Description

Active substance:Somatropin
Similar drugs:Disclose
Included in the list:VED
Dosage form:
solution for subcutaneous injection
Composition:
1 ml of the preparation contains:
active substance: somatropin (genetically engineered human growth hormone) 6.7 mg (10 mg/1.5 ml);
excipients: mannitol, histidine, poloxamer 188, phenol, hydrochloric acid or sodium hydroxide (for pH correction), water for injection.
1 mg of somatropin corresponds to 3 ME (International Units) of somatropin.
Description:
Colorless clear or slightly opalescent solution.
Characterization of the drug:
The drug Norditropin® contains somatropin, a human growth hormone (HG) produced by recombinant DNA (deoxyribonucleic acid) biotechnology.
Somatropin is an anabolic peptide consisting of 191 amino acids, stabilized by two disulfide bridges, with a molecular weight of approximately 22000 Da.
Pharmacotherapeutic group:Somatotropic hormone
ATX:
H01AC01 Somatotropin
Pharmacodynamics:
The drug Norditropin® stimulates skeletal and somatic growth and has a pronounced effect on metabolic processes.
Somatropin, replenishing the deficiency of endogenous GH, promotes normalization of body structure by increasing body muscle mass and decreasing body fat mass.
Most of the effects of somatropin are realized through insulin-like growth factor 1 (IGF-1), produced in all tissues of the body (mainly in the liver).
More than 90% of IGF-1 is bound to proteins (IFRSB), of which IFRSB-3 is the most important.
The lack of lipolytic and protein-saving effects of the hormone becomes particularly important during stress.
Somatropin also enhances bone remodeling, which is manifested by an increase in the activity of biochemical bone markers in plasma. In adults in the first months of treatment due to more pronounced resorption of bone tissue, a decrease in bone mass is observed, but with continued treatment bone mass increases.
Pharmacokinetics:
Intravenous infusions of Norditropin® (33 ng/kg/min for 3 hours) to 9 patients with GH deficiency produced the results described below.
Metabolism
The metabolic clearance rate of the drug was 2.33±0.58 mL/kg/min.
Distribution
The volume of distribution of the drug was 67.6±14.6 mL/kg.
Excretion
The half-life of the drug from blood serum was 21.1±1.7 min.
Indications:
Children:
growth retardation due to GH deficiency;
severe GH deficiency persisting in adolescents after the end of growth (transition period), confirmed as follows:
When there is a high likelihood of persistent GH deficiency, i.e. severe GH deficiency developed in childhood with the presence or absence of deficiencies of two or three other hormones, which may be due to genetic causes; In severe GH deficiency associated with structural hypogalamic-pituitary disorders, central nervous system tumors, or in patients who have received radiation therapy to the cranial region; the presence of specific genetic causes or GH deficiency secondary to pituitary/hypothalamic disease or stroke is considered sufficient evidence of profound GH deficiency if the coefficient of standard deviation (CSD) of IGF-1 levels is <-2 with GH treatment for at least 4 weeks. If the IGF-1 level is > -2 CSR, a provocation test with GH should be performed.
For all other patients (low probability, including idiopathic, isolated GH deficiency, or deficiency of one additional hormone), quantification of IGF-1 and a single GH provocation test are required. The diagnosis of GH deficiency is confirmed if the results of the quantification and provocation test are low.
A low response (GH level) to stimulation (peak GH < 6 µg/L in the insulin tolerance test (ITT), and peak GH < 16.5 µg/L in the test with somatocrinin (GH-RH) + arginine) confirms the diagnosis of GH deficiency;
growth retardation in girls with gonadal dysgenesis (Shereshevsky-Turner syndrome);
growth retardation in prepubertal children due to chronic renal failure (CRF);
stunting in children (CSR of current height < -2.5, CSR of adjusted (parental height) height < -1) who have prenatal growth and birth weight delays below -2 standard deviations (SD) and who have not reached age-standardized growth by age 4 years or later (CSR of growth velocity (GV) < 0 within the last year);
Growth retardation in children with Noonan syndrome.
Adults:
Confirmed GH insufficiency observed during the transition period in childhood.
GH insufficiency and deficiency developed in adulthood.
Severe GH deficiency with established hypothalamic-pituitary disease, radiation therapy to the cranial region, and craniocerebral trauma (deficiency of another hormone other than prolactin), confirmed by a single provocation test after initiation of adequate replacement therapy for deficiency of any other hormone. For adults, the provocative test of choice is ITT, pathologic level: peak GH < 3 µg/L. If ITT is contraindicated, an alternative provocation test should be used. A combination test using arginine and GH-RG is recommended. Arginine or glucagon tests may also be considered, but their diagnostic value is lower than that of ITT.

