Key Benefits:
The Minister of Health and Solidarity,
In view of the social security code;
Given the code of public health;
In the light of the Decree of 8 December 1994 for the application of Article R. 163-2 of the Social Security Code relating to Specialties redeemable;
Seen in the opinion of the Transparency Commission,
Stop:
The list of Pharmaceutical specialities refundable to insured persons shall be amended in accordance with the provisions set out in Annex I. The therapeutic information sheet referred to in Article R. 163-2 of the Social Security Code for OMNITROPE shall be Annex II to this Order.
The Director General of Health and the Director of Social Security are responsible for each As regards the execution of this Decree, which shall be published and its annexes in the Official Journal of the French Republic.
A N N E X E I
(2 entries)
The following specialties are listed on the list of reimbursable drugs for which the insured person's participation is deleted The first paragraph of Article R. 322-2 of the Social Security Code.
The only therapeutic indications which are eligible for care or reimbursement by health insurance are:
In the child:
Delay from Growth linked to somatotropic deficit.
Turner syndrome growth delay.
Chronic renal failure growth delay.
Growth delay (current size-3 SDS (standard deviation score) and size Adjusted parental < - 1 SDS) in children born young for gestational age with weight and/or birth size < - 2 standard deviations (SD), not catching up to growth retardation (growth rate (VC) < 0 SDS at Last year) at age 4 or older.
Prader-Willi Syndrome (SPW), to improve growth and body composition. The diagnosis of SPW must be confirmed by the appropriate genetic test.
In adults:
Substitutive treatment in adults with severe somatotropin deficit.
Patients with severe somatotropin deficits acquired at age Adult are defined as having a known hypothalamic-pituitary pathology and at least one other pituitary hormonal deficit, except prolactin. Only one dynamic test will be performed to diagnose or exclude a growth hormone deficiency in these patients.
In patients with a somatotropically acquired deficit in childhood (no history of pathology Hypothalamo-hypophysary or encephalic irradiation), two dynamic tests should be performed, except in case of low IGF-1 (< - 2 SDS) rates, which can be considered as a test.
Dynamic test limit values must be Strictly defined.
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These specialties are prescribed in accordance with the therapeutic fact sheet Appendix II.
A N N E X E I I
THERAPEUTIC INFORMATION SHEET
EXCEPTION MEDICATION
OMNITROPE
Growth Hormones
OMNITROPE
OMNITROPE 5 mg/ml, powder and solvent
OMNITROPE (somatropine) is a biosynthetic growth hormone produced by an E. strain. Genetically modified coli that accurately mimic the sequence of natural somatotropous hormone.
OMNITROPE is a similar biological drug, or " Biosimilar ", from GENOTONORM.
Several growth hormone-based specialties are marketed. Each of these specialties was evaluated in indications and according to specific criteria. Not all of them have the same indications. Where several of them have the same indication, for historical reasons or administrative procedure (national AMM or mutual recognition), the wording of the indication label is not always perfectly superposable. There are also slight variations in the dosage ranges retained in AMM, given the clinical trials presented in the records.
OMNITROPE, biosynthetic human growth hormone, is a drug Restricted prescription whose terms and conditions of care fall under the exception drugs procedure.
List I.
Initial hospital prescription for specialists in pediatrics or endocrinology and diseases Metabolic services in specialized pediatric or endocrinology and metabolic diseases.
1. Refundable therapeutic indications
In the child:
-Growth delay related to somatotropic deficit.
-Turner syndrome growth delay.
-Deficiency delay Chronic kidney.
-Growth delay (current size < - 3 SDS (standard deviation score) and adjusted parental size < - 1 SDS) in children born young for gestational age with weight and/or birth size < - 2 Standard deviations (SD), having not caught up with growth retardation (growth rate [VC] < 0 SDS over the past year) at age 4 or older.
-Prader-Willi syndrome (SPW), to improve growth and Body composition. The diagnosis of SPW must be confirmed by the appropriate genetic test.
In adults:
Substitutive treatment in adults with severe somatotropin deficit.
Patients with severe somatotropin deficits acquired at age Adult are defined as having a known hypothalamic-pituitary pathology and at least one other pituitary hormonal deficit, except prolactin. Only one dynamic test will be performed to diagnose or exclude a growth hormone deficiency in these patients.
