BENYLIN NON-DROWSY DRY COUGHS 7.5 MG/5ml Syrup

Ireland - English - HPRA (Health Products Regulatory Authority)

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Active ingredient:
DEXTROMETHORPHAN HYDROBROMIDE
Available from:
McNeil Healthcare (Ireland) Ltd
ATC code:
R05DA09
INN (International Name):
DEXTROMETHORPHAN HYDROBROMIDE
Dosage:
7.5 MG/5ml
Pharmaceutical form:
Syrup
Prescription type:
Product not subject to medical prescription
Therapeutic area:
Opium alkaloids and derivatives
Authorization status:
Authorised
Authorization number:
PA0823/029/001
Authorization date:
1994-11-10

Package leaflet: Information for the user

Non-Drowsy

Dry Coughs Syrup

dextromethorphan hydrobromide 7.5 mg/ 5 ml

Read all of this leaflet carefully before you start

using this medicine because it contains important

information for you.

Always use this medicine exactly as described in this leaflet

or as your doctor or pharmacist have told you.

- Keep this leaflet. You may need to read it again.

- Ask your pharmacist if you need more information or

advice.

- If you get any side-effects, talk to your doctor or

pharmacist. This includes any possible side-effects not

listed in this leaflet. See section 4.

- You must talk to a doctor if you do not feel better or if

you feel worse after 5 days.

What is in this leaflet

What Benylin Non-Drowsy Dry Coughs Syrup is and

what it is used for

What you need to know before you use Benylin Non-

Drowsy Dry Coughs Syrup

How to use Benylin Non-Drowsy Dry Coughs Syrup

Possible side-effects

How to store Benylin Non-Drowsy Dry Coughs Syrup

Contents of the pack and other information

1 What Benylin Non-Drowsy

Dry Coughs Syrup is and

what it is used for

Benylin Non-Drowsy Dry Coughs Syrup is a medicine

which is used to help relieve dry, irritating coughs. The

liquid contains dextromethorphan hydrobromide which

is an antitussive to help stop persistent coughing.

The medicine is for use in adults and children aged

12 years and over.

2 What you need to know

before you use Benylin Non-

Drowsy Dry Coughs Syrup

This medicine is suitable for most people but a few people

should not use it. If you are in any doubt, talk to your

doctor or pharmacist.

Do not use Benylin Non-Drowsy Dry

Coughs Syrup…

If you have ever had a bad reaction to

dextromethorphan or any of the other ingredients.

If you suffer from lung disease.

If you are taking, or have taken in the last

two weeks, drugs for depression known as

Monoamine Oxidase Inhibitors (MAOIs).

If you are taking selective serotonin re-uptake

inhibitors (used to treat depression and anxiety

such as fluoxetine, paroxetine and sertraline).

For children under 12 years old.

If any of these apply to you, get advice from a doctor or

pharmacist without using Benylin Non-Drowsy Dry

Coughs Syrup.

Warnings and Precautions

Talk to your doctor or pharmacist…

If you suffer from liver problems.

If you have bronchitis, emphysema or asthma

or have had a cough for a few weeks or a cough

with a lot of mucus (phlegm).

If you have alcohol dependence.

If you have a history of drug abuse.

If you have been told by your doctor that you are a

slow metabolizer of CYP2D6.

If you are taking any other cough and cold

medicines.

If your child is prone to developing certain allergic

reactions (e.g. atopic reactions).

Avoid alcoholic drink when taking this medicine.

Other medicines and Benylin Non-Drowsy

Dry Coughs Syrup

If you are taking any other medicines, including:

Certain drugs for depression such as

norepinephrine-dopamine reuptake inhibitors

(NDRI), which include bupropion.

Antipsychotics (drugs used to treat mood disorders

such as haloperidol, thioridazine, perphenazine).

Anti-arrhythmic agents (drugs used to treat irregular

heart beats such as amiodarone, propafenone,

quinidine and flecainide).

Calcimimetic agents (drugs used to treat secondary

hyperparathyroidism, elevated parathyroid

hormone levels such as cinacalcet).

