Active ingredients: Somatropin
Genotropin 5.3 mg and 12 mg powder and solvent for solution for injection
Genotropin package inserts are available for pack sizes:- Genotropin 5.3 mg and 12 mg powder and solvent for solution for injection
- Genotropin MiniQuick 0.2 mg, 0.4 mg, 0.6 mg, 0.8 mg, 1.0 mg, 1.2 mg, 1.4 mg, 1.6 mg, 1.8 mg, 2.0 mg, powder and solvent for solution for injection
Why is Genotropin used? What is it for?
Genotropin is a recombinant human growth hormone medicine (also called somatropin). It has the same structure as the naturally produced human growth hormone that is needed for the growth of bones and muscles. Growth hormone also helps fat and muscle tissue to develop properly. It is called recombinant as it does not come from human or animal tissue.
In children, Genotropin is used in the treatment of the following growth disorders:
- If it is not growing properly and does not have enough growth hormone.
- If you have Turner syndrome. Turner Syndrome is a chromosomal abnormality that affects girls and can adversely affect growth - your doctor should have told you if you have this disease.
- If you have chronic renal failure. In this case, the kidneys lose their normal function and this can affect growth.
- If you have Prader-Willi syndrome (disease due to a chromosomal disorder). Growth hormone will help him get taller if he is still growing, and improve his body composition. Excess fat will decrease and muscle mass, which is reduced, will improve.
- If he was too small at birth or had a low weight. Growth hormone can help you grow taller if you have failed to achieve or maintain normal growth by the age of 4 or beyond.
In adults, Genotropin is used to treat people with marked growth hormone deficiency. This deficit may arise in adulthood or may have arisen in childhood.
If you were treated with Genotropin during childhood because you have growth hormone deficiency, your growth hormone status will need to be reassessed upon completion of growth. If severe growth hormone deficiency is confirmed, your doctor will suggest that you continue therapy with Genotropin.
This medicine should only be prescribed by a doctor who has experience in the treatment with growth hormone and who has confirmed the diagnosis.
Contraindications When Genotropin should not be used
Do not use Genotropin and tell your doctor
- If you are allergic (hypersensitive) to somatropin or any of the other ingredients of Genotropin.
- If you have an active tumor (cancer). Tumors must be inactive and anticancer therapy must be completed before starting treatment with Genotropin.
- If you are seriously ill (for example, if you have complications following open heart surgery, abdominal surgery, acute respiratory failure, accidental trauma, or similar conditions). you are undergoing a major operation, or if you go to hospital for any other reason, tell your doctor, and remind the other doctors who are following you that you are on growth hormone therapy.
- If Genotropin was prescribed to stimulate growth, but growth has already stopped (the epiphyses have joined).
Precautions for use What you need to know before taking Genotropin
Take special care with Genotropin and tell your doctor if any of these apply to you
- If you are at risk of developing diabetes, your doctor will need to monitor your blood glucose level during treatment with Genotropin.
- If you have diabetes, you should carefully monitor your blood glucose level during treatment with Genotropin and discuss the results with your doctor to see if the dosage of the medicines you take to treat diabetes need to be changed.
- After starting Genotropin therapy some patients may need to start thyroid hormone replacement treatment.
- If you are on thyroid hormone therapy, your dosage may need to be adjusted.
- If you are taking growth hormone to stimulate growth and have a "limp, or if you start to have a" limp during treatment with growth hormone due to hip pain, you should tell your doctor. .
- In case of increased intracranial pressure (with symptoms such as: severe headache, visual disturbances or vomiting) you should inform your doctor.
- If your doctor detects inflammation of the muscles near the injection site caused by the preservative metacresol, you should use Genotropin without metacresol.
- If you are prescribed Genotropin because of a growth hormone deficiency following a previous tumor (cancer), you should be regularly monitored for the return of the tumor or any other cancer.
- If you notice worsening of abdominal pain, you should inform your doctor.
- Experience in patients over 80 years of age is limited. Elderly people may be more sensitive to the action of Genotropin and therefore more prone to the onset of side effects.
Children with chronic renal failure:
- Your doctor should evaluate your kidney function and growth rate before starting treatment with Genotropin. Medical treatment for your kidney condition should continue. Treatment with Genotropin should be discontinued in the event of a kidney transplant.
Children with Prader-Willi Syndrome:
- Your doctor will prescribe a diet to follow to keep your weight under control.
- Before starting treatment with Genotropin, your doctor will check for signs of upper airway obstruction, sleep apnea (interruption of breathing during sleep), or respiratory infections.
- If you show signs of upper airway obstruction during treatment (including the onset or aggravation of snoring), your doctor will need to examine you and may stop your treatment with Genotropin.
- During treatment, your doctor will check for signs of scoliosis, a type of spinal deformity.
- If a lung infection develops during treatment, please tell your doctor so that he can treat the infection.
Babies born small or with low birth weight:
- If you were too small at birth or low in weight and between the ages of 9 and 12, ask your doctor for specific advice about puberty and treatment with this medicine.
- Your doctor will check your blood glucose and insulin levels before starting treatment and every year during treatment.
- Treatment should continue until stunting.
Interactions Which drugs or foods can modify the effect of Genotropin
Tell your doctor or pharmacist if you are taking or have recently taken any other medicines, even those obtained without a prescription.
