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SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Mirtazapine 45 mg orodispersible tablets

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains 45 mg of mirtazapine. Excipient(s): 18 mg of Aspartame (E951) For a full list of excipients, see section 6.1

3 PHARMACEUTICAL FORM

Orodispersible tablet The tablets are white or almost white, 12 mm round, biconvex, uncoated tablets and marked M4.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

Treatment of depressive illness.

4.2 Posology and method of administration

The tablet should be taken out of the blister with dry hands and should be placed on the tongue.

The tablet will disintegrate and can be swallowed without water. The tablet should be swallowed without chewing.

Adults: Treatment should begin with 15 mg daily. The dosage generally needs to be increased to obtain an optimal clinical response. The effective daily dose is usually between 15 and 45 mg.

Elderly: The recommended dose is the same as that for adults. In elderly patients an increase in dosing should be done under close supervision to elicit a satisfactory and safe response.

Children: Since safety and efficacy of Mirtazapine has not been established in children, it is not recommended to treat children with Mirtazapine. Two randomised placebo-controlled trials failed to demonstrate efficacy for Mirtazapine in the treatment of children and adolescents with major depressive

disorder. Safety and efficacy of Mirtazapine in paediatric depression can not be extrapolated from adult data.

Children and adolescents under the age of 18 years

Mirtazapine Tablets should not be used in children and adolescents under the age of 18 years as efficacy was not demonstrated in two short-term clinical trials (see section 5.1) and because of safety concerns (see sections 4.4, 4.8 and 5.1).

The clearance of mirtazapine may be decreased in patients with renal or hepatic insufficiency. This should be taken into account when prescribing Mirtazapine to this category of patients.

Mirtazapine has a half-life of 20-40 hours and therefore Mirtazapine is suitable for once-a-day administration. It should be taken preferably as a single nighttime dose before going to bed. Mirtazapine may also be given in sub-doses equally divided over the day (once in the morning and once at night-time).

Treatment should preferably be continued until the patient has been completely symptom-free for 4-6 months. After this, treatment can be gradually discontinued. Treatment with an adequate dose should result in a positive response within 2-4 weeks. With an insufficient response, the dose can be increased up to the maximum dose. If there is no response within a further 2-4 weeks, then treatment should be stopped.

4.3 Contraindications

Hypersensitivity to mirtazapine or any of the other ingredients of Mirtazapine orodispersible tablets.

Concomitant use of mirtazapine with monoamine oxidase (MAO) inhibitors (see section 4.5).

4.4 Special warnings and precautions for use

Use in children and adolescents under 18 years of age - Mirtazapine should not be used in the treatment of children and adolescents under the age of 18 years. Suicide-related behaviours (suicide attempt and suicidal thoughts), and hostility (predominantly aggression, oppositional behavior and anger) were more frequently observed in clinical trials among children and adolescents treated with antidepressants compared to those treated with placebo. If, based on clinical need, a decision to treat is nevertheless taken, the patient should be carefully monitored for the appearance of suicidal symptoms. In addition, long-term safety data in children and adolescents concerning growth, maturation and cognitive and behavioural development are lacking.

Suicide/suicidal thoughts or clinical worsening

Depression is associated with an increased risk of suicidal thoughts, self harm and suicide (suicide-related events). This risk persists until significant remission occurs. As improvement may not occur during the first few weeks or more of treatment, patients should be closely monitored until such improvement occurs. It is general clinical experience that the risk of suicide may increase in the early stages of recovery.

Patients with a history of suicide-related events, or those exhibiting a significant degree of suicidal ideation prior to commencement of treatment are known to be at greater risk of suicidal thoughts or suicide attempts, and should receive careful monitoring during treatment. A meta-analysis of placebo-controlled clinical trials of antidepressant drugs in adult patients with psychiatric disorders showed an increased risk of suicidal behaviour with antidepressants compared to placebo in patients less than 25 years old.

Close supervision of patients and in particular those at high risk should accompany drug therapy especially in early treatment and following dose changes. Patients (and caregivers of patients) should be alerted about the need to monitor for any clinical worsening, suicidal behaviour or thoughts and unusual changes in behaviour and to seek medical advice immediately if these symptoms present.

