Amaryl 3 mg tablet

Ireland - English - HPRA (Health Products Regulatory Authority)

Buy It Now

Active ingredient:
Glimepiride
Available from:
Sanofi-Aventis Ireland Limited T/A SANOFI
ATC code:
A10BB; A10BB12
INN (International Name):
Glimepiride
Dosage:
3 milligram(s)
Pharmaceutical form:
Tablet
Prescription type:
Product subject to prescription which may be renewed (B)
Therapeutic area:
Sulfonamides, urea derivatives; glimepiride
Authorization status:
Marketed
Authorization number:
PA0540/028/003
Authorization date:
1996-11-29

89034677 - 756736 4/4

89034677 - 756736 1/4

PACK. ITEM:

Arkhé S.n.c.

Tel. 0862.404140

fax 0862.090006

1 - Prima realizzazione

Reflex Blue

Sanofi S.p.A.

Verificare la corrispondenza dell’artwork

approvato - la nostra responsabilità è

limitata al rifacimento dei file forniti.

1

-

-

756736

10 pt su 11,2 pt

28-05-2019

IST AMARYL IE I02

Istruzioni

IE: Ireland

89034677

89034081

62C0007 V.1.0

01100010010

167 x 315mm DP

1

-

-

4, 1 / 4

5. How to store Amaryl

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

Do not use this medicine after the expiry date which is

stated after ‘EXP’ on the blister and carton. The expiry

date refers to the last day of that month.

Amaryl 1 mg, 2 mg, 3 mg, and 4 mg tablets: do not

store above 30°C.

Store in the original package in order to protect from

moisture.

Do not use Amaryl if you notice visible signs of

deterioration.

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. Further information

What Amaryl contains

The active substance is glimepiride

Each tablet contains 1mg or 3mg of glimepiride

depending on the strength indicated on the blister

and carton

The other ingredients are: lactose monohydrate,

sodium starch glycollate (type A), magnesium stearate,

microcrystalline cellulose, povidone 25000

In addition the tablets contain colouring agents:

1 mg tablets contain red iron oxide (E172)

3 mg tablets contain yellow iron oxide (E172)

What Amaryl looks like and contents of the pack

Each tablet of Amaryl is oblong and scored on both

sides. They are different in colour:

1 mg tablets are pink

3 mg tablets are pale yellow

They are supplied in blister packs of 14, 15 (Amaryl

1 mg only), 20, 28, 30, 50, 60, 90, 112, 120 , 280 and

300 tablets. Not all pack sizes and strengths may be

marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder:

Sanofi-aventis Ireland Ltd.

Citywest Business Campus

Dublin 24

Ireland

Tel: 01 403 5600

Fax: 01 403 5687

Email:IEmedinfo@sanofi.com

Manufacturer:

Amaryl 1 mg and 3 mg tablets:

Sanofi S.p.A., Strada Statale 17, Km 22, 67019

Scoppito (L’Aquila), Italy

Sanofi Winthrop Industrie, 30-36 avenue Gustave

Eiffel, 37100 Tours, France

Sanofi-Aventis Deutschland GmbH,

Industriepark Höchst-Brüningstraße50,

65926 Frankfurt am Main,

Germany

Amaryl 3 mg tablets:

Sanofi-Aventis Private Co. Ltd, Budapest Logistics and

Distribution Platform Bdg. DC5, Campona utca1.

Budapest, 1225, Hungary

This medicinal product is authorised in the Member

States of the EEA under the following names:

Amaryl: Austria, Bulgaria, Cyprus, Czech Republic,

Denmark, Estonia, Finland, Germany, Iceland, Ireland,

Italy, Netherlands, Norway, Romania, Slovakia, Spain,

Sweden, United Kingdom

Amaryl Tablete: Slovenia

Amaryl Tabletes: Latvia

Amaryl Tabletès: Lithuania

Amarylle: Belgium, Luxembourg

Amarel: France

Solosa: Greece

This leaflet was last revised in May 2019.

Package leaflet: Information for the user

Glimepiride

Is this leaflet hard to see or read?

Phone 01 403 5600 for help

Read all of this leaflet carefully before you start

taking this medicine because it contains important

information for you.

Keep this leaflet. You may need to read it again

If you have any further questions, ask your doctor

or pharmacist

This medicine has been prescribed for you only. Do

not pass it on to others. It may harm them, even if

their symptoms are the same as yours

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

pharmacist. This includes any possible side effects

not listed in this leaflet.

In this leaflet:

1. What Amaryl is and what it is used for

2. What you need to know before you take Amaryl

3. How to take Amaryl

4. Possible side effects

5. How to store Amaryl

6. Contents of the pack and other information

1. What Amaryl is and what it is used for

Amaryl is an orally active blood sugar lowering medicine.

This medicine belongs to a blood sugar lowering group

of medicines called sulfonylurea. Amaryl works by

increasing the amount of insulin released from your

pancreas. The insulin then lowers your blood sugar levels.