In patients with a somatotropically acquired deficit in childhood (no history of pathology Hypothalamo-hypophysary or encephalic irradiation), two dynamic tests must be performed, except in the case of low IGF-1 (< - 2 SDS), which can be considered as a test.
Dynamic test limit values must be .
2. Dosage and Administration Mode
OMNITROPE 5 mg/ml, powder and solvent for injectable solution.
Diagnosis and treatment by somatropine must be performed and followed by a specialist and experienced physician In the diagnosis and management of patients in the therapeutic indications.
The dosage and regimen of administration should be appropriate for each patient.
The injection should be subcutaneous and the injection site will have to vary To avoid the appearance of lipoatrophy.
Growth delay related to a growth hormone secretion deficit in the child: in general, the recommended dose is 0.025 to 0.035 mg/kg body weight per day or 0.7 to 1 mg/m² Body surface per day. Higher doses were used.
Prader-Willi Syndrome, in order to improve growth and body composition in the child: in general, the recommended dose is 0.035 mg/kg body weight per day, or 1.0 mg/m² Body surface per day. The daily dose should not exceed 2.7 mg. Children whose growth rate is less than 1 cm per year and whose epiphyses are nearly welded should not be treated.
Turner syndrome growth delay: the recommended dosage is 0.045 to 0.050 mg/kg of Body weight per day, or 1.4 mg/m² body surface area per day.
Chronic renal failure growth delay: the recommended dosage is 1.4 mg/m² body surface area per day (approximately 0.045 to 0.050 mg/kg weight Body per day). Higher doses can be used if the rate of growth is too low. It is possible that an adjustment of dosage is required after six months of treatment.
Growth delay in children born young for gestational age: the usual recommended dosage is 0.035 mg/kg body weight Per day (1 mg/m² body surface per day) until the final size is reached. Treatment should be discontinued after the first year of treatment if the rate of growth is less than + 1 SD. Treatment should be discontinued if the rate of growth is < 2 cm/year and if confirmation is required, the bone age is > 14 years (for girls) and 6 years (for boys), corresponding to the weld of epiphyses.
Table 1: Recommended doses in children
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Growth hormone deficiency in Adult: treatment must begin with a low dose, 0.15 to 0.3 mg per day. The dose can be progressively increased according to the needs of the patient, determined by the IGF-1 level in order to obtain IGF-1 concentrations, depending on age, not exceeding the limit of 2 DS. Patients whose rate of IGF-1 is normal at the beginning of treatment will need to receive growth hormone until they reach an IGF-1 level within the upper limits of normal, without exceeding 2 DS.
The clinical response, as well as the Adverse reactions can also guide the adaptation of dosing. Daily maintenance rarely exceeds 1 mg per day.
Women may require higher doses than men, men with an increase in sensitivity of IGF-1 over time.
There is therefore a risk That women, especially those with oral estrogen replacement therapy, should be under-dosed while men would be overdosed. Therefore, the correct adaptation of the dose of somatotropic hormone will have to be monitored every six months. The physiological secretion of growth hormone decreasing with age, a reduction in dosage is possible. The minimum effective dose should be used.
3. Clinical interest
The growth hormone (growth hormone, GH) in the child is used to correct the growth retardation due to a somatotropin deficit. It can also be useful for treating some children with growth retardation without somatotropin deficit, in order to increase their rate of growth (Turner syndrome, prepubertal child with chronic renal failure, born child Small for gestational age).
In adults with a deep deficit in growth hormone, GH treatment may in some cases improve the quality of life and well-being of patients and result in a change in composition Body with an increase in lean mass.
3.1. In child
3.1.1. Somatotropic Deficit Growth Delay
Growth hormone deficiency may be secondary to an organic cause (hypothalamic-pituitary tumour), irradiation (cranio-spinale or total body), or Congenital. It is mostly idiopathic in current practice.
The constitution of historical series shows that in the absence of replacement GH treatment, the adult size of children with a severe GH deficit would be between 130 and 150 cm For boys and between 130 and 140 cm for girls. These series are not representative of the patients currently treated because the lower deficits benefit from GH treatment.
