Norditropin

The following important adverse reactions are also described elsewhere in the labeling:

• Increased mortality in patients with acute critical illness [see WARNINGS AND PRECAUTIONS]
• Fatalities in children with Prader-Willi syndrome [see WARNINGS AND PRECAUTIONS]
• Neoplasms [see WARNINGS AND PRECAUTIONS]
• Glucose intolerance and diabetes mellitus [see WARNINGS AND PRECAUTIONS]
• Intracranial hypertension [see WARNINGS AND PRECAUTIONS]
• Severe hypersensitivity [see WARNINGS AND PRECAUTIONS]
• Fluid retention [see WARNINGS AND PRECAUTIONS]
• Hypoadrenalism [see WARNINGS AND PRECAUTIONS]
• Hypothyroidism [see WARNINGS AND PRECAUTIONS]
• Slipped capital femoral epiphysis in pediatric patients [see WARNINGS AND PRECAUTIONS]
• Progression of preexisting scoliosis in pediatric patients [see WARNINGS AND PRECAUTIONS]
• Otitis media and cardiovascular disorders in patients with Turner syndrome [see WARNINGS AND PRECAUTIONS]
• Lipoatrophy [see WARNINGS AND PRECAUTIONS]
• Pancreatitis [see WARNINGS AND PRECAUTIONS]

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 common 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]. 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 respiratory 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]. 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 and ADVERSE REACTIONS]. 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].

Clinical Trials In Children Born Small For Gestational Age (SGA) With No Catch-Up Growth By Age 2-4 Years

In a multi-center, randomized, double-blind study, 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]. 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.

In a multi-center, randomized, double-blind, parallel-group study, 98 Japanese 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) 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 levels between 100 and 126 mg/dL, or with fasting blood glucose levels > 126 mg/dL. Furthermore, mean hemoglobin A1c 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 > 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 and ADVERSE REACTIONS].

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 > +2) was observed after both longterm (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 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 and ADVERSE REACTIONS]. 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

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.

Post-Marketing Experience

Because these adverse events are reported voluntarily from a population of uncertain 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 and 6.1 in children and adults.

Serious systemic hypersensitivity reactions including anaphylactic reactions and angioedema have been reported with postmarketing use of somatropin products [see WARNINGS AND PRECAUTIONS].

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 and WARNINGS AND PRECAUTIONS].

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 ).

New-onset type 2 diabetes mellitus has been reported.

NORDITROPIN®
(Nor-dee-tro-pin)
(somatropin) Injection for Subcutaneous Use

What is Norditropin?

Norditropin is a prescription medicine that contains human growth hormone, the same growth hormone made by the human body.

Norditropin is given by injection under the skin (subcutaneous) and is used to treat:

• children who are not growing 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
• adults who did not make enough growth hormone when they were children or when they became adults

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 breathing 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)
• you are allergic to somatropin or any of the ingredients in Norditropin. See the end of this leaflet for a complete list of ingredients in Norditropin.

Before taking Norditropin, tell your healthcare provider about all of your medical conditions, including if you:

• have diabetes
• had cancer or any tumor
• have any other medical conditions
• 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.
• are breastfeeding or plan to breastfeed. 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 breastfeed.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Norditropin may affect how other medicines work, and other medicines may affect how Norditropin works.

How should I use Norditropin?

• Read the detailed Instructions for Use that come with Norditropin.
• Norditropin comes in 4 different dosage strengths. Your healthcare provider will prescribe the dose that is right for you.
• Your healthcare provider will show you how to inject Norditropin.
• Use Norditropin exactly as your healthcare provider tells you to.
• Norditropin FlexPro pens are for use for 1 person only.
• Do not share your Norditropin pen and needles with another person. You may give another person an infection or get an infection from them.

What are the possible side effects of Norditropin?

Norditropin may 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 (respiratory) problems
• high risk of death in children with Prader-Willi syndrome who are severely 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). If you have headaches, eye problems, nausea or vomiting, swollen hands and feet due to fluid retention contact your healthcare provider right away.
• serious allergic reactions. Get medical help right away if you have the following symptoms:
  • swelling of your face, lips, mouth, or tongue
  • trouble breathing
  • wheezing
  • severe itching
  • skin rashes, redness, or swelling
  • dizziness or fainting
  • fast heartbeat or pounding in your chest
  • sweating
• decrease in a hormone called cortisol. Your healthcare provider will do blood tests to check your cortisol levels.
• decrease in thyroid hormone levels. Your healthcare provider will do blood tests to check your thyroid hormone levels.
• hip and knee pain or a limp in children (slipped capital femoral epiphysis)
• worsening of curvature of the spine (scoliosis)
• middle ear infection, hearing problems or ear problems in people with Turner syndrome, redness, itching and tissue weakness in the area of skin you inject
• 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:

• headaches
• muscle pain
• joint stiffness
• high blood sugar (hyperglycemia)
• sugar in your urine (glucosuria)

These are not all the possible side effects of NORDITROPIN.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. You may also report side effects to Novo Nordisk at 1-888-668-6444.

How should I store Norditropin?

• Before you use Norditropin FlexPro pens for the first time:
  • Store your new, unused Norditropin pen in a refrigerator between 36°F to 46°F (2°C to 8°C).
  • Do not freeze or expose Norditropin to heat.
  • Keep Norditropin away from direct light.
  • Do not use Norditropin that has been frozen or in temperatures warmer than 77°F (25°C).
  • Do not use Norditropin after the expiration date printed on the carton and the pen.
• After you use Norditropin FlexPro pens and there is still medicine left:
  • Store remaining Norditropin in the refrigerator between 36°F to 46°F (2°C to 8°C) and use within 4 weeks, or
  • Store remaining Norditropin at room temperature no warmer than 77°F (25°C) and use within 3 weeks.

Keep Norditropin and all medicines out of the reach of children.

General information about the safe and effective use of Norditropin.

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. 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. You can ask your pharmacist or healthcare provider for information about NORDITROPIN that is written for health professionals.

What are the ingredients in Norditropin?

Active ingredient: somatropin

Inactive ingredients: Histidine, Poloxamer 188, Phenol, Mannitol, HCl/NaOH (as needed) and Water for Injection

INSTRUCTIONS FOR USE

Norditropin®
(Nor-dee-tro-pin)
FlexPro® (somatropin) injection 5 mg/1.5 mL Pen

Note:

• Norditropin is for use under the skin only (subcutaneous).
• Do not share your Norditropin Pen and needles with another person. You may give another person an infection or get an infection from them.

Figure A

Supplies you will need for a Norditropin Injection. See Figure A.

• Norditropin FlexPro Prefilled Pen
• 1 Novo Nordisk disposable needle. Needles are not included with the Pen.
• 2 alcohol swabs
• flat surface like a table
• a sharps disposal container. See Step 6 for information on how to dispose of used needles and syringes.