Anti fungals (terbinafine).

Opioid analgesics (drugs used to relieve pain e.g.

codeine, tramadol, morphine, methadone).

Antihistamines (drugs used to treat the symptoms of

allergic reactions).

Hypnotics (sleeping tablets including barbiturates).

Tranquilizers (drugs used to relax muscles or

decrease anxiety).

Do not take this medicine if you are taking any

medicines listed in the ‘Do not use this medicine’

section of this leaflet.

If you are not sure about any of the medicines you are

taking, show the bottle or pack to your pharmacist.

If any of these bullet points apply to you now or in the

past, talk to a doctor or pharmacist.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, only use this

medicine on the advice of your doctor.

Driving and using machines

This medicine may cause drowsiness or dizziness. If

affected, do not drive or operate machinery. Avoid

alcoholic drink.

Benylin Non-Drowsy Dry Coughs Syrup

contains sucrose, sorbitol, liquid glucose,

ethanol and sodium

This medicine contains sucrose, sorbitol and liquid

glucose. If you have been told by your doctor that

you have an intolerance to some sugars contact

your doctor before taking this medicinal product.

Contains 2.38 g glucose and 1.6 g sucrose per 5 ml.

This should be taken into account in patients with

diabetes mellitus.

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This medicinal product contains 6 vol% ethanol

(alcohol), i.e. up to 240 mg per 5 ml, equivalent to

6 ml beer, 2.5 ml wine per 5 ml. This can be harmful

for those suffering from alcoholism. To be taken

into account in pregnant or breast-feeding women,

children and high-risk groups such as patients with

liver disease or epilepsy.

The product contains 4.4 mg of sodium per 5 ml.

To be taken into consideration by patients on

a sodium controlled diet.

3 How to use Benylin Non-

Drowsy Dry Coughs Syrup

Check the table that follows to see how

much medicine to take.

For oral use only.

Do not take more medicine than the label tells you to.

Children under 12 years

Do not give to children under 12 years old.

Adults and children aged 12 years and

over

Age

Dose

Adults and

children aged

12 years and over

Take two 5 ml spoonfuls four

times a day.

Do not take more than 4 doses in 24 hours.

If symptoms persist or worsen, talk to your doctor

or pharmacist.

If anyone has too much

If anyone has too much, contact your doctor or

pharmacist immediately.

If you forget to take the medicine

If you forget to take a dose, take the next dose when

needed provided that the last dose was taken at least

4 hours ago. Do not take a double dose.

4 Possible side-effects

Like all medicines, Benylin Non-Drowsy Dry Coughs can

cause side-effects, although not everybody gets them.

If you experience any of the following stop

using this medicine and seek immediate

medical help:

Swelling of the face, lips, mouth, tongue or throat

which may cause difficulty in swallowing or

breathing.

Allergic reactions including skin rashes such as hives

(which may be severe and include blistering or

peeling of the skin) and itching.

Fits.

If you experience any of the following stop

using the medicine and talk to your doctor:

Rare (may affect up to 1 in 1000 people)

Difficulty in breathing.

Feeling confused.

Other effects which may occur but it is not known

how often, include:

Upset stomach, stomach pain or diarrhoea.

Nausea or vomiting.

Dizziness or drowsiness.

Feeling agitated, jittery, or restless.

Difficulty sleeping (insomnia).

Shallow breathing.

Reporting of side-effects

If you get any side-effects, talk to your doctor, pharmacist

or nurse. This includes any possible side-effects not listed

in this leaflet. You can also report side-effects directly via

HPRA Pharmacovigilance, Earlsfort Terrace, IRL-Dublin 2;

Tel: +35316764971; Fax: +35316762517

Website: www.hpra.ie; Email: medsafety@hpra.ie.

By reporting side-effects you can help provide more

information on the safety of the medicine.

5 How to store Benylin Non-

Drowsy Dry Coughs Syrup

Do not store above 30ºC.

Keep the bottle tightly closed in order to protect from light

and moisture.

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is

stated on the label after EXP. The expiry date refers to the

last day of that month.

