Amaryl 1

Patient Information Leaflet

AMARYL 1, 1 mg, tablets
AMARYL 2, 2 mg, tablets
AMARYL 3, 3 mg, tablets
AMARYL 4, 4 mg, tablets
Glimepiride
Please read this leaflet carefully before using the medicine, as it contains
important information for the patient.

• Keep this leaflet so that you can read it again if necessary.
• If you have any questions, please consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If you experience any adverse effects, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of contents

1. What Amaryl is and what it is used for
2. Important information before taking 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 oral antidiabetic medicine that lowers blood glucose (sugar) levels. It belongs to a group of antidiabetic medicines called sulfonylureas. Amaryl works by increasing the amount of insulin released by the pancreas. Insulin reduces blood glucose levels.

What Amaryl is used for:

• Amaryl is used to treat type 2 diabetes when blood glucose levels cannot be controlled by diet, physical exercise, and weight reduction alone.

2. Important information before using Amaryl

When not to use Amaryl:

• if the patient is allergic to glimepiride or other sulfonylurea drugs (medicines used to lower blood glucose levels, e.g. glibenclamide) or sulfonamides (medicines used for bacterial infections, e.g. sulfamethoxazole), or to any of the other ingredients of this medicine (listed in section 6),
• if the patient has insulin-dependent diabetes (type 1 diabetes),
• if the patient has diabetic ketoacidosis (a complication of diabetes causing increased acid levels in the body; symptoms may include fatigue, nausea, frequent urination, and muscle stiffness),
• if the patient has diabetic coma,
• if the patient has severe kidney function impairment,
• if the patient has severe liver function impairment.

Amaryl must not be used if any of the above conditions are present.
In case of any doubts, consult a doctor or pharmacist before using Amaryl.

Warnings and precautions
Before starting treatment with Amaryl, discuss this with your doctor or pharmacist.
Consult your doctor or pharmacist before using Amaryl if:

• the patient has experienced trauma, surgery, infection with fever, or any other stressful condition; inform your doctor, as temporary changes in treatment may be necessary,
• the patient has impaired liver or kidney function.

In case of any doubts, consult a doctor or pharmacist before using Amaryl.
In patients with glucose-6-phosphate dehydrogenase deficiency, reduced hemoglobin levels and red blood cell destruction (hemolytic anemia) may occur.
Information on the use of Amaryl in patients under 18 years of age is limited. Use in this patient group is not recommended.

Important information about hypoglycemia (low blood sugar)
While using Amaryl, the patient may experience hypoglycemia (low blood sugar). Below are additional details about hypoglycemia, its symptoms, and treatment.

The following factors may increase the risk of hypoglycemia:

• reluctance (more common in elderly patients) or inability to cooperate,
• malnutrition, irregular meals, or skipping meals,
• changes in diet,
• taking a higher dose of Amaryl than necessary (overdose),
• kidney function impairment,
• severe liver function impairment,
• certain conditions caused by hormonal disorders (e.g. thyroid, pituitary, or adrenal cortex dysfunction),
• alcohol consumption, especially when combined with skipped meals,
• concomitant use of certain other medicines (see Amaryl and other medicines),
• increased physical exertion compared to usual, especially if meals are insufficient or contain fewer carbohydrates than usual,
• treatment with Amaryl without any medical indication.

Symptoms of hypoglycemia include:

• intense hunger, headache, nausea, vomiting, fatigue, drowsiness, sleep disturbances, restlessness, aggression, difficulty concentrating, altered alertness and reaction time, depression, disorientation, speech and vision disturbances, aphasia (impaired ability to speak), tremors, weakness, sensory disturbances, dizziness, and feelings of helplessness.
• sweating, moist skin, anxiety, rapid heartbeat, increased blood pressure, palpitations, sudden severe chest pain radiating to adjacent body parts (angina pectoris or irregular heart rhythm) may also occur.

If blood glucose levels continue to decrease, symptoms may progress to confusion (delirium), seizures, loss of self-control, shallow breathing, slowed heart rate, and may lead to loss of consciousness or coma.
Low blood sugar may produce symptoms similar to those of a stroke.