Contraindications:
Hypersensitivity to somatropin or any of the excipients of the drug.
Signs of active malignancy (by the start of treatment, the intracranial tumor should be in an inactive state and antitumor therapy has been completed). Treatment should be discontinued if there are signs of tumor growth.
Stimulation of longitudinal growth in children with closed epiphyseal growth zones.
Urgent conditions (including conditions after surgical interventions on the heart, abdominal cavity, multiple trauma as a result of accidents, acute respiratory failure or similar conditions (see section “Special Instructions”);
Prader-Willi syndrome in the presence of one or more of the following risk factors: severe obesity, history of upper airway obstruction or sleep apnea, or unidentified respiratory infection.
Pregnancy.
In children with CKD, treatment with Norditropin® should be interrupted during renal transplantation.
Caution:
Caution should be exercised when using the drug in the following groups of patients and in the following conditions/diseases:
– hypothyroidism;
– diabetes mellitus (DM);
– breastfeeding period;
– Prader-Willi syndrome;
– concomitant glucocorticosteroid (GCS) therapy;
– intracranial hypertension in the stage of compensation.
Pregnancy and lactation:
The use of somatropin during pregnancy is contraindicated. Clinical experience of somatropin use in pregnant women is limited. In normal pregnancy, the concentration of pituitary GH decreases markedly after 20 weeks of pregnancy, being replaced almost completely by placental GH by 30 weeks of pregnancy. In this regard, the need to continue somatropin replacement therapy in the third trimester of pregnancy seems unlikely.
There is no reliable information about the possibility of somatropin penetration into breast milk, but, in any case, absorption of intact protein in the gastrointestinal tract of the child is extremely unlikely. Nevertheless, somatropin should be used with caution during breastfeeding.
Method of administration and dosage:
Somatropin can be prescribed only by a doctor who has special knowledge of the indications for the use of the drug.
Dosing regimen
The dose is selected individually on the basis of individual clinical and biochemical response to therapy.
Standard recommended doses:
Children:
GH insufficiency:
0.025 to 0.035 mg/kg/day or 0.7 to 1.0 mg/m2/day.
If GH deficiency is present after patients have stopped growing, GH therapy should be continued until full somatic adult development, including fat-free body weight and bone mineral gain, is achieved (see subsection “Adults: Replacement Therapy”).
Shereshevsky-Turner syndrome:
0.045-0.067 mg/kg/day or 1.3-2.0 mg/m2/day.
CKD:
0.050 mg/kg/day or 1.4 mg/m2/day (see Special Instructions section).
Stunting in children with prenatal growth retardation:
0.035 mg/kg/day or 1.0 mg/m2/day
A dose of 0.035 mg/kg/day is generally recommended until final growth is achieved.
Treatment should be discontinued after the first year of therapy if the CSR of growth rate is less than +1.
Treatment should be discontinued if the growth rate is < 2 cm/year and, if confirmation is required, by the time of epiphyseal growth zone closure (bone age >14 years for girls or >16 years for boys).
Noonan syndrome:
The recommended dose is 0.066 mg/kg/day, but in some cases a dose of 0.033 mg/kg/day may be sufficient.
Treatment should be discontinued by the time the epiphyseal growth zones have closed (see Special Instructions section).
Adults:
Substitution therapy:
The dose is prescribed based on the individual patient’s needs.
In pediatric patients with GH insufficiency, the recommended dose for resumption of therapy is 0.2 to 0.5 mg/day with subsequent dose adjustment based on IGF-1 concentration determination.
In adult patients with GH insufficiency it is recommended to start treatment with low doses of the drug: 0.1 – 0.3 mg/day and gradually increase the dose every month based on clinical response and tolerability of the drug. The serum IGF-1 concentration can be used as a benchmark for dose titration. Women may require a higher dose of the drug than men because men become hypersensitive to IGF-1 over time. This means that women (especially those receiving oral hormone replacement therapy with estrogen) are at risk of under-dosing and men are at risk of over-dosing.