6 Steps you should follow for a Norditropin injection:

Step 1. Preparing the Norditropin FlexPro Pen

Step 2. Attaching the needle to the Norditropin FlexPro Pen

Step 3. Priming a new Pen

Step 4. Selecting the correct dose of Norditropin

Step 5. Selecting the injection site and injecting the dose of Norditropin

Step 6. What to do after the injection is completed.

Step 1. Preparing the Norditropin FlexPro Pen.

• Pull off the Pen cap. See Figure B.

Figure B

• Look in the growth hormone scale window. Check that the liquid medicine 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. See Figure C.

Figure C

• Wash your hands well and dry them.
• Wipe the front stopper on the needle thread with an alcohol swab. See Figure D.

Figure D

Step 2. Attaching the needle to the Norditropin FlexPro Pen.

• Never place a needle on your Pen until you are ready to give an injection.
• Take a new disposable needle and tear off the paper tab. See Figure E.

Figure E

• Holding the Pen with one hand, firmly press the needle onto the needle thread of the Pen.
• Screw the needle in a clockwise direction until the needle will not turn anymore. See Figure F.

Figure F

• Pull off the outer needle cap. See Figure G.

Figure G

• Pull off the inner needle cap and throw them both away. See Figure H. If you try to put the needle caps back on, you may accidentally hurt yourself with the needle.
• A drop of liquid may appear at the needle tip. This is normal.

Figure H

Step 3. Priming a new Pen.

• Checking the growth hormone flow in the pen (priming) is not needed for a Pen you have used before. If the Pen has already been primed, go to Step 4.
• Before you use a new Pen you must first prepare it for use. Hold the Pen with one hand and turn the dose selector clockwise to select 0.025 mg. You will hear a faint click when you turn the dose selector. This is the smallest amount of medicine for a dose. See Figure I.

Figure I

• Hold the Pen with the needle pointing up. Tap the top of the Pen gently a few times to let any air bubbles rise to the top. See Figure J.

Figure J

• 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. See Figure K.

Figure K

• If no drop appears, repeat Step 3 again up to 6 times.
• If you still do not see a drop of liquid, change the needle and repeat Step 3 again.
• If a drop of liquid still does not appear after repeating Step 3 and changing the needle, call Novo Nordisk at 1-888-668-6444 for help.

Step 4. Selecting the correct dose of Norditropin.

• 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.
• To start, check that the pointer on the Pen is set at “0”. See Figure L.

Figure L

• Select the dose you need by turning the dose selector clockwise. If you go beyond your dose, turn the dose selector counterclockwise until the right number of mg lines up with the pointer.
• To guide you, the dose selector click sound is different when turned clockwise (softer click) or counterclockwise (louder click). You will hear a click for every single unit dialed.
• When dialing counterclockwise, be careful not to press the dose button as liquid will come out.
• You can use the growth hormone scale on the side of the Pen to see approximately how much growth hormone is left in the Pen. You can also 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 number that lines up with the pointer shows how many mg is left in the Pen.
• You cannot set a dose higher than the number of mg left in the Pen.
• If 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.
• Remember to subtract the dose already received. For example, if the dose is 0.7 mg and you can only set the dose selector to 0.35 mg, you should inject another 0.35 mg with a new Norditropin FlexPro Pen. See Figure L.

Important:

• Never use the Pen clicks to count the number of mg you select. Only the display window and pointer will show the exact number.
• Never use the growth hormone scale to measure how much liquid to inject. Only the display window and pointer will show the exact number.

Step 5. Selecting the injection site and injecting the dose of Norditropin.

• Change the injection site every day.
• Select the injection site and wipe the skin with an alcohol swab as your healthcare provider showed you.
• Insert the needle under the skin as your healthcare provider showed you. See Figure M.

Figure M

• After inserting the needle into the skin, push and hold the dose button in as far as it will go to give the dose. 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. See Figure M.
• If you remove your finger from the dose button before the “0” is in the display window the full dose has not been received. Leave the needle in the skin and press and hold the dose button again until the “0” lines up with the pointer.

If the injection button cannot be pushed in completely or “0” does not appear in the display window, you did not receive the full dose. Call Novo Nordisk at 1-888-668-6444 for assistance. You may need a new Pen.

• 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. Let go of the dose button while you wait.

Important:

• Always press the dose button to inject the dose. Turning the dose selector will not inject the dose.
• Never touch the display window when you inject, as this can block the injection.
• Carefully lift the pen to remove the needle from the 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. See Figure N.

Figure N

Step 6. What to do after the injection is completed.

• Do not recap the needle. Recapping a needle can lead to a needle stick injury. Remove the needle from the Pen after each injection.
• Carefully remove the needle from the Pen by turning the needle in a counterclockwise direction. See Figure O.

Figure O

• Put the Pen cap back on.
• If there is medicine left in the Pen, store the Pen as directed in the Patient Information that comes with this Pen.
• If the Pen is empty, throw the Pen away as directed below. Put your used needles and Pen in a FDA-cleared sharps disposal container right away after use. Do not throw away (dispose of) loose needles and Pens in your household trash.
• If you do not have a FDA-cleared sharps disposal container, you may use a household container that is:
  • made of a heavy-duty plastic,
  • can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out,
  • upright and stable during use,
  • leak-resistant, and
  • properly labeled to warn of hazardous waste inside the container.
• When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used needles and Pens. For more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA’s website at: http://www.fda.gov/safesharpsdisposal.
• Do not dispose of your used sharps disposal container in your household trash unless your community guidelines permit this. Do not recycle your used sharps disposal container.

Care of your Norditropin FlexPro Pen:

You must take care of your Norditropin FlexPro Pen:

• Do not drop your Pen or knock it against hard surfaces. If you drop it or think that something is wrong with it, always screw on a new disposable needle and check the growth hormone flow (priming) before you inject.
• Do not try to refill your Pen. It is prefilled.
• Do not try to repair your Pen or pull it apart.
• Do not expose your Pen to dust, dirt or any kind of liquid.
• Do not try to wash, soak or lubricate your Pen. Clean the Norditropin FlexPro Pen with a mild detergent on a moistened cloth.
• Always keep your Pen and needles out of reach of others, especially children.

INSTRUCTIONS FOR USE

Norditropin®
(Nor-dee-tro-pin) FlexPro®
(somatropin) injection
10 mg/1.5 mL Pen

Note:

• Norditropin is for use under the skin only (subcutaneous).
• Do not share your Norditropin Pen and needles with another person. You may give another person an infection or get an infection from them.

Figure A

Supplies you will need for a Norditropin Injection. See Figure A.

