Solosa - Package Leaflet

Indications Contraindications Precautions for use Interactions Warnings Dosage and method of use Overdose Unwanted Effects Shelf Life

Active ingredients: Glimepiride

SOLOSA 1 mg tablets
SOLOSA 2 mg tablets
SOLOSA 3 mg tablets
SOLOSA 4 mg tablets

Solosa package inserts are available for pack sizes:
  • SOLOSA 1 mg tablets, SOLOSA 2 mg tablets, SOLOSA 3 mg tablets, SOLOSA 4 mg tablets
  • SOLOSA 6 mg tablets

Why is Solosa used? What is it for?

Solosa is an orally active drug that lowers blood sugar levels. This drug belongs to a group of blood sugar lowering medicines called sulfonylureas. Solosa works by increasing the amount of insulin released by the pancreas. The insulin then lowers blood sugar levels.

What is Solosa used for:

  • Solosa is used to treat a form of diabetes (type 2 diabetes mellitus) when diet, exercise and weight reduction alone are not enough to control blood sugar levels.

Contraindications When Solosa should not be used

Do not take Solosa and tell your doctor if:

  • You are allergic to: glimepiride or other sulfonylureas (medicines used to lower blood sugar levels such as glibenclamide) or sulfonamides (medicines for bacterial infections such as sulfamethoxazole) or any of the other ingredients of this medicine
  • Have insulin dependent diabetes (type 1 diabetes mellitus)
  • You have diabetic ketoacidosis (a complication of diabetes in which acid levels in the body have increased and you may have some of the following signs: fatigue, nausea, frequent urination and muscle soreness)
  • He is in a diabetic coma
  • You suffer from severe kidney disease
  • You suffer from severe liver disease
Do not take this medicine if any of these apply to you. If you are not sure, talk to your doctor or pharmacist before taking Solosa.

Precautions for use What you need to know before taking Solosa

Consult your doctor or pharmacist before taking this medicine if

  • you are recovering from injury, surgery, an infection with fever or other forms of stress tell your doctor as your treatment may need to be changed temporarily
  • suffer from severe liver or kidney disease

If you are not sure if any of these apply to you, consult your doctor or pharmacist before taking Solosa

Low hemoglobin levels and breakdown of red blood cells (haemolytic anemia) can occur in patients who do not have glucose-6-phosphate dehydrogenase enzyme.

There is limited information available on the use of Solosa in people under the age of 18.

Therefore, use in these patients is not recommended.

Important information about hypoglycaemia (low blood sugar levels)

When you take Solosa, you may have hypoglycaemia (low blood sugar levels). Read below for more information on hypoglycemia, its symptoms and its treatment.

The following factors can increase the risk of having hypoglycemia:

  • Is not eating enough, eating irregularly, has missed or delayed meals, or is fasting
  • He changed his diet
  • He took more Solosa than necessary
  • Has decreased kidney function
  • You suffer from severe liver disease
  • You suffer from particular hormone-induced disorders (thyroid, pituitary or adrenal cortex disorders)
  • Drink alcoholic beverages (particularly if you miss a meal)
  • You are taking some other medicines (see "Other medicines and Solosa" below).
  • If you are exercising more and not eating enough or eating foods that contain fewer carbohydrates than usual

Warning symptoms of hypoglycemia include:

  • Hunger pangs, headaches, nausea, vomiting, sluggishness, drowsiness, sleep disturbances, restlessness, aggression, difficulty concentrating, decreased alertness, decreased ability to react, depression, confusion, and speech and speech disorders vision, slurred speech, tremor, partial paralysis, sensory disturbances, dizziness, weakness.
  • The following symptoms may also occur: sweating, clammy skin, anxiety, rapid heartbeat, high blood pressure, palpitations, sudden chest pain that can spread to nearby areas (angina pectoris and cardiac arrhythmias)

If your sugar levels continue to drop you may suffer from considerable confusion (delirium), develop seizures, loss of self-control, your breathing may become weak and your heartbeat may slow down, and you may lose consciousness. The clinical picture of sugar levels in very small blood can resemble that of a stroke.

