Humatrope

Package leaflet: Information for the user

Humatrope 6 mg / 12 mg / 24 mg powder and solvent for injectable solution

somatropin
Please read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, because it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet:

1. What Humatrope is and what it is used for
2. What you need to know before using Humatrope
3. How to use Humatrope
4. Possible side effects
5. How to store Humatrope
6. Contents of the pack and other information

1. What Humatrope is and what it is used for

The medicine prescribed for you or the person in your care is called Humatrope. It
contains human growth hormone, also known as somatropin. Humatrope is produced by a
special process known as recombinant DNA technology and has the same structure as the growth hormone
produced by the human body.
Growth hormone regulates the growth and development of cells within the body. When
it stimulates growth of the cells in the spine and the long bones of the legs, it causes an
increase in height.
In cases of growth hormone deficiency, growth hormone also increases bone mineral content, the number and size of muscle cells, and reduces body fat deposits.
Humatrope is used for

• The treatment of children and adolescents with any of the following growth disorders:
• Inadequate production of growth hormone (growth hormone deficiency).
• Partial or complete absence of the sex-linked X chromosomes in short females (Turner Syndrome).
• A condition in which the kidneys are damaged (chronic kidney problems) in pre-pubertal children with growth failure.
• Small for gestational age (SGA = small for gestational age) who have not achieved normal height by age 4 years or beyond.
• Presence of an SHOX gene alteration (SHOX gene defect).
• The treatment of adults with confirmed growth hormone deficiency that began during adolescence or adulthood.

2. What you need to know before using Humatrope

Do not use Humatrope

• if you are allergic (hypersensitive) to somatropin or any of the other ingredients of Humatrope (e.g. metacresol, glycerol contained in the solvent); see section 6.
• and inform your doctor if you have an active tumour (cancer). Before starting treatment with Humatrope, tumours must be inactive and anti-tumour treatment must have been completed.
• if you have already completed the growth process and wish to induce further height increase (the growth plates of the long bones have fused). Your doctor will carry out tests to determine whether you still need to take Humatrope after your bones have finished growing.
• if you are very ill and require intensive medical care following a major heart or abdominal surgery, are being treated for multiple traumas after an accident, or require mechanical ventilation due to acute respiratory failure.

Warnings and precautions
Talk to your doctor or pharmacist before using Humatrope.
If you are receiving glucocorticoid replacement therapy, you must consult your doctor regularly, as your glucocorticoid dose may need to be adjusted.
If you were treated for growth hormone deficiency during adolescence, your doctor will reassess you for growth hormone deficiency to determine whether you require any further treatment with Humatrope in adulthood.
If you have previously undergone anti-tumour therapy, a brain scan may be required before starting treatment with Humatrope. You must undergo regular diagnostic checks to ensure that the tumour does not recur or begin to grow again.
In patients who have survived a tumour and have been treated with somatropin, an increased risk of developing a second tumour (either benign or malignant) has been reported. Among these second tumours, the most common have been brain tumours.
If you experience symptoms such as recurrent or severe headache, nausea and/or visual disturbances, report them to your doctor immediately. Your doctor should perform an eye examination to check for increased intracranial pressure. Depending on the results of this examination, treatment with Humatrope may need to be discontinued.
If you develop a limp or experience hip pain, consult your doctor. During periods of growth, hip bone disorders may occur.
When starting treatment, administration of Humatrope may alter the levels of circulating thyroid hormones. If thyroid hormone levels are low, this may reduce the therapeutic response to Humatrope. Therefore, thyroid function tests should be normal, regardless of whether you are receiving thyroid hormone therapy.
If you are a child, ensure that you continue treatment until final height is achieved.
If you take a higher dose of Humatrope than prescribed, you may experience excessive growth of certain body parts such as the ears, nose, jaw, hands and feet. Overdosing may also lead to elevated blood sugar levels and sugar in the urine. Always use Humatrope exactly as prescribed by your doctor.
If you have a growth disorder due to kidney disease, treatment with Humatrope must be stopped before undergoing kidney transplantation.
If you require intensive care, your doctor must be informed about your ongoing treatment. Deaths have been reported in patients receiving somatropin during intensive care therapy.
If you have growth hormone deficiency and also have Prader-Willi Syndrome (a genetic disorder), your doctor must examine you for respiratory problems and airway infections before starting treatment with Humatrope, especially if you are overweight, have previously had severe respiratory problems (particularly during sleep), or have had a lung or airway infection. If you develop signs of respiratory problems (such as snoring) during treatment, treatment must be stopped and the cause investigated by your doctor.
Humatrope may affect the way your body processes sugars from food and drinks, interfering with how your body uses insulin. Therefore, if you take Humatrope, your doctor must monitor whether your body is processing sugars correctly.
If you have diabetes mellitus, your insulin dose may need to be adjusted after starting treatment with Humatrope. Your doctor will monitor your blood sugar levels and may need to adjust your diabetes therapy.
If you have a growth disorder associated with being born small for gestational age, blood sugar and insulin levels will be monitored before starting therapy and regularly during treatment.
Elderly patients (over 65 years of age) may be more sensitive to the effects of Humatrope and more prone to experiencing side effects.
Humatrope may cause inflammation of the pancreas, resulting in severe abdominal and back pain. Contact your doctor if you or your child develops stomach pain after taking Humatrope.
Scoliosis (increased lateral curvature of the spine) may progress in any child during rapid growth. Signs of scoliosis should be monitored during treatment.

