Article Contents
- 1. NAME OF THE MEDICINAL PRODUCT
- 2. QUALITATIVE AND QUANTITATIVE COMPOSITION
- 4.1
- 4.2 Posology and method of administration
- 4.3 Contraindications
- 4.4 Special warnings and precautions for use
- 4.5 Interaction with other medicinal products and other forms of interaction
- 4.6 Fertility, pregnancy and lactation
- 4.7 Effects on ability to drive and use machines
- 4.8 Undesirable effects
- 4.9 Overdose
- 5.1
- 5.2 Pharmacokinetic properties
- 5.3 Preclinical safety data
- 6.1
- 6.2 Incompatibilities
- 6.3 Shelf life
- 6.4 Special precautions for storage
- 6.5 Nature and contents of container
- 7. MARKETING AUTHORISATION HOLDER
- 8. MARKETING AUTHORISATION NUMBER(S)
- 9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE
- 10. DATE OF REVISION OF THE TEXT
1. NAME OF THE MEDICINAL PRODUCT
Valtropin 5 mg/1.5 ml powder and solvent for solution for injection
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
One vial of powder contains 5 mg somatropin (corresponding to 15 IU).
technology.
3. | PHARMACEUTICAL FORM |
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Powder and solvent for solution for injection. |
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White or almost white powder. The solvent is a clear solution. |
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After reconstitution with the solvent provided, Valtropin has a pH of pproximately 7.5 and an | |||
osmolality of approximately 320 mOsm/kg. | longer | authorised | |
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4. | CLINICAL PARTICULARS |
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4.1 | Therapeutic indications |
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Paediatric population |
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| growth failure due to an inadequate secretion of normal endogenous growth hormone. | ||
- | Treatment of short stature in children with Turner syndrome, confirmed by chromosome | ||
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| Medicinal |
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- | Treatment of growth ret rdationproductin | ||
Adult patients |
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- | Replacement therapy adults with pronounced growth hormone deficiency of either childhood- | ||
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Patients with severe growth hormone deficiency in adulthood are defined as patients with known
4.2 Posology and method of administration
Therapy with Valtropin should be initiated and monitored by physicians adequately experienced in the diagnosis and management of patients with growth hormone deficiency.
Posology
The dosage and administration schedule should be individualised for each patient.
Dosage in paediatric population
Growth hormone deficiency in children
The recommended dosage is 0.025 - 0.035 mg/kg body weight per day.
Children with Turner syndrome
The recommended dosage is 0.045 - 0.050 mg/kg body weight per day, given as a subcutaneous injection.
The recommended dosage is 0.045 - 0.050 mg/kg body weight per day, given as a subcutaneous injection.
Dosage in adult patients | authorised |
Growth hormone deficiency in adults |
The recommended starting dose is 0.15 - 0.30 mg/day, given as a subcutane us injection. A lower starting dose may be necessary in older and obese patients.
This dose should be gradually increased according to individual patient requirements based on the clinical response and serum
The minimum effective dose should be used.
| no |
The dosage of somatropin should be decreased in caseslongerof persistent oedema or severe paresthesia, in | |
order to avoid the development of carpal tunnel sy drome. | |
product |
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Experience of prolonged treatment (over 5 years) with somatropin in adults is limited.
Elderly | Medicinal |
Experience of somatropin tre tment in patients above 60 years of age is limited. A lower starting dose | |
may be necessary older patients. Dose requirements may decline with increasing age. |
Renal impairment
Currently available data on renal insufficiency are described in section 4.4, but no recommendation on a posology can be made.
Hepatic impairment
In patients with severe liver dysfunction a reduction of somatropin clearance has been noted. The clinical significance of this decrease is unknown.
Method of administration
Valtropin is administered by subcutaneous injection.
The injection sites should be varied in order to avoid
For further information on reconstitution and administration see section 6.6.
4.3 Contraindications
-Hypersensitivity to the active substance or to any of the excipients (e.g. metacresol) (see section 4.4).