Treatment of hypoglycemia:
In many cases, symptoms of low blood glucose resolve quickly after consuming certain types of sugar, such as sugar cubes, sweet fruit juice, or sweetened tea.
Always carry sugar (e.g. sugar cubes) with you.
Note that artificial sweeteners are not effective in treating hypoglycemia. Contact a doctor or go to hospital if symptoms do not improve after consuming sugar.

Laboratory tests
Regularly monitor blood or urine glucose levels. Your doctor may also perform regular blood tests to assess liver function and blood cell counts.

Amaryl and other medicines
Inform your doctor or pharmacist about all medicines currently or recently taken, as well as any medicines you plan to take.
Your doctor may adjust the dose of Amaryl if you are taking other medicines that may weaken or enhance Amaryl’s effect on blood glucose levels.

The following medicines may enhance the effect of Amaryl on blood glucose levels, potentially leading to hypoglycemia (low blood sugar):

• other antidiabetic medicines (e.g. insulin or metformin),
• medicines used to treat pain and inflammation (phenylbutazone, azapropazone, oxyphenbutazone, drugs with acetylsalicylic acid-like action),
• medicines used to treat urinary tract infections (including certain long-acting sulfonamides),
• medicines used to treat bacterial and fungal infections (tetracyclines, chloramphenicol, fluconazole, miconazole, quinolone antibiotics, clarithromycin),
• anticoagulants (coumarin derivatives, e.g. warfarin),
• anabolic steroids used to increase muscle mass,
• medicines used for androgen replacement therapy,
• antidepressants (fluoxetine, MAO inhibitors),
• lipid-lowering medicines (fibrates),
• antihypertensive medicines (ACE inhibitors),
• antiarrhythmic medicines used to prevent heart rhythm disorders (disopyramide),
• medicines used to treat gout (allopurinol, probenecid, sulfinpyrazone),
• anticancer medicines (cyclophosphamide, ifosfamide, trofosfamide),
• weight-loss medicines (fenfluramine),
• medicines used to improve circulation, administered intravenously in high doses (pentoxifylline),
• medicines used to treat nasal allergies, e.g. hay fever (tritoqualine),
• medicines known as sympatholytics, used to treat high blood pressure, heart failure, or symptoms of prostate disease,
• fenyramidol,
• guanethidine.

The following medicines may reduce the effect of Amaryl on blood glucose levels, potentially leading to hyperglycemia (high blood sugar):

• medicines containing female sex hormones (estrogens, progestogens),
• diuretics (water pills), saluretics,
• thyroid-stimulating medicines (e.g. levothyroxine),
• medicines used to treat allergies and inflammation (glucocorticosteroids),
• medicines used to treat severe psychiatric disorders (chlorpromazine and phenothiazine derivatives),
• medicines stimulating the heart, used in asthma, nasal congestion, cough, colds, weight loss, or life-threatening emergencies (adrenaline and sympathomimetics),
• medicines used to treat high cholesterol (nicotinic acid and its derivatives),
• long-term use of laxatives for constipation,
• antiepileptic medicines (phenytoin),
• medicines used to treat anxiety and sleep disorders (barbiturates),
• medicines used to treat increased intraocular pressure (acetazolamide),
• medicines used to treat high blood pressure and low blood sugar (diazoxide),
• medicines used to treat infections, tuberculosis (rifampicin),
• medicines used to treat life-threateningly low blood sugar (glucagon).

The following medicines may either increase or decrease the effect of Amaryl on blood glucose levels:

• medicines used to treat stomach ulcers (H-\receptor antagonists),
• medicines used to treat high blood pressure or heart failure, e.g. beta-\blockers, clonidine, and reserpine. These medicines may also mask the symptoms of hypoglycemia; therefore, caution is required when using them.

Amaryl may increase or decrease the effect of the following medicines:

• anticoagulants (coumarin derivatives, e.g. warfarin).

Colesevelam (a bile acid sequestrant) binds to Amaryl and reduces its absorption from the gastrointestinal tract. This interaction has not been observed when Amaryl is administered at least 4 hours before colesevelam. Therefore, Amaryl should be taken at least 4 hours before colesevelam.

Amaryl with food, drink, and alcohol
Alcohol consumption may unpredictably enhance or weaken the effect of Amaryl.