You should tell your doctor if you are taking:
- medicines to treat diabetes,
- thyroid hormones,
- synthetic adrenal hormones (corticosteroids),
- sex hormones (for example estrogen),
- ciclosporin (medicine that depresses the immune system after a transplant),
- medicines that control epilepsy (anticonvulsants).
Your doctor may evaluate the need to change the dosage of these medicines or the dosage of Genotropin.
For those who carry out sporting activities: the use of the drug without therapeutic necessity constitutes doping and can in any case determine positive anti-doping tests.
Warnings It is important to know that:
Pregnancy and breastfeeding
If you are pregnant, think you are pregnant or if you are planning to become pregnant you should not use Genotropin.
Ask your doctor for advice before using this medicine while breastfeeding.
Ask your doctor or pharmacist for advice before taking any medicine.
Important information about some of the ingredients of Genotropin
This medicinal product contains less than 1 mmol sodium (23 mg) per dose; this means it is practically "sodium free".
Dose, Method and Time of Administration How to use Genotropin: Posology
Recommended dosage
The dosage depends on your body size, the disorder you are being treated for and how effective the growth hormone is on you. Each person is different. Your doctor will recommend the dose of Genotropin in milligrams (mg) that is right for you, based on your body weight in kilograms (kg) or your body surface area, calculated in square meters (m2) based on your height and weight, as well as the appropriate administration schedule for you Do not change either the dosage or the administration schedule without consulting your doctor.
Children with growth hormone deficiency:
Dose of 0.025 - 0.035 mg per kg of body weight per day or 0.7-1.0 mg per m2 of body surface area per day. Higher doses can also be given. When growth hormone deficiency continues into adolescence, Genotropin should be used until full physical development.
Children with Turner syndrome:
Dose of 0.045 - 0.050 mg per kg of body weight per day or 1.4 mg per m2 of body surface area per day.
Children with chronic renal failure:
Dose of 0.045 - 0.050 mg per kg of body weight per day or 1.4 mg per m2 of body surface area per day. Higher doses may be needed if the growth rate is too slow. Dose adjustment may be needed after 6 months of treatment.
Children with Prader-Willi Syndrome:
Dose of 0.035 mg per kg of body weight per day or 1.0 mg per m2 of body surface area per day. The daily dose of 2.7 mg should not be exceeded. The treatment should not be used in children whose growth has almost stopped after puberty.
Babies born small or with low birth weight and with growth disturbances:
Dose of 0.035 mg per kg of body weight per day or 1 mg per m2 of body surface area per day. It is important to continue the treatment until its final height is reached. You must stop treatment after the first year if it does not respond to therapy or if it reaches its final height and stops growing.
Adults with growth hormone deficiency:
If you continue Genotropin therapy after treatment in childhood, you should start with a dose of 0.2-0.5 mg per day. This dosage should be gradually increased or decreased based on blood test results, clinical response and side effects.
If growth hormone deficiency occurs in adulthood, treatment should be started with 0.15-0.3 mg per day. This dosage should be gradually increased based on blood test results, clinical response and side effects. The daily maintenance dose rarely exceeds 1.0 mg per day. Women may need higher dosages than men. Dosage should be checked every 6 months. People over 60 years of age should start with a dose of 0.1-0.2 mg per day, which should be gradually increased according to individual needs. The lowest effective dose should be used. The daily maintenance dose rarely exceeds 0.5 mg per day. Follow the instructions your doctor has given you.
Genotropin injection:
Genotropin must be administered subcutaneously, i.e. injected into the fatty tissue just under the skin, through a short injection needle. Your doctor must have already shown you how to use Genotropin. Always inject Genotropin exactly as your doctor told you. If in doubt, consult your doctor or pharmacist.
Instructions for using the GoQuick pre-filled pen are provided in the container with the pre-filled pen.
Instructions for using Genotropin dual chamber cartridges with Genotropin Pen or Genotropin Mixer are provided with the devices.
Consult the instructions for use before using this medicine.
When using the pre-filled pen, injection pen or reconstitution device, the needle must be screwed on before reconstitution. Use a new needle for each injection. Do not reuse needles.
Preparation of the injection
You can take Genotropin out of the refrigerator half an hour before the injection. This allows the product to heat up slightly, thus facilitating injection.
The GoQuick pre-filled pen contains the two-compartment cartridge which in turn contains both growth hormone and solvent. The growth hormone and solvent present are mixed by shaking the pouch holder of the cartridge (see the precise steps in the Instructions for Use) A separate device is not required.
Genotropin in two compartment cartridge contains both growth hormone and solvent and must be used with a Genotropin device. The growth hormone and solvent present in the two compartment cartridge can be mixed using the Genotropin Mixer device or by screwing the Genotropin Pen device.
For both the GoQuick pre-filled pen and the two-chamber cartridge, dissolve the powder by gently inverting it 5-10 times until dissolved.
While mixing Genotropin, DO NOT SHAKE the solution. You mix it gently. Shaking the solution can lead to foaming and damage the active ingredient. Check the solution and do not inject if the solution is cloudy or contains particles.
Genotropin injection
Remember to wash your hands and cleanse the skin before the injection.
Inject growth hormone at about the same time each day. It is recommended to inject at bedtime as it is easier to remember. It is also normal to have higher growth hormone levels at night.