Bone marrow depression

Bone marrow depression, usually presenting as granulocytopenia or agranulocytosis, has been reported during treatment with Mirtazapine.

Reversible white blood cell disorders including agranulocytosis, leukopenia and granulocytopenia have been reported as a rare occurrence with Mirtazapine. This mostly appears after 4-6 weeks of treatment and is in general reversible after termination of treatment. With respect to agranulocytosis the physician should be alert to symptoms such as fever, sore throat, stomatitis or other signs of infection; when such symptoms occur, treatment should be stopped and blood counts taken. Patients should also be advised of the importance of these symptoms. In the postmarketing period with Mirtazapine very rare cases of agranulocytosis have been reported, mostly reversible, but in some cases fatal. Fatal cases mostly concerned patients with an age above 65. The physician should be alert for symptoms like fever, sore throat, stomatitis or other signs of infection; when such symptoms occur, treatment should be stopped and blood counts taken.

Jaundice

Treatment should be discontinued if jaundice occurs.

Conditions which need supervision

Careful dosing as well as regular and close monitoring is necessary in patients with: - Epilepsy and organic brain syndrome. As with other antidepressants, mirtazapine should be introduced cautiously in patients who have a history of seizures. Treatment should be discontinued in any patient who develops seizures, or where there is an increase in seizure frequency. Antidepressants should be avoided in patients with unstable seizure disorders/epilepsy and patients with controlled epilepsy should be carefully monitored. From clinical experience it appears that insults occur rarely in patients treated with Mirtazapine

-    Hepatic impairment: Following a single 15 mg oral dose of mirtazapine, the clearance of mirtazapine was approximately 35 % decreased in mild to moderate hepatically impaired patients, compared to subjects with normal hepatic function. The average plasma concentration of mirtazapine was about 55 % increased.

-    renal impairment: Following a single 15 mg oral dose of mirtazapine, in patients with moderate (creatinine clearance < 40 ml/min) and severe (creatinine clearance < 10 ml/min) renal impairment the clearance of mirtazapine was about 30 % and 50 % decreased respectively, compared to normal subjects. The average plasma concentration of mirtazapine was about 55 % and 115 %increased respectively. No significant differences were found in patients with mild renal impairment (creatinine clearance < 80 ml/min) as compared to the control group.

-    cardiac diseases like conduction disturbances, angina pectoris and recent myocardial infarct, where normal precautions should be taken and concomitant medicines carefully administered

-    low blood pressure

-    diabetes mellitus. In patients with diabetes, antidepressants may alter glycaemic control. Insulin and/or oral hypoglycaemic dosage may need to be adjusted and close monitoring is recommended.

As with other antidepressants care should be taken in patients with:

-    Worsening of psychotic symptoms can occur when antidepressants are administered to patients with schizophrenia or other psychotic disturbances; paranoid thoughts can be intensified.

-    When the depressive phase of bipolar disorder is being treated, it can transform into the manic phase. Patients with a history of mania/hypomania should be closely monitored. Mirtazapine should be discontinued in any patient entering a manic phase.

-    Although Mirtazapine is not addictive, post-marketing experience shows that abrupt termination of treatment after long term administration may sometimes result in withdrawal symptoms. The majority of withdrawal reactions are mild and self-limiting. Among the various reported withdrawal symptoms, dizziness, agitation, anxiety, headache and nausea are the most frequently reported. Even though they have been reported as withdrawal symptoms, it should be realized that these symptoms may be related to the underlying disease. As advised in section 4.2, it is recommended to discontinue treatment with mirtazapine gradually.

- Care should be taken in patients with micturition disturbances like prostate hypertrophy (although problems are not to be expected because Mirtazapine possesses only very weak anticholinergic activity)

-    acute narrow-angle glaucoma and increased intra-ocular pressure (also here little chance of problems with Mirtazapine because of its very weak anticholinergic activity)

-    Akathisia/psychomotor restlessness: The use of antidepressants have been associated with the development of akathisia, characterised by a subjectively unpleasant or distressing restlessness and need to move often accompanied by an inability to sit or stand still. This is most likely to occur within the first few weeks of treatment. In patients who develop these symptoms, increasing the dose may be detrimental.