Do not throw away any medicines via wastewater or

household waste. Ask your pharmacist how to throw away

medicines you no longer use. These measures will help

protect the environment.

6 Contents of the pack and

other information

What Benylin Non-Drowsy Dry Coughs

Syrup contains

The active ingredient in 5 ml of Benylin Non-Drowsy

Dry Coughs Syrup is: 7.5 mg Dextromethorphan

hydrobromide.

Other ingredients are: Sorbitol solution (70%) E420,

glycerol, sucrose, liquid glucose, citric acid monohydrate,

sodium benzoate (E211), caramel, saccharin sodium,

imitation peach flavour, levomenthol, ethanol (96% v/v),

carbomer and purified water.

What the medicine looks like and the

contents of the pack

Benylin Non-Drowsy Dry Coughs is a pale brown coloured,

peach flavoured syrup, available in 30 ml, 125 ml and 300 ml

glass bottles. Not all pack sizes may be marketed.

Marketing Authorisation Holder: McNeil Healthcare

(Ireland) Limited, Airton Road, Tallaght, Dublin 24, Ireland.

Manufacturer: Famar Orléans, 5 avenue de Concyr,

45071 Orleans, Cedex 2, France.

This leaflet was revised in April 2018.

Benylin is a registered trade mark.

LN507902

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Summary of Product Characteristics

1 NAME OF THE MEDICINAL PRODUCT

Benylin Non-Drowsy Dry Coughs, Syrup

Dextromethorphan hydrobromide 7.5mg/5ml

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Benylin Non-Drowsy Dry Coughs, Syrup contains dextromethorphan hydrobromide 7.5 mg in each 5 ml.

Each 5ml of

Benylin Non-Drowsy Dry Coughs, Syrup also contains:

For a full list of excipients see section 6.1.

3 PHARMACEUTICAL FORM

Syrup

A clear amber coloured syrup with a characteristic smell of peaches.

4 CLINICAL PARTICULARS

4.1 Therapeutic Indications

BENYLIN Non-Drowsy Dry Coughs, Syrup is indicated for the relief of non-productive irritating cough.

4.2 Posology and method of administration

Adults and children 12 years and over:

Oral. 15mg (10 ml syrup) 3-4 times a day.

Maximum daily dose: 40 ml syrup

Children under 12 years:

This product is contraindicated in children under the age of 12 years (See section 4.3).

Hepatic dysfunction

Due to the extensive hepatic metabolism of dextromethorphan, caution should be exercised in the presence of hepatic

impairment (See sections 4.4 and 5.2).

4.3 Contraindications

This product is contraindicated in individuals with known hypersensitivity to dextromethorphan or to any of the

excipients listed in section 6.1.

Dextromethorphan should not be used in patients taking monoamine oxidase inhibitors (MAOIs), or within 14 days of

stopping MAOI treatment (see section 4.5). There is a risk of serotonin syndrome with the concomitant use of

Sorbitol solution

E420

Sucrose

1625

Glucose

2380

Sodium

Ethanol

96% v/v

0.311

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dextromethorphan and MAOIs and the concomitant use of these medications may cause a rise in blood pressure and

hypertensive crisis (see section 4.5).

This product is contraindicated in patients taking serotonin reuptake inhibitors (SSRIs, see section 4.5).

Dextromethorphan, should not be given to patients in, or at risk of developing respiratory failure.

Benylin Non-Drowsy Dry Coughs, Syrup is contraindicated for use in children under 12 years of age.

4.4 Special warnings and precautions for use

Use with caution in patients with hepatic dysfunction.

Patients with the following conditions should not use this product, unless directed by a physician: acute or chronic

asthma, a persistent or chronic cough such as occurs with chronic bronchitis or emphysema, or where cough is

accompanied by excessive secretions.

Cases of dextromethorphan abuse have been reported. Caution is particularly recommended for adolescents and young

adults as well as in patients with a history of drug abuse of psychoactive substances. There is no evidence of drug

dependence at therapeutic doses.