With increasing age of the patient, the need for GH decreases. The maintenance dose of the drug is selected individually, but rarely exceeds 1.0 mg/day.
Method of administration
The drug Norditropin® should be administered subcutaneously once a day, preferably before bedtime. To prevent the development of lipoatrophy it is necessary to change the injection sites. To perform the injection procedure, see the “Guide for the use of the drug”. For the injection procedure see “Guide for the use of the drug”.
General recommendations on dosing of the drug are presented below.
Recommendations for use of the drug Norditropin® in NordyFlex® syringe-pen
The preparation Norditropin® in prefilled NordyFlex® syringe pens is designed for use with disposable NovoFine® needles up to 8 mm in length.
A NordyFlex® syringe pen pre-filled with Norditropin® Yumg/1.5 mL allows a maximum of 3 mg of somatropin to be administered in a single dose in 0.05 mg somatropin increments.
Before the first injection, it is necessary to check that the syringe handle is ready for use (remove air) in order to ensure correct dosing and to avoid the introduction of air during injection. The dose is selected by turning the dose selector until the required dose appears in the dose indicator window. If the dose has been set incorrectly, turn the dose selector forward or backward until the correct dose is set. The start button must be pressed to administer the dose.
Patients should be reminded to wash their hands thoroughly with soap and water and/or disinfectant before any contact with the NordyFlex® Syringe Pen. The NordyFlex® syringe pen should not be shaken vigorously.
Guidelines for the use of Norditropin® in the NordyFlex® syringe pen are enclosed. Patients should be advised to study it carefully.
The preparation Norditropin® in NordyFlex® syringe-pen should not be used if it is turbid, i.e. it is no longer transparent and colorless. You can check this by turning the syringe-pen up and down once or twice.
The preparation Norditropin® in a NordyFlex® syringe-pen should not be used if a drop of growth hormone solution does not appear at the end of the needle.
Instructions for use of the drug:
Guidelines for the use of the drug Norditropin® in NordyFlex® syringe pen 10 mg/1.5 ml
How to use a NordyFlex® syringe pen prefilled with Norditropin®
Read these instructions carefully before you start using the NordyFlex® Syringe Pen.
The NordyFlex® Syringe Pen is a multi-dose, single-dose, pre-filled syringe pen for multiple injections containing human growth hormone solution for subcutaneous administration.
Use the dose selector to choose a dose from 0.05 to 3 mg in 0.05 mg increments. Your doctor will determine the dose of growth hormone you need.
The NordyFlex® syringe pen prefilled with Norditropin® is designed for use with NovoFine® disposable needles up to 8 mm in length.
Check the name and dosage on the drug syringe pen label to make sure it contains the growth hormone in the dosage you need.
You can only use the drug if the solution in the cartridge is clear and colorless.
Use a new needle for each injection.
Always check the drug supply before using a new pen – see section 3.
Never give your syringe pen or needles to other people. This can lead to cross-infection.
Always keep your syringe pen and needles out of the reach of children.
Caregivers should handle used needles with extreme care to avoid accidental needle sticking and cross-infection.
1.Checking the syringe pen
Check the name and dosage on the label of the NordyFlex® syringe pen to make sure it contains the growth hormone dosage you need.
Remove the syringe pen cap [A].
Make sure the solution in the syringe pen cartridge is clear and colorless by turning it up and down once or twice.
Only inject the drug if the solution in the cartridge is clear and colorless.
2.Needle Attachment
Always use a new needle for each injection. This will reduce the risk of contamination, infection, leakage of drug solution, needle blockage and administration of the wrong dose of drug. Be careful not to bend or damage the needle.
Remove the protective label from the needle.
Screw the needle onto the syringe handle [B]. Make sure the needle is screwed on tightly.
The needle is covered by two caps. Both caps must be removed:
Remove the outer needle cap and retain it to properly remove the needle after injection.
Remove the inner needle cap by pulling the tab in the center part of the needle and discard it.
3.Checking the drug delivery
Before the first injection using a new syringe pen, check the drug inflow to ensure that the correct dose of drug is administered and to prevent air bubbles:
Select 0.05 mg [C]. This is the next click after 0.0 on the dose selector located at the end of the syringe handle.
Holding the syringe handle with the needle up, tap the syringe handle several times to move the air bubbles upward [D].
While holding the syringe handle with the needle up, press the trigger located at the end of the syringe handle as far as it will go [E]. A drop of solution will appear at the end of the needle.
If no drop of solution appears, repeat steps C through E up to 6 times until a drop of solution appears. If a drop still does not appear, replace the needle with a new one and repeat steps C through E again.
Do not use the syringe pen if a drop of drug solution does not appear.
Use a new syringe pen.
Always check the drug supply before using a new syringe pen. Check for drug flow if the syringe pen has been dropped or struck against a hard surface, or if you have any doubts about whether the syringe pen is fully functional.
4. Setting the dose
Check that the dose selector is set to 0.0. Select the number of mg of the drug prescribed by your doctor[F].
The dose can be increased or decreased by turning the dose selector forward or backward. When turning the dose selector backwards, be careful not to press the trigger, as this will cause the solution to spill out. You cannot set a dose that exceeds the number of mg of drug remaining in the syringe handle.
5. Injection
Use the injection technique recommended by your doctor or nurse.
Alternate injection sites to avoid damaging your skin.
Insert the needle under the skin. Administer the dose by pushing the trigger button all the way in. Be careful to press only the trigger [G] during injection.
Keep the trigger fully depressed and leave the needle under the skin for at least 6 seconds. This will ensure that the full dose is administered.
6.Removing the needle
Carefully place the outer cap over the needle without touching it. Unscrew the needle and, using caution, discard it as recommended by your doctor or nurse [H].
Never try to put the inner cap back on the needle.
You may prick yourself.
Put the cap back on the syringe pen after each use.
Remove and discard the needle after each injection and store the syringe pen with the needle disconnected. This reduces the risk of contamination, infection, somatropin drug leakage, needle clogging, and administration of the wrong dose of drug.
Discard the used syringe pen with the needle disconnected as recommended by your doctor, nurse or local requirements.
Caregivers should handle used needles with extreme care to reduce the risk of pricking and cross-infection.
7.Storage and care
Handle the NordyFlex® syringe pen with care.
Do not drop or bump the syringe pen against a hard surface. If you drop the syringe pen or are in doubt, attach a new needle and check the drug flow before injecting.
Do not refill a pre-filled syringe pen.
Do not attempt to repair or disassemble the syringe pen yourself.
Protect the syringe pen from dust, dirt, freezing and direct sunlight.
Do not wash, immerse, or lubricate the syringe pen. If necessary, the syringe pen can be cleaned with a damp cloth dampened with mild detergent.
Do not freeze the syringe pen and, if stored in a refrigerator, do not store it near cooling elements.
Observe the storage conditions stated on the carton pack and in the Storage Conditions section of these instructions.
Side Effects:
Intercellular volume deficiency is common in patients with GH insufficiency. With the start of treatment with somatropin this deficit is corrected. Fluid retention in the form of peripheral edema is more common in adults. Non-serious arthralgia, myalgia and paresthesia may also occur, which usually do not require additional treatment. Symptoms are transient, dose-dependent and may require temporary dose reduction.
Adverse reactions in children are infrequent or rare.
Data obtained from clinical trials:
Organ system class