• Norditropin FlexPro Prefilled Pen
• 1 Novo Nordisk disposable needle. Needles are not included with the Pen.
• 2 alcohol swabs
• flat surface like a table
• a sharps disposal container. See Step 6 for information on how to dispose of used needles and syringes.

6 Steps you should follow for a Norditropin injection:

Step 1. Preparing the Norditropin FlexPro Pen

Step 2. Attaching the needle to the Norditropin FlexPro Pen

Step 3. Priming a new Pen

Step 4. Selecting the correct dose of Norditropin

Step 5. Selecting the injection site and injecting the dose of Norditropin

Step 6. What to do after the injection is completed.

Step 1. Preparing the Norditropin FlexPro Pen.

• Pull off the Pen cap. See Figure B.

Figure B

• Look in the growth hormone scale window. Check that the liquid medicine 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. See Figure C.

Figure C

• Wash your hands well and dry them.
• Wipe the front stopper on the needle thread with an alcohol swab. See Figure D.

Figure D

Step 2. Attaching the needle to the Norditropin FlexPro Pen.

• Never place a needle on your Pen until you are ready to give an injection.
• Take a new disposable needle and tear off the paper tab. See Figure E.

Figure E

• Holding the Pen with one hand, firmly press the needle onto the needle thread of the Pen.
• Screw the needle in a clockwise direction until the needle will not turn anymore. See Figure F.

Figure F

• Pull off the outer needle cap. See Figure G.

Figure G

• Pull off the inner needle cap and throw them both away. See Figure H. If you try to put the needle caps back on, you may accidentally hurt yourself with the needle.
• A drop of liquid may appear at the needle tip. This is normal.

Figure H

Step 3. Priming a new Pen.

• Checking the growth hormone flow in the pen (priming) is not needed for a Pen you have used before. If the Pen has already been primed, go to Step 4.
• Before you use a new Pen you must first prepare it for use. Hold the Pen with one hand and turn the dose selector clockwise to select 0.05 mg. You will hear a faint click when you turn the dose selector. This is the smallest amount of medicine for a dose. See Figure I.

Figure I

• Hold the Pen with the needle pointing up. Tap the top of the Pen gently a few times to let any air bubbles rise to the top. See Figure J.

Figure J

• 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. See Figure K.

Figure K

• If no drop appears, repeat Step 3 again up to 6 times.
• If you still do not see a drop of liquid, change the needle and repeat Step 3 again.
• If a drop of liquid still does not appear after repeating Step 3 and changing the needle, call Novo Nordisk at 1-888-668-6444 for help.

Step 4. Selecting the correct dose of Norditropin.

• 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.
• To start, check that the pointer on the Pen is set at “0”. See Figure L.

Figure L

• Select the dose you need by turning the dose selector clockwise. If you go beyond your dose, turn the dose selector counterclockwise until the right number of mg lines up with the pointer.
• To guide you, the dose selector click sound is different when turned clockwise (softer click) or counterclockwise (louder click). You will hear a click for every single unit dialed.
• When dialing counterclockwise, be careful not to press the dose button as liquid will come out.
• You can use the growth hormone scale on the side of the Pen to see approximately how much growth hormone is left in the Pen. You can also 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 number that lines up with the pointer shows how many mg is left in the Pen.
• You cannot set a dose higher than the number of mg left in the Pen.
• If 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.
• Remember to subtract the dose already received. For example, if the dose is 1.4 mg and you can only set the dose selector to 0.7 mg, you should inject another 0.7 mg with a new Norditropin FlexPro Pen. See Figure L.

Important:

• Never use the Pen clicks to count the number of mg you select. Only the display window and pointer will show the exact number.
• Never use the growth hormone scale to measure how much liquid to inject. Only the display window and pointer will show the exact number.

Step 5. Selecting the injection site and injecting the dose of Norditropin.

• Change the injection site every day.
• Select the injection site and wipe the skin with an alcohol swab as your healthcare provider showed you.
• Insert the needle under the skin as your healthcare provider showed you. See Figure M.

Figure M

• After inserting the needle into the skin, push and hold the dose button in as far as it will go to give the dose. 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. See Figure M.
• If you remove your finger from the dose button before the “0” is in the display window the full dose has not been received. Leave the needle in the skin and press and hold the dose button again until the “0” lines up with the pointer.

If the injection button cannot be pushed in completely or “0” does not appear in the display window, you did not receive the full dose. Call Novo Nordisk at 1-888-668-6444 for assistance. You may need a new Pen.

• 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. Let go of the dose button while you wait.

Important:

• Always press the dose button to inject the dose. Turning the dose selector will not inject the dose.
• Never touch the display window when you inject, as this can block the injection.
• Carefully lift the pen to remove the needle from the 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. See Figure N.

Figure N

Step 6. What to do after the injection is completed.

• Do not recap the needle. Recapping a needle can lead to a needle stick injury. Remove the needle from the Pen after each injection.
• Carefully remove the needle from the Pen by turning the needle in a counterclockwise direction. See Figure O.

Figure O

• Put the Pen cap back on.
• If there is medicine left in the Pen, store the Pen as directed in the Patient Information that comes with this Pen.
• If the Pen is empty, throw the Pen away as directed below. Put your used needles and Pen in a FDA-cleared sharps disposal container right away after use. Do not throw away (dispose of) loose needles and Pens in your household trash.
• If you do not have a FDA-cleared sharps disposal container, you may use a household container that is:
  • made of a heavy-duty plastic,
  • can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out,
  • upright and stable during use,
  • leak-resistant, and
  • properly labeled to warn of hazardous waste inside the container.
• When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used needles and Pens. For more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA’s website at: http://www.fda.gov/safesharpsdisposal.
• Do not dispose of your used sharps disposal container in your household trash unless your community guidelines permit this. Do not recycle your used sharps disposal container.

Care of your Norditropin FlexPro Pen:

You must take care of your Norditropin FlexPro Pen:

• Do not drop your Pen or knock it against hard surfaces. If you drop it or think that something is wrong with it, always screw on a new disposable needle and check the growth hormone flow (priming) before you inject.
• Do not try to refill your Pen. It is prefilled.
• Do not try to repair your Pen or pull it apart.
• Do not expose your Pen to dust, dirt or any kind of liquid.
• Do not try to wash, soak or lubricate your Pen. Clean the Norditropin FlexPro Pen with a mild detergent on a moistened cloth.
• Always keep your Pen and needles out of reach of others, especially children.

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Norditropin® FlexPro®
(somatropin) injection 10mg/1.5mL Prefilled Pen

Note:

• Norditropin is for use under the skin only (subcutaneous).
• Do not share your Norditropin Pen and needles with another person. You may give another person an infection or get an infection from them.

Figure A

Supplies you will need for a Norditropin Injection. See Figure A.