What Amaryl is used for:

Amaryl is used to treat a certain form of diabetes

(type 2 diabetes mellitus) when diet, physical exercise

and weight reduction alone have not been able to

control your blood sugar levels

2. What you need to know before you take

Amaryl

Do not take Amaryl and tell your doctor if:

You are allergic to: glimepiride or other sulfonylureas

(medicines used to lower your blood sugar such

as glibenclamide) or sulfonamides (medicines for

bacterial infections such as sulfamethoxazole) or any

of the other ingredients of this medicine (listed in

section 6)

You have insulin dependent diabetes (type 1 diabetes

mellitus)

You have diabetic ketoacidosis (a complication

of diabetes when your acid level is raised in your

body and you may have some of the following signs:

fatigue, feeling sick (nausea), frequent urination and

muscular stiffness)

You are in a diabetic coma

You have severe kidney disease

You have a severe liver disease

Do not take this medicine if any of the above apply to

you. If you are not sure, talk to your doctor or pharmacist

before taking Amaryl.

Warnings and precautions

Talk to your doctor or pharmacist before taking

your medicine if:

You are recovering from an injury, operation, infections

with fever, or from other forms of stress, inform your

doctor as temporary change of treatment may be

necessary

You have a severe liver or kidney disorder

If you are not sure if any of these apply to you, talk

to your doctor or pharmacist before taking Amaryl.

Lowering of the haemoglobin level and breakdown

of red blood cells (haemolytic anemia) can occur in

patients missing the enzyme glucose-6-phosphate

dehydrogenase.

The information available on the use of Amaryl in

people under 18 years of age is limited. Therefore, its

use in these patients is not recommended.

Important information about hypoglycaemia (low

blood sugar)

When you take Amaryl, you may get hypoglycaemia (low

blood sugar). Please see below for additional information

about hypoglycaemia, its signs and treatment.

Following factors could increase the risk of you

getting hypoglycaemia:

Undernourishment, irregular meal time, missed or

delayed meal or period of fasting

Changes to your diet

Taking more Amaryl than needed

Having decreased kidney function

Having severe liver disease

If you suffer from particular hormone-induced

disorders (disorders of the thyroid glands, of the

pituitary gland or adrenal cortex)

Drinking alcohol (especially when you skip a meal)

Taking certain other medicines (see below “Other

medicines and Amaryl”)

If you increase your body exercise and you do not

eat enough or eat food containing less carbohydrate

than normal

Signs of hypoglycaemia include:

Hunger

pangs,

headache,

nausea,

vomiting,

sluggishness, sleepiness, disordered sleep, restlessness,

aggression, impaired concentration, reduced alertness

and reaction time, depression, confusion, speech and

visual disorders, slurred speech, shakiness, partial

paralysis, sensory disturbances, dizziness, helplessness

The

following

signs

also

occur:

sweating,

clammy skin, anxiety, accelerated heart beat, high

blood pressure, palpitations, sudden strong pain in

the breast that may radiate into neighbouring areas

(angina pectoris and cardiac arrhythmias)

If blood sugar levels continue to drop you may suffer from

considerable confusion (delirium), develop convulsions,

lose self control, breathing may be shallow and your heart

beat slowed down, you may fall into unconsciousness.

The clinical picture of a severe reduced blood sugar

level may resemble that of a stroke.

Treating hypoglycaemia:

In most cases the signs of reduced blood sugar vanish

very quickly when you consume some form of sugar,

e.g. sugar cubes, sweet juice, sweetened tea.

You should therefore always take some form of sugar

with you (e.g. sugar cubes). Remember that artificial

sweeteners are not effective. Please contact your doctor

or go to the hospital if taking sugar does not help or

if the symptoms recur.

89034677 - 756736 2/4

89034677 - 756736 3/4

PACK. ITEM:

Arkhé S.n.c.

Tel. 0862.404140

fax 0862.090006

1 - Prima realizzazione

Reflex Blue

Sanofi S.p.A.

Verificare la corrispondenza dell’artwork

approvato - la nostra responsabilità è

limitata al rifacimento dei file forniti.

1

-

-

756736

10 pt su 11,2 pt

28-05-2019

IST AMARYL IE I02

Istruzioni

IE: Ireland

89034677

89034081

62C0007 V.1.0

01100010010

167 x 315mm DP

1

-

-

2, 3 / 4

Laboratory tests

The level of sugar in your blood or urine should be

checked regularly. Your doctor may also take blood tests

to monitor your blood cell levels and liver function.

Children and adolescents

Amaryl is not recommended for use in children under

18 years of age

Other medicines and Amaryl

Tell your doctor or pharmacist if you are taking, have

recently taken or might take any other medicines.

Your doctor may wish to change your dose of Amaryl

if you are taking other medicines, which may weaken

or strengthen the effect of Amaryl on the level of sugar

in your blood.