Most people inject in the thigh or buttock. Give the injection where your doctor has shown you. Fatty tissue in the skin may shrink at the injection site. To prevent this from happening, give a slightly different injection each time. This allows the skin and underlying tissue to recover from the previous injection before another injection is given at the same site.
Remember to put Genotropin back in the refrigerator immediately after the injection.
If you forget to use Genotropin
Do not take a double dose to make up for a forgotten dose. It is best to take growth hormone on a regular basis.
If you forget to take a dose, give your next injection the next day at the usual time. Make a note of any injections you have forgotten to give and report it to your doctor at the first check-up.
If you stop taking Genotropin
Ask your doctor for advice before stopping treatment with Genotropin.
For more information on how to use this medicine, ask your doctor or pharmacist.
Overdose What to do if you have taken too much Genotropin
If you have injected too much Genotropin, contact your doctor or pharmacist as soon as possible. Your blood sugar level may drop too low and later rise too much. You may feel shaking, sweating, sleepy or feeling "not in yourself" and may pass out.
Side Effects What are the side effects of Genotropin
Like all medicines, Genotropin can cause side effects, although not everybody gets them. The very common and common side effects in adults may appear within the first months of treatment and may stop spontaneously or if the dose is reduced.
Very common side effects (may affect more than 1 in 10 patients) include:
In adults
- Joint pain
- Water retention (which occurs with swollen fingers or ankles).
Common side effects (may affect less than 1 in 10 patients) include:
In children:
- Temporary redness, itching, or pain at the injection site;
- Pain in the joints.
In adults:
- Numbness / tingling
- Sore arms and legs, muscle pain
- Pain or burning sensation in the hands or armpits (known as Carpal Tunnel Syndrome).
Uncommon side effects (may affect less than 1 in 100 patients) include:
In children:
- Fluid retention (manifesting as swollen fingers or ankles for a short period of time at the start of treatment)
Rare side effects (may affect less than 1 in 1,000 patients) include:
In children:
- Numbness / tingling
- Leukemia (has been reported in a limited number of growth hormone deficient patients, some of whom were previously treated with somatropin. However, there is no evidence that the incidence of leukemia is higher in those receiving growth hormone without predisposing factors);
- Increased intracranial pressure (causing symptoms such as severe headache, visual disturbances or vomiting)
- Muscular pain.
Not known: frequency cannot be estimated from the available data:
- Type 2 diabetes;
- Decrease in the levels of the hormone cortisol in the blood.
In children:
- Soreness in the arms and legs.
In adults:
- Increased intracranial pressure (causing symptoms such as severe headache, visual disturbances or vomiting)
- Redness, itching or pain at the injection site.
Formation of antibodies to the injected growth hormone, which however do not seem to stop the action of the growth hormone.
The skin around the injection site may become bumpy or lumpy, but this does not have to happen if you inject at a different place each time.
A very rare side effect that can occur due to the preservative metacresol is inflammation of the muscles near the injection site. If your doctor finds that you have this side effect, you should use Genotropin without metacresol.
There have been rare cases of sudden death in patients with PraderWilli Syndrome. However, these cases were not associated with Genotropin treatment.
If hip or knee discomfort or pain occurs during treatment with Genotropin, your doctor may consider slippage of the proximal femoral epiphysis and Legg-Calvé-Perthes disease.
Other possible side effects related to growth hormone treatment may include the following cases. You (or your child) may have high blood sugar levels (blood sugar) or low thyroid hormone levels. This may be checked by your doctor. who, if necessary, will prescribe an appropriate treatment. Rarely, patients treated with growth hormone have reported inflammation of the pancreas.
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.
Reporting of side effects
If you get any side effects, please tell your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Italian Medicines Agency website: http://agenziafarmaco.gov.it/it/responsabili. By reporting side effects you can help provide more information on the safety of this medicine.
Expiry and Retention
Keep out of the sight and reach of children.
Do not use this medicine after the expiry date indicated on the package as Month / Year. The expiry date refers to the last day of the month.
Before reconstitution:
Store in the refrigerator (+ 2 ° C - + 8 ° C). Keep the two-compartment cartridge in the outer carton to protect from light.
Before opening, the product can be removed from the refrigerator, without being put back in the refrigerator, for a maximum period of 1 month at a temperature not exceeding 25 ° C, after which it must be discarded.
After reconstitution:
Store in the refrigerator (2 ° C-8 ° C) for up to 4 weeks. Do not freeze. Keep the GoQuick pre-filled pen in the outer carton of the GoQuick pen, or the two-compartment cartridge in the outer carton of the Genotropin Pen to protect from light.
Do not use the medicine if there are particles in the solution or if it is not clear.
Do not freeze or expose Genotropin to cold. If it freezes, don't use it.
Never throw away empty or incompletely used needles or cartridges with household waste.
After using a needle, he must discard it carefully so that no one can use it or prick himself. You can obtain a special container for "sharp materials" at the hospital or center where you are being treated.
Never dispose of medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
Other information
What does Genotropin contain
- The active ingredient is somatropin *.
- One cartridge contains 5.3 mg or 12 mg of somatropin *.
- After reconstitution the concentration of somatropin * is 5.3 mg or 12 mg per ml. The other ingredients of the powder are: glycine (E640), mannitol (E421), monobasic anhydrous sodium phosphate (E339), anhydrous dibasic sodium phosphate (E339).
- The other ingredients of the solvent are: water for injections, mannitol (E421) and metacresol.