Treatment of hypoglycemia:

In many cases, the symptoms of low blood sugar go away very quickly if you consume sugars, such as sugar cubes, sugar-sweetened drinks or sweetened tea.

So always carry sugar with you (for example sugar cubes).

Remember that artificial sweeteners are not effective. Contact your doctor or go to a hospital if you find that taking sugar does not help or if the symptoms recur.

Laboratory tests

You need to check your blood or urine sugar levels regularly. Your doctor may also order blood tests to check your blood cell levels and liver function.

Children and adolescents

The use of Solosa in children under the age of 18 is not recommended.

Interactions Which drugs or foods can modify the effect of Solosa

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.

Your doctor may change the dose of Solosa if you take other medicines that can decrease or increase the effects of Solosa on blood sugar levels.

The following medicines may increase the blood sugar lowering effects of Solosa. This can lead to a risk of hypoglycemia (low blood sugar levels):

  • Other medicines used to treat diabetes mellitus (such as insulin or metformin)
  • Medicines used to treat pain and inflammation (phenylbutazone, azopropazone, oxyphenbutazone, aspirin-like drugs)
  • Medicines used to treat urinary infections (such as some long-acting sulfonamides)
  • Medicines used to treat bacterial and fungal infections (tetracyclines, chloramphenicol, fluconazole, miconazole, quinolones, clarithromycin)
  • Medicines used to inhibit blood clotting (coumarin derivatives such as warfarin)
  • Medicines used to strengthen muscles (anabolics)
  • Medicines used for hormone replacement therapy in humans
  • Medicines used to treat depression (fluoxetine, MAO inhibitors)
  • Medicines used to lower high cholesterol levels (fibrates)
  • Medicines used to lower high blood pressure (ACE inhibitors)
  • Medicines called antiarrhythmic agents used to control abnormal heartbeats (disopyramide)
  • Medicines used to treat gout (allopurinol, probenecid, sulfinpyrazone)
  • Medicines used to treat cancer (cyclophosphamide, ifosfamide, trophosfamide)
  • Medicines used to reduce weight (fenfluramine)
  • Medicines used to increase circulation when given as a high-dose intravenous infusion (pentoxifylline)
  • Medicines used to treat nose allergies, such as hay allergy (tritoqualine)
  • Medicines called sympatholytics used to treat high blood pressure, heart failure or prostate symptoms

The following medicines may decrease the blood sugar lowering effects of Solosa. This can lead to a risk of hyperglycemia (high blood sugar levels):

  • Medicines that contain female sex hormones (estrogen, progestin)
  • Medicines used to aid in the production of urine (thiazide diuretics)
  • Medicines used to stimulate the thyroid gland (such as levothyroxine)
  • Medicines used to treat allergies and inflammation (glucocorticoids)
  • Medicines used to treat severe mental disorders (chlorpromazine and other phenothiazine derivatives)
  • Medicines used to increase heart rate, to treat asthma or nasal congestion, coughs and colds, used to reduce weight, or used in life-threatening emergencies (adrenaline and sympathomimetics)
  • Medicines used to treat high cholesterol (nicotinic acid)
  • Medicines used to treat constipation when used for a long time (laxatives)
  • Medicines used to treat seizures (phenytoin)
  • Medicines used to treat nervousness and sleep disorders (barbiturates)
  • Medicines used to treat increased pressure in the eye (acetazolamide)
  • Medicines used to treat high blood pressure or low blood sugar (diazoxide)
  • Medicines used to treat infections and tuberculosis (rifampicin)
  • Medicines used to treat very low blood sugar (glucagon) levels

The following medicines may increase or decrease the blood sugar lowering effects of Solosa:

  • Medicines used to treat stomach ulcers (called H2 blockers)
  • Medicines used to treat high blood pressure or heart failure such as beta blockers, clonidine, guanitidine and reserpine. These can also hide the symptoms of hypoglycaemia, so special care is required when taking these medicines.