Very frequent
≥ 1/10

Frequently
≥ 1/100; < 1/10

Infrequently
≥ 1/1000; < 1/100

Rarely
≥ 1/10000; < 1/1000

Metabolic and nutritional disorders

In adults, type 2 diabetes mellitus (see post-registration data).

Nervous system disorders

In adults – headache and paresthesia

In adults – tunnel syndrome.
In children – headache

Skin and subcutaneous tissue disorders

In adults – itching

In children – unspecified rash.

Muscle, skeletal and connective tissue disorders

In adults – arthralgia, joint stiffness and myalgia

In adults – muscle stiffness

In children – arthralgia and myalgia

Reproductive system and breast disorders

Gynecomastia in adults and children

General disorders and reactions at the site of administration

In adults – peripheral edema (see description above).

In adults and children – pain at the injection site.
In children – unspecified reaction at the injection site

In children – peripheral edema

Increased upper and lower extremity size has been reported in children with Shereshevsky-Turner syndrome during treatment with GH.
In two clinical trials, there was a trend toward middle ear and outer ear otitis media in patients with Shereshevsky-Turner syndrome treated with high doses of Norditropin®. However, inflammatory ear disease did not result in more medical manipulations compared to the group of patients receiving lower doses of the drug.
Post-registration data:
Rarely (less than 1 in 1000) generalized hypersensitivity reactions (including anaphylactic reactions) have been reported. In addition to the above listed adverse reactions, the following are adverse reactions based on spontaneous reports, which are considered as possibly relevant to the use of the drug Norditropin®.
Immune system disorders
Hypersensitivity. Formation of antibodies to somatropin was rarely observed during treatment with Norditropin®. Titers and binding capacity of these antibodies were very low and did not affect the growth response when using Norditropin®.
Endocrine system disorders
Hypothyroidism. Decrease in serum thyroxine (T4) concentration.
Very rarely, a decrease in serum thyroxine (T4) concentration during treatment with Norditropin® has been reported.
Metabolic and nutritional disorders
Hyperglycemia.
Nervous system disorders
Benign intracranial hypertension.
Hearing and labyrinth disorders
Otitis media.
Muscle, skeletal and connective tissue disorders
Epiphyseolysis of the femoral head.
Legg-Calve-Perthes disease. Legg-Calve-Perthes disease may occur more frequently in patients with stunting.
Laboratory and instrumental findings
Increased plasma alkaline phosphatase activity.
Overdose:
Acute overdose of somatropin may result in hypoglycemia followed by hyperglycemia. Prolonged overdose may lead to the development of signs and symptoms of gigantism and/or acromegaly, consistent with the known effects of excess GH.
Treatment: withdrawal of somatropin preparation, symptomatic therapy.
Further monitoring of thyroid function is recommended.
Interactions:
Concomitant GCS therapy may inhibit growth and thus interfere with the growth effect of Norditropin®. Careful selection of GCS replacement therapy in patients with adrenocorticotropic hormone (ACTH) deficiency is necessary to avoid neutralization of somatropin action.
Growth hormone reduces the conversion of cortisone to cortisol and contributes to the symptoms of previously undiagnosed hypoadrenalism or renders low-dose GCS replacement therapy ineffective (see section “Special instructions”).
In women receiving oral estrogen replacement therapy, a higher dose of somatropin may be required to achieve the treatment goal (see section “Special indications”).
Data obtained in an interaction study conducted in adult patients with GH deficiency showed that somatropin administration may increase the clearance of compounds metabolized by the CYP3A4 isoenzyme of the cytochrome P450 system. Clearance of compounds metabolized by CYP3A4 isoenzyme of cytochrome P450 system (including sex steroid hormones, GCS, anticonvulsants and cyclosporine) may be strongly increased, leading to a decrease in the plasma concentration of these compounds. The clinical significance of such an interaction has not been studied.
In patients receiving insulin, dose adjustment may be required after initiation of treatment with somatropin (see section “Special instructions”).
Concomitant therapy with other hormones, such as gonadotropin, anabolic steroids, estrogens and thyroid hormones, may also affect the efficacy of the drug (in terms of final growth).
Incompatibility
Compatibility studies have not been conducted, therefore the preparation Norditropin® should not be mixed with other medicinal products.
Special instructions:
A specialist in the field of growth pathology should regularly monitor the condition of children receiving somatropin. Treatment with Norditropin® should always be initiated by a physician with specialized knowledge in the field of GH deficiency and its treatment. This also applies to the treatment of growth retardation in Scherzewski Turner syndrome, CKD, stunting in children with a history of prenatal growth retardation and Noonan syndrome. Data on final adult growth after use of Norditropin® are limited for children with Noonan syndrome and are not available for children with CKD.
The maximum recommended daily dose should not be exceeded (see section “Administration and dosage”).
Stimulation of longitudinal growth can be performed in children until closure of epiphyseal growth zones.
GH deficiency in adults
GH insufficiency in adults is lifelong and requires appropriate treatment, but at present, experience with treatment of patients over 60 years of age, as well as the results of therapy lasting more than 5 years, is limited.
Pancreatitis
Occasionally, patients, especially pediatric patients treated with somatropin, may experience abdominal pain, which may indicate pancreatitis.
Shereshevsky-Turner syndrome
In patients with Shereshevsky-Turner syndrome, monitoring of proportional growth of the upper and lower extremities is recommended during somatropin treatment, and if increased growth is detected, the dose of the drug should be reduced to the lower end of the dose range.
Girls with Shereshevsky-Turner syndrome usually have an increased risk of otitis media and should be monitored by an otorhinolaryngologist. A check-up by an otorhinolaryngologist should be performed at least once a year.
CPN
Growth impairment in children with CPN should be accurately determined prior to somatropin treatment by growth monitoring on optimal CPN therapy for one year. During somatropin therapy, conservative treatment of uremia with conventional medications and dialysis, if necessary, should be continued.
Patients with CKD usually experience a decline in renal function, which is a natural manifestation of this disease. Therefore, as a precautionary measure, renal function should be monitored in patients with CKD during somatropin treatment for a marked decrease or increase in the glomerular filtration rate (which may indicate hyperfiltration).
Scoliosis
Scoliosis is known to be more common in certain groups of patients treated with somatropin, such as those with Sherechevsky-Turner syndrome and Noonan syndrome. In addition, rapid growth in any child can cause progression of scoliosis. There are no data on the increase in the incidence or severity of scoliosis on the background of somatropin therapy. Signs of scoliosis should be monitored during treatment.
Tumors
There is no evidence of increased risk of new primary malignant tumors in children or adults treated with somatropin.
In patients with complete remission of tumors or cancer, somatropin treatment has not been associated with an increased recurrence rate.
Overall, a nonsignificant increase in secondary tumors was found in pediatric cancer survivors treated with GH. Intracranial tumors, particularly meningiomas, were the most frequent. The major risk factor for the development of secondary tumors is most likely prior radiation therapy. It is not known whether there is any association in adult patients treated with somatropin and central nervous system tumor recurrence.
Active malignant process
There is a risk of progression of malignancy when somatropin treatment is given to patients with the presence of malignancy. Somatropin treatment can only be initiated if the preexisting malignancy is inactive and treatment has been completed. After initiation of somatropin treatment, patients who have achieved complete remission, patients with secondary growth hormone deficiency after intracranial tumors should be closely monitored for recurrence of malignancy.
If malignancy occurs or recurs, somatropin treatment should be discontinued.
New malignant neoplasm during somatropin treatment
Because pediatric patients with certain rare genetic diseases have an increased risk of developing malignant neoplasms, the risks and benefits of initiating Norditropin® in these patients should be carefully considered. If Norditropin® has been prescribed, these patients should be carefully monitored for the development of neoplasms.
All patients receiving Norditropin® therapy should also be closely monitored for increased growth or potential malignant changes in pre-existing nevi. Inform the patient/caregivers to report noticeable changes in behavior, onset of headaches, visual disturbances, and/or changes in skin pigmentation or changes in the appearance of preexisting nevi.
Leukemia
Few cases of leukemia have been reported in patients with GH deficiency, with some of them treated with somatropin. However, the incidence of leukemia in patients without predisposing factors has not been shown to increase with somatropin treatment.