• Norditropin FlexPro Prefilled Pen
• 1 Novo Nordisk disposable needle. Needles are not included with the Pen.
• 2 alcohol swabs
• flat surface like a table
• a sharps disposal container. See Step 6 for information on how to dispose of used needles and syringes.

6 Steps you should follow for a Norditropin injection:

Step 1. Preparing the Norditropin FlexPro Pen

Step 2. Attaching the needle to the Norditropin FlexPro Pen

Step 3. Priming a new Pen

Step 4. Selecting the correct dose of Norditropin

Step 5. Selecting the injection site and injecting the dose of Norditropin

Step 6. What to do after the injection is completed.

Step 1. Preparing the Norditropin FlexPro Pen.

• Pull off the Pen cap. See Figure B.

Figure B

• Look in the growth hormone scale window. Check that the liquid medicine 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. See Figure C.

Figure C

• Wash your hands well and dry them.
• Wipe the front stopper on the needle thread with an alcohol swab. See Figure D.

Figure D

Step 2. Attaching the needle to the Norditropin FlexPro Pen.

• Never place a needle on your Pen until you are ready to give an injection.
• Take a new disposable needle and tear off the paper tab. See Figure E.

Figure E

• Holding the Pen with one hand, firmly press the needle onto the needle thread of the Pen.
• Screw the needle in a clockwise direction until the needle will not turn anymore. See Figure F.

Figure F

• Pull off the outer needle cap. See Figure G.

Figure G

• Pull off the inner needle cap and throw them both away. See Figure H.
• If you try to put the needle caps back on, you may accidentally hurt yourself with the needle.
• A drop of liquid may appear at the needle tip. This is normal.

Figure H

Step 3. Priming a new Pen.

• Checking the growth hormone flow in the pen (priming) is not needed for a Pen you have used before. If the Pen has already been primed, go to Step 4.
• Before you use a new Pen you must first prepare it for use. Hold the Pen with one hand and turn the dose selector clockwise to select 0.1 mg. You will hear a faint click when you turn the dose selector. This is the smallest amount of medicine for a dose. See Figure I.

Figure I

• Hold the Pen with the needle pointing up. Tap the top of the Pen gently a few times to let any air bubbles rise to the top. See Figure J.

Figure J

• 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. See Figure K.

Figure K

• If no drop appears, repeat Step 3 again up to 6 times.
• If you still do not see a drop of liquid, change the needle and repeat Step 3 again.
• If a drop of liquid still does not appear after repeating Step 3 and changing the needle, call Novo Nordisk at 1-888-668-6444 for help.

Step 4. Selecting the correct dose of Norditropin.

• 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.
• To start, check that the pointer on the Pen is set at “0”. See Figure L.

Figure L

• Select the dose you need by turning the dose selector clockwise. If you go beyond your dose, turn the dose selector counterclockwise until the right number of mg lines up with the pointer.
• To guide you, the dose selector click sound is different when turned clockwise (softer click) or counterclockwise (louder click). You will hear a click for every single unit dialed.
• When dialing counterclockwise, be careful not to press the dose button as liquid will come out.
• You can use the growth hormone scale on the side of the Pen to see approximately how much growth hormone is left in the Pen. You can also 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 number that lines up with the pointer shows how many mg is left in the Pen.
• You cannot set a dose higher than the number of mg left in the Pen.
• If 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.
• Remember to subtract the dose already received. For example, if the 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. See Figure L.

Important:

• Never use the Pen clicks to count the number of mg you select. Only the display window and pointer will show the exact number.
• Never use the growth hormone scale to measure how much liquid to inject. Only the display window and pointer will show the exact number.

Step 5. Selecting the injection site and injecting the dose of Norditropin.

• Change the injection site every day.
• Select the injection site and wipe the skin with an alcohol swab as your healthcare provider showed you.
• Insert the needle under the skin as your healthcare provider showed you. See Figure M.

Figure M

• After inserting the needle into the skin, push and hold the dose button in as far as it will go to give the dose. 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. See Figure M.
• If you remove your finger from the dose button before the “0” is in the display window the full dose has not been received. Leave the needle in the skin and press and hold the dose button again until the “0” lines up with the pointer.

If the injection button cannot be pushed in completely or “0” does not appear in the display window, you did not receive the full dose. Call Novo Nordisk at 1-888-668-6444 for assistance. You may need a new Pen.

• 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. Let go of the dose button while you wait.

Important:

• Always press the dose button to inject the dose. Turning the dose selector will not inject the dose.
• Never touch the display window when you inject, as this can block the injection.
• Carefully lift the pen to remove the needle from the 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. See Figure N.

Figure N

Step 6. What to do after the injection is completed.

• Do not recap the needle. Recapping a needle can lead to a needle stick injury. Remove the needle from the Pen after each injection.
• Carefully remove the needle from the Pen by turning the needle in a counterclockwise direction. See Figure O.

Figure O

• Put the Pen cap back on.
• If there is medicine left in the Pen, store the Pen as directed in the Patient Information that comes with this Pen.
• If the Pen is empty, throw the Pen away as directed below. Put your used needles and Pen in a FDA-cleared sharps disposal container right away after use. Do not throw away (dispose of) loose needles and Pens in your household trash.
• If you do not have a FDA-cleared sharps disposal container, you may use a household container that is:
  • made of a heavy-duty plastic,
  • can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out,
  • upright and stable during use,
  • leak-resistant, and
  • properly labeled to warn of hazardous waste inside the container.
• When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used needles and Pens. For more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA's website at: http://www.fda.gov/safesharpsdisposal.
• Do not dispose of your used sharps disposal container in your household trash unless your community guidelines permit this. Do not recycle your used sharps disposal container.

Care of your Norditropin FlexPro Pen:

You must take care of your Norditropin FlexPro Pen:

• Do not drop your Pen or knock it against hard surfaces. If you drop it or think that something is wrong with it, always screw on a new disposable needle and check the growth hormone flow (priming) before you inject.
• Do not try to refill your Pen. It is prefilled.
• Do not try to repair your Pen or pull it apart.
• Do not expose your Pen to dust, dirt or any kind of liquid.
• Do not try to wash, soak or lubricate your Pen. Clean the Norditropin FlexPro Pen with a mild detergent on a moistened cloth.
• Always keep your Pen and needles out of reach of others, especially children.

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Norditropin® FlexPro®
(somatropin) injection 15mg/1.5mL Prefilled Pen

Supplies you will need:

• Norditropin FlexPro prefilled Pen
• Novo Nordisk disposable needles up to a length of 8 mm
• a sharps container

How to use your Norditropin FlexPro Pen

5 steps you should follow for a Norditropin injection:

Step 1: Prepare your Norditropin FlexPro Pen

Step 2: Check the Norditropin flow with each new Pen

Step 3: Select your dose

Step 4: Inject your dose

Step 5: After your injection

For further information about your Pen:

Frequently Asked Questions

Important information

Patient Information

Norditropin is for use under the skin only (subcutaneous).