* Produced by Escherichia Coli cells by recombinant DNA technology.
Description of what Genotropin looks like and contents of the pack
Genotropin comes as a powder and solvent for solution for injection, in a two-compartment cartridge containing the powder in one compartment and the solvent in the other compartment (5.3 mg / ml or 12 mg / ml). The cartridge can be contained in a pre-filled pen Pack sizes are 1 or 5 pre-filled pens, or 1 or 5 or 20 cartridges.
Not all strengths and not all pack sizes may be marketed.
The powder is white and the solvent is transparent.
You can use the cartridges with the specific injection pen for Genotropin. Genotropin cartridges are color-coded and must be used with the matching colored Genotropin Pen for the correct dose to be administered: The 5.3 mg Genotropin cartridge (blue) must be used with the 5.3 mg Genotropin Pen (blue ). The 12 mg Genotropin cartridge (purple) is for use with the Genotropin Pen 12 (purple). The instructions for using the device are included in the package of the device. You must ask your doctor for an injection or reconstitution device if you do not have one yet.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
GENOTROPIN 5,3 MG OR 12 MG POWDER AND SOLVENT FOR SOLUTION FOR INJECTION
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
* produced in Escherichia Coli cells by recombinant DNA technology.
For the full list of excipients see section 6.1
03.0 PHARMACEUTICAL FORM
Powder and solvent for solution for injection. The two-chamber cartridge contains a white powder in the front compartment and a clear solution in the rear compartment.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Children
Growth disturbances due to insufficient increase in somatotropic hormone (growth hormone deficiency, GHD) and growth disturbances associated with Turner syndrome or chronic renal failure.
Growth disturbance [standard deviation points (SDS) of current height stature of parents short stature born small for gestational age (SGA), with weight and / or length at birth less than - 2 SD, who did not recover of growth, [with a growth rate (HV)
Prader-Willi syndrome for the improvement of growth and body composition. The diagnosis of Prader-Willi Syndrome must be confirmed by appropriate genetic testing.
Adults
Replacement treatment in adult patients with marked growth hormone deficiency.
Onset in adulthood : Patients who have severe growth hormone deficiency associated with multiple hormone deficiencies as a result of known hypothalamic or pituitary disease, and who have at least one pituitary hormone deficiency, except prolactin. These patients should undergo an appropriate dynamic test for the diagnosis or for the exclusion of growth hormone deficiency.
Onset in childhood : Growth hormone deficient patients in childhood from congenital, genetic, acquired, or idiopathic causes. Patients with childhood-onset GHD should be re-evaluated for growth hormone secretory capacity upon completion of longitudinal growth. to hypothalamic-pituitary damage, levels of insulin-like growth factor-I (IGF-I) with SDSsufficient sign of total GHD.
For all other patients, IGF-I levels and a growth hormone stimulation test are required.
04.2 Posology and method of administration
Dosage and administration schedule must be individualized.
The injection should be administered subcutaneously and the site changed to prevent lipoatrophy from occurring.
Growth disturbance due to insufficient increase in somatotropic hormone in children :
a dose of 0.025 - 0.035 mg / kg body weight per day or 0.7 - 1.0 mg / m2 body surface area per day is generally recommended. Higher doses were also used.
When childhood-onset GHD persists into adolescence, treatment must be continued to achieve complete somatic development (body composition, bone mass). For monitoring, a normal peak bone mass defined by a T score> -1 (standardized to mean peak bone mass in an adult population measured by DEXA, Axial X-ray Densitometry, considering gender and race) represents one of the therapeutic goals during the transition period. see the paragraph dedicated to adults below.
Prader-Willi syndrome for the improvement of growth and body composition in children : A dose of 0.035 mg / kg body weight per day or 1.0 mg / m2 body surface area per day is generally recommended. The daily dose of 2.7 mg should not be exceeded. The treatment should not be used in children with a growth rate of less than 1 cm per year and next sealing of the epiphyses.
Growth Disorders Due to Turner Syndrome : a dose of 0.045 - 0.050 mg / kg body weight per day or 1.4 mg / m2 body surface area per day is recommended.
Growth disturbances in chronic renal failure : a dose of 0.045 - 0.050 mg / kg of body weight per day is recommended (1.4 mg / m2 of body surface area per day). Higher doses may be needed if the growth rate is too slow.Dose adjustment may be required after 6 months of treatment.
Growth disturbances in small children born small for gestational age : a dose of 0.035 mg / kg body weight per day (1 mg / m2 body surface area per day) is generally recommended until final height is reached (see section 5.1).
Treatment should be discontinued after the first year of therapy if growth rate is less than +1 SDS. Treatment should be stopped if the growth rate is 14 years (for girls) or> 16 years (for boys), corresponding to the sealing of the epiphyses.
Recommended doses in children
Growth hormone deficiency in the adult patient : In patients who continue growth hormone therapy after childhood GHD, the recommended restarting dose is 0.2-0.5 mg per day. The dose should be gradually increased or decreased according to the needs of the patients. individual patients, determined based on IGF-I concentrations.
In patients with onset of GHD in adulthood, therapy should be started with a low dose, 0.15-0.3 mg per day which should be gradually increased according to the individual needs of individual patients, determined based on IGF concentrations. -THE.
In both cases, the goal of treatment is to obtain IGF-I growth factor concentration values within 2 SDS of the age-corrected mean value.