The following medicines can increase the blood sugar

lowering effect of Amaryl. This can lead to a risk of

hypoglycaemia (low blood sugar):

Other medicines to treat diabetes mellitus (such as

insulin or metformin)

Medicines

treat

pain

inflammation

(phenylbutazone, azopropazone, oxyphenbutazone,

aspirin-like medicines)

Medicines to treat urinary infections (such as some

long acting sulfonamides)

Medicines to treat bacterial and fungal infections

(tetracyclines,

chloramphenicol,

fluconazole,

miconazole, quinolones, clarithromycin)

Medicines

inhibit

blood

clotting

(coumarin

derivatives such as warfarin)

Medicines supporting muscle build up (anabolics)

Medicines used for male sex hormone replacement

therapy

Medicinal to treat depression (fluoxetine, MAO-

inhibitors)

Medicines lowering high cholesterol level (fibrates)

Medicines

lowering

high

blood

pressure

(ACE

inhibitors)

Medicines called anti-arrhythmic agents used to

control abnormal heart beat (disopyramide)

Medicines to treat gout (allopurinol, probenecid,

sulfinpyrazone)

Medicines

treat

cancer

(cyclophosphamide,

ifosfamide, trofosfamide)

Medicines used to reduce weight (fenfluramine)

Medicines to increase circulation when given in a high

dose intravenous infusion (pentoxifylline)

Medicines to treat nasal allergies such as hay fever

(tritoqualine)

Medicines called sympatholytics to treat high blood

pressure, heart failure, or prostate symptoms

The following medicines may decrease the blood sugar

lowering effect of Amaryl. This can lead to a risk of

hyperglycaemia (high blood sugar level):

Medicines

containing

female

hormones

(oestrogens, progestogens)

Medicines supporting urine production (thiazide

diuretics)

Medicines used to stimulate the thyroid gland (such

as levothyroxine)

Medicines

treat

allergies

inflammation

(glucocorticoids)

Medicines

treat

severe

mental

disorders

(chlorpromazine and other phenothiazine derivatives)

Medicines used to raise heart beat, to treat asthma or

nasal congestion, coughs and colds, used to reduce

weight, or used in life-threatening emergencies

(adrenaline and sympathomimetics)

Medicines to treat high cholesterol level (nicotinic acid)

Medicines to treat constipation when they are used

long term (laxatives)

Medicines to treat seizures (phenytoin)

Medicines to treat nervousness and sleep problems

(barbiturates)

Medicines to treat increased pressure in the eye

(azetazolamide)

Medicines to treat high blood pressure or low blood

sugar (diazoxide)

Medicines to treat infections, tuberculosis (rifampicine)

Medicines to treat severe low blood sugar levels

(glucagon)

The following medicines can increase or decrease the

blood sugar lowering effect of Amaryl:

Medicines

treat

stomach

ulcers

(called

antagonists)

Medicines to treat high blood pressure or heart

failure such as beta-blockers, clonidine, guanethidine

and reserpine. These can also hide the signs of

hypoglycaemia, so special care is needed when

taking these medicines

Amaryl may either increase or weaken the effects of

the following medicines:

Medicines

inhibiting

blood

clotting

(coumarin

derivatives such as warfarin)

Colesevelam, a medicine used to reduce cholesterol,

has an effect on the absorption of Amaryl. To avoid

this effect, you should be advised to take Amaryl at

least 4 hours before colesevelam.

Amaryl with food, drink and alcohol

Alcohol intake may increase or decrease the blood sugar

lowering action of Amaryl in an unpredictable way.

Pregnancy and breast-feeding

Pregnancy

Amaryl should not be taken during pregnancy. Tell

your doctor if you are, you think you might be or are

planning to become pregnant.

Breast feeding

Amaryl may pass into breast milk. Amaryl should not

be taken during breast feeeding.

Ask your doctor or pharmacist for advice before taking

any medicine.

Driving and using machines

Your ability to concentrate or react may be impaired if

your blood sugar is lowered (hypoglycaemia), or raised

(hyperglycaemia) or if you develop visual problems as a

result of such conditions. Bear in mind that you could

endanger yourself or others (e.g. when driving a car

or using machines). Please ask your doctor whether

you can drive a car if you:

have frequent episodes of hypoglycaemia,

have fewer or no warning signals of hypoglycaemia

Amaryl contains lactose.

If you have been told by your doctor that you cannot

tolerate some sugars, contact your doctor before taking

this medicine.

3. How to take Amaryl

Always take this medicine exactly as your doctor has told

you. You should check with your doctor or pharmacist

if you are not sure.

Taking this medicine

Take this medicine by mouth, just before or with

the first main meal of the day (usually breakfast).

If you do not have breakfast you should take the

medicine on schedule as prescribed by your doctor.

It is important not to leave out any meal when you

are on Amaryl

Swallow the tablets whole with at least half glass of

water. Do not crush or chew the tablets

Each tablet can be divided into equal doses

How much to take

The dose of Amaryl depends on your needs, condition

and results of blood and urine sugar tests and is

determined by your doctor. Do not take more tablets

than your doctor has prescribed.

The usual starting dose is one Amaryl 1 mg tablet

once a day

If necessary, your doctor may increase the dose after

each 1 - 2 weeks of treatment

The maximum recommended dose is 6 mg Amaryl

per day

A combination therapy of glimepiride plus metformin

or of glimepiride plus insulin may be initiated. In such

a case your doctor will determine the proper doses of

glimepiride, metformin or insulin individually for you

If your weight changes or if you change your lifestyle,

or you are in a stress situation this may require changed

Amaryl doses, therefore inform your doctor

If you feel the effect of your medicine is too weak

or too strong do not change the dose yourself, but

ask your doctor

If you take more Amaryl than you should

If you happen to have taken too much Amaryl or an

additional dose there is a danger of hypoglycaemia

(signs of hypoglycaemia see section 2) and therefore you

should instantly consume enough sugar (e.g. a small bar

of sugar cubes, sweet juice, sweetened tea) and inform

a doctor immediately. When treating hypoglycaemia

due to accidental intake in children, the quantity of

sugar given must be carefully controlled to avoid the

possibility of producing dangerous hyperglycaemia.