Hyponatraemia

Hyponatraemia, probably due to inappropriate antidiuretic hormone secretion (SIADH), has been reported very rarely with the use of mirtazapine. Caution should be exercised in patients at risk, such as elderly patients or patients concomitantly treated with medications known to cause hyponatraemia.

Serotonin syndrome

Interaction with serotonergic active substances: serotonin syndrome may occur when selective serotonin reuptake inhibitors (SSRIs) are used concomitantly with other serotonergic active substances (see section 4.5). Symptoms of serotonin syndrome may be hyperthermia, rigidity, myoclonus, autonomic instability with possible rapid fluctuations of vital signs, mental status changes that include confusion, irritability and extreme agitation progressing to delirium and coma. Caution should be advised and a closer clinical monitoring is required when these active substances are combined with mirtazapine. Treatment with mirtazapine should be discontinued if such events occur and supportive symptomatic treatment initiated. From post marketing experience it appears that serotonin syndrome occurs very rarely in patients treated with Mirtazapine alone (see section 4.8).

Elderly patients

elderly patients are often more sensitive, especially with regard to the side-effects of antidepressants. During clinical research with Mirtazapine, side-effects have not been reported more often in elderly patients than in other age groups; however, experience until now is limited.

- Mirtazapine orodispersible tablets contain aspartame a source of phenylalanine. Each tablet with 15 mg mirtazapine corresponds to 3 mg phenylalanine, respectively.

May be harmful for patients with phenylketonuria.

4.5 Interaction with other medicinal products and other forms of interaction

Pharmacodynamic interactions

-    Mirtazapine should not be administered concomitantly with MAO inhibitors or within two weeks of cessation of therapy with these agents.

-    In the opposite way about two weeks should pass before patients treated with mirtazapine should be treated with MAO inhibitors (see section 4.3).

-    In addition, as with SSRIs, co-administration with other serotonergic active substances (L-tryptophan, triptans, tramadol, linezolid, SSRIs, venlafaxine, lithium and St. John's Wort - Hypericum perforatum - preparations) may lead to an incidence of serotonin associated effects (serotonin syndrome: see section 4.4). Caution should be advised and a closer clinical monitoring is required when these active substances are combined with mirtazapine.

-    Mirtazapine may potentiate the sedative effects of benzodiazepines and other sedatives (notably most antipsychotics, antihistamine H1 antagonists, opioids). Caution should be taken when these drugs are prescribed together with Mirtazapine.

-    Mirtazapine may potentiate the central nervous dampening action of alcohol; patients should therefore be advised to avoid alcohol during treatment with Mirtazapine.

-    Mirtazapine dosed at 30 mg once daily caused a small but statistically significant increase in the international normalized ratio (INR) in subjects treated with warfarin. As at a higher dose of mirtazapine a more pronounced effect cannot be excluded, it is advisable to monitor the INR in case of concomitant treatment of warfarin with mirtazapine.

Pharmacokinetic interactions

Carbamazepine, an inducer of CYP3A4, increased mirtazapine clearance about twofold, resulting in a decrease in plasma levels of 45-60%. Phenytoin increased the clearance of mirtazapine in a similar fashion. When carbamazepine or another inducer of drug metabolism (such as rifampicin) is added to mirtazapine therapy, the mirtazapine dose may have to be increased. If treatment with an inducer is stopped, mirtazapine dosing may have to be decreased.

Co-administration of the potent inhibitor of CYP3A4, ketoconazole increased the peak plasma levels and AUC by approximately 40% and 50% respectively.

-    In vitro data suggest that mirtazapine is a very weak competitive inhibitor of the cytochrome P450 enzymes CYP1A2, CYP2D6 and CYP3A4.

-    Caution is needed and the dose may need to be decreased when strong CYP3A4 inhibitors, such as the HIV protease inhibitors, azole antifungals, erythromycin and nefazodone are coadministered with mirtazapine.

Bioavailability of mirtazapine increased by more than 50% when co-administered with cimetidine. The mirtazapine dose may have to be decreased when concomitant treatment with cimetidine is started or increased when cimetidine treatment is ended.