Solosa may increase or decrease the effects of the following medicines:

  • Medicines used to inhibit blood clotting (coumarin derivatives such as warfarin)

Colesevelam, a medicine used to lower cholesterol, has an effect on the absorption of Solosa. To avoid this effect, you are recommended to take Solosa at least 4 hours before colesevelam.

Solosa with food, drink and alcohol

Drinking alcoholic beverages can increase or decrease the blood sugar-lowering effects of Solosa unpredictably.

Warnings It is important to know that:

Pregnancy and breastfeeding

Pregnancy

Solosa must not be taken during pregnancy. Tell your doctor if you are planning to become pregnant or if you are already pregnant or think you are pregnant

Feeding time

Solosa can pass into breast milk. Solosa must not be taken if you are breastfeeding.

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 levels are low (hypoglycaemia) or raised (hyperglycaemia), or if you develop vision problems as a result of these conditions. Please note that you could pose a risk to both yourself and others (for example by driving a car or using machines). Talk to your doctor for advice on whether you should drive if:

  • have frequent hypoglycemic attacks,
  • have few or no warning symptoms of hypoglycemia.

Solosa contains lactose.

If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.

Dose, Method and Time of Administration How to use Solosa: Posology

Always take this medicine exactly as your doctor has told you. If in doubt, consult your doctor or pharmacist.

Take 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 at the time your doctor prescribes it. It is important not to skip any meals when taking Solosa.
  • Swallow the tablets with at least half a glass of water. Do not crush or chew the tablets.

How much medicine to take

The dose of Solosa 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 prescribed by your doctor.

The usual starting dose of Solosa is one 1 mg tablet once a day

If necessary, your doctor may increase the dose every 1-2 weeks of treatment

The maximum recommended dose of Solosa is 6 mg per day

Glimepiride + metformin or glimepiride + insulin combination therapy may be initiated. In this case, your doctor will work out the right dose of glimepiride, metformin or specific insulin for you

If your weight changes, or you change your lifestyle, or you are in a stressful situation, your doses of Solosa may need to be adjusted, so tell your doctor.

If you think the effects of the medicine are too weak or too strong do not change the dose yourself, but ask your doctor

Overdose What to do if you have taken too much Solosa

If you have taken too much Solosa or if you have taken an extra dose there is a risk of hypoglycaemia (for symptoms of hypoglycaemia see Section 2) and therefore you must immediately take a sufficient amount of sugar (eg. A small bar of sugar cubes, sugary drinks or sugared tea) and inform your doctor immediately. Unconscious persons should not be given food or drink.

Since the state of hypoglycaemia can last for some time, it is very important that the patient is carefully monitored until the danger has ceased. Hospitalization may be required, including as a precautionary measure. Show the remaining box or tablets to the doctor so that the doctor can see what has been taken.

Severe cases of hypoglycemia with unconsciousness and severe neurological insufficiency are medical emergencies that require immediate medical treatment and hospitalization. It must be ensured that there is always an informed person who can call the doctor in case of an emergency.

If you forget to take Solosa

If you have forgotten to take a dose, do not take a double dose to make up for a forgotten dose.

If you stop taking Solosa

If you interrupt or stop treatment you should be aware that it will not achieve the desired sugar lowering effect and that the disease will get even worse.