Persons in a state of unconsciousness must not be

given food or drink.

Since the state of hypoglycaemia may last for some

time it is very important that the patient is carefully

monitored until there is no more danger. Admission

into hospital may be necessary, also as a measure of

precaution. Show the doctor the package or remaining

tablets, so the doctor knows what has been taken.

Severe cases of hypoglycaemia accompanied by loss of

consciousness and severe neurological failure are cases

of medical emergency requiring immediate medical

treatment and admission into hospital. It should be

ensured that there is always a pre-informed person

that can call a doctor in case of emergency.

If you forget to take Amaryl

If you forget to take a dose, do not take a double dose

to make up for forgotten doses.

If you stop taking Amaryl

If you interrupt or stop the treatment you should be

aware that the desired blood sugar lowering effect is

not achieved or that the disease will deteriorate again.

Keep taking Amaryl until your doctor tells you to stop.

If you have any further questions on the use of this

medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects,

although not everybody gets them.

Tell your doctor immediately if you experience

any of the following symptoms:

Allergic reactions (including inflammation of blood

vessels, often with skin rash) which may develop into

serious reactions with difficulty in breathing, fall in

blood pressure and sometimes progressing to shock

Abnormal liver function including yellowing of the

skin and eyes (jaundice), problems with the bile flow

(cholestasis), inflammation of the liver (hepatitis)

or liver failure

Allergy (hypersensitivity) of the skin such as itching,

rash, hives and increased sensitivity to sun. Some mild

allergic reactions may develop into serious reactions

Severe hypoglycaemia including loss of consciousness,

seizures or coma

Some patients experienced the following side effects

whilst taking Amaryl:

Rare side effects (may affect up to 1 in 1,000 people)

Lower blood sugar than normal (hypoglycaemia) (See

Section 2 - Take special care with Amaryl)

Decrease in the number of blood cells:

Blood platelets (which increases risk of bleeding

or bruising)

White blood cells (which makes infections more

likely)

Red blood cells (which can make the skin pale and

cause weakness or breathlessness)

These problems generally get better after you stop

taking Amaryl

Weight gain

Hair loss

Very rare side effects (may affect up to 1 in 10,000

people)

Allergic reactions (including inflammation of blood

vessels, often with skin rash) which may develop

into serious reactions with difficulty in breathing,

fall in blood pressure and sometimes progressing

to shock. If you experience any of these symptoms,

tell your doctor immediately

Abnormal liver function including yellowing of the

skin and eyes (jaundice), impairment of the bile flow

(cholestasis), inflammation of the liver (hepatitis) or

liver failure. If you experience any of these symptoms,

tell your doctor immediately

Feeling or being sick, diarrhoea, feeling full or bloated,

and abdominal pain

Decrease in the amount of sodium level in your

blood (shown by blood tests)

Changes in your sense of taste

Not known, frequency cannot be estimated from

the available data

Allergy (hypersensitivity) of the skin may occur such

as itching, rash, hives and increased sensitivity to sun.

Some mild allergic reactions may develop into serious

reactions with swallowing or breathing problems,

swelling of your lips, throat or tongue. Therefore

in the event of one of these side effects, tell your

doctor immediately

Allergic reactions with sulfonylureas, sulfonamides,

or related drugs may occur

Problems with your sight may occur when beginning

treatment with Amaryl. This is due to changes in

blood sugar levels and should soon improve

Increased liver enzymes

Severe unusual bleeding or bruising under the skin

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: +353 1 6764971; Fax: +353 1 6762517,

Website: www.hpra.ie, e-mail: medsafety@hpra.ie.

By reporting side effects you can help provide more

information on the safety of this medicine.

Summary of Product Characteristics

1 NAME OF THE MEDICINAL PRODUCT

Amaryl 3 mg tablet

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains 3 mg glimepiride.

Excipients: also contains 137.0 mg lactose monohydrate per tablet.

For the full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Tablet

The tablets are pale yellow, oblong and scored on both sides.

The tablet can be divided into equal doses.

4 CLINICAL PARTICULARS

4.1 Therapeutic Indications

Amaryl

is indicated for the treatment

of type 2 diabetes mellitus,

when diet,

physical

exercise and weight

reduction

alone are not adequate.

4.2 Posology and method of administration

For oral administration

The basis for successful treatment of diabetes is a good diet, regular physical activity, as well as routine checks of

blood and urine. Tablets or insulin cannot compensate if the patient does not keep to the recommended diet.

Posology

Dose is determined by the results of blood and urinary glucose determinations.

The starting dose is 1 mg glimepiride per day. If good control is achieved this dose should be used for maintenance

therapy.

For the different dose regimens appropriate strengths are available.

If control is unsatisfactory the dose should be increased, based on the glycaemic control, in a stepwise manner with an

interval of about 1 to 2 weeks between each step, to 2, 3 or 4 mg glimepiride per day.

A dose of more than 4 mg glimepiride per day gives better results only in exceptional cases. The maximum

recommended dose is 6 mg glimepiride per day.

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In patients not adequately controlled with the maximum daily dose of metformin, concomitant glimepiride therapy can

be initiated.