Do not share your Norditropin Pen and needles with another person. You may give another person an infection or get an infection from them.

Do not use your Pen without proper training from your healthcare provider.

Make sure that you are confident in making an injection with the Pen before you start your treatment. If you are blind or have poor eyesight and cannot read the dose counter on the Pen, do not use this Pen without help. Get help from a person with good eyesight who is trained to use the Pen.

Step 1. Prepare your Norditropin FlexPro Pen

• Wash your hands with soap and water.
• Check the name, strength, and colored label on your Pen to make sure that it contains Norditropin in the right strength.
• Pull off the Pen cap.
• Turn the Pen upside down once or twice to check that the Norditropin in your Pen is clear and colorless. See figure A. If the Norditropin looks cloudy, do not use the Pen.

• When you are ready to take your injection, take a new disposable needle, and tear off the paper tab.
• Push the needle straight onto the Pen. Turn the needle clockwise until it is on tight. See figure B.

• Always use a new needle for each injection. This reduces the risk of contamination, infection, leakage of Norditropin, and blocked needles leading to incorrect dosing.
• Pull off the outer needle cap and dispose of it. See figure C.

• Pull off the inner needle cap and dispose of it. See figure D.
• A drop of Norditropin may appear at the needle tip. This is normal, but you must still check the Norditropin flow with each new Pen. See step 2.

• Never use a bent or damaged needle.

Step 2. Check the Norditropin flow with each new Pen

If your Pen is already in use, proceed to step 3.

Before using a new Pen, check the Norditropin flow to make sure the growth hormone can flow through the Pen and needle.

• Turn the dose selector clockwise one tick mark to select 0.1 mg. You will hear a faint click. See figure E.

• One tick mark equals 0.1 mg in the dose counter. See figure F.

• Hold the Pen with the needle pointing up. Press and hold in the dose button until the dose counter returns to 0. The 0 must line up with the dose pointer. See figure G.

• Check that a drop of Norditropin appears at the needle tip. See figure H.
• If no Norditropin appears,repeat step 2 up to 6 times.

If you still do not see a drop of Norditropin, change the needle and repeat step 2 again.

Do not use the Pen if a drop of Norditropin still does not appear after repeating step 2. Call Novo Nordisk at 1-888-668-6444 for help.

Step 3. Select your dose

• To start, check that the dose counter is set at 0.
• Turn the dose selector clockwise to select the dose you need. See figure I.
  When you have selected your dose, you can proceed to step 4.
• If there is not enough Norditropin left to select a full dose, see Frequently Asked Questions.

• The dose counter shows the dose in mg. See figures J and K. Always use the dose counter to select the exact dose. Do not count the Pen clicks. Do not use the Pen scale.

• If you select the wrong dose, you can turn the dose selector clockwise or counterclockwise to the correct dose. See figure L.

The Pen clicks sound and feel differently when the dose selector is turned clockwise, counterclockwise, or if you accidentally force it past the number of mg left.

Step 4. Inject your dose

• Norditropin can be injected under the skin (subcutaneously) of your hips, stomach area (abdomen), buttocks, upper legs (thighs), upper arms, or as otherwise instructed by your healthcare provider. Change the injection site every day.
• Insert the needle into your skin as your healthcare provider has shown you. See figure M.

Make sure you can see the dose counter. Do not cover it with your fingers. This could block the injection.

• Press and hold down the dose button until the dose counter shows 0. See figure N. The 0 must line up with the dose pointer. You may then hear or feel a click.
• Continue to hold the needle in your skin.
• If 0 does not appear in the dose counter after continuously pressing the dose button, your needle may be blocked or damaged, see Frequently Asked Questions.

• Keep the needle in your skin after the dose counter has returned to 0. Count slowly to 6 to ensure that the full dose has been delivered. See figure O.

• Carefully remove the needle from your skin. See figure P. If blood appears at the injection site, press lightly. Do not rub the area.
• You may see a drop of Norditropin at the needle tip after injecting. This is normal and does not affect your dose.

Step 5. After your injection

• Carefully remove the needle from the Pen by turning counterclockwise. See figure Q.

• Place the needle in a sharps container immediately to reduce the risk of needle sticks. See figure R.

• Do not try to put the needle caps back on. You may stick yourself with the needle.
• Put the Pen cap on your Pen after each use to protect the Norditropin from direct light. See figure S.

To store your Pen, see the Patient Information section.

• Always dispose of the needle after each injection. Put the needle and any empty or discarded Pen still containing Norditropin in an FDA-cleared sharps disposal container. See figure T.

For further information about safe sharps disposal, see Frequently Asked Questions.

• Always remove the needle from your Pen. This reduces the risk of contamination, infection, leakage of Norditropin, and blocked needles leading to incorrect dosing.

Frequently Asked Questions

How do I see how much Norditropin is left in my Pen?

The Pen scale shows you approximately how much Norditropin is left in your Pen. See figure U below.

To see how much Norditropin is left, use the dose counter: Turn the dose selector clockwise until the dose counter stops. You can select a maximum dose of 8.0 mg. If it shows 8.0 mg, at least 8.0 mg are left in your Pen. If it shows 3.8, only 3.8 mg are left in your Pen. See figure V below.

What if I need a larger dose than what is left in my Pen?

It is not possible to select a larger dose than the amount of mg left in your Pen. If you need more Norditropin than you have left in your Pen, you can use a new Pen or split your dose between your current Pen and a new Pen. Only if trained or advised by your healthcare provider, may you split your dose. Use a calculator to plan the doses as instructed by your healthcare provider.

Be very careful to calculate correctly. If you are not sure how to split your dose using two Pens, then select and inject the dose you need with a new Pen.

What if no Norditropin appears when I check the flow?

A. Your needle may be blocked or damaged, if no Norditropin appears at the needle tip. Remove the needle as described in step 5 and repeat steps 1 and 2.

B. Your Pen may be defective,if Norditropin still does not appear after changing the needle. Do not use the Pen. Contact Novo Nordisk at 1-888-668-6444.

What if 0 does not appear after completing my injection?

In this case the needle may be blocked or damaged, and you have not received any Norditropin – even though the dose counter has moved from the original dose that you have set. Remove the needle as described in step 5 and repeat steps 1 to 4.

How should I take care of my Pen?

Be careful not to drop your Pen or knock it against hard surfaces. Do not expose your Pen to dust, dirt, liquid, or direct light.

If there is Norditropin left in the Pen, store the Pen as directed in the Patient Information section How do I store Norditropin.

Do not try to refill your Pen, it's prefilled.