Absence of interactions

• In in vivo interaction studies, mirtazapine did not influence the pharmacokinetics of risperidone or paroxetine (CYP2D6 substrate), carbamazepine (CYP3A4 substrate), amitriptyline and cimetidine.

No relevant clinical effects or changes in pharmacokinetics have been observed in man with concurrent administration of mirtazapine and lithium.

A number of clinical interaction studies, and a study of mirtazapine treatment following SSRI treatment failure have been performed with mirtazapine and SSRIs. Until now no clinical interactions, pharmacodynamic or pharmacokinetic, have been encountered.

4.6 Pregnancy and lactation

The safety of Mirtazapine in human pregnancy has not been established.

Epidemiological data have suggested that the use of SSRIs in pregnancy, particularly in late pregnancy, may increase the risk of persistent pulmonary hypertension in the newborn (PPHN). Although no studies have investigated the association of PPHN to mirtazapine treatment, this potential risk cannot be ruled out taking into account the related mechanism of action (increase in serotonin concentrations).

Reproduction studies in pregnant rats and rabbits at doses up to 100 mg/kg and 40 mg/kg (approx. 3 and 5 times respectively the maximum recommended human dose on the basis of exposure) have revealed no evidence of teratogenic effects. There was, however, in rats an increase in postimplantation loss; there was also an increase in pup deaths during the first three days of lactation (cause of death unknown) and a decrease in pup birth weights. These findings are common with CNS-active drugs at high dose levels in animals.

As the relevance of these findings to humans is not certain the use of Mirtazapine during pregnancy is not recommended. Women of child-bearing potential should employ an adequate method of contraception if taking Mirtazapine.

Although animal experiments show that mirtazapine is excreted only in very small amounts in the milk, the use of Mirtazapine in nursing mothers is not recommended since no human data in breast milk are available.

4.7 Effects on ability to drive and use machines

Mirtazapine has minor or moderate influence on the ability to drive and use machines. Mirtazapine may impair concentration and alertness (particularly in the initial phase of treatment). Patients should avoid the performance of potentially dangerous tasks, which require alertness and good concentration, such as driving a motor vehicle or operating machinery, at any time when affected.

4.8 Undesirable effects

Depressed patients display a number of symptoms that are associated with the illness itself. It is therefore sometimes difficult to ascertain which symptoms are a result of the illness itself and which are a result of treatment with Mirtazapine.

The most commonly reported adverse reactions, occurring in more than 5 % of patients treated with Mirtazapine in randomized placebo-controlled trials (see below) are somnolence, sedation, dry mouth, weight increased, increase in appetite, dizziness and fatigue.

All randomized placebo-controlled trials in patients (including indications other than major depressive disorder), have been evaluated for adverse reactions of Mirtazapine. The meta-analysis considered 20 trials, with a planned duration of treatment up to 12 weeks, with 1501 patients (134 person years) receiving doses of mirtazapine up to 60 mg and 850 patients (79 person years) receiving placebo. Extension phases of these trials have been excluded to maintain comparability to placebo treatment.

Table 1 shows the categorized incidence of the adverse reactions, which occurred in the clinical trials statistically significantly more frequently during treatment with Mirtazapine than with placebo, added with adverse reactions from spontaneous reporting. The frequencies of the adverse reactions from spontaneous reporting are based on the reporting rate of these events in the clinical trials. The frequency of adverse reactions from spontaneous reporting for which no cases in the randomized placebo-controlled patient trials were observed with mirtazapine has been classified as 'not known'.