While maintaining the metformin dose, the glimepiride therapy is started with a low dose, and is then titrated up

depending on the desired level of metabolic control up to the maximum daily dose. The combination therapy should be

initiated under close medical supervision.

In patients not adequately controlled with the maximum daily dose of Amaryl, concomitant insulin therapy can be

initiated if necessary. While maintaining the glimepiride dose, insulin treatment is started at low dose and titrated up

depending on the desired level of metabolic control. The combination therapy should be initiated under close medical

supervision.

Normally a single daily dose of glimepiride is sufficient. It is recommended that this dose be taken shortly before or

during a substantial breakfast or

if none is taken

shortly before or during the first main meal.

If a dose is forgotten, this should not be corrected by increasing the next dose.

If a patient has a hypoglycaemic reaction on 1 mg glimepiride daily, this indicates that they can be controlled by diet

alone.

In the course of treatment, as an improvement in control of diabetes is associated with higher insulin sensitivity,

glimepiride requirements may fall. To avoid hypoglycaemia timely dose reduction or cessation of therapy must

therefore be considered. Change in dose may also be necessary, if there are changes in weight or life style of the

patient, or other factors that increase the risk of hypo

or hyperglycaemia.

Switch over from other oral hypoglycaemic agents to Amaryl

A switch over from other oral hypoglycaemic agents to Amaryl can generally be done. For the switch over to Amaryl

the strength and the half

life of the previous medicinal product has to be taken into account. In some cases, especially

in antidiabetics with a long half

life (e.g. chlorpropamide), a wash out period of a few days is advisable in order to

minimise the risk of hypoglycaemic reactions due to the additive effect.

The recommended starting dose is 1 mg glimepiride per day. Based on the response the glimepiride dose may be

increased stepwise, as indicated earlier.

Switch over from Insulin to Amaryl

In exceptional cases, where type 2 diabetic patients are regulated on insulin, a changeover to Amaryl may be indicated.

The changeover should be undertaken under close medical supervision.

Special Populations

Patients with renal or hepatic impairment

See section 4.3.

Paediatric population

There are no data available on the use of glimepiride in patients under 8 years of age. For children aged 8 to 17 years,

there are limited data on glimepiride as monotherapy (see sections 5.1 and 5.2).

The available data on safety and efficacy are insufficient in the paediatric population and therefore such use is not

recommended.

Method of administration

Tablets should be swallowed without chewing with some liquid.

4.3 Contraindications

Glimepiride is contraindicated in patients with the following conditions:

hypersensitivity to glimepiride, other sulfonylureas or sulfonamides or to any of the excipients listed in section

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Diabetes mellitus type 1

diabetic coma,

ketoacidosis,

severe renal or hepatic function disorders. In case of severe renal or hepatic function disorders, a change over to

insulin is required.

4.4 Special warnings and precautions for use

Amaryl must be taken shortly before or during a meal.

When meals are taken at irregular hours or skipped altogether, treatment with Amaryl may lead to hypoglycaemia.

Possible symptoms of hypoglycaemia include: headache, ravenous hunger, nausea, vomiting, lassitude, sleepiness,

disordered sleep, restlessness, aggressiveness, impaired concentration, alertness and reaction time, depression,

confusion, speech and visual disorders, aphasia, tremor, paresis, sensory disturbances, dizziness, helplessness, loss of

self

control, delirium, cerebral convulsions, somnolence and loss of consciousness up to and including coma, shallow

respiration and bradycardia. In addition, signs of adrenergic counter

regulation may be present such as sweating,

clammy skin, anxiety, tachycardia, hypertension, palpitations, angina pectoris and cardiac arrhythmias.

The clinical picture of a severe hypoglycaemic attack may resemble that of a stroke.

Symptoms can almost always be promptly controlled by immediate intake carbohydrates (sugar). Artificial sweeteners

have no effect.

It is known from other sulfonylureas that, despite initially successful countermeasures, hypoglycaemia may recur.

Severe hypoglycaemia or prolonged hypoglycaemia, only temporarily controlled by the usual amounts of sugar, require

immediate medical treatment and occasionally hospitalisation.

Factors favouring hypoglycaemia include:

unwillingness or (more commonly in older patients) incapacity of the patient to cooperate,

undernutrition, irregular mealtimes or missed meals or periods of fasting,

alterations in diet,

imbalance between physical exertion and carbohydrate intake,

consumption of alcohol, especially in combination with skipped meals,

impaired renal function,

serious liver dysfunction,

overdose with Amaryl,

certain uncompensated disorders of the endocrine system affecting carbohydrate metabolism or counter

regulation

of hypoglycaemia (as for example in certain disorders of thyroid function and in anterior pituitary or adrenocortical

insufficiency),

concurrent administration of certain other medicinal products (see section 4.5).

Treatment with Amaryl requires regular monitoring of glucose levels in blood and urine. In addition determination of

the proportion of glycosylated haemoglobin is recommended.

Regular hepatic and haematological monitoring (especially leucocytes and thrombocytes) are required during treatment

with Amaryl.

In stress

situations (e.g. accidents, acute operations, infections with fever, etc.) a temporary switch to insulin may be

indicated.

No experience has been gained concerning the use of Amaryl in patients with severe impairment of liver function or

dialysis patients. In patients with severe impairment of renal or liver function change over to insulin is indicated.