Frequently Asked Questions

What if I drop my Pen?

If you drop your Pen or think that something is wrong with it, attach a new disposable needle and check the Norditropin flow before you inject, see steps 1 and 2. Do not try to repair your Pen or pull it apart.

How do I clean my Pen?

Do not wash, soak, or lubricate your Pen. If necessary, clean it with mild detergent on a moistened cloth.

How do I dispose of needles and Pens?

Empty Pens should be disposed of as directed below. Put your used needles and Pen in an FDA-cleared sharps disposal container right away after use. Do not dispose of loose needles and Pens in your household trash. If you do not have an FDA-cleared sharps disposal container, you may use a household container that is: made of a heavy-duty plastic, can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out, upright and stable during use, leak-resistant, and properly labeled to warn of hazardous waste inside the container.

Follow your community guidelines on how to dispose of your sharps disposal container. There may be state or local laws about how you should dispose of used needles and Pens. For specific information about safe sharps disposal in the state that you live in, go to the FDA's website at: http://www.fda.gov/safesharpsdisposal.

Do not dispose of your used sharps disposal container in your household trash unless your community guidelines permit this. Do not recycle your used sharps disposal container.

• Important information
  • Caregivers must be very careful when handling needles – to reduce the risk of needle sticks and cross-infection.
  • Always keep your Pen and needles out of reach of others, especially children.
  • Norditropin® FlexPro® 30 mg/3 mL Pen is not compatible with FlexPro® PenMate® .
  • To store your Pen, see How do I store Norditropin in the Patient Information.

Norditropin®FlexPro®
(Nor-dee-tro-pin)
(somatropin) injection 30 mg/3 mL Instructions for use

Norditropin®
(Nor-dee-tro-pin)

FlexPro®
(somatropin) injection Prefilled Pen with PenMate®

Read this Instructions for Use before you start using your Pen with PenMate.

• PenMate hides the needle when you inject your Norditropin growth hormone with Norditropin FlexPro 5 mg, 10 mg, and 15 mg Pens so that you cannot see it. Use your PenMate only after you have been trained by a healthcare provider.
• Blind people or people with severe vision problems should only use the PenMate and Pen with help from another person with good eyesight who is trained to use the PenMate and Pen.
• The figures in these instructions show PenMate being used with a Norditropin FlexPro 5 mg Pen and a NovoFine needle that is 8 mm long. Even if you are using a 10 mg or 15 mg Pen or a different needle that is 8 mm long the instructions are the same.
• Do not share your Norditropin Pen and needles with another person. You may give another person an infection or get an infection from them.

Supplies you will need to use your Pen with PenMate:

• 1 PenMate. See figure A.
• 1 Norditropin FlexPro Pen. See figure B. PenMate does not work with other injection devices.
• 1 disposable needle up to a length of 8 mm. See figure C. Needles are not included with your PenMate or Pen.
• 2 alcohol swabs. See figure C.
• a sharps disposal container. See figure C. See ”How should I dispose of my Pen and needles” at the end of these instructions for information on how to dispose of used needles.

PenMate:

Figure A

Norditropin FlexPro 5 mg, 10 mg or 15 mg Pen:

Figure B

Needle parts:

Figure C

Pen case:

Figure D

Step 1: Preparing your Pen with PenMate:

Wash your hands with soap and water and dry them. Check the name and the colored label on your Pen to make sure it contains the growth hormone strength prescribed by your healthcare provider.

Pull off the PenMate cap.

See figure E.

Figure E

Pull off the Pen cap and throw it away. See figure F.

You will not need the Pen cap with your PenMate. Pen cap

Figure F

Look in the Pen window. Check that the liquid medicine in your Pen is clear and colorless by tipping it upside down 1 or 2 times. See figure G.

If the liquid looks cloudy or unclear, do not use the Pen.

Figure G

Wipe the front stopper on the needle thread of the Pen with an alcohol swab. See figure H.

Figure H

Insert the Pen into the PenMate. Twist the Pen clockwise until you hear or feel a click. See figure I.

The Pen is correctly attached in your PenMate when the display window on the Pen lines up with the insertion button on your PenMate. Display window Insertion button

Figure I

Step 2. Attaching the needle to your Pen:

• Do not place a needle on your Pen until you are ready to give an injection.
• Always use a new needle for each injection.
• Do not use a bent or damaged needle.

Take a new disposable needle and tear off the paper tab. See figure J.

Figure J

Holding the Pen with 1 hand, firmly press the needle onto the needle thread of the Pen. Screw the needle in a clockwise direction until the needle will not turn anymore. See figure K.

Figure K

Pull off the outer needle cap and save it. See figure L.

You will need the outer needle cap after the injection so you can safely remove the needle from the Pen.

Figure L

Pull off the inner needle cap and throw it away. See figure M.

A drop of liquid may appear at the needle tip. This is normal.

Figure M

Step 3. Priming a new Pen:

Checking the growth hormone flow in the Pen (priming) is not needed for a Pen you have used before. If the Pen has already been primed, go to Step 4.

Before you use a new Pen you must prepare it for use. Hold the Pen with 1 hand and turn the dose selector clockwise 1 tick mark to select the minimum dose. See figure N.

You may hear or feel a click when you turn the dose selector.

Figure N

When you turn the dose selector 1 tick mark, you select the smallest amount of medicine for a dose. See figure O.

Figure O

This lowest dose will be used for your Norditropin flow check dose.

Hold your Pen with PenMate with the needle pointing up. You may see air bubbles in the PenMate window. Gently tap the top of PenMate a few times to let any air bubbles rise to the top. See figure P.

Figure P

Press the dose button until the dose pointer lines up with the “0” in the display window on the Pen and a drop of liquid appears at the needle tip. See figure Q.

Figure Q

If no drop of liquid appears at the needle tip, repeat Step 3 again up to 6 times. If there is still no drop of liquid at the needle tip, change the needle and repeat Step 3 again.

If a drop of liquid still does not appear at the needle tip after repeating Step 3 and changing the needle, call Novo Nordisk at 1-888-668-6444 for assistance.

Step 4. Selecting the correct dose of Norditropin:

Use the dose selector on your Pen to make sure you have the exact dose selected. Your dose will be in a certain number of mg (milligrams).

To start, check that the dose pointer on the Pen is set at “0”.

Select the dose you need by turning the dose selector clockwise. If you go beyond your dose, turn the dose selector counterclockwise until the right number of mg lines up with the dose pointer. See figure R. Dose selector

Figure R

To guide you, the dose selector click sound is different when turned clockwise (softer click) or counterclockwise (louder click). You will hear a click for every single unit dialed.

When dialing counterclockwise, be careful not to press the dose button as liquid will come out.