Benign intracranial hypertension
Benign intracranial hypertension with optic disc edema, visual disturbance, headache, nausea and/or vomiting has been reported in a small number of patients receiving somatropin therapy. Symptoms usually occurred within the first eight weeks after initiation of somatropin therapy. In all reported cases, signs and symptoms associated with benign intracranial hypertension disappeared rapidly after discontinuation of therapy or reduction of the somatropin dose. A routine ocular fundus examination should be performed before starting Norditropin® to rule out pre-existing optic disc edema, and should be performed periodically thereafter. If ocular fundus examination reveals optic disc edema during somatropin treatment, somatropin therapy should be discontinued. If benign intracranial hypertension is diagnosed, therapy with Norditropin® can be resumed from a lower dose after disappearance of signs and symptoms associated with benign intracranial hypertension. Patients with Shereshevsky-Turner syndrome may have an increased risk of developing benign intracranial hypertension.
Thyroid function
Somatropin treatment activates the conversion of the hormone T4 (thyroxine) to TK (triiodothyronine), which can be used to detect hypothyroidism in its initial stages. Therefore, thyroid function monitoring should be performed in all patients. Patients with hypopituitarism should be carefully monitored when somatropin therapy is administered.
Patients with advanced pituitary disease may develop hypothyroidism. Undiagnosed/untreated hypothyroidism may interfere with an optimal response to Norditropin® therapy, particularly growth response in pediatric patients.
Patients with Shereshevsky-Turner syndrome have an increased risk of developing primary hypothyroidism associated with antithyroid antibodies.
In patients with GH deficiency, central (secondary) hypothyroidism may first manifest or worsen during somatropin treatment.
Thus, patients should have regular thyroid function evaluations. If hypothyroidism is diagnosed, thyroid hormone replacement therapy should be prescribed or adjusted.
Antibodies
During treatment with somatropin-containing drugs, a small proportion of patients may develop antibodies to somatropin. The binding capacity of these antibodies is low and they do not affect growth rate. Patients who do not respond to therapy should be screened for somatropin antibodies.
Acute adrenal cortex insufficiency
Initiation of somatropin therapy may result in inhibition of 11βHSD-1 (11-beta-hydroxysteroid dehydrogenase type 1) and decreased serum cortisol concentrations. Patients treated with somatropin may exhibit previously undiagnosed central (secondary) hypoadrenalism and may require GCS replacement therapy. In addition, patients receiving GCS replacement therapy for previously diagnosed hypoadrenalism may require an increase in maintenance or stress dose after initiation of somatropin therapy (see Interactions with Other Drugs).
Use in conjunction with oral estrogen administration
If a woman treated with somatropin begins therapy with oral estrogen, it may be necessary to increase the somatropin dose to maintain serum IGF-1 concentrations within the normal age range. Conversely, if a woman treated with somatropin discontinues oral estrogen therapy, the dose of somatropin may need to be reduced to avoid excess growth hormone and/or adverse reactions (see Interactions with Other Drugs).
Epiphyseolysis of the femoral head
In patients with endocrine disorders, including GH deficiency, displacement of the epiphysis at the hip joint may occur more frequently than in the general population. A patient treated with somatropin who develops claudication or presents with complaints of hip or knee pain should be evaluated by a physician.
Impaired glucose tolerance and diabetes mellitus
Somatropin therapy decreases insulin sensitivity, especially at high doses in patients with high sensitivity, which may cause the development of hyperglycemia in patients with inadequate insulin secretion.
As a result, previously undiagnosed impaired glucose tolerance and DM may be detected during somatropin therapy.
Therefore, periodic monitoring of glucose concentration is necessary in all patients receiving somatropin, especially in patients at high risk of diabetes: patients with obesity, Shereshevsky-Turner syndrome or with a family history of diabetes. Patients with diagnosed type 1 or type 2 DM or impaired glucose tolerance require closer monitoring during somatropin treatment (see section “Interaction with other medicinal products”). In such patients, the need for dose adjustment of hypoglycemic agents (insulin and/or oral hypoglycemic agents) during somatropin administration should be evaluated.
IGF-1