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Treatment of patients with G6PD

deficiency with sulfonylurea agents can lead to hemolytic anaemia. Since

glimepiride belongs to the class of sulfonylurea agents, caution should be used in patients with G6PD

deficiency and a

sulfonylurea alternative should be considered.

Amaryl contains lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase

deficiency or glucose

galactose malabsorption should not take this medicine.

4.5 Interaction with other medicinal products and other forms of interaction

If glimepiride is taken simultaneously with certain other medicinal products, both undesired increases and decreases in

the hypoglycaemic action of glimepiride can occur. For this reason, other medicinal products should only be taken with

the knowledge (or at the prescription) of the doctor.

Glimepiride is metabolized by cytochrome P450 2C9 (CYP2C9). Its metabolism is known to be influenced by

concomitant administration of CYP2C9 inducers (e.g. rifampicin) or inhibitors (e.g. fluconazole).

Results from an in vivo interaction study reported in literature show that glimepiride AUC is increased approximately

fold by fluconazole, one of the most potent CYP2C9 inhibitors.

Based on the experience with glimepiride and with other sulfonylureas the following interactions have to be mentioned.

Potentiation of the blood

glucose

lowering effect and, thus, in some instances hypoglycaemia may occur when one of

the following medicinal products is taken, for example:

- phenylbutazone, azapropazone and oxyfenbutazone,

- insulin and oral antidiabetic products, such as metformin,

- salicylates and p

amino

salicylic acid,

- anabolic steroids and male sex hormones,

- chloramphenicol, certain long acting sulfonamides, tetracyclines, quinolone antibiotics and clarithromycin,

- coumarin anticoagulants,

- fenfluramine,

- disopyramide,

- fibrates,

- ACE inhibitors,

- fluoxetine, MAO

inhibitors,

- allopurinol, probenecid, sulfinpyrazone,

- sympatholytics,

- cyclophosphamide, trophosphamide and iphosphamides,

- miconazole, fluconazole,

- pentoxifylline (high dose parenteral),

- tritoqualine.

Weakening of the blood

glucose

lowering effect and, thus raised blood glucose levels may occur when one of the

following medicinal products is taken, for example:

- oestrogens and progestogens,

- saluretics, thiazide diuretics,

- thyroid stimulating agents, glucocorticoids,

- phenothiazine derivatives, chlorpromazine,

- adrenaline and sympathicomimetics,

- nicotinic acid (high doses) and nicotinic acid derivatives,

- laxatives (long term use),

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- phenytoin, diazoxide,

- glucagon, barbiturates and rifampicin,

- acetazolamide.

antagonists, beta

blockers, clonidine and reserpine may lead to either potentiation or weakening of the

blood

glucose

lowering effect.

Under the influence of sympatholytic medicinal products such as beta

blockers, clonidine, guanethidine and reserpine,

the signs of adrenergic counter

regulation to hypoglycaemia may be reduced or absent.

Alcohol intake may potentiate or weaken the hypoglycaemic action of glimepiride in an unpredictable fashion.

Glimepiride may either potentiate or weaken the effects of coumarin derivatives.

Colesevelam binds to glimepiride and reduces glimepiride absorption from the gastro-intestinal tract. No interaction

was observed when glimepiride was taken at least for 4 hours before colesevelam. Therefore, glimepiride should be

administered at least 4 hours prior to colesevelam.

4.6 Fertility, pregnancy and lactation

Pregnancy

Risk related to the diabetes

Abnormal blood glucose levels during pregnancy are associated with a higher incidence of congenital abnormalities

and perinatal mortality. So the blood glucose level must be closely monitored during pregnancy in order to avoid the

teratogenic risk. The use of insulin is required under such circumstances. Patients who consider pregnancy should

inform their physician.

Risk related to glimepiride

There are no adequate data from the use of glimepiride in pregnant women. Animal studies have shown reproductive

toxicity which likely was related to the pharmacologic action (hypoglycaemia) of glimepiride (see section 5.3).

Consequently, glimepiride should not be used during the whole pregnancy.

In case of treatment by glimepiride, if the patient plans to become pregnant or if a pregnancy is discovered, the

treatment should be switched as soon as possible to insulin therapy.

Lactation

The excretion in human milk is unknown. Glimepiride is excreted in rat milk. As other sulfonylureas are excreted in

human milk and because there is a risk of hypoglycaemia in nursing infants, breast

feeding is advised against during

treatment with glimepiride.

Fertility

No data on fertility is available.

4.7 Effects on ability to drive and use machines

No studies on the effects on the ability to drive and use machines have been performed.

The patient's ability to concentrate and react may be impaired as a result of hypoglycaemia or hyperglycaemia or, for

example,

as a result of visual impairment.

This may constitute a risk in situations where these abilities are of special

importance (e.g. driving a car or operating machinery).

Patients should be advised to take precautions to avoid hypoglycaemia whilst driving. This is particularly important in

those who have reduced or absent awareness of the warning symptoms of hypoglycaemia or have frequent episodes of

hypoglycaemia. It should be considered whether it is advisable to drive or operate machinery in these circumstances.

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4.8 Undesirable effects

The following adverse reactions from clinical investigations were based on experience with Amaryl and other

sulfonylureas, were listed below by system organ class and in order of decreasing incidence (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).