In GH-treated children, clinical studies show a particularly strong catch-up Net the first year with a growth rate of 8 to 9 cm, smaller the following year. Follow-up of treated children confirms the maintenance of a statural gain in the third year, but catch-up is generally no longer significant beyond. For patients whose treatment began in the early 1990s, the average final size is 166 cm in the boy and 154 cm in the girl, which brings them closer to the average sizes observed in France. There are large inter-individual variations, also the assessment of the effect of treatment on the final size is difficult, especially in moderate forms of deficit. However, patients with a deep and early deficit best respond to treatment.
Subcutaneous (SC) administration is preferable because of better bioavailability and higher growth rates than The intramuscular (IM) pathway. In addition, the effect on growth is all the more pronounced as the frequency of injections is greater, leading to a recommendation for HC treatment 7 days a week.
Treatment is more effective in children With organic deficits compared to those with an idiopathic deficit. Cranio-spinal irradiation is associated with the most unfavourable results.
The final size is higher when a gonadotropic deficit is associated with the somatotropin deficit and the two deficits are corrected, when GH treatment Was early and when the statural delay was moderate.
3.1.2. Turner syndrome growth retardation
Turner's syndrome is characterized by an anomaly in the number and/or structure of the X chromosome. The growth retardation may be present at birth. It progressively increases to less than two standard deviations (- 2 SD) to 5-6 years and-4 DS at 12-13 years of age.
In the absence of any treatment, there is no peak of pubertal growth and growth extends beyond The usual age. Adult size is reached between 18 and 20 years of age; it is 142 cm on average outside of any GH treatment.
The indication of treatment with exogenous GH is based on the enhancement of the effect of endogenous GH. In these children, a higher dose than in the treatment of GH deficit causes a significant increase in the rate of growth.
The increase in the rate of growth in the first year is in the order of 2 to 5 cm for a Dose of 0.035 mg/kg/day but tends to decrease in subsequent years. The average final gain is about 4 to 9 cm in relation to projected size.
GH is not alone involved in statural growth; the ovarian insufficiency of these patients also plays a role. Too early induction of puberty can cause loss of GH-induced earnings. However, the optimal age and therapeutic regimen of steroid replacement therapy remain controversial.
3.1.3. Chronic
Renal Deficiency (CRI) Growth Delay in Children
Chronic renal insufficiency (CKD) is defined by a decreased renal function of at least 50 % compared to normal. About half of children with CKD have a significant statural delay in relation to children of the same age.
In children treated with GH, a significant statural gain is observed in the first year, less net in the second year, such as this Which has been observed in the other indications of GH; there is little data available on adult sizes after GH treatment.
The effect on growth appears to be less pronounced when the children are dialyzed. The therapeutic response was inversely correlated with creatinine clearance at the time of initiation of treatment. There was no evidence of significant acceleration of bone maturation.
3.1.4. Growth Delay in Small-born
Children for Gestational Age
Children born young for gestational age are smaller than the reference numbers for a given gestation period. The limiting limit corresponds to minus 2 standard deviations (- 2 DS) of the reference curves.
In these children, in the majority of cases, post-natal growth is marked by an acceleration enabling them to be completed by the end of the 2nd year of Control their delay. However, 10 to 20 % of them, according to the studies, maintain a statural disability with a size of less than-2 DS relative to the average of the population.
Among children who did not catch up at the age of 3, the Establishment of a historical series has established that adult sizes of untreated children whose size before puberty is < - 2.5 DS are very clearly below the normal range. The adult size is about 158 cm in the boy and 146 cm in the girl.
Uncertainties about the final size remain because there may be an acceleration of bone maturation during treatment and a slowing of the Growth after stopping, leading to a statural loss of about 0.25 DS within one year of stopping, in a number of children.
It should be noted that, in non-loss-making children, the benefit of hormone treatment Growth is not shown in terms of the improvement in the final size. In addition, uncertainties about the long-term tolerance of such treatment exist in these same children.
In view of these uncertainties, growth hormone is only reimbursed in this indication for children whose size is When the treatment is introduced is less than or equal to-3 SD. The Committee on Transparency wishes to reassess growth hormones with a similar indication as soon as possible.