Use of dextromethorphan with alcohol or other CNS depressants may increase the effects on the CNS and cause

toxicity in relatively smaller doses. While taking this product, patients should be advised to avoid alcoholic drinks and

consult a healthcare professional prior to taking with central nervous system depressants.

Dextromethorphan is metabolised by hepatic cytochrome P450 2D6. The activity of this enzyme is genetically

determined. About 10% of the general population are poor metabolisers of CYP2D6. Poor metabolisers and patients

with concomitant use of CYP2D6 inhibitors may experience exaggerated and/or prolonged effects of

dextromethorphan. Caution should therefore be exercised in patients who are slow metabolizers of CYP2D6 or use

CYP2D6 inhibitors (see also section 4.5).

This product should be used with caution in atopic children due to histamine release.

Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase

insufficiency should not take this product.

This medicinal product contains 6 vol% ethanol (alcohol), i.e. up to 240 mg per 5ml, equivalent to 6 ml beer, 2.5 ml

wine per 5 ml. This can be harmful for those suffering from alcoholism. To be taken into account in pregnant or breast-

feeding women, children and high-risk groups such as patients with liver disease or epilepsy

Patients who are taking other medication including cough and cold medicines and / or who are under the care of a

physician, should consult their doctor / pharmacist before taking this product.

4.5 Interaction with other medicinal products and other forms of interaction

Dextromethorphan should not be used concurrently in patients taking monoamine oxidase inhibitors (MAOIs) or within

14 days of stopping treatment with MAOIs as there is a risk of serotonin syndrome (pyrexia, hypertension,

arrhythmias).

CYP2D6 inhibitors

Dextromethorphan is metabolized by CYP2D6 and has an extensive first-pass metabolism. Concomitant use of potent

CYP2D6 enzyme inhibitors can increase the dextromethorphan concentrations in the body to levels multifold higher

than normal. This increases the patient's risk for toxic effects of dextromethorphan (agitation, confusion, tremor,

insomnia, diarrhoea and respiratory depression) and development of serotonin syndrome. Potent CYP2D6 enzyme

inhibitors include SSRIs such as fluoxetine and paroxetine, quinidine and terbinafine. In concomitant use with

quinidine, plasma concentrations of dextromethorphan have increased up to 20-fold, which has increased the CNS

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adverse effects of the agent. Amiodarone, flecainide and propafenone, sertraline, bupropion, methadone, cinacalcet,

haloperidol, perphenazine and thioridazine also have similar effects on the metabolism of dextromethorphan. If

concomitant use of CYP2D6 inhibitors and dextromethorphan is necessary, the patient should be monitored and the

dextromethorphan dose may need to be reduced.

Dextromethorphan might exhibit additive CNS depressant effects when co-administered with alcohol, antihistamines,

psychotropics, and other CNS depressant drugs.

4.6 Fertility, pregnancy and lactation

Although dextromethorphan has been in widespread use for many years without apparent ill consequence, there is

insufficient information on the effects of administration during human pregnancy. In addition, it is not known whether

dextromethorphan or its metabolites are excreted in breast milk.

Benylin Non-Drowsy for Dry Coughs should therefore only be used when the potential benefit of treatment to the

mother exceeds any possible hazards to the developing foetus or nursing infant.

4.7 Effects on ability to drive and use machines

Although the overall data do not support that dextromethorphan impacts driving, due to its potential for somnolence

and dizziness, caution should be used when driving a motor vehicle or operating machinery.

4.8 Undesirable effects

Post-marketing Data:

Adverse drug reactions (ADRs) identified during clinical trials and post-marketing experience with Dextromethorphan

are listed below by System Organ Class (SOC). The frequencies are provided according to the following convention:

Very common

1/10

Common

1/100 and <1/10

Uncommon

1/1,000 and <1/100

Rare

1/10,000, <1/1,000

Very rare

<1/10,000

Not known

(cannot be estimated from the available data)

ADRs are presented by frequency category based on 1) incidence in adequately designed clinical trials or epidemiology

studies, if available, or 2) when incidence cannot be estimated, frequency category is listed as ‘Not known’.