In patients with normal IGF-I concentrations at the start of treatment, growth hormone should be administered up to obtaining IGF-I values tending to the upper limit of the normal range, without exceeding 2 SDS.
Clinical response and side effects can also be used as a reference for dose titration. It is known that there are patients with GHD for whom the IGF-I values do not normalize despite the good clinical response and consequently in these cases it is not necessary to increase the dosage.
The maintenance dose rarely exceeds 1.0 mg per day.
Women may require higher dosages than men for whom "increased sensitivity of IGF-I over time is demonstrated."
Therefore, there may be a risk that women, especially those undergoing oral estrogen replacement therapy, may take an insufficient dosage; the same dosage could instead be excessive for men.
The accuracy of the growth hormone dose should therefore be checked every six months. As physiological growth hormone production decreases with age, the required dose is reduced. In patients over 60 years of age, therapy should be started with a dose of 0.1-0.2 mg per day which should be gradually increased according to the needs of individual patients. The lowest effective dose should be used. The maintenance dose rarely exceeds 0.5 mg per day.
04.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients.
Somatropin should not be used if there is evidence of tumor activity. Intracranial tumors must be inactive and anticancer therapy must be completed before starting growth hormone therapy. In case of tumor growth it is necessary to stop the treatment.
GENOTROPIN should not be used to promote growth in patients with epiphysis sealing.
Critically ill patients suffering from complications following open heart surgery, abdominal surgery, multiple accidental trauma, acute respiratory failure or similar conditions should not be treated with GENOTROPIN. replacement, see section 4.4).
04.4 Special warnings and appropriate precautions for use
Diagnosis and Therapy with GENOTROPIN must be promoted and monitored by qualified doctors with the necessary experience in the diagnosis and treatment of patients for whom therapeutic use is indicated.
Myositis is a very rare adverse event that may be related to the preservative metacresol. In the event of myalgia or excessive pain at the injection site, the possibility of myositis should be considered and if confirmed, a pack of GENOTROPIN without metacresol should be used.
It is necessary not to exceed the maximum recommended daily dose (see section 4.2).
Sensitivity to insulin
Somatropin may reduce insulin sensitivity. Patients with diabetes mellitus may need to adjust the insulin dose when somatropin therapy is instituted. Patients with diabetes, glucose intolerance, or with risk factors additives for diabetes should be monitored closely during somatropin therapy.
Thyroid function
Growth hormone increases extrathyroid conversion from T4 to T3 which can result in a reduction in T4 concentration and an increase in serum T3. Peripheral thyroid hormone levels remained within reference limits in most subjects healthy while theoretically hypothyroidism can develop in subjects with subclinical hypothyroidism. Therefore, monitoring of thyroid function should be performed in all patients. In patients with hypopituitarism on standard replacement therapy, the potential effects of growth hormone treatment on thyroid function must be be carefully monitored.
In growth hormone deficiency secondary to the treatment of malignant diseases, it is recommended to pay particular attention to detect any symptoms of relapse of the neoplasm.
In patients with endocrine system disorders, including growth hormone deficiency, slippage of the hip epiphysis may occur more frequently than in the rest of the population.
Any eventual claudication occurring in children during somatropin therapy should be monitored clinically.
Benign intracranial hypertension
In case of severe or recurrent headache, visual disturbances, nausea and / or vomiting it is recommended to perform a fundoscopy to detect the possible presence of papillary edema. If this is diagnosed, a diagnosis of benign intracranial hypertension should be considered and, if appropriate, growth hormone therapy should be discontinued.
At present, insufficient information is available to give a specific warning on the continuation of growth hormone treatment in patients in whom intracranial hypertension has resolved. If growth hormone therapy is resumed, careful patient monitoring is required to detect any symptoms of intracranial hypertension.
Leukemia
Leukemia has been found in a small number of patients with growth hormone deficiency, some of whom have been treated with somatropin. However, there is no evidence that the incidence of leukemia increases in individuals who took growth hormone without predisposing factors.
Antibodies
As with all somatropin-containing products, a small percentage of patients may develop antibodies to GENOTROPIN. GENOTROPIN resulted in the formation of antibodies in approximately 1% of patients. The binding capacity of these antibodies is low and there is no effect on the growth rate. Tests for antibodies to somatropin should be performed in patients with a failure. otherwise unexplained response to medication.
Elderly patients
There is limited experience in the treatment of patients over 80 years of age. Elderly patients may be more sensitive to the action of GENOTROPIN and consequently more exposed to the onset of adverse reactions.
Critical clinical conditions
The effects of GENOTROPIN on healing were studied in two placebo-controlled studies involving 522 critically ill adult patients suffering from complications following open heart surgery, abdominal surgery, multiple accidental trauma or acute respiratory failure. Mortality was higher in patients treated with GENOTROPIN 5.3 or 8 mg daily compared to patients treated with placebo, 42% versus 19%. Based on this information, this type of patient should not be treated with GENOTROPIN. As no information is available on the safety of growth hormone replacement therapy in critically ill patients, the benefits of continued treatment in this situation should be weighed against the potential risks.
The possible benefit of treatment with GENOTROPIN should be weighed against the potential risk in all patients who develop other or similar acute critical illnesses.
Prader-Willi syndrome
In patients with Prader-Willi syndrome, therapy must always be combined with a low-calorie diet.