Pregnancy, breastfeeding, and fertility
Amaryl must not be used during pregnancy or breastfeeding. If the patient is pregnant or breastfeeding, suspects she may be pregnant, or plans to become pregnant, she should consult her doctor or pharmacist before using this medicine.
Amaryl may pass into breast milk.
There is no data available on the effect of Amaryl on fertility.

Driving and operating machinery
The ability to concentrate or react quickly may be impaired due to low blood glucose (hypoglycemia) or high blood glucose (hyperglycemia). Be aware that this may pose a risk to yourself or others (e.g. when driving or operating machinery). Patients should consult their doctor whether they can drive or operate machinery if:

• they frequently experience hypoglycemia,
• warning symptoms of hypoglycemia are reduced or absent.

Amaryl contains lactose
If the patient has previously been diagnosed with an intolerance to certain sugars, they should consult their doctor before taking this medicine.

Amaryl contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e. it is considered "sodium-free".

3. How to use Amaryl

This medicine should always be taken exactly as directed by the physician. In case of doubt, consult
your doctor or pharmacist.
Administration of the medicine
The medicine should be taken orally, just before or during the first meal of the day (usually
breakfast) or another main meal. The medicine should be taken in accordance with the physician's instructions.
If you are taking Amaryl, you must follow the recommended diet.
The tablet should be swallowed whole, without chewing or crushing, with a glass of liquid.

Recommended dose
The dose of Amaryl depends on the patient's condition and the results of blood and urine glucose tests,
and is determined by the physician. Do not take more tablets than prescribed by your doctor.

• The initial dose is one Amaryl tablet - 1 mg once daily.
• Your doctor may increase the dose after 1–2 weeks of treatment, if necessary.
• The maximum recommended dose is 6 mg of Amaryl per day.
• Your doctor may recommend concomitant use of glimepiride with metformin or glimepiride with insulin. In such cases, your doctor will prescribe appropriate, individually adjusted doses of glimepiride with metformin or insulin.
• If there are changes in body weight, lifestyle, or if the patient is under stress, inform your doctor so that the dose of the medicine can be adjusted if necessary.
• If the patient feels that the effect of the medicine is too weak or too strong, do not change the dose independently; contact your doctor.

Taking more Amaryl than prescribed
Taking too many Amaryl tablets or an additional dose is dangerous for the patient, as it may cause hypoglycaemia (for symptoms of hypoglycaemia, see section 2. Warnings and precautions). In such a case, consume an adequate amount of sugar immediately (e.g. sugar cubes, sweetened fruit juice, sweetened tea) and contact your doctor as soon as possible.
In children who have accidentally taken the medicine, the amount of sugar given must be carefully controlled to avoid the risk of hyperglycaemia. Do not give food or drink to unconscious individuals.
In cases of prolonged hypoglycaemia, it is very important that the patient remains under medical supervision until the danger has passed. Hospitalization may be necessary as a precaution. Show the doctor the packaging or remaining tablets so that he or she knows which medicine has been taken.
Severe cases of hypoglycaemia with loss of consciousness and severe neurological disturbances require immediate medical attention, usually in a hospital. Ensure that someone nearby, previously informed of this possibility, is available to call a doctor in an emergency.

If you miss a dose of Amaryl
Do not take a double dose to make up for a missed dose.

Stopping Amaryl
After stopping Amaryl, the achieved reduction in blood glucose levels will not be maintained and the disease may worsen. Continue taking Amaryl for as long as your doctor recommends.
If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
You should contact your doctor immediately if any of the following symptoms occur:

• Allergic reactions (including inflammation of blood vessels, often with a rash), which may develop into severe reactions with breathing difficulties, low blood pressure, or even shock.
• Liver function disorders, including yellowing of the skin and eyes (jaundice), impaired bile flow (cholestasis), liver inflammation or liver failure.
• Skin allergy (hypersensitivity), manifesting as itching, rash, urticaria, or photosensitivity. Some mild allergic reactions may progress to severe reactions with difficulty swallowing or breathing, swelling of the lips, throat, or tongue.
• Severe hypoglycaemia, loss of consciousness, seizures, or coma.