Other medicines and Humatrope
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
In particular, inform your doctor if you are taking or have recently taken any of the following medicines: Your doctor may need to adjust the dose of Humatrope or of other medicines:

• Medicines for the treatment of diabetes mellitus, which may require dose adjustments.
• Adrenal steroid hormones (glucocorticoids), such as cortisone or prednisolone; your doctor may need to adjust the dose, as combining these medicines with Humatrope may reduce the effectiveness of both treatments.
• Orally administered estrogens or other sex hormones, as they may affect the response to growth hormone treatment. If the route of estrogen administration is changed (e.g. from oral to transdermal, i.e. through the skin), the dose of Humatrope may need to be adjusted.
• Medicines used to prevent epileptic seizures ( antiepileptics ) or cyclosporine.

Pregnancy and breastfeeding
Humatrope must not be used during pregnancy unless your doctor specifically tells you to do so. If you become pregnant, inform your doctor immediately.
It is not known whether somatropin passes into breast milk. If you are breastfeeding or plan to breastfeed, consult your doctor before using Humatrope.

Driving and using machines
Humatrope has no known effect on the ability to drive or operate machinery.

Humatrope contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per daily dose, i.e. it is essentially ‘sodium-free’.

For individuals engaged in sports: using this medicine without a therapeutic need constitutes doping and may lead to a positive result in anti-doping tests.

3. How to use Humatrope

Use this medicine exactly as your doctor has instructed you. If you have any doubts, consult your doctor or pharmacist.

• Always make sure to use the cartridge concentration prescribed by your doctor (6 mg, 12 mg, or 24 mg concentration) and the appropriate Humatrope injection pen device bearing the CE mark. Never use cartridges from other medicines in the Humatrope pen.
• Each Humatrope cartridge is supplied with a syringe containing a solvent (solvent for injectable solution) for reconstitution (mixing and preparing the injectable solution).
• Do not mix or inject Humatrope until you have received adequate training from your doctor or other qualified healthcare professionals.
• For detailed instructions on how to prepare and inject Humatrope, see the section "How to inject Humatrope" at the end of this leaflet. You must only mix Humatrope with the provided solvent. Never mix it with anything else unless your doctor specifically instructs you to do so.
• After reconstitution, Humatrope must be injected into the fatty tissue just beneath the skin using a short needle and the Humatrope injection pen device.
• Injection sites should be rotated to avoid localized reduction and hardening of the subcutaneous fatty tissue (lipoatrophy).
• After mixing Humatrope, do not leave it outside the refrigerator for longer than 30 minutes per day.
• Store the pen containing the remaining Humatrope solution in the refrigerator. After 28 days from the time of mixing, do not use any remaining Humatrope in the pen.