System Organ Class (SOC)

Frequency category

Adverse Drug Reaction (Preferred Term)

Psychiatric Disorders

Rare

Confusional state

Not known

Agitation

Not known

Insomnia

Nervous System Disorders

Not known

Dizziness

Not known

Psychomotor hyperactivity

Not known

Seizure

Not known

Somnolence

Respiratory, Thoracic and

Mediastinal Disorders

Rare

Bronchoconstriction

Rare

Dyspnoea

Not known

Respiratory depression

Gastrointestinal Disorders

Not known

Abdominal pain

Not known

Diarrhoea

Not known

Nausea

Not known

Vomiting

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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 HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2; Tel: +353 1 6764971;

Fax: +353 1 6762517. Website: www.hpra.ie; E-mail: medsafety@hpra.ie.

4.9 Overdose

Dextromethorphan is thought to be of low toxicity, but the effects in overdose will be potentiated by simultaneous

ingestion of alcohol and psychotropic drugs.

Symptoms of overdose may include:

Psychiatric Disorders

Agitation

Confusional state

Conversion disorder

Hallucination, mixed

Psychotic disorder

Nervous System Disorders

Ataxia

Clumsiness

Coma

Depressed level of consciousness

Dizziness

Dysarthria

Lethargy

Nystagmus

Seizures

Serotonin syndrome

Somnolence

Tremor

Eye Disorders

Miosis

Mydriasis

Respiratory, Thoracic and Mediastinal Disorders

Respiratory depression. Death may occur as a result of respiratory failure.

Gastrointestinal Disorders

Nausea

Vomiting

Renal and Urinary Disorders

Urinary retention

Management

Treatment of overdose should be symptomatic and supportive. Gastric lavage may be of use. Naloxone has been used

Skin and Subcutaneous Tissue

Disorders

Not known

Angioedema

Not known

Pruritus

Not known

Rash

Not known

Urticaria

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successfully to reverse central or peripheral opioid effects of dextromethorphan in children (0.01mg/kg body weight).

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Cough suppressant

ATC code: R05DA09

Dextromethorphan is the dextrorotatory isomer of 3-methoxy-N-methyl-morphinan. It is a synthetic morphine

derivative that, in contrast to its levoisomer, has no significant analgesic, respiratory depressant or physical dependency

properties at recommended doses.

Dextromethorphan is a cough suppressant and acts centrally on the cough centre in the medulla oblongata to elevate the

threshold for coughing.

The onset of antitussive effects are realised within 15 to 30 minutes of oral administration, lasting for approximately 3

to 6 hours.

The major metabolite of dextromethorphan, dextrorphan, binds with high affinity to

receptors to produce its

antitussive activity without exhibiting the classic opiate effects that occur from binding into µ- and

-receptors.

Dextrorphan also exhibits binding activity at serotonergic receptors and was shown to enhance serotonin activity by

inhibiting the reuptake of serotonin.

5.2 Pharmacokinetic properties

Absorption

Dextromethorphan is rapidly absorbed from the gastrointestinal tract with peak plasma concentrations reached in

approximately 2 to 2.5 hours. The low plasma levels of dextromethorphan suggest low oral bioavailability secondary to

extensive first-pass (presystemic metabolism) in the liver. The maximum clinical effects occur 5 to 6 hours after

ingestion of dextromethorphan.

Distribution

Dextromethorphan is widely distributed in the human body.

Dextromethorphan and its active metabolite, dextrorphan,

are actively taken up and concentrated in brain tissue. It is not known if dextromethorphan or dextrorphan are excreted

in breast milk or cross the placenta.

Metabolism

Dextromethorphan undergoes rapid and extensive first-pass metabolism in the liver after oral administration.

Genetically controlled O-demethylation (CYD2D6) is the main determinant of dextromethorphan pharmacokinetics in

human volunteers.