3.1.5. Prader-Willi Syndrome Growth Delay
Prader-Willi syndrome is a rare genetic disease (1/10 000 to 1/25 000 births) characterized in infants by hypotonia and difficulty Food, quickly replaced in children and adults by massive obesity with bulimia. Other manifestations include dysmorphic elements, more or less characteristic, and mental retardation of varying severity. Most children are small. They have abnormalities in body composition (increase in fat mass, lean mass decrease) more marked than in common obesity, where lean mass is relatively conserved.
The benefit of a hormone treatment Growth in these patients is moderate. It relates to size gain, and changes in body composition by increasing lean mass and decreasing fat mass.
3.2. Somatotropic Deficit in Adults
Among the causes of somatotropic deficit in adults, tumour pathology is the first. Hypophyseal adenomas are the most common. Most idiopathic defects in childhood GH do not persist in adulthood. Normal growth hormone secretion was found in 70 to 80 % of the patients reassessed after puberty. In the case of anterior pituitary insufficiency, even if it is correctly substituted for the thyreotropic, corticotropic, and gonadotropic axes, symptoms attributed to the unsubstituted GH deficit persist.
Induced adult somatotropic deficit A change in body composition with an increase in fat mass mainly at the abdominal level, decreased lean mass and muscle mass, increased fatigability, and decreased bone density. Retrospective epidemiological studies show an increase in the incidence of cardiovascular disease mortality in patients with overall anterior pituitary insufficiency despite hormone replacement therapy Usual. However, the actual location of the somatotropin deficit in this decrease in life expectancy is not known.
GH treatment alters body composition with an increase in lean mass and decrease in fat mass. This results in a reduction in the size/hip ratio as well as the skin fold. In addition, treated patients reported a subjective improvement in their physical capacity and resistance to exercise. The first days or weeks may be marked by a discrete weight gain and by the occurrence of malleolar oedema related to the hydrosodée retention induced by GH treatment.
GH treatment appears to improve modestly the Lipid profile. The evolution of blood sugar and insulin levels varies greatly from one study to another. Currently available studies do not assess the effect of GH treatment on atheromatous risk and mortality of patients with GH deficit.
GH treatment for 12 months increases moderately Bone mineral density. There are few studies evaluating the effect of GH treatment on fracture incidence.
There is no long-term data on the efficacy and tolerance of growth hormone treatment.
4. Terms of Use
Treatment needs to be implemented in the hospital by specialists in pediatrics and/or in endocrinology and metabolic diseases in pediatric and/or endocrinology specialty services
Every year, the interest in treatment must be reassessed in the hospital by the same specialists.
The renewal of the initial prescription to the same dosage is possible, in intermediate periods, by all Physician.
There are cases of non-responders, for whom no predictive factors have been identified, both in the child and the adult.
To allow for better patient monitoring, the change in GH is not Recommended during treatment, unless the hospital prescriber who initiated the treatment considers it justified.
Stopping treatment is imperative in the event of an appearance or evolution of a tumour process.
Children's Specificity: GH treatment that does not improve the growth of patients whose epiphyses are welded, it is important to weigh the decision to introduce sex steroid hormones.
The Compliance with the updated legal mentions of the AMM is essential. Parents and/or families should be informed of the possible occurrence of some adverse reactions and patients undergoing regular medical surveillance. 4.1. Processing
The qualified specialist must ensure that the patient meets the criteria for treatment; the absence of contraindications must be verified; the prescribed specialty must possess Required indication.
4.1.1. In child
Growth delay related to somatotropic deficit:
Two conditions are required for processing:
-size-2 DS according to French reference data;
-speed of Growth in the past year below normal for age (- 1 SD) or < 4 cm/year.
In addition, the diagnosis of the GH deficit must be adequately proven by appropriate explorations. Since GH secretion is variable in the diel, a single dose is insufficient to assert the GH deficit.
Two separate stimulation tests must be performed on different dates, at least one coupled: Insulin/arginine, glucagon/propranolol, glucagon/betaxolol, clonidine/betaxolol. It is recommended that a recombinant GH (1 mg = 3 IU) be used in the assays as a standard. The results are expressed in mIU/l (or µ g/L). The data set leads to:
-a complete GH deficit: 2 proofs < 10 mIU/l (3.3 µ g/l);
-a possibility of a partial deficit: peaks between 10 and 20 mIU/l (3.3 µ g/l to 6.6 µ g/l).