Dosage
Your doctor will advise you on the appropriate dosage and administration method. Do not change the dosage without first discussing it with your doctor.
Usually, treatment with Humatrope is long-term; your doctor may need to adjust the dose over time based on your body weight and response to treatment. Generally, the dose, administered once daily, is calculated according to the following recommendations:
Children and adolescents with :

• Growth hormone deficiency: 0.025 - 0.035 mg/kg body weight per day.
• Turner syndrome: 0.045 - 0.050 mg/kg body weight per day.
• Chronic kidney problems: 0.045 - 0.050 mg/kg body weight per day.
• Small for gestational age (SGA) infants: 0.035 mg/kg body weight per day. Treatment should be discontinued after the first year of therapy if growth velocity is inadequate.
• Growth failure due to SHOX gene deficiency: 0.045 - 0.050 mg/kg body weight per day.

Adult growth hormone deficiency:
Treatment should be initiated with a low daily dose of 0.15 - 0.30 mg. Lower initial doses may be required in older and overweight patients. The initial dose may be gradually increased based on individual needs. The total daily dose usually does not exceed 1 mg.
Dose requirements may decrease with increasing age. Women, especially those on oral estrogen replacement therapy, may require higher doses than men.

If you use more Humatrope than you should
If you have injected more Humatrope than prescribed, contact your doctor for advice.

• If you have injected too much Humatrope, your blood sugar level may initially drop too low (hypoglycemia), and subsequently rise too high (hyperglycemia).
• If you have used too much Humatrope over a long period (years), you may develop excessive growth of certain body parts such as the ears, nose, jaw, hands, and feet (acromegaly).

If you forget to use Humatrope
Do not inject a double dose to make up for a missed dose. Continue with the prescribed dosing schedule. If you forget to inject Humatrope and have any doubts about what to do, consult your doctor.

If you stop using Humatrope
Consult your doctor before stopping treatment. Interrupting or prematurely stopping Humatrope treatment may compromise the treatment's effectiveness.

If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone experiences them.
After injection of Humatrope, some of the following side effects may occur.
The following convention has been used to classify adverse reactions:
Very common side effects may affect more than 1 in 10 people
Common side effects may affect between 1 in 100 and 1 in 10 people
Uncommon side effects may affect between 1 in 1,000 and 1 in 100 people
Rare side effects may affect between 1 in 10,000 and 1 in 1,000 people
Very rare side effects may affect fewer than 1 in 10,000 people, including isolated cases
Other possible side effects (frequency cannot be estimated from the available data)

The effect of insulin may be reduced.
Leukemia has been observed in a limited number of children treated with growth hormone.
However, there is no evidence that the incidence of leukemia is increased in individuals receiving growth
hormone.
Reporting of adverse reactions
If you experience any adverse reactions, including those not listed in this leaflet, talk to your doctor or
pharmacist. You may also report adverse reactions directly through the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting adverse reactions, you can help provide more information on the safety of this medicine.

5. How to store Humatrope

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label and carton. The expiry date refers to the
last day of that month.
Do not use this medicine if the solution appears cloudy or contains particles.
Always store Humatrope in a refrigerator (2°C - 8°C). Do not freeze.
After reconstitution, do not leave Humatrope outside the refrigerator for longer than a total of 30 minutes per
day. After reconstitution, Humatrope may be used for 28 days if stored in the refrigerator and for no more than
30 minutes each day at room temperature.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of
medicines no longer used. This will help protect the environment.

6. Package contents and other information

What Humatrope contains
Powder in the cartridge
The active substance is somatropin. Depending on the concentration, each cartridge contains 6 mg, 12 mg or 24 mg. After reconstitution:

• Humatrope 6 mg contains 2.08 mg of somatropin per ml of solution
• Humatrope 12 mg contains 4.17 mg of somatropin per ml of solution
• Humatrope 24 mg contains 8.33 mg of somatropin per ml of solution

The other components are: mannitol, glycine, disodium phosphate. [Phosphoric acid or sodium hydroxide (or both) may have been used during the manufacturing process to adjust pH].

Sterile solvent in the syringe
The pre-filled syringe containing solvent includes: glycerol, metacresol, water for injections.
[Hydrochloric acid or sodium hydroxide (or both) may have been used during the manufacturing process to adjust pH].