In patients with Shereshevsky-Turner syndrome and children with prenatal growth retardation, it is recommended to measure serum IGF-1 concentration before the start of somatropin therapy and then 2 times a year. If repeated measurements confirm that the concentration of serum IGF-1 exceeds the standard for age and pubertal status by +2 CRMs, it is necessary to reduce the dose of the drug to achieve IGF-1 concentration within the range of normal values.
Some of the growth gain achieved with somatropin treatment in children with prenatal growth retardation may be lost if treatment is discontinued before final growth is achieved.
Treatment of growth hormone deficiency in patients with Prader-Willi syndrome
Cases of sudden death have been reported during somatropin treatment of patients with Prader-Willi syndrome who had one or more risk factors such as: severe obesity, history of upper airway obstruction, sleep apnea, or unidentified respiratory infections. Male patients with one or more of these risk factors may be at greater risk than females. Patients with Prader-Willi syndrome should be evaluated for evidence of upper airway obstruction or sleep apnea prior to treatment with somatropin. If patients develop signs of upper airway obstruction (including the onset or worsening of snoring) and/or signs of the onset of sleep apnea during treatment with Norditropin®, treatment should be discontinued. Patients with Prader-Willi syndrome treated with Norditropin® should also monitor their weight and be monitored for signs of respiratory infection, which should be diagnosed as early as possible and treated intensively (see section “Contraindications”).
Severe hypersensitivity
Serious systemic hypersensitivity reactions, including anaphylactic reactions and angioedema, have been reported in the post-registration period of the drug administration. Patients and caregivers should be informed that such reactions are possible and that immediate medical attention should be sought if an allergic reaction occurs (see section “Contraindications”).
Lipoatrophy
Subcutaneous injection of Norditropin® at the same site over a prolonged period of time may result in tissue atrophy. It is necessary to change injection sites to reduce this risk.
Laboratory tests
Serum levels of inorganic phosphorus, alkaline phosphatase, parathyroid hormone (PTH), and IGF-1 may increase following therapy with Norditropin®.
Data from clinical trials
Two placebo-controlled clinical trials involving 522 adult ICU patients in critical condition due to complications from open-heart surgery, abdominal surgery, multiple accidental injuries, or acute respiratory failure demonstrated increased mortality in patients receiving high-dose somatropin (5.3 to 8 mg/day) compared to patients receiving placebo (41.9% and 19.3%, respectively). The safety of continuing somatropin replacement therapy within the reported indications in patients with the listed conditions has not been established. Accordingly, the potential risk/benefit ratio of continuing somatropin treatment in patients in an urgent condition should be carefully evaluated.
Monitoring the use of the drug
To improve monitoring of the administration of a biological drug product, the name and series number of the drug applied should be clearly indicated.
Excipients
The drug Norditropin® contains less than 1 mmol of sodium (23 mg) per 1.5 mL. That is, in fact, does not contain sodium.
Effect on the ability to drive vehicles and machinery:
The drug has no effect on the ability to drive vehicles and mechanisms.
Form of release/dosage:
Solution for subcutaneous injection 10 mg/1.5 ml.
Packaging:
1.5 ml into cartridges made of glass, capped with caps with disks of bromobutyl rubber/polyisoprene on one side and pistons of bromobutyl rubber on the other. The cartridge is sealed in a plastic multi-dose disposable syringe pen for multiple injections (pre-filled syringe pen) NordyFlex®.
1 pre-filled syringe-pen each together with instructions for use in a cardboard pack.
Storage conditions:
Keep out of reach of children
Store at a temperature of 2°C-8°C (in the refrigerator).
Store the syringe pen in a cardboard package to protect it from light.
Do not store near cooling elements. Do not freeze
For syringe pen in use: store for 4 weeks at 2°C-8°C (in the refrigerator) or for 3 weeks at a temperature not exceeding 25°C.
Do not store near cooling elements. Do not freeze
Shelf life:
2 years. Do not use after the expiry date indicated on the syringe pen label and packaging.
Conditions of release from pharmacies:By prescription
Registration number:P N015447/01
Date of registration:2009-03-16
Revocation date:2024-09-12
Date of re-registration:2023-02-03
Registration Certificate Holder:
NOVO NORDISK A/S Denmark
Manufacturer:
NOVO NORDISK A/S Denmark
Representation:
NOVO NORDISK Ltd Denmark
Date of information update: 2024-09-12