The following adverse reactions have been reported in some patients treated with Amaryl:
Uncommon (may occur in no more than 1 in 1,000 patients)

• Lower than normal blood glucose levels (hypoglycaemia, see section 2. Important information before taking Amaryl, subsection Warnings and precautions).
• Decreased numbers of blood cells, such as:
  • Platelets, increasing the risk of bleeding or bruising (thrombocytopenia),
  • White blood cells, increasing the likelihood of infections (leukopenia, granulocytopenia, agranulocytosis),
  • Red blood cells, which may cause paleness, weakness, or shortness of breath (erythropenia, haemolytic anaemia),
  • Platelets, white and red blood cells, leading to deficiency of these blood components (pancytopenia). These disorders usually resolve after discontinuation of Amaryl.

Very rare (may occur in no more than 1 in 10,000 patients)

• Allergic reactions (including inflammation of blood vessels, often with a rash), which may develop into severe reactions with breathing difficulties, low blood pressure, or even shock.
• Impaired liver function, including yellowing of the skin and eyes (jaundice), impaired bile flow (cholestasis), liver inflammation or liver failure.
• Nausea, vomiting, diarrhoea, bloating, abdominal discomfort, and abdominal pain.

Frequency not known (frequency cannot be estimated from available data)

• Taste disturbances.
• Hair loss (alopecia).
• Marked decrease in platelet count (below 10,000/microlitre) and cases of thrombocytopenic purpura.
• Visual disturbances, particularly at the beginning of treatment. These are caused by changes in blood glucose levels and symptoms should resolve quickly.
• Increased liver enzyme activity (in blood tests).
• Allergic reactions to sulfonylurea derivatives, sulfonamides, or related drugs may occur.
• Skin allergy (hypersensitivity) with itching, rash, urticaria. Some mild allergic reactions may progress to severe reactions with difficulty swallowing or breathing, swelling of the lips, throat, or tongue.
• The active substance in Amaryl - glimepiride - like all sulfonylurea derivatives, may cause weight gain and hypersensitivity to sulfonylurea derivatives, sulfonamides, or related drugs.
• Decreased sodium levels in blood (in blood tests), allergic vasculitis, photosensitivity.

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions at the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products:
Al. Jerozolimskie 181 C, 02-222 Warsaw.
Tel.: +48 22 4921301, fax: +48 22 4921309, website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorisation holder or its representative in Poland.
Reporting adverse reactions helps provide more information on the safety of the medicine.

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 stated on the blister and carton following:
"Expiry date (EXP):". The expiry date refers to the last day of the stated month.
Do not store above 30°C.
Do not use Amaryl if there are any signs of deterioration.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the package and other information

What Amaryl contains

• The active substance is glimepiride. Each tablet contains 1 mg, 2 mg, 3 mg, or 4 mg of glimepiride, depending on the strength indicated on the blister and carton.
• The other ingredients are: lactose monohydrate, sodium carboxymethyl starch (type A), magnesium stearate, microcrystalline cellulose, povidone 25 000.
• The tablets also contain colouring agents:
  • 1 mg tablets contain iron oxide red (E172),
  • 2 mg tablets contain iron oxide yellow (E172) and indigo carmine lake (E132),
  • 3 mg tablets contain iron oxide yellow (E172),
  • 4 mg tablets contain indigo carmine lake (E132).

What Amaryl looks like and contents of the pack
All strengths of Amaryl tablets are oblong and scored on both sides. The tablets may be divided into two equal doses along the break line.
The tablets differ in colour depending on the strength:

• 1 mg are pink,
• 2 mg are green,
• 3 mg are light yellow,
• 4 mg are light blue.

The pack contains 30 or 120 tablets in blisters, placed in a cardboard carton.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Sanofi-Aventis Deutschland GmbH
Brüningstrasse 50
D-65926 Frankfurt am Main
Germany

Manufacturer
Sanofi S.r.l., Strada Statale 17 Km 22, 67019 Scoppito (AQ), Italy
Sanofi Winthrop Industrie, 30-36 avenue Gustave Eiffel, 37100 Tours, France

For further information, contact the local representative of the Marketing Authorisation Holder in Poland:
Sanofi Sp. z o.o.
ul. Marcina Kasprzaka 6
01-211 Warsaw
tel.: +48 22 280 00 00