Description of Humatrope appearance and package contents

It is possible that not all pack sizes are marketed.
Marketing Authorization Holder
ELI LILLY ITALIA S.p.A.
Via Gramsci 731/733
50019 Sesto Fiorentino (FI)
Tel.: +39 055 42571
Manufacturer
Lilly France
Rue du Colonel Lilly
F-67640 Fegersheim
France
For further information on Humatrope, please contact the Marketing Authorization Holder (or local representative):
ELI LILLY ITALIA S.p.A.
Via Gramsci 731/733
50019 Sesto Fiorentino (FI)
Tel.: +39 055 42571
This medicinal product is authorized in the European Economic Area Member States under the following names:
In the European Economic Area Member States where this medicinal product is authorized, it is marketed under the name “Humatrope”, except in France where it is authorized under the name “Umatrope”.
How to inject Humatrope 6 mg / 12 mg / 24 mg
The following instructions explain how to inject Humatrope. Read the instructions carefully and follow them step by step.
Preparation: Components
You will need five items:

1. A cartridge of Humatrope of the correct concentration
2. A syringe filled with solvent
3. A Humatrope pen with CE mark
4. A sterile pen needle
5. An alcohol-impregnated cotton swab

Wash your hands before proceeding to the next steps.
Only use the components supplied in the kit to prepare the Humatrope cartridge.
*Note: The liquid is colourless. It appears blue in the figure for graphical representation purposes only.
The following steps will help you prepare a new cartridge for use
Step 1 Unpackaging

• You must mix Humatrope only with the provided solvent. Never mix it with anything else unless instructed by your doctor.
• Read the instruction manual provided with the pen. This will remind you of what your doctor or healthcare professional has taught you.
• Read the instructions below the figures

Grasp the needle cap, remove the needle cap from the bottom of the syringe containing the solvent and discard it. DO NOT press the plunger of the syringe yet. It is normal for a drop of liquid to appear. There is no need to expel air from the syringe containing the solvent.
Remove ALL components of the kit from the tray.
Note: This device is designed to be used with either the right or left hand, allowing you to use the one you find most comfortable.
Steps 2 and 3 Inserting the cartridge

Hold the cartridge with the black triangles facing upwards. Align the cartridge and the syringe containing the solvent in a straight line. Push the cartridge straight in until it stops and the black triangles are COMPLETELY COVERED. You may hear or feel a click. DO NOT insert the cartridge at an angle. DO NOT bend the cartridge.
Step 4 Mixing Humatrope

Hold together the syringe containing the solvent and the cartridge with BOTH HANDS. Push and release the plunger two or three times until the solvent is in the cartridge. Lift your thumb off the plunger and check that the syringe containing the solvent is empty (it is normal for small drops of solvent to remain in the syringe).
Steps 5 and 6 Removing the cartridge and discarding the solvent

With your thumb away from the plunger, pull the cartridge away from the solvent syringe. Place the end cap on a hard, flat surface. Insert the solvent syringe into the end cap and immediately discard it according to the instructions given by your healthcare professional.
Step 7 Gently mixing

• Mix the solution by gently inverting the cartridge 10 times. DO NOT SHAKE THE CARTRIDGE. Leave the cartridge to stand for 3 minutes, then carefully inspect the solution.
• If the solution appears cloudy or contains particles, gently mix the cartridge a further 10 times. Leave the cartridge to stand for another 5 minutes. If the solution remains cloudy or contains particles, DO NOT USE THE CARTRIDGE.

Check the solution. The Humatrope solution must be clear.
Gently mix the cartridge by inverting it up and down 10 times, then leave it to stand for 3 minutes. DO NOT SHAKE.
Step 8 Injecting Humatrope using a suitable pen injection device

• If the solution is clear, the cartridge is now ready to be inserted into a suitable Humatrope pen.
• Insert the cartridge into the pen (see the pen user manual).
• Always use a new sterile needle for each injection.
• Clean the skin thoroughly with an alcohol-impregnated cotton swab. Allow the skin to dry.
• Set the correct dose (see the pen user manual).
• Inject slowly under the skin (subcutaneously) as instructed by your doctor.
• Remove the needle from the skin and dispose of it safely, as shown by your doctor or healthcare professional.
• Store the pen with the remaining Humatrope in the refrigerator. After 28 days from mixing, do not use any remaining Humatrope in the pen.

Humatrope is a registered trademark of Eli Lilly and Company Limited