A single test that resulted in a GH response > 20 mUl/l (6.6 µ g/l) must eliminate the diagnosis of somatotropic deficit.
In the case of a partial deficit associated with overweight > 20 %, the results of GH stimulation tests are falsely lowered and Difficult to interpret. The diagnosis is based on the dosage of IGF1: a normal or even higher than normal result excludes the diagnosis of GH deficit associated with obesity and invites to practice a reevaluation about 6 months after caloric restriction and loss
In the case of a partial deficit associated with a small size of one or both parents, the GH treatment decision is based in addition to the size (- 2 DS) and the rate of growth over the past year (< - 1 DS for age or < 4 cm/year), bone age, and adult size predicted (lower than target size).
The search for a cause (MRI or pituitary scan) and associated pituitary deficits is an important step in the process.
In case History of leukaemia or tumour, it is strongly advised to wait for one year of remission before the treatment is started.
Turner Syndrome Growth Delay:
The diagnosis is based on the karyotype. This allows you to define the number and/or structure anomalies for the X chromosome.
There is no lower limit of treatment age, but the upper limit for treatment is a 12-year-old bone age.
One Estrogenic substitutive treatment should be introduced late in progressive dosage in order not to lose the benefit induced by GH.
Chronic renal failure growth retardation:
When conservative treatment is not Is sufficient to maintain an adequate rate of growth for age, GH treatment may be indicated. Renal function, as determined by the measurement of creatinine clearance, must be less than 60 ml/mn/1, 73 m² (normal 120 20 ml/mn/1, 73 m²).
In order to confirm the growth retardation, growth should have been followed in advance One year before the treatment is started.
The criteria for the allocation of hormonal treatment by GH are:
-size-2 DS according to French reference data;
-growth rate in the past year less than Normal for age (- 1 DS);
-chronological age > 2 years;
-bony age < 13 years in daughter and < 14 years of age in boys;
-prepubertal or early puberty children (testicular volume less than 10 ml or stage of Mammary development S3).
Symptomatic, conservative treatment of chronic renal failure (correction of dehydration and acidosis, prevention of renal osteodystrophy and optimization of nutrient intakes) Have been introduced in advance (at least one year) and will be maintained throughout the duration of the growth hormone treatment.
Growth delay in children born young for gestational age:
The decision to use treatment Growth hormone supplementation should be taken with caution in children who are not carded. The long-term effects of exposure to supraphysiological amounts of growth hormone are highly unknown. The pathological effects of excess growth hormone are well known in adults. Stimulating the production of IGF 1, a cytokine capable of stimulating the growth of tumours, should not be neglected.
Other causes or treatments that may account for growth retardation should be excluded before beginning Treatment.
Stimulation of growth in children can only be done before weld epiphyses.
The experience of early treatment just before puberty in children born young for gestational age is limited. Therefore, it is not recommended to begin processing just before puberty.
The criteria for allocating GH treatment are:
-birth size less than-2 DS for gestational age;
-size at time of Introduction of treatment-3 ROs for chronological age;
-children who did not catch up with growth retardation (growth rate < 0 SD over the past year) at 4 + years of age;
-adjusted parental size < - 1 DS.
Prader-Willi Syndrome Growth Delay:
The diagnosis of Prader-Willi syndrome is difficult to assert clinically. That is why a genetic test must be carried out. Several confirmatory tests exist:
-either the methylation analysis of the PWS locus by PCR or Southern Blot (currently recommended as a first-line test with excellent sensitivity and specificity);
-either Research of a microdeletion of region 15 (q11-13) in molecular cytogenetics (in situ hybridization, sensitivity of the order of 70 %);
-the demonstration of a uniparenteral disomic of region 15 (q11-13) (sensitivity of the order of 13 %).
The completion of one of these tests with the presence of an anomaly is sufficient to confirm the diagnosis. In the absence of data on the patient over 12 years of age and information on long-term tolerance, it is recommended to limit the prescription of OMNITROPE to the child under 12 years of age with Prader-Willi syndrome confirmed by test Appropriate genetics.
4.1.2. In adults
Growth hormone treatment should not be systematic in subjects with biological growth hormone deficiency criteria.
There is no data to recommend Initiation of GH treatment in adults over 60 years of age.
