Advanced Search

Decree Of 24 February 2003 Amending The List Of Reimbursable Pharmaceutical Specialties To Insured Persons

Original Language Title: Arrêté du 24 février 2003 modifiant la liste des spécialités pharmaceutiques remboursables aux assurés sociaux

Subscribe to a Global-Regulation Premium Membership Today!

Key Benefits:

Subscribe Now for only USD$40 per month.

Text information




JORF No. 64 of 16 March 2003 Page 4600
Text No. 19



Decree of 24 February 2003 amending the list of pharmaceutical specialities reimbursable to social insured persons

NOR: SANS0320696A ELI: https://www.legifrance.gouv.fr/eli/arrete/2003/2/24/SANS0320696A/jo/texte


The Minister of Health, Family and Disability Issues,
Given the Social Security Code;
Given the Public Health Code ;
In view of the order of 8 December 1994 for the application of Article R. 163-2 of the Code of Social Security and on Reimbursable Specialties;
In view of the Order of 24 January 1997 amending the list of pharmaceutical specialities Payable to insured persons;
In view of the Order of 21 October 2002 amending the list of reimbursable pharmaceutical specialities to social insured persons;
After the opinion of the Commission on Transparency;
After the opinion of the High Medical Committee of Social Security,
Stop:

Item 1


The list of pharmacy specialties refundable to social policyholders is modified as follows:
For Specialties listed in Appendix I, the only therapeutic indications that are eligible for support or reimbursement are:
In the child:
Growth retardation due to a somatotrope deficit or growth retardation Associated with Turner syndrome or chronic renal failure.
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 somatotropic deficits.
Patients with severe adult somatotropics are defined as those with 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 patients with a somatotropically acquired deficit in childhood (no history of hypothalamic-pituitary pathology or Encephalic irradiation), two dynamic tests must be performed, except in the case of low IGF-1 (< - 2 DS), which can be considered as a test. The limit values for dynamic tests should be strictly defined.
The therapeutic fact sheet provided for in Article R. 163-2 of the Social Security Code for GENOTONORM is set out in Annex II to this Order.

Article 2


The therapeutic fact sheet for GENOTONORM, which appeared in the appendix to the decree of 21 October 2002, is Repealed.

Article 3


The Director General of Health and the Director of Social Security are responsible for each Concerning the execution of this Order, which shall be published and its annexes in the Official Journal of the French Republic.


A N N E X E I I

  • THERAPEUTIC INFORMATION SHEET


    EXCEPTION MEDICATION
    GENOTONORM
    Hormones Growth
    GENOTONORM


    GENOTONORM KABIVIAL 5.3 mg/1 ml, with preservative, powder and solvent for cartridge injectable solution
    GENOTONORM 5.3 mg/1 ml, 12 mg/1 ml, with preservative, powder and solvent for solution Cartridge injectable
    GENOTONORM MiniQuick 0.2 mg/0, 25 ml, 0.4 mg/0, 25 ml, 0.6 mg/0, 25 ml, 0.8 mg/0, 25 ml, 1 mg/0, 25 ml, 1.2 mg/0, 25 ml, 1.4 mg/0, 25 ml, 1.6 mg/0, 25 ml, 1.8 mg/0, 25 ml, 2 mg/0, 25 ml, powder and solvent for injectable solution in Pre-filled syringe (B/7).


    Opinion of the High Medical Committee on Social Security
    (Art. R. 163-2, 3rd paragraph, of the Social Security Code)


    GENOTONORM, a biosynthetic human growth hormone, is a restricted prescription drug with the conditions of care under the procedure Exception drugs.


    Refundable therapeutic indications


    In the child:
    -growth retardation due to somatotropism or retardation of growth associated with Turner syndrome Or chronic renal failure;
    -Prader-Willi syndrome (SPW) to improve growth and body composition. The diagnosis of SPW must be confirmed by an appropriate genetic test.
    In adults:
    Substitutive treatment in adults with severe somatotropin deficit.
    Patients with severe somatotropin deficits acquired at age Adults are defined as those with 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 deficit.
    In patients with a somatotropically acquired deficit in childhood (no history of hypothalamic-pituitary pathology or encephalic irradiation), two dynamic tests should be performed, except in the case of low rates of IGF-1 (< - 2 DS), which can be considered a test. The limit values for dynamic tests should be strictly defined.
    Treatment will be initiated only in adults under 60 years of age. It should not be systematic in subjects with biological criteria for growth hormone deficiency.
    There are currently no validated criteria for evaluating the efficacy of treatment in adults. Improvement is essentially subjective. There is no long-term data on the efficacy and tolerance of growth hormone treatment.