Blood and lymphatic system disorders

Rare: thrombocytopenia, leukopenia, granulocytopenia, agranulocytosis, erythropenia, haemolytic anaemia and

pancytopenia, which are in general reversible upon discontinuation of medication. Not known: severe

thrombocytopenia with platelet count less than 10,000/µl

and thrombocytopenic purpura.

Immune system disorders

Very rare: leukocytoclastic vasculitis, mild hypersensitivity reactions that may develop into serious reactions with

dyspnoea, fall in blood pressure and sometimes shock.

Not known: cross

allergenicity with sulfonylureas, sulfonamides or related substances is possible.

Metabolism and nutrition disorders

Rare: hypoglycaemia.

These hypoglycaemic reactions mostly occur immediately, may be severe and are not always easy to correct. The

occurrence of such reactions depends, as with other hypoglycaemic therapies, on individual factors such as dietary

habits and dose (see further under section 4.4).

Eye disorders

Not known: visual disturbances, transient, may occur especially on initiation of treatment, due to changes in blood

glucose levels.

Gastrointestinal disorders

Very rare: nausea, vomiting, diarrhoea, abdominal distension, abdominal discomfort and abdominal pain, which

seldom lead to discontinuation of therapy.

Rare: dysgeusia.

Hepato-biliary disorders

Not known: hepatic enzymes increased.

Very rare: hepatic function abnormal (e.g. with cholestasis and jaundice), hepatitis and hepatic failure.

Skin and subcutaneous tissue disorders

Not known: hypersensitivity reactions of the skin may occur as pruritus, rash, urticaria and photosensitivity.

Rare: alopecia.

Investigations

Very rare: blood sodium decrease.

Rare: weight gain.

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

Symptoms

After ingestion of an overdose hypoglycaemia may occur, lasting from 12 to 72 hours, and may recur after an initial

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recovery. Symptoms may not be present for up to 24 hours after ingestion. In general observation in hospital is

recommended. Nausea, vomiting and epigastric pain may occur. The hypoglycaemia may in general be accompanied

by neurological symptoms like restlessness, tremor, visual disturbances, co

ordination problems, sleepiness, coma and

convulsions.

Management

Treatment primarily consists of preventing absorption by inducing vomiting and then drinking water or lemonade with

activated charcoal (adsorbent) and sodium

sulphate (laxative). If large quantities have been ingested, gastric lavage is

indicated, followed by activated charcoal and sodium

sulphate. In case of (severe) overdose hospitalisation in an

intensive care department is indicated. Start the administration of glucose as soon as possible, if necessary by a bolus

intravenous injection of 50 ml of a 50% solution, followed by an infusion of a 10% solution with strict monitoring of

blood glucose. Further treatment should be symptomatic.

In particular when treating hypoglycaemia due to accidental intake of Amaryl in infants and young children, the dose of

glucose given must be carefully controlled to avoid the possibility of producing dangerous hyperglycaemia. Blood

glucose should be closely monitored.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Blood glucose lowering drugs, excl. insulins: Sulfonylureas. ATC Code: A10B B12.

Glimepiride is an orally active hypoglycaemic substance belonging to the sulfonylurea group. It may be used in

insulin dependent diabetes mellitus.

Glimepiride acts mainly by stimulating insulin release from pancreatic beta cells.

As with other sulfonylureas this effect is based on an increase of responsiveness of the pancreatic beta cells to the

physiological glucose stimulus. In addition, glimepiride seems to have pronounced extrapancreatic effects also

postulated for other sulfonylureas.

Insulin release

Sulfonylureas regulate insulin secretion by closing the ATP

sensitive potassium channel in the beta cell membrane.

Closing the potassium channel induces depolarisation of the beta cell and results

by opening of calcium channels

an increased influx of calcium into the cell.

This leads to insulin release through exocytosis.

Glimepiride binds with a high exchange rate to a beta cell membrane protein which is associated with the

sensitive potassium channel but which is different from the usual sulfonylurea binding site.

Extrapancreatic activity

The extrapancreatic effects are for example an improvement of the sensitivity of the peripheral tissue for insulin and a

decrease of the insulin uptake by the liver.

The uptake of glucose from blood into peripheral muscle and fat tissues occurs via special transport proteins, located in

the cells membrane. The transport of glucose in these tissues is the rate limiting step in the use of glucose. Glimepiride

increases very rapidly the number of active glucose transport molecules in the plasma membranes of muscle and fat

cells, resulting in stimulated glucose uptake.

Glimepiride increases the activity of the glycosyl

phosphatidylinositol

specific phospholipase C which may be

correlated with the drug

induced lipogenesis and glycogenesis in isolated fat and muscle cells.

Glimepiride inhibits the glucose production in the liver by increasing the intracellular concentration of

fructose

bisphosphate, which in its turn inhibits the gluconeogenesis.

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General

In healthy persons, the minimum effective oral dose is approximately 0.6 mg. The effect of glimepiride is

dose

dependent and reproducible. The physiological response to acute physical exercise, reduction of insulin secretion,

is still present under glimepiride.

There was no significant difference in effect regardless of whether the medicinal product was given 30 minutes or

immediately before a meal. In diabetic patients, good metabolic control over 24 hours can be achieved with a single

daily dose.