Exploratory studies should only be performed in patients with a pathology that refers to a somatotropic deficit and must be:
-a pathology Whether or not the hypothalamo-hypophysary has surgery;
-is undergoing cephalic radiation;
-has a somatotropic deficit in childhood.
It is not necessary to seek a somatotropic deficit in patients with a micro-adenoma Pituitary (less than 1 cm in diameter) unless another prior pituitary deficit (except prolactin deficit) is present.
Alternative treatment for other hormonal deficits will have to be adapted and stable over the past three months. A low plasma GH value does not provide evidence of the somatotropic deficit.
The diagnosis of somatotropin deficit must be confirmed in adulthood. The necessary criterion is an GH peak of less than 10 mIU/l (3.3 µ g/l) when tested for growth hormone stimulation by insulin hypoglycemia, outside of its contraindications.
The injection-induced hypoglycemia test Intravenous insulin with a blood glucose level of 0.40 g/l (2.2 mmol/L) is used to distinguish the somatotropin deficit from the reduction in GH secretion that is usually associated with aging or obesity.
This test must be performed in Endocrinology services accustomed to its implementation. It is contraindicated in patients with electrocardiographic evidence or a history of ischemic heart disease and/or epilepsy. In these cases, another stimulation test will be used.
Other explorations may be required depending on the patient's clinical features.
Acquired somatotrope deficit:
Somatotropic deficits isolated from Childhood needs to be re-evaluated in a particular way. In these patients, the adult GH deficit is less likely. In these cases, two GH stimulation tests are necessary, namely the insulin hypoglycemia test and a second test (GHRH test, coupled test: GHRH-arginine, GHRH-ornithine, glucagon-betaxolol, glucagon-propranolol), except in case of rate Low IGF-1 (< - 2 DS) that is considered a test.
Somatotropic Deficit Acquired as Adult:
Patients should have:
-a secondary somatotropic deficit to a hypothalamic or pituitary pathology and,
-at least one Other associated anhypophysary deficit (except prolactin deficit) and correctly substituted (in this case, only one GH stimulation test may be sufficient).
Treatment should be reserved for patients who have met the above criteria With a marked deterioration in the quality of life as well as a change in body composition (abdominal fat with increasing size/hip ratio).
Before taking any substitutive treatment with GH, all Pituitary deficits must be properly substituted. This obvious attitude in the case of thyreotropic deficiency (L-thyroxine) and corticotropic (hydrocortisone acetate) must also apply to the gonadotropic deficit (sex steroids) in the absence of contraindication.
The objective of the treatment is Obtain maximum benefit by limiting the side effects. It is recommended to begin treatment with low dosages of 0.15 to 0.30 mg/d in the subcutaneous subcutaneous. The goal of treatment is to obtain a normal concentration of insulin-like growth factor I (IGF1) for sex and age.
At the beginning of treatment, patients must be evaluated every 1 to 2 months, clinically and by an IGF1 dosage; the GH dose should be adapted to the clinical tolerance and concentrations of IGF1. The minimum effective dose should be used. The introduction of treatment with low doses associated with the progressive increase every 1 to 2 months reduces the occurrence of side effects. Depending on the results and the tolerance, the dosage may be increased in the space of 3 to 6 months without exceeding the maximum doses of the AMM.
Patients should be informed of the side effects occurring frequently: oedema Limbs, arthralgia and myalgia, rigidity of the extremities, paresthesias. These symptoms are usually transient and dose-dependent. Posologies should be decreased in case of persistent symptoms.
In the case of a tumour process, in the absence of a specific diagnosis of tumour pathology or if the tumour is clinically known to repeat frequently, it is not recommended To introduce GH treatment. In other cases, prior to the introduction of replacement therapy, it is appropriate to ensure that the evolutionary process is not restarted by pre-monitoring, the frequency of which is to be determined with oncologists and/or neurosurgeons through imaging (IRM).
4.2.
4.2.1 processing tracking. In child
4.2.1.1. General
Children treated with GH will be followed every 3 to 6 months in consultation with at least one clinical examination (height, weight, blood pressure, speed of growth, pubertal signs ...). Bone age will be determined on a yearly basis, especially around puberty ages.