    Terms of Use


    Treatment needs to be implemented in the hospital by Specialists in pediatrics and/or endocrinology and metabolic diseases practicing pediatric and/or endocrinology and metabolic diseases.
    Every year, the interest in treatment must be reassessed in hospital by
    The renewal of the initial prescription to the same dosage is possible, in the intermediate periods, by any physician.
    There are cases of non-responders, for whom there is no predictive factor. Currently identified in both the child and the adult.
    To allow for better follow-up of patients, the change in growth hormone is not recommended during treatment, unless the hospital prescriber who initiated the
    The cessation of processing is imperative in the event of an appearance or evolution of a tumour process.
    Respect for the updated legal mentions of the marketing authorisation is essential.
    Parents and/or families must be Informed of the possible occurrence of some adverse reactions and patients undergoing regular medical surveillance. Systematic monitoring of prescriptions should be carried out in collaboration with the National Requirements Observatory.
    Children's Specificity: Growth hormone treatment does not improve the growth of patients The epiphyses are welded, hence the interest in the introduction of the steroidal hormone treatment.
    The procedure for " Exception drugs " Includes the drafting of the requirement, in all cases, on a A special order certifying compliance with the indications of the therapeutic fact sheet. The conditions for taking charge of GENOTONORM are long-term illnesses within the meaning of Article L. 324-1 of the Social Security Code, that is to say, requiring continuous care of more than six months and under this heading. Joint review procedure between attending physician and medical consultant.


    *
    * *


    GENOTONORM (somatropine) is a biosynthetic growth hormone produced by an E. coli strain that reproduces Exactly the sequence of natural somatotropic hormone.
    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 MAs, given the clinical trials presented in the records.
    GENOTONORM, a biosynthetic human growth hormone, is a drug Restricted prescription subject to the exception drug procedure


    1. Refundable therapeutic indications
    1.1. In the child


    Growth retardation due to somatotropin deficit or growth retardation associated with Turner syndrome or chronic renal failure.
    Prader-Willi Syndrome (SPW), in order to improve growth And body composition. The diagnosis of SPW must be confirmed by an appropriate genetic test.


    1.2. In adults


    Substitutive treatment in adults with severe somatotropic deficits.
    Patients with severe somatotropically acquired deficit in adulthood are defined as those with pathology Known hypothalamo-hypophysary 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 patients with a somatotropically acquired deficit in childhood (no history of hypothalamic-pituitary pathology, or Encephalic irradiation), two dynamic tests must be performed, except in the case of low IGF-1 (< - 2 DS), which can be considered as a test. The limit values for dynamic tests must be strictly defined.


    2. Dosage and Administration


    The dosage and regimen of administration should be appropriate for each patient.
    In general, it is recommended that the drug be administered subcutaneously in the evening. The injection site will vary in order to avoid the appearance of lipoatrophy.


    2.1.
    Growth Delay Associated with Somatotropic Deficit in Children


    In general, the recommended dosage is 0.025 to 0.035 mg/kg body weight per day or 0.7 to 1.0 mg/m² body surface area per day. Higher doses can be used.


    2.2. Turner Syndrome Growth Delay


    The recommended dosage is 0.045 to 0.050 mg/kg per day, or 1.4 mg/m² body surface per day.


    2.3.
    growth delay related to chronic renal failure


    The recommended dosage is 1.4 mg/m² body surface area per day (approximately 0.045 to 0.050 mg/kg body weight per day). Higher doses can be used if the rate of growth is too low. It is possible that a dosage adjustment is required after 6 months of treatment.
    2.4. Growth delay linked to a Prader-Willi syndrome in order to improve growth and body composition in the child
    In general, the recommended dosage is 0.035 mg/kg body weight per day, 1 mg/m² body surface area 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 almost welded should not be treated.


    You can consult the table in OJ
    No 64, 16/03/2003 page 4600 at 4607



    2.5. Growth hormone deficiency in adults


    Treatment should begin with a low dose, from 0.15 to 0.3 mg per day. The dose can be progressively increased according to the patient's needs, determined by the rate of IGF-1, in order to obtain IGF-1 concentrations in terms of age not exceeding the 2 SD limit. 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. The daily maintenance dose rarely exceeds 1.0 mg per day.
    Women may require higher doses than men; men with an increase in IGF-1 sensitivity over time
    The risk that women, especially those with oral estrogen replacement therapy, would be under-dosed while men would be overdosed. Therefore, the correct adaptation of the dose of somatotropic hormone should be monitored every 6 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 a somatotrope deficit, in order to increase their rate of growth (Turner syndrome, a child with chronic renal failure) or to improve their Body composition (Prader-Willi syndrome).
    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 lead to Change in body composition with increasing 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 net catch-up 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, so the assessment of the effect of treatment on final size is sensitive, 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 adverse 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 is 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 exogenous GH treatment 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, 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 lag compared 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 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. 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 more or less characteristic dysmorphic elements and a 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 change in body composition by increasing lean mass and decreasing fat mass.