There have been reports of deaths associated with the use of growth hormone in pediatric patients with Prader-Willi Syndrome, with one or more of the following risk factors: severe obesity, (patients whose weight / height ratio exceeds 200%), history of impaired respiratory function or sleep apnea, or unidentified respiratory infection. Patients with one or more of these risk factors may be at increased risk.
Before initiating somatropin treatment in patients with Prader-Willi syndrome, signs of upper airway obstruction, sleep apnea, or respiratory infections should be evaluated.
If pathological signs are observed during evaluation of upper respiratory obstruction, the child should be referred to an ENT specialist for treatment and resolution of the respiratory disorder before starting growth hormone treatment.
Sleep apnea should be assessed for sleep apnea using recognized methods such as polysomnography or sleep oximetry before initiation of growth hormone treatment, and monitoring should be performed if sleep apnea is suspected.
If patients show signs of upper airway obstruction (including the onset or aggravation of snoring) during treatment with somatropin, treatment should be discontinued and a new ENT evaluation performed.
All Prader-Willi Syndrome patients with suspected sleep apnea should be monitored.
Patients should be monitored for signs of respiratory infections, which should be diagnosed as early as possible and treated aggressively.
All patients with Prader-Willi Syndrome should also undergo careful weight control before and during growth hormone treatment.
Scoliosis is common in patients with Prader-Willi syndrome. Scoliosis can progress in any child with rapid growth. During treatment, signs of scoliosis should be monitored.
There is limited experience in the prolonged treatment of adult patients and patients with Prader-Willi syndrome.
Babies born small for gestational age
Other causes or treatments that could explain growth disturbance in short children born small for gestational age (SGA) should be ruled out before starting treatment.
In infants born small for gestational age (SGA), it is recommended that fasting insulin and glucose levels be checked prior to initiation of therapy and annually thereafter. In patients at increased risk of developing diabetes mellitus (eg family history of diabetes, obesity, severe insulin resistance, acanthosis nigricans) oral glucose load curve (OGTT) should be performed. In the case of overt diabetes, growth hormone should not be administered.
In children born small for gestational age (SGA) it is recommended to monitor IGF-I levels before the start of therapy and twice a year during treatment. If greater than + 2SD with respect to the normal range for the age and stage of pubertal development, the IGF-I / IGFBP-3 ratio should be considered for a possible dosage adjustment.
There is "limited experience with initiation of treatment in SGA patients near pubertal onset. It is therefore not recommended to initiate treatment during this period. There is limited experience in patients with Silver-Russell syndrome."
In small children born small for gestational age (SGA), a partial loss of part of the benefit, in terms of height gain obtained with growth hormone treatment, may occur if therapy is stopped before reaching height. definitive.
Chronic renal failure
In chronic renal failure, renal function must be less than 50% of normal values before starting growth hormone therapy. To check for growth disturbance, growth must be monitored for one year before starting therapy. During this period, conservative treatment of renal insufficiency (including control of acidosis, hyperparathyroidism and nutritional status) should be instituted and maintained during treatment and maintained during treatment. Treatment must be discontinued afterwards. kidney transplant.
To date, no data are available on final height in chronic renal failure patients treated with GENOTROPIN.
04.5 Interactions with other medicinal products and other forms of interaction
Concomitant treatment with glucocorticoids may inhibit the growth favored by somatropin products. Consequently, the growth of patients treated with glucocorticoids must be carefully monitored to assess their potential impact on growth.
Data from an interaction study performed in growth hormone deficient adult patients indicate that administration of somatropin may increase the clearance of substances metabolised by cytochrome P450 isoenzymes. The clearance of substances metabolised by cytochrome P450 3A4 (sex steroids, corticosteroids, anticonvulsants and cyclosporine) can be particularly increased so that the plasma levels of these substances are lower.The clinical significance of this is unknown.
See also section 4.4 regarding diabetes mellitus and thyroid disorders and section 4.2 regarding oral estrogen replacement therapy.
04.6 Pregnancy and breastfeeding
Pregnancy
Animal studies are insufficient to evaluate effects on pregnancy, embryofoetal development, parturition and postnatal growth (see section 5.3). There are no clinical studies available in women taking the drug during pregnancy. Therefore the use of products containing somatropin is not recommended during pregnancy and in women of childbearing age who do not adopt suitable contraceptive measures.
Feeding time
No clinical studies have been performed with somatropin products in lactating women. There is no information on the passage of somatropin into breast milk, but it is extremely unlikely that the protein in its intact form will be absorbed from the gastrointestinal tract of the newborn. Therefore somatropin products should be used with caution in lactating women.
04.7 Effects on ability to drive and use machines
GENOTROPIN does not affect the ability to drive and use machines.
04.8 Undesirable effects
Patients with growth hormone deficiency are characterized by an extracellular volume deficiency. Once somatropin treatment is initiated, this deficiency is corrected quickly. In adult patients, side effects related to fluid retention are common, such as peripheral edema, muscle stiffness -skeletal, arthralgia, myalgia and paraesthesia Generally these adverse events are mild or moderate, occur in the first months of treatment and regress spontaneously or by reducing the dose.
The incidence of these adverse events is related to the dose administered, the age of the patient and can be inversely linked to the age of the patient at the time of onset of growth hormone deficiency. In children, these effects are uncommon.