You can use the growth hormone scale on the side of the Pen to see approximately how much growth hormone is left in the Pen. You can also use the dose selector to see exactly how much growth hormone is left in the Pen.

If the Pen contains less than 2 mg, 4 mg, or 8 mg (depending on whether you use a 5 mg, 10 mg, or 15 mg Pen), turn the dose selector until it stops. The number that lines up with the dose pointer shows how many mg are left in the Pen. You cannot set a dose higher than the number of mg left in the Pen.

If there is not enough Norditropin left in the Pen for your full dose, use a new Norditropin FlexPro Pen to inject the remaining amount of your dose or contact your healthcare provider.

Remember to subtract the dose already received. For example, if the dose is 0.7 mg and you can only set the dose selector to 0.35 mg, you should inject another 0.35 mg with a new Norditropin FlexPro Pen.

Important:

Do not use the Pen clicks to count the number of mg you select. Only the display window and dose pointer will show the exact number.

Do not use the growth hormone scale to measure how much liquid to inject. Only the display window and dose pointer will show the exact number.

Step 5. Selecting your injection site and injecting the dose of Norditropin:

Change your injection site every day. Select the injection site and wipe your skin with an alcohol swab as your healthcare provider showed you.

Norditropin can be injected under your skin (subcutaneously) of your hips, stomach area (abdomen), upper legs (thighs), upper arms, or as otherwise instructed by your healthcare provider. See Figure S.

Figure S

Hold onto both the PenMate and your Pen without touching the insertion button on the PenMate or the dose button on the Pen.

Do not press the insertion button on the PenMate before you are ready to inject your dose. This lowers the risk of hurting yourself with the needle.

Hold the PenMate firmly with 1 hand and pull the Pen out with your other hand until you hear and feel a click. See figure T.

The needle is now hidden in PenMate.

Figure T

Norditropin is for use under your skin only (subcutaneous). Hold the PenMate against your skin. Press the insertion button on the PenMate until you hear or feel a click. When you hear or feel the click, the needle has been inserted automatically into your skin. See figure U.

You are now ready to inject your dose.

Figure U

Press the dose button on the Pen to inject your dose. Do not turn the dose button while you are pressing it. If you turn the dose button, you will not inject growth hormone.

Make sure you can see the display window. Do not cover it with your fingers. Press and hold down the dose button on the Pen until the display window returns to “0”.

The “0” must line up with the dose pointer. You may then hear or feel a firm click. See figure V.

Figure V

If the dose button cannot be pushed in completely or “0” does not appear in the display window, you did not receive the full dose. Call Novo Nordisk at 1-888-668-6444 for assistance. You may need a new Pen.

After the display window has returned to “0”, leave the needle under your skin for at least 6 secondsto make sure you get your full dose. See figure V.

Let go of the dose button while you wait.

Important: Always press the dose button to inject the dose. Turning the dose selector will not inject the dose.

Do not touch the display window when you inject, as this can block the injection.

Carefully lift the Pen to remove the needle from the skin. See figure W.

Figure W

Step 6. What to do after your injection is completed:

Carefully put the outer needle cap back on the needle. Remove the needle from the Pen after each injection. See figure X.

Figure X

Unscrew the needle by turning it counterclockwise. Do not touch the needle. Hold the Pen with 1 hand and carefully remove the needle from the Pen with your other hand. See figure Y.

Dispose of the needle as directed by a healthcare provider. See “How should I dispose of my Pen and needles?” at the end of these instructions.

Figure Y

Put the PenMate cap back on your PenMate after each use to protect the growth hormone from light. See figure Z.

Figure Z

Important safety information to remember:

• Be careful not to drop your PenMate and Pen or knock them against a hard surface. If this happens you will need to check the growth hormone flow.
• Do nottry to put the inner needle cap back on the needle. You may stick yourself with the needle. Be careful when handling used needles to avoid needle stick injuries.
• After each use always remove and dispose of the needle from your Pen.
• Do notshare your Pen or needles with other people.
• If your PenMate is damaged or lost, you can still use your Pen without your PenMate.
• Always keep your Pen and needles out of reach of others, especially children.

How should I replace an empty Pen?

PenMate is reusable and should not be disposed of. Reuse your PenMate by replacing your Pen when it is empty.

When your Pen is empty, twist the Pen until you hear or feel a click. See figure AA.

Figure AA

Gently pull the Pen out of PenMate. See figure BB.

Before disposing of your empty Pen, make sure the needle has been removed. Dispose of the empty Pen as recommended by your healthcare provider. See “How should I dispose of my Pen and needles?” at the end of these instructions.

Figure BB

Insert the new Pen into your PenMate. See figure CC.

Figure CC

Twist the Pen until you hear or feel a click. See figure DD.

The Pen is correctly attached in your PenMate when the display window on the Pen lines up with the insertion button on your PenMate. Display window Insertion button

Figure DD

How should I store my PenMate and Pen?

• Do not expose your PenMate or Pen to dust, dirt, or any kind of liquid.
• Store your PenMate and Pen in their case. See figure D at the beginning of these instructions.
• When your Pen is inserted in PenMate, store it as described in the Patient Information Leaflet that comes with your Pen.

How should I care for and clean my Pen with PenMate?

• Do not try to refill your Pen. It is prefilled.
• Do not try to repair your PenMate or your Pen.
• Only clean your PenMate or Pen with a mild detergent on a moistened cloth.
• Do not wash, soak, or lubricate your PenMate or Pen. Do not use products containing bleaching agents, such as chlorine, iodine, or alcohol to clean your PenMate or Pen. These products may damage them.
• If there is liquid growth hormone on the outside of your PenMate or Pen, clean it with a mild detergent on a moistened cloth before it dries up.

How should I dispose of my Pen and needles?

• Put your used needles and Pens in a FDA-cleared sharps disposal container right away after use. Do not throw away (dispose of) loose needles and Pens in your household trash.
• If you do not have a FDA-cleared sharps disposal container, you may use a household container that is:
  • made of a heavy-duty plastic,
  • can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out,
  • upright and stable during use,
  • leak-resistant, and
  • properly labeled to warn of hazardous waste inside the container.
• When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used needles and Pens. For more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA's website at: www.fda.gov/safesharpsdisposal.
• Do not dispose of your used sharps disposal container in your household trash unless your community guidelines permit this. Do not recycle your used sharps disposal container.

Need help?

PenMate must only be used according to the instructions provided. The manufacturer cannot be held responsible for any problems with PenMate if these instructions have not been followed.

If you find that your PenMate or case is defective, make sure to have Novo Nordisk replace it. Call the number below to order a new PenMate or case and arrange return of the defective item for inspection.

For assistance or further information, write to:

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Before you receive somatropin, tell your doctor if you have ever had an allergic reaction to a growth hormone medicine, or to drug preservatives such as benzyl alcohol, metacresol or glycerin.