-Somatropin must not be used when there is any evidence of activity of a tumour. Intracranial tumours must be inactive and antitumour therapy must be completed prior to starting GH therapy. Treatment should be discontinued if there is evidence of tumour growth.
-Valtropin should not be used for growth promotion in children with closed epiphyses.
-Patients with acute critical illness due to complications following open heart or abdominal surgery, multiple accidental trauma, or patients having acute respiratory failure.
4.4 Special warnings and precautions for use
The maximum recommended daily dose should not be exceeded (see section 4.2).
Pituitary
There is no evidence to suspect that growth hormone replacement influences the recurrence rate or
- Nutropinaq - somatropin
- Somatropin biopartners - somatropin
- Omnitrope - somatropin
Prescription drugs listed. Substance: "Somatropin"
regrowth of intracranial neoplasms, but standard clinical practice requiresauthorisedregular pituitary imaging in
patients with a history of pituitary pathology. A baseline scan is recommended in th se patients before instituting growth hormone replacement therapy.
Tumour control
If the patient has had a brain tumour, the patient should be
In childhood cancer survivors, a higher risk of a second neoplasm (benign malignant) has been reported in patients treated with somatropin. Intracraniallongertumou s, in particular, were the most common of these second neoplasms.
Intracranial hypertension
In cases of severe or recurrent headache, visualnopr blems, nausea, and/or vomiting, a fundoscopy for papilloedema is recommended. If papilloedema is c nfirmed, a diagnosis of benign intracranial hypertension should be considered and, if appropriate, the growth hormone treatment should be discontinued. At present, there isproductinsufficient evidence to guide clinical decision making in patients with resolved intracranial hypertension. If growth hormone treatment is restarted, careful monitoring for symptoms of intracranial hypertensi n is necessary.
Insulin sensitivity
Thyroid function
Because humanMedicinalgrowth hormone may induce a state of insulin resistance, patients treated with somatropin should be mo itored for evidence of glucose intolerance.
Growth hormone increases the extrathyroidal conversion of T4 to T3 and may, as such, unmask incipient hypothyroidism. Monitoring of thyroid function should therefore be conducted in all patients. In patients with hypopituitarism, standard replacement therapy must be closely monitored when somatropin therapy is administered.
Slipped capital epiphyse
Patients with endocrine disorders, including growth hormone deficiency, may develop slipped capital epiphyses more frequently. Any child with the onset of a limp during growth hormone therapy should be evaluated.
Growth hormone deficiency after epiphyseal closure
Subjects who had been treated with growth hormone during childhood, until final height was attained, should be
Treatment after the end of growth in children
For children, the treatment should be continued until the end of the growth has been reached. It is advisable not to exceed the recommended dosage in view of the potential risks of acromegaly, hyperglycaemia, and glucosuria.
Valtropin is not indicated for the treatment of patients with growth failure due to
Renal insufficiency |
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Before instituting treatment with somatropin for growth retardation secondary to chronic renal | ||
insufficiency, children should have been followed for one year to verify growth disturbance. | ||
Conservative treatment for renal insufficiency (which includes control of acidosis, | ||
| authorised | |
hyperparathyroidism, and nutritional status for one year prior to the treatment) should have been | ||
established and should be maintained during treatment. Treatment with somatropin should be | ||
discontinued at the time of renal transplantation. |
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Gender and dosing |
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In order to reach the defined treatment goal, men may need lower grow | ormone doses than women. |
Oral oestrogen administration increases the dose requirements in women. An increasing sensitivity to growth hormone (expressed as change in
6 months.
Turner syndrome |
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Patients with Turner syndrome should be evaluated carefullylongerfor otitis media and other ear disorders | ||
since these patients have an increased risk of ear r hearing disorders. | ||
Pancreatitis in children | product |
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Children treated with somatropin have an increased risk of developing pancreatitis compared to adults treated with somatropin. Although rare, pancreatitis should be considered in
Accidental intramuscularMedicinalinjection
After accidental intramuscular injection, hypoglycaemia may appear. Any unwanted reaction should be followed. No spe ial treatment is recommended.