Although the hydroxy metabolite of glimepiride caused a small but significant decrease in serum glucose in healthy

persons, it accounts for only a minor part of the total drug effect.

Combination therapy with metformin

Improved metabolic control for concomitant glimepiride therapy compared to metformin alone in patients not

adequately controlled with the maximum dose of metformin has been shown in one study.

Combination therapy with insulin

Data for combination therapy with insulin are limited. In patients not adequately controlled with the maximum dose of

glimepiride, concomitant insulin therapy can be initiated. In two studies, the combination achieved the same

improvement in metabolic control as insulin alone; however, a lower average dose of insulin was required in

combination therapy.

Special populations

Paediatric population

An active controlled clinical trial (glimepiride up to 8 mg daily or metformin up to 2,000 mg daily) of 24 weeks

duration was performed in 285 children (8-17 years of age) with type 2 diabetes.

Both glimepiride and metformin exhibited a significant decrease from baseline in HbA

(glimepiride

0.95 (se 0.41);

metformin

1.39 (se 0.40). However, glimepiride did not achieve the criteria of non

inferiority to metformin in mean

change from baseline of HbA

The difference between treatments was 0.44% in favour of metformin. The upper limit

(1.05) of the 95% confidence interval for the difference was not below the 0.3% non-inferiority margin.

Following glimepiride treatment, there were no new safety concerns noted in children compared to adult patients with

type 2 diabetes mellitus. No long

term efficacy and safety data are available in paediatric patients.

5.2 Pharmacokinetic properties

Absorption

The bioavailability of glimepiride after oral administration is complete. Food intake has no relevant influence on

absorption, only absorption rate is slightly diminished. Maximum serum concentrations (C

) are reached approx.

2.5 hours after oral intake (mean 0.3 µg/ml during multiple dosing of 4 mg daily) and there is a linear relationship

between dose and both C

and AUC (area under the time/concentration curve).

Distribution

Glimepiride has a very low distribution volume (approx. 8.8 litres) which is roughly equal to the albumin distribution

space, high protein binding (>99%), and a low clearance (approx. 48 ml/min).

In animals, glimepiride is excreted in milk. Glimepiride is transferred to the placenta. Passage of the blood brain barrier

is low.

Biotransformation and elimination

Mean dominant serum half

life, which is of relevance for the serum concentrations under multiple-dose conditions, is

about 5 to 8 hours. After high doses, slightly longer half

lives were noted.

After a single dose of radiolabelled glimepiride, 58% of the radioactivity was recovered in the urine, and 35% in the

faeces. No unchanged substance was detected in the urine. Two metabolites

most probably resulting from hepatic

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metabolism (major enzyme is CYP2C9)

were identified both in urine and faeces: the hydroxy derivative and the

carboxy derivative. After oral administration of glimepiride, the terminal half-lives of these metabolites were 3 to 6 and

5 to 6 hours respectively.

Comparison of single and multiple once

daily dosing revealed no significant differences in pharmacokinetics, and the

intraindividual variability was very low. There was no relevant accumulation.

Special populations

Pharmacokinetics were similar in males and females, as well as in young and elderly (above 65 years) patients. In

patients with low creatinine clearance, there was a tendency for glimepiride clearance to increase and for average serum

concentrations to decrease, most probably resulting from a more rapid elimination because of lower protein binding.

Renal elimination of the two metabolites was impaired. Overall no additional risk of accumulation is to be assumed in

such patients.

Pharmacokinetics in five non

diabetic patients after bile duct surgery were similar to those in healthy persons.

Paediatric population

A fed study investigating the pharmacokinetics, safety, and tolerability of a 1 mg single dose of glimepiride in 30

paediatric patients (4 children aged 10-12 years and 26 children aged 12-17 years) with type 2 diabetes showed mean

(0-last)

, Cmax and t

similar to that previously observed in adults.

5.3 Preclinical safety data

Preclinical effects observed occurred at exposures sufficiently in excess of the maximum human exposure as to indicate

little relevance to clinical

use,

or were due to the pharmacodynamic action (hypoglycaemia) of the compound.

This

finding is based on conventional

safety pharmacology,

repeated dose toxicity,

genotoxicity,

carcinogenicity,

reproduction toxicity studies. In the latter (covering embryotoxicity, teratogenicity and developmental toxicity), adverse

effects observed were considered to be secondary to the hypoglycaemic effects induced by the compound in dams and

in offspring.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Lactose monohydrate

Sodium starch glycollate (type A)

Magnesium stearate

Microcrystalline cellulose

Povidone 25000

Yellow iron oxide (E172)

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

3 years.

6.4 Special precautions for storage

Do not store above 30°C.

Store in the original package in order to protect from moisture.

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6.5 Nature and contents of container

PVC/Aluminium blisters.

14, 20, 28, 30, 50, 60, 90, 112, 120, 280 and 300 tablets.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

No special requirements

7 MARKETING AUTHORISATION HOLDER

sanofi-aventis Ireland Limited, T/A SANOFI

Citywest Business Campus

Dublin 24

Ireland

8 MARKETING AUTHORISATION NUMBER

PA 540/28/3

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorization: 29 November 1996

Date of last renewal: 20 February 2010

10 DATE OF REVISION OF THE TEXT

June 2017

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