Table 1. Adverse reactions of Mirtazapine

	Rare (>1/10,000 to < 1/1,000 )	Uncommon (> 1/1,000 to < 1/100)	Common (> 1/100 to < 1/10)	Very common (> 1/10)	Frequency not known
Blood and the lymphatic system disorders	Reversible agranulocytosis has been reported as a rare occurrence with Mirtazapine. (see also section 4.4 'Special warnings and special precautions for use')				Bone marrow depression (granulocytop enia, agranulocytos is, aplastic anemia, thrombocytop enia), Eosinophilia
Metabolism and nutrition disorders				Increase in appetite and weight gaina	Hyponatraemia
Psychiatric disorders	Aggression	Nightmares/vivid dreamsb, Mania, Agitiationb, Hallucinations Psychomotor restlessness (incl, akathisia, hyperkinesia)	Abnormal dreams, Confusion, Anxietyb,e Insomniac,e		Suicidal f ideation, Suicidal f behaviour
Nervous system disorders	Myoclonus.	Paraesthesiab Restless legs Syncope	Lethargya, Dizziness, Tremor	Somnolen ce, Sedationa,d Headacheb	Convulsions (insults) Serotonin syndrome, Oral paraethesia, Dysarthria
Vascular disorders		Hypotension6	(Orthostatic) hypotension.
Hepato-biliary disorders	Elevation in serum transaminase activities
Skin and subcutaneous tissue disorders	Rash		Exanthema13		Stephens- Johnson Syndrome, Dermatitis bullous, Erythema multiforme, Toxic

					epidermal necrolysis
Musculoskeletal, connective tissue and bone disorders			Arthralgia Myalgia Back pain
General disorders			Generalised or local oedemaa. Drowsiness/sedat ion/ fatigue, generally occurring during the first few weeks of treatment. (N.B. dose reduction generally does not lead to less sedation but can jeopardise antidepressant efficacy)		Somnambulism
Gastrointestinal disorders	Pancreatitis	Oral hypoaesthesia	Diarrhoeab, Vomitingb, Nauseac	Dry mouth	Mouth oedema, Increased salivation
Endocine disorders					Inappropriate antidiuretic hormone secretion

^a In clinic al trials these events occurred statically significant more frequently during treatment with Mirtazapine than with placebo.

^b In clinical trials these events occurred more frequently during treatment with placebo than with Mirtazapine, however not statistically significantly more frequently.

^c In clinical trials these events occurred statistically significantly more frequently during treatment with placebo than with Mirtazapine

^d N.B, dose reduction generally does not lead to less somnolence/sedation but can jeopardize antidepressant efficacy.

^e Upon treatment with antidepressants in general, anxiety and insomnia (which may be symptoms of depression) can develop or become aggravated. Under mirtazapine treatment, development or aggravation of anxiety and insomnia had been reported

f

Cases of suicidal ideation and suicidal behaviours have been reported during mirtazapine therapy or early after treatment discontinuation (see section 4.4)

In laboratory evaluations in clinical trials transient increases in transaminases and gamma-glutamyltransferase have been observed (however associated adverse events have not been reported statistically significantly more frequently with Mirtazapine than with placebo).

An increased risk of bone fractures has been observed in patients taking this type of medicine.

Although mirtazapine does not cause dependence, post-marketing experience shows that abrupt termination of treatment after long term administration may sometimes result in withdrawal symptoms. The majority of withdrawal reactions are mild and self-limiting. Among the various reported withdrawal symptoms, nausea, anxiety and agitation are the most frequently reported. Even though they have been reported as withdrawal symptoms, it should be realised that these symptoms may be related to underlying disease. As advised in section 4.2, treatment with mirtazapine should be discontinued gradually.

Paediatric Population:

The following adverse events were observed commonly in clinical trials in children: Weight gain, urticaria and hypertriglyceridaemia (see also section 5.1)

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme; website: www.mhra.gov.uk/yellowcard

4.9 Overdose

Present experience concerning overdose with Mirtazapine alone indicates that symptoms are usually mild.

Depression of the central nervous system with disorientation and prolonged sedation have been reported, together with tachycardia and mild hyper- or hypotension. However, there is a possibility of more serious outcomes (including fatalities) at dosages much higher than the therapeutic dose, especially with mixed overdoses.

Cases of overdose should be treated with appropriate symptomatic and supportive therapy for vital functions.

Activated charcoal or gastric lavage should also be considered.

5 PHARMACOLOGICAL PROPERTIES

Mirtazapine is an antidepressant, which can be given as treatment for episodes of major depression. The presence of symptoms such as anhedonia, psychomotor inhibition, sleep disturbances (early wakening) and weight loss, increase the chance of a positive response. Other symptoms are: loss of interest, suicidal thoughts and changes in mood (better in the evening than in the morning). Mirtazapine begins to exert its effect in general after 1-2 weeks of treatment.