Sensitivity to metacresol
Valtropin should not be reconstituted with the supplied solvent for patients with a known sensitivity to metacresol. If sensitivity to the accompanying solvent occurs, the vials should be reconstituted with water for injections and used as a single use vial (see section 6.3).
4.5Interaction with other medicinal products and other forms of interaction
Excessive glucocorticoid therapy will inhibit the
In women taking oral oestrogens, a higher dose of somatropin may be required to achieve the treatment goal.
Patients taking insulin for diabetes mellitus should be carefully monitored during treatment with somatropin. An adjustment of the insulin dose may be required.
Data from an interaction study performed in growth hormone deficient adults, suggests that somatropin administration may increase the clearance of compounds known to be metabolised by cytochrome P450 isoenzymes. The clearance of compounds metabolised by cytochrome P 450 3A4 (e.g. sex steroids, corticosteroids, anticonvulsants and cyclosporine) may be especially increased resulting in lower plasma levels of these compounds. The clinical significance of this is unknown.
4.6 Fertility, pregnancy and lactation
Pregnancy
For Valtropin no clinical data on exposed pregnancies are available. Animal studies are insufficient with respect to effects on pregnancy, embryofoetal development, parturition or postnatal development (see section 5.3). Therefore Valtropin should not be used during pregnancy unless clearly necessary.
authorised |
There have been no clinical studies conducted with Valtropin in
no effect on fertili y parameters.
4.7 Effects on ability to drive and use machines
Valtropin has no or negligible influence on the ability tolongerdrive and use machines.
- Ribavirin biopartners - BioPartners GmbH
- Somatropin biopartners - BioPartners GmbH
Prescription drugs listed. Manufacturer: "BioPartners GmbH"
4.8 Undesirable effects
Summary of the safety profile | no |
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The most common frequent adverse reactions are associated with the injection site, of endocrine nature, and headache, paresthesiaproductand joint pain and disorder (arthralgia) in adults.
During clinical studies 128 children (98 children with growth hormone deficiency and 30 with Turner syndrome) were exposed to Valt opin. The safety profile of Valtropin observed in these clinical
studies was consistent with that re orted with the reference medicinal product used in these studies The followingMedicinaladverse reactions and their frequencies have been observed under treatment with somatropin based on published information:
and other somatropin cont ining medicinal products.
Very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare
(≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000), not known (cannot be estimated from the available data), including isolated reports
Tabulated summary of adverse reactions
Neoplasms benign, malignant and |
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unspecified (including cysts and polyps) | Uncommon: Neoplasm malignant, neoplasm |
Blood and lymphatic system disorders | Uncommon: Anaemia |
Immune system disorders | Common: Antibody building |
| Not known: Single case of acute hypersensitivity |
| involving urticaria and pruritus |
Endocrine disorders | Common: Hypothyroidism |
Metabolism and nutrition disorders | Common: Glucose tolerance impaired |
| Common: Mild hyperglycaemia (1% in children; |
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| 1% - 10% in adults) |
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| Uncommon: Hypoglycaemia, hyperphosphatemia | ||
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| Rare: Diabetes mellitus | ||
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| Not known: Insulin resistance | ||
Psychiatric disorders |
| Uncommon: Personality disorder | ||
Nervous system disorders |
| Very common: Headache in adults | ||
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| Very common: Paresthesia in adults | ||
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| Common: Hypertonia | ||
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| Common: Insomnia in adults | ||
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| Common: Carpal tunnel syndrome in adults | ||
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| Uncommon: Carpal tunnel syndrome in children | ||
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| Uncommon: Nystagmus | ||
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| Rare: Neuropathy, intracranial pressure increased | ||
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| Rare: Benign intracranial hypertension | ||
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| Rare: Paresthesia in children | ||