    3.1.5. 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 an anterior pituitary deficiency, 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 Any 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 processing is imperative if a tumour process appears or evolves.
    Child Specificity:
    Since GH treatment does not improve the growth of patients whose epiphyses are welded, it is important to weigh the decision to introduce sex steroid
    . AMM's updated legal system 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 A qualified specialist must ensure that the patient meets the criteria for treatment; the absence of contraindications must be verified; the prescribed specialty must have the required indication.


    4.1.1. In child
    4.1.1.1. Somatotropic Deficit Growth Delay


    Two conditions are required for processing:
    -size less than or equal to-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 mIU/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 Interpretable. The diagnosis is based on the IGF dosage 1: 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 A history of leukemia or tumours, it is strongly advised to wait for one year of remission before the treatment is started.


    4.1.1.2. Turner Syndrome Growth Delay


    The diagnosis is based on the karyotype. It is used to define the number and/or structure anomalies for the X chromosome.
    There is no lower limit of treatment age, but the upper treatment limit is a 12-year-old bone age.
    One Estrogenic replacement therapy should be introduced late in progressive dosage in order not to lose the benefit of GH.


    4.1.1.3.
    growth delay related to chronic renal failure


    When conservative treatment is not 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 less than or equal to-2 SD according to the French reference data;
    -growth rate during the year Elapsed less than normal for age (- 1 DS);
    -chronological age > 2 years;
    -bony age < 13 years in daughter and < 14 years in boys;
    -prepubertal or early puberty child (testicular volume less than 10 ml or Mammary developmental stage S 3).
    Symptomatic treatment of chronic renal failure (correction of dehydration and acidosis, prevention of renal osteodystrophy and optimization of nutrient intakes) Must have been established in advance (at least one year) and will be maintained for the duration of the growth hormone treatment.


    4.1.1.4. 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);
    -the search A micro-deletion of region 15 (q11-13) in molecular cytogenetics (in situ hybridization, sensitivity of the order of 70 %);
    -the demonstration of a maternal uniparental feature of the region 15 (q11-13) (sensitivity of the order of 30 %).
    The completion of one of these tests with an anomaly is sufficient to confirm the diagnosis.
    In the absence of data on the patient older than 12 years and long-term tolerance information, it is recommended that the GENOTONORM prescription to children under 12 years of age with Prader-Willi syndrome confirmed by appropriate genetic testing.


    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 (size less than 1 cm in diameter) unless another prior pituitary deficit (except prolactin deficit) is present.
    The alternative treatment of other hormonal deficits will have to be adapted and stable from 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.
    Further explorations may be required depending on the patient's clinical features.


    4.1.2.1. Somatotropic Deficit Acquired During Childhood


    The isolated somatotropic deficits of childhood must be reassessed in a particular manner. 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 (< - 2DS) that is considered a test.


    4.1.2.2. Somatotropic Deficit Acquired in adulthood


    Patients should have:
    -a secondary somatotropic deficit with a hypothalamic or pituitary pathology,
    and
    -at least one other associated anhypophysary deficit (except prolactin deficiency) 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 and have a marked deterioration in Quality of life as well as a change in body composition (abdominal fat with increasing size/hip ratio).
    Before taking GH-substitutive treatment, all pituitary deficits must be Correctly 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, ranging from 0.15 to 0.30 mg/d in subcutaneous subcutaneous. The goal of treatment is to obtain a normal concentration of insulin-like growth factor I (IGF 1) for sex and age.
    At the beginning of treatment, patients must be evaluated every 1 to 2 months, clinically and by an IGF 1 dosage; the Dose of GH should be adapted to clinical tolerance and IGF concentrations 1. 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 ...). The bone will be Determined every year, especially around puberty ages.
    Because of the effect of growth hormone on carbohydrate metabolism, patients should be monitored for fasting blood glucose every year.
    Hypothyroidism May not be treated; it may interfere with the response to GH treatment. Annual control of the 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 used. Concomitant treatment with glucocorticoids (prednisolone family, high-dose inhaled corticosteroids, corticosteroids) may inhibit the effect on GH treatment growth and is to be avoided as much as possible.
    In Severe or repeated headache, visual impairment, nausea and/or vomiting, it is recommended that a background be used 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.
    Dosage must be adjusted on a quarterly basis The weight or body surface of the child.


    4.2.1.2. Specific Cases by
    Indications of Growth Deficit for Somatotropic Deficit


    When the somatotropic deficit is secondary to an intracranial lesion, radiological explorations (MRI) will have to be performed Regularly, in collaboration with oncologists and/or neurosurgeons, to detect any progression or relapse.