In approximately 1% of patients GENOTROPIN caused the formation of antibodies whose binding capacity is low and no clinical significance was associated with their formation, see section 4.4.
The following undesirable effects have been observed and reported during treatment with GENOTROPIN with the following frequency: Very common (≥1 / 10); Common (≥ 1/100 e
Adverse reactions are listed according to the following classification:
Very common: ≥ 1/10
Common: ≥ 1/100 e
Uncommon: ≥ 1 / 1,000 and
Rare: ≥ 1 / 10,000 e
Very rare:
Neoplasms benign, malignant and unspecified (including cysts and polyps)
Very rare: Leukemia *.
Disorders of the immune system
Common: Formation of antibodies.
Endocrine pathologies
Rare: Type II diabetes mellitus.
Nervous system disorders
Common: In adults: Paresthesia.
Uncommon: In adults: Carpal tunnel syndrome. In children: Paresthesia.
Rare: Benign intracranial hypertension.
Skin and subcutaneous tissue disorders
Common: In children: transient injection site reactions
Musculoskeletal and connective tissue disorders
Common: In adults: musculoskeletal stiffness, arthralgia, myalgia
Uncommon: In children: musculoskeletal stiffness, arthralgia, myalgia
General disorders and administration site conditions
Common: In adults: Peripheral edema
Uncommon: In children: Peripheral edema
Somatropin has been reported to reduce plasma cortisol levels, possibly by affecting transporter proteins or by increasing hepatic clearance. The clinical relevance of these findings may be limited. However, corticosteroid replacement therapy should be optimized before initiating therapy with GENOTROPIN.
Rare cases of sudden death in patients with Prader-Willi syndrome treated with somatropin have been reported during post-marketing experience, although a causal relationship has not been demonstrated.
* Very rare cases of leukemia have been reported in growth hormone deficient children treated with GENOTROPIN, but the incidence appears to be similar to that in non-growth hormone deficient children, see section 4.4.
04.9 Overdose
Symptoms:
Acute overdose may initially lead to hypoglycemia and subsequently hyperglycemia. Long-term overdose may cause signs and symptoms similar to the effects of excessive amounts of human growth hormone.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: Hormones of the anterior pituitary lobe and analogues
ATC code: H01AC01
Somatropin is a potent metabolic hormone important for the metabolism of lipids, carbohydrates and proteins. In children with insufficient growth hormone elevation, somatropin stimulates linear growth and increases the rate of growth.
In adults, as in children, somatropin maintains normal body composition by increasing nitrogen retention and stimulating musculoskeletal growth and by mobilizing body fat. Visceral adipose tissue reacts particularly to somatropin. increasing lipolysis, somatropin decreases the accumulation of triglycerides in fat stores. Serum concentrations of IGF-I and IGFBP3 (Insulin-like Growth Factor Binding Protein 3) are increased by somatropin.
The following actions were also demonstrated:
- Lipid metabolism: Somatropin induces hepatic LDL cholesterol receptors and affects the serum lipid and serum lipoprotein profile. Generally, administration of somatropin to patients with growth hormone deficiency leads to a reduction in serum LDL and apolipoprotein B. A reduction in total serum cholesterol may also be observed.
- Carbohydrate metabolism: Somatropin increases insulin but fasting blood glucose usually remains unchanged.
Fasting hypoglycemia may occur in children with hypopituitarism. This condition is nullified by somatropin.
- Water and mineral metabolism: Growth hormone deficiency is associated with decreased plasma and extracellular volumes. Both increase rapidly after treatment with somatropin. Somatropin induces retention of sodium, potassium and phosphorus.
- Bone metabolism: Somatropin stimulates the turnover of skeletal bone tissue. Long-term administration of somatropin to growth hormone deficient patients with osteopenia leads to an increase in bone mineral content and density of structures under weight.
Physical capacity: Muscle strength and exercise capacity improve after long-term somatropin treatment. Somatropin also increases cardiac output, but the mechanism has not yet been elucidated. A decrease in peripheral vascular resistance may contribute to this effect.
In clinical trials involving short children born small for gestational age (SGA), doses of 0.033 and 0.067 mg / kg body weight per day were used for treatment until final height was reached. In 56 treated patients continuously until the (almost) definitive height was reached, the change in the mean height value from the start of treatment was +1.90 SDS (0.033 mg / kg body weight per day) and +2, 19 SDS (0.067 mg / kg body weight per day). The data in the literature concerning SGA children who have not received treatment and who have not experienced an initial spontaneous recovery from growth retardation, suggest the subsequent appearance of a height gain of +0.5 SDS Long-term safety data are still limited.
05.2 Pharmacokinetic properties
Absorption
After subcutaneous administration, the bioavailability of somatropin is approximately 80%, both in healthy subjects and in patients with growth hormone deficiency. A subcutaneous administration of 0.035 mg / kg of somatropin results in plasma values of Cmax and Tmax in the range of 13-35 ng / ml and 3-6 hours, respectively.
Elimination
The mean terminal half-life of somatropin following intravenous administration in growth hormone deficient adults is approximately 0.4 hours. However, after subcutaneous administration the half-life is 2-3 hours. The observed difference is probably due to slow absorption from the injection site after subcutaneous administration.
Subpopulation
After subcutaneous administration the absolute bioavailability of somatropin appears to be similar in males and females.