Keep taking Solosa until your doctor tells you to stop.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

Side Effects What are the side effects of Solosa

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Tell your doctor right away if any of the following symptoms occur:

  • Allergic reactions (including inflammation of blood vessels, often with skin rash) which can become a severe reaction with difficulty in breathing, drop in blood pressure and sometimes progressing to shock
  • Abnormal liver function including yellowing of the skin and eyes (jaundice), problems with the flow of bile (cholestasis), inflammation of the liver (hepatitis) or liver failure
  • Allergy (hypersensitivity) of the skin such as itching, rash, hives and increased sensitivity to the sun. Some mild allergic reactions can turn into severe reactions.
  • Severe hypoglycaemia with loss of consciousness, seizures or coma Some patients have experienced the following adverse events while taking Solosa:

Rare side effects (affects 1 to 10 users in 10,000)

  • Lower than normal blood sugar levels (hypoglycaemia) (See section 2)
  • Decrease in the number of blood cells:
  • Platelets (which increases the risk of bleeding or bruising)
  • White blood cells (which increases the risk of infections)
  • Red blood cells (which can make the skin pale and cause weakness and shortness of breath)

These problems usually get better when you stop taking Solosa

Very rare side effects (may affect less than 1 in 10,000 patients)

  • Allergic reactions (including inflammation of blood vessels, often with skin rash) which can become a severe reaction with difficulty in breathing, drop in blood pressure and sometimes progressing to shock. If any of these symptoms occur, tell your doctor immediately
  • Abnormal liver function including yellowing of the skin and eyes (jaundice), impaired flow of bile (cholestasis), inflammation of the liver (hepatitis) or liver failure. If any of these symptoms occur, tell your doctor immediately
  • Nausea or vomiting, diarrhea, fullness or bloating, and abdominal pain
  • Decrease in blood sodium levels (seen in blood tests)

Other side effects include:

  • Allergy (hypersensitivity) of the skin such as itching, rash, hives and increased sensitivity to the sun. Some mild allergic reactions can develop into severe reactions with trouble swallowing or breathing, swelling of the lips, throat or tongue. Therefore, in the event of any of these adverse events occurring, please inform your doctor immediately
  • Allergic reactions may occur with sulfonylureas, sulfonamides or related drugs
  • Problems with vision may occur at the start of treatment with Solosa. This is due to the change in blood sugar levels, and should improve soon.
  • Increased liver enzymes
  • Unusual severe 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 the national reporting system at www.aifa.gov.it/responsabili

By reporting side effects you can help provide more information on the safety of this medicine.

Expiry and Retention

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 carton and blister after EXP. The expiry date refers to the last day of that month.

Solosa 1 mg, 2 mg, 3 mg, and 4 mg tablets: Do not store above 30 ° C.

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

Do not use this medicine if you notice visible signs of deterioration.

Do not throw any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.

What Solosa contains

  • The active ingredient 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 25000.
  • In addition, the tablets contain dyes:
  • 1 mg tablets contain red iron oxide (E172)
  • The 2 mg tablets contain yellow iron oxide (E172) and indigo carmine aluminum lake (E132)
  • The 3 mg tablets contain yellow iron oxide (E172)
  • 4 mg tablets contain indigo carmine aluminum lake (E132)

Description of what Solosa looks like and the contents of the pack

All Solosa tablets are oblong and scored on both sides. Each tablet can be divided into two equal doses. They are different in color:

The 1 mg tablets are pink in color

The 2 mg tablets are green in color

The 3 mg tablets are pale yellow

The 4 mg tablets are light blue

They are available in blister packs of 14, 15 (only for Solosa 1 mg), 20, 28, 30, 50, 60, 90, 112, 120 and 280 tablets.

Not all pack sizes and strengths may be marketed.

Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.