Because of the effect of growth hormone on carbohydrate metabolism, patients should be monitored for fasting blood glucose every
. Hypothyroidism may be at the decor of treatment; untreated, it can interfere with GH treatment. An annual control of thyroid function (T4 free) must be performed and, if necessary, replacement therapy will be introduced.
In the case of a corticotropic deficit, the effective minimum doses of hydrocortisone should be
. Concomitant treatment with glucocorticoids (prednisolone family, high-dose inhaled corticosteroids, corticosteroids) may inhibit the effect on GH treatment growth and should be avoided to the extent possible.
In case Severe or repeated headache, visual impairment, nausea and/or vomiting, it is recommended that a background be carried out to investigate possible papillar edema and to eliminate benign intracranial hypertension. This diagnosis may lead to the interruption of GH treatment.
The decision to continue treatment must be made on a case-by-case basis, depending on compliance, treatment tolerance, and statural catch-up.
In the child Transient skin reactions at the injection site are common.
Endocrine-related patients, including those with GH deficits, are at increased risk of epiphysiolysis. Any child with a claudication or pain in the hip or knee during treatment with the growth hormone will be subject to an appropriate clinical and radiological examination.
The dosage must be adjusted quarterly in The weight or body surface of the child.
4.2.1.2. Special Cases as Indications
Somatotropic Deficit Growth Delay:
When the somatotropic deficit is secondary to an intracranial lesion, radiological explorations (MRI) must be Performed regularly, in collaboration with oncologists and/or neurosurgeons, in order to detect any progression or relapse.
In patients with panhypopituitarianism, the balance of the associated substitutions will have to be Be monitored regularly.
Growth gain after the first year of treatment must have been at least 2 cm compared to the year prior to treatment in order to conclude efficacy. In the following years, the rate of growth must be at least equal to the average for chronological age and/or for bone and better than before treatment.
Growth delay associated with Turner syndrome:
Treatment is If the gain in growth in the first year is at least 2 cm compared to the previous year. In the following years, the rate of growth should be:
4.5 cm/year up to 12 years;
3 cm/year when bone age has reached or exceeded 12 years.
Chronic renal failure growth delay:
Although the decrease in Glomerular filtration does not appear to be modified by GH, renal function should be monitored for excessive degradation. Growth gain after the first year of treatment must have been at least 2 cm from the year prior to treatment. In the following years, the rate of growth must be at least equal to the average for age and better than before treatment. The initial dosage may be increased if necessary.
Growth delay in children born young for gestational age:
The administration scheme should be adapted to each patient.
The usual recommended dosage is 0.035 mg/kg body weight per day (1 mg/m² body surface per day) until the final size is reached.
The Commission on Transparency will make possible a confirmation of its favourable opinion on the establishment of a A systematic follow-up of prescriptions will be carried out with patients treated by OMNITROPE. The physician should be involved in the collection of data put in place by the Sandoz laboratory, in collaboration with the Commission on Transparency, in the ambulatory and hospital sectors.
Growth Delay in Prader-Willi Syndrome :
Special monitoring should include:
-Glucidic tolerance, due to the risk of non-insulin-dependent diabetes in this condition;
-The examination of the skeleton, as a result of the onset or possible worsening of scoliosis
In addition, the benefit analysis should focus on both growth and body composition, which is recommended to be followed by appropriate reviews.
Clinical trial data has focused on the The need for overall care, in particular dietetics, of the condition. The isolated use of GH treatment is not effective. Indeed, the medical service rendered by GH in this pathology is moderate with an effective ratio of efficacy/adverse effects.
4.2.2. In adults
There are currently no validated criteria for evaluating the efficacy of treatment in adults. The improvement is essentially subjective.
A follow-up of prescriptions will be performed with patients newly treated by OMNITROPE. The attending physician must participate in the collection of data set up by the Sandoz laboratory, at the request of the Commission of Transparency in the ambulatory and hospital sectors.
Patients treated with GH should benefit from a Clinical examination (weight, circumference/hip, blood pressure) every 1 to 2 months until optimal doses are obtained. When the treatment is stabilized, 1 to 2 visits per year are sufficient.
An assessment of the quality of life as well as the parameters of body composition, comparing them with the data of the examination before treatment, makes it possible to decide on the continuation Treatment.