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| Very rare: Insomnia in children | ||
Eye disorders |
| Uncommon: Papilloedema, diplopia | ||
Ear and labyrinth disorders |
| Uncommon: Vertigo |
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Cardiac disorders |
| Common: Hypertension in adults | ||
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| Uncommon: Tachyca dia | ||
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| Rare: Hypertension in children | ||
Respiratory, thoracic and mediastinal |
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disorders |
| Comm n: Dyspnoea in adults | ||
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| C mm n: Sleep apnoea in adults | ||
Gastrointestinal disorders |
| U common: Vomiting, abdominal pain, flatulence, nausea | ||
| product | Rare: Diarrhoea |
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| Uncommon: Lipodystrophy, skin atrophy, exfoliative | ||
Skin and subcutaneous tissue disorders | dermatitis, urticaria, hirsutism, skin hypertrophy | |||
Musculoskeletal and connective tissue |
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disorders |
| Very common: Arthralgia in adults | ||
Medicinal |
| Common: Arthralgia in children | ||
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| Common: Myalgia |
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| Uncommon: Muscle atrophy, bone pain | ||
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| Uncommon: Urinary incontinence, haematuria, polyuria, | ||
Renal and urinary disorders |
| urine frequency/pollakiuria, urine abnormality | ||
Reproductive system and breast disorders | Uncommon: Genital discharge | |||
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| Uncommon: Gynaecomastia in adults | ||
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| Very rare: Gynaecomastia in children | ||
General disorders and administration site |
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conditions |
| Very common: Oedema, peripheral oedema in adults | ||
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| Common: Oedema, peripheral oedema in children | ||
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| Common: Injection site reactions, asthenia | ||
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| Uncommon: Injection site atrophy, injection site | ||
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| haemorrhage, injection site mass, hypertrophy, weakness | ||
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Investigations |
| Rare: Renal function test abnormal |
Description of selected adverse reactions
4.9 Overdose
In a clinical study with Valtropin, 3% of children with growth hormone deficiency developed antibodies to somatropin. The binding capacity of these antibodies was low and there was no effect on growth rate. Testing for antibodies to somatropin should be carried out in any patient who fails to respond to therapy.
Paediatric population
Mild and transient oedema was observed early during the course of treatment with somatropin.
Adult patients
In adult patients with
disorders were reported early in therapy and tended to be transient.
excess human growth hormone. Treatment is symptomatic and supportive. There is no antidote for somatropin overdose. It is recommended to monitor thyroid function following an overdose.
Acute overdose could lead initially to hypoglycaemia and subsequentlyauthorisedto hyperglycaemia.
5. | PHARMACOLOGICAL PROPERTIES | longer |
5.1 | Pharmacodynamic properties | |
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Pharmacotherapeutic group: Pituitary and hypothalamic hormones and analogues, somatropin and somatropin agonists; ATC code: H01AC01
Somatropin is a polypeptide hormone of recombinant DNA origin. It has 191 amino acid residues and
a molecular weight of 22,125 dalt | ns. The amino acid sequence of the medicinal product is identical to |
that of human growth hormone of | ituitary origin. Valtropin is synthesised in yeast cells |
Medicinal |
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(Saccharomyces cerevisiae). |
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The biological effects of somatropin are equivalent to those of human growth hormone of pituitary origin.
The most promin nt effect of somatropin is that it stimulates the growth plates of long bones. Additionally, it promotes cellular protein synthesis and nitrogen retention.
Somatropin stimulates lipid metabolism; it increases plasma fatty acids and
Somatropin therapy has a beneficial effect on body composition in growth
Somatropin may induce insulin resistance. Large doses of somatropin may impair glucose tolerance.
Clinical studies
The efficacy and safety of Valtropin has been assessed in a randomised,
differences between Valtropin and the reference medicinal product with regard to height velocity and height velocity SDS.