Further information on Solosa can be found in the "Summary of Characteristics" tab. 01.0 NAME OF THE MEDICINAL PRODUCT 02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION 03.0 PHARMACEUTICAL FORM 04.0 CLINICAL PARTICULARS 04.1 Therapeutic indications 04.2 Posology and method of administration 04.3 Contraindications 04.4 Special warnings and appropriate precautions for use 04.5 Interactions with other medicinal products and other forms of interaction04.6 Pregnancy and lactation04.7 Effects on ability to drive and use machines04.8 Undesirable effects04.9 Overdose05.0 PHARMACOLOGICAL PROPERTIES05.1 Pharmacodynamic properties05.2 Pharmacokinetic properties05.3 Preclinical safety data06.0 INFORMATION PHARMACEUTICALS 06.1 Excipients 06.2 Incompatibilities 06.3 Shelf life 06.4 Special precautions for storage 06.5 Nature of the immediate packaging and contents of the package 06.6 Instructions for use and handling 07.0 MARKETING AUTHORIZATION HOLDER08 .0 MARKETING AUTHORIZATION NUMBER 09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION 10.0 DATE OF REVISION OF THE TEXT 11.0 FOR RADIOPharmaceuticals, FULL DATA ON INTERNAL RADIATION DOSIMETRY 12.0 FOR RADIO DRUGS, FURTHER DETAILED INSTRUCTIONS ON ESTEMPORANEA PREPARATION AND CONTROL

01.0 NAME OF THE MEDICINAL PRODUCT

ONLY TABLETS

02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains 1 mg of glimepiride.

Excipients: also contains 69.0 mg of lactose monohydrate per tablet.

Each tablet contains 2 mg of glimepiride.

Excipients: also contains 137.2 mg of lactose monohydrate per tablet.

Each tablet contains 3 mg of glimepiride.

Excipients: also contains 137.0 mg of lactose monohydrate per tablet.

Each tablet contains 4 mg of glimepiride.

Excipients: also contains 135.9 mg of lactose monohydrate per tablet.

For the full list of excipients, see section 6.1.

03.0 PHARMACEUTICAL FORM

Tablets.

Solosa 1 mg

The tablets are pink, oblong and scored on both sides.

Solosa 2 mg

The tablets are green, oblong and scored on both sides.

Solosa 3 mg

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

Solosa 4 mg

The tablets are light blue, oblong and scored on both sides.

The tablet can be divided into equal halves.

04.0 CLINICAL INFORMATION

04.1 Therapeutic indications

Solosa is indicated for the treatment of type 2 diabetes mellitus when diet, exercise and weight reduction alone are not sufficient.

04.2 Posology and method of administration

For oral use.

At the basis of an optimal diabetes treatment there must be a controlled diet, regular physical exercise, in addition to the systematic control of blood sugar and glycosuria. Oral antidiabetics or insulin cannot compensate for the patient's failure to follow the diet.

Dosage

The dose is determined based on the glucose values ​​in the blood and urine.

The starting dose is 1 mg of glimepiride per day. If the control achieved is satisfactory, this posology can be adopted as maintenance therapy.

Appropriate dosages are available for the different dosage regimens.

If control is unsatisfactory, the dose should be increased on the basis of glycemic control, gradually with an interval, for each increase, of approximately 1-2 weeks, up to 2, 3 or 4 mg of glimepiride per day.

A dose of more than 4 mg per day of glimepiride leads to better therapeutic results only in exceptional cases. The maximum recommended dose of glimepiride is 6 mg per day.

In patients inadequately controlled with the maximum daily dose of metformin, concomitant therapy with glimepiride may be initiated.

While maintaining the metformin dose constant, glimepiride therapy is initiated with low doses, increasing these doses until the desired metabolic compensation is achieved up to the maximum daily dose. Combination therapy should be initiated under close medical supervision.

In patients inadequately controlled with the maximum daily dose of Solosa, concomitant insulin therapy may be initiated if necessary. While maintaining the glimepiride dose constant, insulin therapy is initiated with low doses, increasing these doses until the desired metabolic compensation is achieved.

Combination therapy should be initiated under close medical supervision.

A once daily dose of glimepiride is usually sufficient. It is recommended that this dose be taken shortly before or during a large breakfast, or else, immediately before or during the main meal.

If a dose is forgotten, the forgotten dose should not be corrected by taking a higher dose later.