When the deficit is secondary to an intracranial injury, patients will have to be examined on a regular basis (followed by MRI) in order to screen for possible progression or recidivism. Any recurrence or progression of the tumour involves stopping the treatment.
Compliance and the results of the substitutive treatment of associated anterior pituitary deficits must be verified at least once a year.
The experience of a Long-term growth hormone treatment in adults is limited.
4.3. Stop
4.3.1 processing permanently. In the child
Growth delay related to a somatotrope deficit, or associated with Turner syndrome:
-Onset or evolution of a tumour process;
-Growth rate below 3 cm/year Regardless of age;
-bony age > 15 years or size > 170 cm in the boy; > 13 years or size > 160 cm in the girl.
These last two criteria for stopping treatment can be discussed in the case of severe hormone deficiency in Growth, if the genetic statural potential is not reached.
Chronic renal failure growth delay:
-Onset or evolution of a tumour process;
-Growth rate below 3 cm/year Regardless of age;
-bony age > 15 years or size > 170 cm in the boy; > 13 years or size > 160 cm in the girl.
These last two criteria for stopping treatment can be discussed in the case of severe hormone deficiency in Growth, if the genetic statural potential is not reached.
-Renal Transplantation.
Growth delay in children born young for gestational age:
-Onset or evolution of a tumour process,
According to the RCP, the Processing will need to be stopped:
-After the first year of processing if the growth rate is less than + 1 DS;
-If the growth rate is < 2 cm/year;
-And if the bony age is > 14 years (for girls) and > 16 years (for boys), corresponding to the weld of epiphyses.
Prader-Willi Syndrome:
-Onset or evolution of a tumour process;
-After 14 years of age or growth rate below 3 cm/year Regardless of age;
-Bone age: > 15 years or size > 170 cm in boy; > 13 years or size > 160 cm in daughter.
4.3.2. In adults
There is no criterion for stopping GH treatment in adults. In studies, 12 % to 35 % of patients stop treatment after 12 months and 75 % at 24 months. The need for daily subcutaneous injections is one of the main reasons for these processing interruptions.
5. Terms of Use
These specialties are handled with strict aseptic conditions.
OMNITROPE must be reconstituted only with the solvent provided by the laboratory. The reconstituted solution must not be agitated vigorously because this can denature the active principle.
Storage: maximum duration and special precautions.
You can view the table in the OJ
No 112, 15/05/2007 text number 140
6. Prescribing Prescribers
Prescribers should be cautioned that the benefit/risk ratio is only evaluated for the therapeutic indications selected by the WMA. The use of growth hormones in situations that have no justification in medical practice is not without risk and raises ethical concerns.
The medical profession must be aware of the risks associated with this Misuse.
7. Economic and medico-social specifications
7.1. Prescribing and dispensing conditions
List I.
Initial annual hospital prescription reserved for pediatric and/or endocrine specialists and metabolic diseases engaged in services Specialized in pediatrics and/or in endocrinology and metabolic diseases.
Renewal of the initial prescription at the same dosage (same dosage per kilogram or per square metre for the child), in intermediate periods, possible by Any doctor.
The pharmacopoeial pharmacist must ensure that the qualification of the prescriber appearing on the original hospital prescription is in compliance; when the prescription is renewed, it ensures that the prescription is filed Hospital dated less than one year.
7.2. Support conditions
Reimbursement rate: 100 %.
The prescription must be written on an exception drug order, in accordance with the therapeutic indications that qualify for the refund Mentioned in this sheet.
7.3. Cost of processing
Growth hormones are very expensive drugs that should be used only after an individual estimate of the expected therapeutic benefit.
You can Consult the table in OJ
No 112 of 15/05/2007 text number 140
7.4. Comparable Drugs
You can view the table in OJ
No 112, 15/05/2007 text number 140
AMM holder and operator: Sandoz.
Any remark or Requests for further information should be addressed to:
Haute Autorité de santé, DEAPS, service evaluation des medicines, 2, avenue du Stade de France, 93218, Saint-Denis-La Plaine Cedex.
Done at Paris, April 4, 2007.
For the Minister and by delegation:
The
funding
subsystem of the care system,
J.-P. Vinquant
The Head of Health Policy
and Quality of the Health System,
Assistant to the Director General Health,
D. Eyssartier