An open
5.2 Pharmacokinetic properties
A
5.3 Preclinical safety data
Animal studies with Valtropin are not sufficient to assess the reproductive xicity potential. From
Powder:
reproductive toxicity studies performed with other somatropin medicinal products there is no evidence | |||||
of an increased risk of adverse reactions for the embryo or foetus. | authorised | ||||
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studies in animals after subcutaneous injection of Valtropin. However, in single and | |||||
general toxicity studies no adverse reactions at the injection sites were reported. | |||||
6. | PHARMACEUTICAL PARTICULARS | longer |
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6.1 | List of excipients | product | no |
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Glycine
Mannitol
Sodium hydroxide (for pH adjustment)
- Omnitrope - H01AC01
- Nutropinaq - H01AC01
- Somatropin biopartners - H01AC01
Prescription drugs listed. ATC Code: "H01AC01"
Hydrochloric acid (for pH adjustment).
Sodium dihydrogenMedicinalphosph te nhydrous
Disodium phosphate hydrous
Solvent:
Metacresol
Water for injections.
6.2Incompatibilities
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
6.3Shelf life
3 years
After first opening or following reconstitution with the solvent provided:
After reconstitution with the solvent provided, chemical and physical
Following reconstitution with water for injections:
After reconstitution with water for injections, the medicinal product must be used immediately and must be used as a single use vial. If not used immediately,
6.4 Special precautions for storage
Store in a refrigerator (2°C - 8°C). Do not freeze.
For the purpose of transport and/or ambulatory use, the
The date of refrigerator removal and the new expiry date should be written on the outer carton. At the end of the new expiry date, the medicinal product should have been used or be disposed of.
For storage conditions of the reconstituted medicinal product, see section 6.3.
6.5 Nature and contents of container
5 mg of powder in a vial (Type I glass) closed with a stopper (butyl rubber) and
1.5 ml of solvent in a | |
rubber) | authorised |
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Pack size of 1 vial and 1 |
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6.6 Special precautions for disposal and other handlinglonger |
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Detailed instructions for the handling of the medicinalno product are given at the end of the package
leaflet.product
metacresol (see section 4.3). If sensitivity to the accompanying solvent occurs, the vials should be
Valtropin should not be reconstituted with the supplied solvent for patients with a known sensitivity to reconstitutedMedicinalwith water for injections and used as a single use vial.
Reconstitution with the solvent provided
Each vial of Valtropin should be reconstituted using the accompanying solvent. The solvent should not be used if it is discoloured or cloudy. The solvent should be injected into the vial by aiming the stream of liquid against the glass wall. Following reconstitution, the vial should be swirled with a GENTLE rotary motion until the contents are completely dissolved. DO NOT SHAKE. The resulting solution should be clear, without particulate matter. If the solution is discoloured, cloudy or contains particulate matter, the contents MUST NOT be injected. Before and after every injection, the septum of the vial should be wiped with alcohol to prevent contamination of the contents by repeated needle insertions. If reconstituted with the solvent, then the solution is for multidose use (see section 6.3).
Reconstitution with water for injections
After reconstitution with water for injections the medicinal product must be used immediately (see section 6.3) and the solution is for single use only.
Administration
Sterile disposable syringes and needles should be used for administration of Valtropin. The volume of the syringe should be small enough so that the prescribed dose can be withdrawn from the vial with reasonable accuracy.
Disposal
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
7. MARKETING AUTHORISATION HOLDER
BioPartners GmbH
Kaiserpassage 11
- Tovanor breezhaler
- Possia
- Actelsar hct
- Protopic
- Optaflu
- M-m-rvaxpro
Prescription drugs listed:
Germany
8. MARKETING AUTHORISATION NUMBER(S)
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE
authorisedAUTHORISATION
10. DATE OF REVISION OF THE TEXT
Detailed information on this medicinal product is avai ab n the website of the European Medicines | |||
Agency http://www.ema.europa.eu/ | no | longer | |
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Medicinal |
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