If a patient experiences a hypoglycaemic reaction with a dose of 1 mg of glimepiride per day, it means that the patient can be controlled with diet alone.

During the course of treatment, the demand for glimepiride may decrease, since the improvement in diabetes control is associated with an increased sensitivity to insulin. To avoid the onset of hypoglycaemia, a prompt dose reduction or discontinuation of therapy should therefore be considered. A change in dosage may also be necessary in the event of a change in the patient's weight, a change in lifestyle, and in the event that other factors increase the risk of hypoglycemia or hyperglycemia.

Switching from other oral antidiabetics to Solosa

Switching from other oral antidiabetics to Solosa can generally be made. When switching to Solosa, the efficacy and half-life of the previous medicine should be considered. In some cases, especially with antidiabetic agents with a long half-life (eg chlorpropamide), a break period of a few days is advisable in order to minimize the risk of hypoglycaemic reactions due to an additive effect.

The recommended starting dose is 1 mg of glimepiride per day. Based on the therapeutic response the glimepiride dose can be gradually increased as indicated above.

Switching from using insulin to Solosa.

In exceptional cases in patients with type 2 diabetes, controlled with insulin, a switch to Solosa may be indicated. The transition must take place under strict medical supervision.

Special populations

Patients with renal or hepatic impairment

See section 4.3.

Pediatric population:

There are no data available on the use of glimepiride in patients below 8. For children 8 to 17 years, there are limited data on glimepiride monotherapy (see sections 5.1 and 5.2).

There are insufficient safety and efficacy data available in the pediatric population and therefore such use is not recommended.

Method of administration

The tablets should be swallowed with some liquid without chewing them.

04.3 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 6.1;

- insulin-dependent diabetes;

- diabetic coma;

- ketoacidosis;

- severe renal or hepatic function disorders.

Insulin replacement is required in case of severe renal or hepatic function disorders.

04.4 Special warnings and appropriate precautions for use

Solosa should be taken shortly before or during a meal.

When meals are taken at irregular times or are not even consumed, treatment with Solosa can lead to hypoglycaemia. Possible symptoms of hypoglycemia include: headache, ravenous hunger, nausea, vomiting, fatigue, drowsiness, sleep disturbances, restlessness, aggression, difficulty concentrating, altered alertness and reaction time, depression, confusion, speech disturbances and vision, aphasia, tremor, paresis, sensory disturbances, dizziness, weakness, loss of self-control, delirium, brain seizures, drowsiness and loss of consciousness up to and including coma, shallow breathing and bradycardia. adrenergic regulation such as sweating, clammy skin, anxiety, tachycardia, hypertension, palpitations, angina pectoris and cardiac arrhythmias.

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

Symptoms can almost always be quickly controlled with immediate carbohydrate (sugar) intake. Artificial sweeteners are ineffective.

From experience with other sulfonylureas it is known that, despite the initial success of the countermeasures, hypoglycemia can reappear.

Severe or prolonged hypoglycemia, controlled only temporarily by the administration of usual amounts of sugar, requires immediate medical treatment and, occasionally, hospitalization.

Factors favoring hypoglycemia include:

- poor cooperation or, more commonly in older patients, the patient's inability to cooperate,

- malnutrition, irregular mealtimes, omitted meals or fasting periods,

- change in diet,

- imbalance between physical activity and carbohydrate intake,

- alcohol consumption, especially if concomitant with not consuming a meal,

- impaired renal function,

- severe liver dysfunction,

- overdose of Solosa,

- some uncompensated endocrine system disorders that affect carbohydrate metabolism or the counter-regulation of hypoglycemia (such as in some disorders of thyroid function and anterior pituitary gland or in the case of adrenal insufficiency),

- concomitant administration of some other medicinal products (see section 4.5).

Treatment with Solosa requires regular checks of blood and urinary glucose levels. In addition, the determination of the percentage of glycosylated hemoglobin is recommended.

