning to be pregnant or breastfeeding e had a kidney transplant If any of the above applies to you Norditropin NordiFlex may not be suitable Your doctor will give you advice How should I use Norditropin NordiFlex Carefully follow the Instructions for Use on the other side of this patient guide You should inject Norditropin NordiFlex under the skin in the evening just before bedtime You should change the injection area so you do not harm your skin NovoFine disposable needles are designe
107. ven if they have the same symptoms that you have It may harm them This Patient Information summarizes the most important information about Norditropin If you would like more information talk with your healthcare provider You can ask your pharmacist or healthcare provider for information about Norditropin that is written for healthcare professionals What are the ingredients in Norditropin Active ingredient somatropin rDNA origin Inactive ingredients Histidine Poloxamer 188 Phenol Mannitol HCI NaQH as needed and Water for Injection Date of Issue March 2 2010 Version 7 US Patent Nos 6 235 004 6 004 297 6 582 404 6 716 198 6 899 699 5 849 704 5 691 169 5 618 697 and other patents pending Norditropin FlexPro and Norditropin NordiFlex are registered trademarks of Novo Nordisk Health Care AG Novo Nordisk is a registered trademark of Novo Nordisk A S For assistance or further information write to Novo Nordisk Inc 100 College Road West Princeton NJ 08540 USA 1 888 NOVO 444 1 888 668 6444 norditropin us com Manufactured by Novo Nordisk A S O DK 2880 Bagsvaerd Denmark 2004 2010 Novo Nordisk Health Care AG 143038 11 10 novo nordisk norditropin somatropin rDNA origin injection HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use Norditropin Cartridges safely and effectively See full prescribing informa
108. ype 1 11BHSD 1 7 2 Pharmacologic Glucocorticoid Therapy and Supraphysiologic Glucocorticoid Treatment 7 3 Cytochrome P450 Metabolized Drugs 74 Oral Estrogen 7 5 Insulin and or Oral Injectable Hypoglycemic Agents Doses of concurrent antihyperglycemic drugs in diabetics may require adjustment 5 4 e Intracranial Hypertension Exclude preexisting papilledema May develop and is usually reversible after discontinuation or dose reduction 5 5 e Fluid Retention i e edema arthralgia carpal tunnel syndrome especially in adults May occur frequently Reduce dose as necessary 5 6 e Hypothyroidism May first become evident or worsen 5 7 e Slipped Capital Femoral Epiphysis May develop Evaluate children with the onset of a limp or hip knee pain 5 8 e Progression of Preexisting Scoliosis May develop 5 9 e Pancreatitis Consider pancreatitis in patients with persistent severe abdominal pain 5 14 ADVERSE REACTIONS Other common somatropin related adverse reactions include injection site reactions rashes and lipoatrophy 6 1 and headaches 6 3 To report SUSPECTED ADVERSE REACTIONS contact Novo Nordisk at 1 888 NOVO 444 1 888 668 6444 or FDA at 1 800 FDA 1088 or www fda gov medwatch DRUG INTERACTIONS e Inhibition of 118 Hydroxysteroid Dehydrogenase Type 1 May require the initiation of glucocorticoid replacement therapy Patients treated with glucocorticoid replacement for previously diagnosed hypoadr

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