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Other Antidepressants, ATC code: NO6AX11

Mirtazapine is a centrally active presynaptic a2-antagonist, which increases central noradrenergic and serotonergic neurotransmission. The enhancement of serotonergic neurotransmission is specifically mediated via 5-HT1 receptors, because 5-HT2 and 5-HT3 receptors are blocked by mirtazapine.

Both enantiomers of mirtazapine are presumed to contribute to the antidepressant activity, the S(+) enantiomer by blocking a2 and 5-HT2 receptors and the R(-) enantiomer by blocking 5-HT3 receptors.

The histamine H1-antagonistic activity of mirtazapine is responsible for its sedative properties. Mirtazapine is generally well tolerated. It has practically no anticholinergic activity and, at therapeutic doses, has practically no effect on the cardiovascular system.

Paediatric population:

Two randomised, double-blind, placebo-controlled trials in children aged between 7 and 18 years with major depressive disorder (n=259) using a flexible dose for the first 4 weeks (15-45mg mirtazapine) followed by a fixed dose (15, 30 or 45 mg mirtazapine) for another 4 weeks failed to demonstrate significant differences between mirtazapine and placebo on the primary and all secondary endpoints. Significant weight gain (>7%) was observed in 48.8% of the mirtazapine treated subjects compared to 5.7% in the placebo arm. Urticaria (11.8% vs 6.8%) and hypertriglyceridaemia (2.9% vs 0%) were also commonly observed.

5.2 Pharmacokinetic properties

After oral administration of Mirtazapine, the active constituent mirtazapine is rapidly and well absorbed (bioavailability 50%), reaching peak plasma levels after about 2 hours. Binding of mirtazapine to plasma proteins is approx. 85%. The mean half-life of elimination is 20-40 hours; longer half-lives, up to 65 hours, have occasionally been recorded and shorter half-lives have been seen in young men. The half-life of elimination is sufficient to justify once-a-day dosing. Steady state is reached after 3-4 days, after which there is no further accumulation. Mirtazapine displays linear pharmacokinetics within the recommended dose range. Food intake has no influence on the pharmacokinetics of mirtazapine. Mirtazapine is extensively metabolised and eliminated via the urine and faeces within a few days. Major pathways of biotransformation are demethylation and oxidation, followed by conjugation. In vitro data from human liver microsomes indicate that cytochrome P450 enzymes CYP2D6 and CYP1A2 are involved in the formation of the 8-hydroxy metabolite of mirtazapine, whereas CYP3A4 is considered to be responsible for the formation of the N-demethyl and N-oxide metabolites. The demethyl metabolite is pharmacologically active and appears to have the same pharmacokinetic profile as the parent compound. There are no differences in the pharmacokinetic parameters of racemic mirtazapine or its demethyl metabolite in extensive and poor metabolisers. Plasma metabolite profiles for the individual enantiomers are qualitatively similar in extensive and poor metabolisers.

The clearance of mirtazapine may be decreased as a result of renal or hepatic insufficiency.

5.3 Preclinical safety data

Preclinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, carcinogenicity or genotoxicity.

In reproductive toxicity studies in rats and rabbits no teratogenic effects were observed. At two-fold systemic exposure compared to maximum human therapeutic exposure, there was an increase in post-implantation loss, decrease in the pup birth weights, and reduction in pup survival during the first three days of lactation in rats.

Mirtazapine was not genotoxic in a series of tests for gene mutation and chromosomal and DNA damage. Thyroid gland tumours found in a rat carcinogenicity study and hepatocellular neoplasms found in a mouse carcinogenicity study are considered to be species-specific, non-genotoxic responses associated with long-term treatment with high doses of hepatic enzyme inducers.

6    PHARMACEUTICAL PARTICULARS

6.1    List of excipients

Mannitol DC Microcrystalline cellulose Crospovidone

Hydroxylpropyl cellulose low substituted

Magnesium carbonate heavy

Silica colloidal anhydrous

Methionine

Purified water

Magnesium stearate

Guar Gum Aspartame (E951)

Orange flavour

6.2 Incompatibilities

Not applicable.

DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

24/07/2007

DATE OF REVISION OF THE TEXT

29/01/2016