Information on the pharmacokinetics of somatropin in the elderly and infant population, in different races and in patients with renal, hepatic or cardiac insufficiency is not available or is incomplete.
05.3 Preclinical safety data
Studies on general toxicity, local tolerability and reproductive toxicity did not reveal clinically relevant effects. Genotoxicity studies in vitro and in vivo on genetic mutations and on the induction of chromosomal aberrations were negative.
An increase in chromosomal fragility was observed in an in vitro study on lymphocytes collected from patients after long-term treatment with somatropin and after the addition of the radiomimetic drug bleomycin. The clinical significance of this finding is unclear.
In another study, no increase in chromosomal abnormalities was found in the lymphocytes of patients receiving long-term somatropin therapy.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
For the list of presentations see paragraph 2
Presentations 1-2:
Dust (front compartment):
glycine (E640)
monobasic sodium phosphate anhydrous (E339)
anhydrous dibasic sodium phosphate (E339)
mannitol (E421)
Solvent (rear compartment):
Water for injections
metacresol
mannitol (E421)
06.2 Incompatibility
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
06.3 Period of validity
3 years
Shelf life after reconstitution
Chemical and physical stability after reconstitution has been demonstrated for 4 weeks at temperatures between + 2 ° C - + 8 ° C.
From a microbiological point of view, the product, once reconstituted, can be stored at a temperature between + 2 ° C - + 8 ° C for 4 weeks. Other storage conditions and times after reconstitution are the responsibility of the user.
06.4 Special precautions for storage
Before reconstitution: Store in the refrigerator (+ 2 ° C - + 8 ° C), for a maximum period of 1 month at a temperature equal to or below + 25 ° C. Keep the two-chamber cartridge / pre-filled pen in the pouch to protect from light.
After reconstitution: Store in the refrigerator (+ 2 ° C - + 8 ° C). Do not freeze. Keep the dual compartment cartridge / pre-filled pen in the outer carton to protect from light. For storage conditions of the reconstituted medicinal product, see section 6.3.
06.5 Nature of the immediate packaging and contents of the package
Powder and 1 ml of solvent in a two-compartment glass cartridge (type I glass) separated by a rubber plunger (bromobutyl). The cartridge is sealed at one end with a rubber disc (bromobutyl) and an aluminum cap, and at the other end with a rubber stopper (bromobutyl). The two-chamber cartridge is provided for use in a reusable device for injection, GENOTROPIN Pen, or a reconstitution device, GENOTROPIN Mixer, or sealed in a disposable multidose pre-filled pen, GoQuick.
The GENOTROPIN Pens have different colors, and to give the correct dose they must be used with the two-compartment cartridge for GENOTROPIN of the corresponding color. GENOTROPIN Pen 5.3 (blue) must be used with the GENOTROPIN 5.3 mg (blue) cartridge. GENOTROPIN Pen 12 (purple) is for use with the GENOTROPIN 12.0 mg (purple) cartridge.
The 5.3 mg GoQuick pre-filled pen is colored blue. The 12 mg GoQuick pre-filled pen is purple in color.
Not all pack sizes may be marketed.
06.6 Instructions for use and handling
The powder should only be reconstituted with the appropriate solvent provided.
Two-compartment cartridge: The solution is prepared by screwing the parts of the reconstitution device or the injection device or the GoQuick pre-filled pen to mix the solvent and powder in the two-chamber cartridge. Dissolve the product by gently inverting. Do not shake vigorously as the active ingredient can denature. The reconstituted solution is almost colorless or slightly opalescent. Before use, the reconstituted solution should be checked and only clear, particle-free solutions should be used.
Detailed instructions on preparing and administering the reconstituted Genotropin product are provided in the package leaflet, section 3, "Genotropin Injection" and in the Instructions for Use provided with the particular device you are about to use.
When using an injection device the injection needle must be screwed on before reconstitution.
Disposal indications: The unused product or the waste deriving from this medicinal product must be disposed of in accordance with current legislation.
Empty GoQuick pre-filled pens must never be refilled and must be disposed of properly.
07.0 MARKETING AUTHORIZATION HOLDER
Pfizer Italia S.r.l.
Via Isonzo 71
04100 Latina
08.0 MARKETING AUTHORIZATION NUMBER
Genotropin 5.3 mg powder and solvent for solution for injection
A.I.C. 026844098 / M
Genotropin 12 mg powder and solvent for solution for injection - 1 A.I.C. 026844163 / M
Genotropin 12 mg powder and solvent for solution for injection - 5 A.I.C. 026844175 / M
Genotropin 5.3 mg powder and solvent for solution for injection - 1 pre-filled Goquick pen with double chamber cartridge
A.I.C. 026844340
Genotropin 5.3 mg powder and solvent for solution for injection - 5 pre-filled Goquick pens with double chamber cartridge
A.I.C. 026844353
Genotropin 12 mg powder and solvent for solution for injection - 1 pre-filled Goquick pen with double chamber cartridge
A.I.C. 026844365
Genotropin 12 mg powder and solvent for solution for injection - 5 pre-filled Goquick pens with double chamber cartridge
A.I.C. 026844377
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
European renewal date: February 2010
Genotropin 5.3 mg
Genotropin 12 mg, 1 cartridge
Genotropin 12 mg, 5 cartridges
10.0 DATE OF REVISION OF THE TEXT
11 October 2012