Regular monitoring of blood (especially leukocytes and thrombocytes) and liver values ​​is required during treatment with Solosa.

In stressful situations (such as trauma, surgery, infections with fever, etc.), a temporary switch to insulin may be indicated.

There is insufficient experience with the use of Solosa in patients with severe hepatic impairment or in patients on dialysis. Switching to insulin is indicated in patients with severe renal or hepatic impairment.

Treatment of patients with G6PD deficiency with sulfonylureas can lead to haemolytic anemia.

Since glimepiride belongs to the class of sulfonylureas, caution should be exercised in patients with G6PD deficiency and an alternative other than a sulfonylurea should be considered.

Solosa contains lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

04.5 Interactions with other medicinal products and other forms of interaction

If glimepiride is co-administered with some medicines, both undesirable increases and decreases in the blood glucose-lowering action of glimepiride may occur. For this reason, other medicines should only be taken after informing or prescribing your doctor.

Glimepiride is metabolised by cytochrome P450 2C9 (CYP2C9). Its metabolism is known to be affected by concomitant administration of CYP2C9 inducers (e.g. rifampicin) or inhibitors (e.g. fluconazole).

The results of an interaction study in vivo reported in the literature, have shown that the AUC of glimepiride nearly doubled in the presence of fluconazole, which is one of the strongest inhibitors of CYP2C9.

Based on the experience gained with glimepiride and other sulfonylureas the following interactions should be mentioned.

An enhancement of the hypoglycaemic effect and, therefore, in some cases hypoglycaemic reactions may occur with the intake of one of the following medicines, for example:

- phenylbutazone, azapropazone and oxyphenbutazone,

- insulins and other oral antidiabetic products, such as metformin, salicylates and para-amino-salicylic acid,

- anabolic steroids and male sex hormones,

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

- coumarin anticoagulants,

- fenfluramine,

- disopyramide,

- bundles,

- ACE inhibitors,

- fluoxetine, MAO inhibitors,

- allopurinol, probenecid, sulfinpyrazone, sympatholytics,

- cyclophosphamide, trophosphamide and ifosfamidi, miconazole, fluconazole

- pentoxifylline (high parenteral doses), tritoqualine.

A decrease in the hypoglycemic action and consequent increase in blood sugar can occur with the intake of one of the following medicinal products, for example:

- estrogens and progestogens, saluretics, thiazide diuretics,

- thyroid stimulating agents, glucocorticoids,

- phenothiazine derivatives, chlorpromazine, adrenaline and sympathomimetics,

- nicotinic acid (in high doses) and nicotinic acid derivatives, laxatives (after prolonged use),

- phenytoin, diazoxide,

- glucagon, barbiturates and rifampicin, acetazolamide.

H2-antagonists, beta-blockers, clonidine and reserpine can induce both an increase and a decrease in the hypoglycemic effect.

Under the influence of sympatholytic drugs such as beta-blockers, clonidine, guanethidine and reserpine the effects of adrenergic counter-regulation of hypoglycaemia may be reduced or absent.

Alcohol intake may increase or reduce the hypoglycemic action of glimepiride in an unpredictable way.

Glimepiride can both potentiate and reduce the effects of coumarin derivatives.

Colesevelam binds to glimepiride and reduces the absorption of glimepiride from the gastrointestinal tract. No interactions were observed when glimepiride was taken at least 4 hours before colesevelam. Therefore, glimepiride should be administered at least 4 hours before colesevelam.

04.6 Pregnancy and lactation

Pregnancy

Risk related to diabetes

During pregnancy, abnormal blood glucose concentrations are associated with a higher incidence of congenital anomalies and perinatal mortality. Therefore blood glucose must be closely monitored during pregnancy to avoid the risk of teratogenesis. In such circumstances the use of insulin is required. Patients planning to become pregnant should inform their physician.

Risk related to glimepiride

There are insufficient data from the use of glimepiride in pregnant women. Animal studies have shown reproductive toxicity possibly related to the pharmacological (hypoglycaemic) action of glimepiride (see section 5.3).