You should not use this medication if you are allergic to somatropin, or if you have:

• diabetic retinopathy (a serious eye condition caused by diabetes);
• cancer; or
• Prader-Willi syndrome and are also overweight or have sleep apnea or severe respiratory (lung) problems.

You should also not use somatropin if you have a serious medical condition after having:

• open heart surgery or stomach surgery;
• trauma or other medical emergency; or
• breathing problems (such as lung failure).

To make sure you can safely take somatropin, tell your doctor if you have any of these other conditions:

• liver disease;
• kidney disease (or if you are on dialysis);
• diabetes;
• a pituitary gland disorder;
• scoliosis;
• high blood pressure (hypertension);
• a pancreas disorder (especially in children);
• a history of cancer;
• carpal tunnel syndrome;
• underactive thyroid; or
• a brain tumor or lesion.

FDA pregnancy category B. Some brands of somatropin are not expected to harm an unborn baby, including Genotropin, Omnitrope, Saizen, Serostim, and Zorbtive.

FDA pregnancy category C. It is not known whether certain other brands of somatropin will harm an unborn baby, including Humatrope, Norditropin, Nutropin, and Tev-tropin.

Tell your doctor if you are pregnant or plan to become pregnant while using this medication.

It is not known whether somatropin passes into breast milk or if it could harm a nursing baby. Do not use somatropin without telling your doctor if you are breast-feeding a baby.

Use the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not use extra medicine to make up the missed dose.

Call your doctor if you miss more than 3 doses in a row.

This section provides information on the proper use of a number of products that contain somatropin, e-coli derived. It may not be specific to Norditropin. Please read with care.

This medicine is given as a shot under your skin. Somatropin may sometimes be given at home to patients who do not need to be in the hospital. If you are using this medicine at home, your doctor will teach you how to prepare and inject the medicine. Be sure that you understand exactly how the medicine is prepared and injected.

This medicine comes with a patient information insert. Read and follow the instructions in the insert carefully. Ask your doctor if you have any questions.

There are many different forms (eg, vial, cartridge, injection device) available for this medicine. Read all instructions carefully to be sure you know how to use your device.

Each time you get your medicine, check to be sure you have received the proper device. Talk to your pharmacist if you have questions about the device that you were given.

You will be shown the body areas where this shot can be given. Use a different body area each time you give yourself a shot. Keep track of where you give each shot to make sure you rotate body areas. This will help prevent skin problems from the injections.

Use a new needle, unopened vial, or syringe each time you inject your medicine.

You might not use all of the medicine in each vial (glass container) or prefilled syringe. Use each vial or syringe only one time. Do not save an open vial or syringe. If the medicine in the vial or syringe has changed color, or if you see particles in it, do not use it.

Use only the brand of this medicine that your doctor prescribed. Different brands may not work the same way.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For injection dosage form:
  • For all indications:
    • Adults—Dose is usually based on body weight (depending on the brand of somatropin you are using) and dose must be determined by your doctor. Your doctor will adjust your dose as needed.
    • Children—Dose is based on body weight and must be determined by your doctor. Your doctor will adjust your child's dose as needed.

Missed Dose

This medicine needs to be given on a fixed schedule. If you miss a dose or forget to use your medicine, call your doctor or pharmacist for instructions.

Storage

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Store this medicine in the refrigerator, away from direct light. Do not freeze or shake.

Throw away used needles in a hard, closed container that the needles cannot poke through. Keep this container away from children and pets.

Pediatric Patients

Norditropin (somatropin) injection is indicated for the treatment of pediatric patients with growth failure due to inadequate secretion of endogenous growth hormone (GH).

Norditropin (somatropin) injection is indicated for the treatment of pediatric patients with short stature associated with Noonan syndrome.

Norditropin (somatropin) injection is indicated for the treatment of pediatric patients with short stature associated with Turner syndrome.

Norditropin (somatropin) 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.

Adult Patients

Norditropin (somatropin) injection is indicated for the replacement of endogenous GH in adults with growth hormone deficiency (GHD) who meet either of the following two criteria:

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 exceptions: (1) patients with multiple other pituitary hormone deficiencies due to organic disease; and (2) patients with congenital/genetic growth hormone deficiency.

Norditropin is available preloaded in the Norditropin FlexPro pens:

 Norditropin FlexPro prefilled pens (somatropin) injection 5 mg/1.5 mL, 10 mg/1.5 mL, 15 mg/1.5 mL, and 30 mg/3 mL:

Norditropin FlexPro is individually cartoned as 5 mg/1.5 mL, 10 mg/1.5 mL, 15 mg/1.5 mL or 30 mg/3 mL prefilled pens.

Norditropin FlexPro 5 mg/1.5 mL (orange), 10 mg/1.5 mL (blue), 15mg/1.5 mL (green), and 30 mg/3 mL (purple) prefilled pens:

Unused Norditropin FlexPro prefilled pens must be stored at 2°C to 8°C/36°F to 46°F (refrigerator). Do not freeze. Avoid direct light.

After the initial injection, a Norditropin FlexPro prefilled pen may be EITHER stored in the refrigerator (2ºC to 8ºC/36ºF to 46ºF) and used within 4 weeks OR stored for up to 3 weeks at room temperature not more than 25ºC (77ºF). Discard unused portion.

See FDA-approved patient labeling.

Patients being treated with Norditropin FlexPro prefilled pens, (and/or their parents) should be informed about the potential risks and benefits associated with somatropin treatment.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 prefilled pens, should receive appropriate 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 FlexPro, physicians should instruct patients to read the PATIENT INFORMATION and INSTRUCTIONS FOR USE leaflets provided with the Norditropin FlexPro prefilled pens.

Never Share a Norditropin Pen Between Patients

Counsel patients that they should never share a Norditropin pen with another person, even if the needle is changed. Sharing of the pen between patients may pose a risk of transmission of infection.

Novo Nordisk® is a registered trademark of Novo Nordisk A/S.

Norditropin® and FlexPro® are registered trademarks of Novo Nordisk Health Care AG.

© 2002-2017 Novo Nordisk Health Care AG

For information contact:

Novo Nordisk Inc.

800 Scudders Mill Road

Plainsboro, New Jersey 08536, USA

1-888-668-6444

Manufactured by:

Novo Nordisk A/S

DK-2880 Bagsvaerd, Denmark

Norditropin®  FlexPro®

(somatropin) injection

10 mg/1.5 mL Prefilled Pen

1 x 1.5 mL prefilled disposable pen

Each 1.5 mL contains 10 mg somatropin

CONTAINS ONE

Norditropin® FlexPro® 10 mg/1.5 mL

Single patient use only

Rx only

NDC 0169-7705-21

List: 770521