    In patients with panhypopituitarianism, the balance of the associated substituted therapies 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.


    Turner syndrome growth delay


    Processing is continued if the growth gain in the first year is at least 2 cm from the previous year. In the following years, the rate of growth must be:
    4.5 cm/year up to 12 years;
    3 cm/year when bone 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.


    Prader-Willi syndrome growth delay


    The specific monitoring should be:
    -the carbohydrate tolerance, of the The risk of non-insulin-dependent diabetes in this condition;
    -the examination of the skeleton as a result of the appearance or possible worsening of scoliosis in this indication.
    In addition, the analysis of the benefit will have to bear both the Growth and body composition recommended to be followed by appropriate reviews.
    Clinical trial data focused on the need for overall, specific dietary management 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.
    Systematic monitoring of prescriptions will be performed in patients newly treated by GENOTONORM. The attending physician will be involved in the collection of data set up by the Pharmacia SAS laboratory, in collaboration with the National Observatory on Drug Requirements and Consumption in the ambulatory and hospital
    . 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 checked at least 1 time per year.
    Treatment experience The long-term growth hormone in adults is limited.


    4.3. Stop
    4.3.1 processing permanently. In the child
    In cases of a somatotrope deficit
    or Turner syndrome


    Onset or evolution of a tumour process.
    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.
    These last two stop treatment criteria can be discussed in the case of severe GH deficit, if the genetic statural potential Is not reached.


    In
    growth retardation due to chronic renal failure


    Onset or evolution of a tumour process
    Growth rate under treatment less than 3 Cm/year regardless of age.
    Bone age:
    > 15 years or size > 170 cm in the boy;
    > 13 years or size > 160 cm in the girl.
    These last two stop treatment criteria can be discussed in the case of severe GH deficit, If the genetic statural potential is not reached.
    Renal Transplantation.


    In Prader-Willi syndrome


    Onset or evolution of a tumour process
    After 14 years of age or A rate of growth below 3 cm/year, regardless of age.
    Bone age:
    > 15 years or size > 170 cm for the 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.
    GENOTONORM must be reconstituted only with the solvent provided by the laboratory. The reconstituted solution should not be shaken vigorously because it can denature the active principle.
    Storage: maximum duration and special precautions.


    You can view the table in the OJ
    n ° 64, 16/03/2003 page 4600 to 4607



    These presentations, with the exception of GENOTONORM Miniquick presentations, are summed up by a conservative, the metacresol, likely to cause rare reactions
    GENOTONORM MiniQuick and GENOTONORM KABIVIAL 5.3 mg/1 ml are administered with syringes; GENOTONORM 5.3 mg/1 ml and 12 mg/1 ml are to be used with the reconstitution device and Injection for each dosage.


    6. Prescribing Prescribers


    Prescribers should be cautioned that the adverse event/benefit report is evaluated only for the therapeutic indications selected by the MA. 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 for pediatric and/or endocrine specialists and metabolic diseases in specialty services In pediatrics and/or in endocrinology and metabolic diseases.
    Renewal of the initial prescription at the same dosage (same dosage per kg or per m² for the child), in intermediate periods, possible by any physician.
    The Pharmacopoeial pharmacist must ensure that the qualification of the prescriber appearing on the original hospital prescription is in compliance; at the time of the renewal of the prescription, it ensures the filing of the hospital prescription Less than 1 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 treatment


    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 64, 16/03/2003 page 4600 to 4607




    7.4. Comparable Drugs


    You can view the table in OJ
    No. 64, 16/03/2003 page 4600 to 4607




    AMM and Operator Laboratory: Pharmacia SAS.
    All Remark or request for further information should be directed to:
    AFSSAPS-DEMEIS, 143-147, boulevard Anatole-France, 93285 Saint-Denis Cedex.


    boys and girls average sizes and weights from 1 month to 20 years; and Half
    (based on Sempé and Pedron curves, 1979)
    Boys


    You can view the table in OJ
    n ° 64, 16/03/2003 page 4600 to 4607



    Girls


    You can view the table in OJ
    No 64, 16/03/2003 page 4600 to 4607

Appendix


A N N E X E I


You can view the table in OJ
No. 64, 16/03/2003, page 4600 to 4607


Done at Paris, February 24, 2003.


For the Minister and by delegation :By preventing the Director

from Social Security:

The

subdirector of the

funding for the care system,

S. Seiller

By preventing

from the Director General of Health:

The

policy

policy for health products,

H. Sainte Marie


Download the document in RTF (weight < 1MB) Facsimile (format: pdf, weight < 3.5 MB) Download document to RDF (format: rdf, weight < 1MB)