It appears that there are distinct phenotypes for this oxidation process resulting in highly variable pharmacokinetics

between subjects. Unmetabolised dextromethorphan, together with the three demethylated morphinan metabolites

dextrorphan (also known as 3-hydroxy-N-methylmorphinan), 3- hydroxymorphinan and 3-methoxymorphinan have

been identified as conjugated products in the urine.

Dextrorphan, which also has antitussive action, is the main metabolite. In some individuals metabolism proceeds more

slowly and unchanged dextromethorphan predominates in the blood and urine.

Excretion

Dextromethorphan is primarily excreted via the kidney as unchanged parent drug and its active metabolite,

dextrorphan. Dextrorphan and 3-hydroxy-morphinan are further metabolised by glucuronidation and are eliminated via

the kidneys.

The elimination half-life of the parent compound is between 1.4 to 3.9 hours; dextrorphan is between 3.4 to 5.6 hours.

The half life of dextromethorphan in poor metabolisers is extremely prolonged, in the range of 45 hours.

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5.3 Preclinical safety data

5.3.1.

General Toxicology

Acute oral toxicity studies conducted with Dextromethorphan report the following LD

values (mg/kg): mouse, 210

and rat, 116. Acute subcutaneous toxicity with Dextromethorphan reports the LD

value (mg/kg): mouse, 112. Acute

intravenous toxicity with Dextromethorphan reports the LD

value (mg/kg): rat, 16.3.

Repeat dose toxicity studies conducted in rats for 13 weeks duration at doses up to 100 mg/kg and 27 weeks at 10

mg/kg, and of 14 weeks in dogs by oral gavage at doses up to 4 mg/kg on five days per week. The only effect recorded

was of reduced body weight gain in the rat 13-week study at the highest dose.

5.3.2.

Genetic Toxicology

Dextromethorphan hydrobromide was negative in the bacterial reverse mutation assay (Ames test). Dextromethorphan

39 mg/kg is reported to be negative in in-vivo mouse micronucleus test and comet assay. Dextromethorphan was

reported to be negative in in vitro chromosome aberration assay tested up to 200 µg/ml.

5.3.3.

Carcinogenicity

There are no known reports of animal carcinogenicity studies for Dextromethorphan. There is no evidence of a

carcinogenic risk to humans.

The overall weight of evidence for Dextromethorphan and its structural analogues, supports the conclusion that this

class of phenanthrene-based chemicals, and Dextromethorphan, in particular, are not genotoxic in vitro or in vivo, and

do not represent a carcinogenic risk to patients.

5.3.4.

Teratogenicity

There was no association between dextromethorphan and malformations, Dextromethorphan is generally considered

safe to use during pregnancy.

5.3.5.

Fertility

Mating, gestation, fertility, littering and lactation were studied in rats at doses upto 50 mg/kg and no adverse effects

were found. There is no evidence of a fertility impairment risk to humans.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Levomenthol

Sodium benzoate (E211)

Sucrose

Glycerol

Liquid glucose

Sorbitol, Liquid (non-crystallising) 70% (E420)

Saccharin sodium

Citric acid monohydrate

Ethanol 96%

Caramel T12

Imitation peach flavour

Carbomer

Purified Water

6.2 Incompatibilities

Not applicable.

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6.3 Shelf life

3 years.

6.4 Special precautions for storage

Store below 30°C. Keep the bottle tightly closed in order to protect from light and moisture.

6.5 Nature and contents of container

30 ml, 125 ml and 300 ml round amber glass bottles with ROPP aluminium caps or 3 piece child resistant, tamper

evident closures fitted with a PE- Alu- PET or polyethylene/expanded polyethylene laminated wad or with a plastic

HDPE cap fitted with a PE-Alu-PET wad.

6.6 Special precautions for disposal

No special requirements.

Any unused product or waste material should be disposed of in accordance with local requirements.

7 MARKETING AUTHORISATION HOLDER

McNeil Healthcare (Ireland) Ltd.

Airton Road

Tallaght

Dublin 24.

8 MARKETING AUTHORISATION NUMBER

PA0823/029/001

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 10 November 1994

Date of last renewal: 10 November 2009

10 DATE OF REVISION OF THE TEXT

April 2018

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