Therefore, glimepiride should not be used during the entire period of pregnancy.

If the patient on glimepiride therapy intends to become pregnant or if pregnancy is ascertained, the treatment should be replaced with insulin therapy as soon as possible.

Feeding time

It is not known whether excretion in human milk occurs. Glimepiride is excreted in rat milk. Since other sulfonylureas pass into breast milk and there is a risk of hypoglycaemia in the infant, breastfeeding is not recommended during therapy with glimepiride.

04.7 Effects on ability to drive and use machines

No studies 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 hypoglycemia or hyperglycemia or as a result of impaired vision for example. This can be a risk in situations where these skills are of particular importance (eg driving cars or operating machinery).

Patients should be advised to take precautions to avoid hypoglycaemia while driving. This is particularly important in those patients who have reduced or no warning symptoms of hypoglycaemia or who are prone to frequent episodes of hypoglycaemia. This should be taken into account in such circumstances. whether or not it is advisable to drive or operate machinery.

04.8 Undesirable effects

The following undesirable effects are based on experience with Solosa and other sulfonylureas and are listed below by organ system and by decreasing incidence (very common: ≥ 1/10; common: ≥ 1/100,

Disorders of the blood and lymphatic system

Rare: thrombocytopenia, leukopenia, granulocytopenia, agranulocytosis, erythropenia, haemolytic anemia and pancytopenia which are generally reversible upon discontinuation of therapy.

Not known: severe thrombocytopenia with platelet count less than 10,000 / mcl and purpura thrombocytopenic.

Disorders of the immune system

Very rare: leukocytoclastic vasculitis, mild hypersensitivity reactions which can develop into severe reactions, with dyspnoea, drop in blood pressure and sometimes shock.

Frequency not known: Cross allergy with sulfonylureas, sulfonamides or related substances is possible.

Metabolism and nutrition disorders

Rare: hypoglycemia.

These hypoglycaemic reactions mostly occur immediately, can be severe and not easy to correct. The occurrence of these reactions depends, as with other hypoglycaemic therapies, on individual factors such as dietary habits and dose (see also section 4.4).

Eye disorders

Frequency not known: visual disturbances, transient, can occur in particular at the beginning of treatment and are caused by changes in blood glucose.

Gastrointestinal disorders

Very rare: nausea, vomiting, diarrhea, abdominal distension, abdominal discomfort and abdominal pain which rarely lead to discontinuation of treatment.

Hepatobiliary disorders

Frequency not known: increase in liver enzymes.

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

Skin and subcutaneous tissue disorders

Frequency not known: skin hypersensitivity reactions such as itching, rash, urticaria and photosensitivity may occur.

Diagnostic tests

Very rare: reduction of sodium in the blood.

Reporting of suspected adverse reactions.

Reporting of suspected adverse reactions that occur after authorization of the medicinal product is important as it allows continuous monitoring of the benefit / risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system to address www.aifa.gov.it/responsabili

04.9 Overdose

Symptoms

By ingestion of excessive doses, a state of hypoglycemia can occur which can last from 12 to 72 hours and which can reappear after an initial recovery. Symptoms may not present until 24 hours after taking the drug. In general, observation in a hospital setting is recommended. Nausea, vomiting, and epigastric pain may occur. Hypoglycemia can generally be accompanied by neurological symptoms such as restlessness, tremors, visual disturbances, coordination problems, sleepiness, coma and convulsions.

Treatment

The treatment consists first of all in preventing the absorption of the ingested drug by causing vomiting, then by drinking water or lemonade with the addition of activated carbon (adsorbent) and sodium sulphate (laxative). In case a large quantity of drug has been ingested, it is gastric lavage followed by administration of activated charcoal and sodium sulphate is indicated. In the case of (severe) overdose, admission to an intensive care unit is indicated. 50% intravenous bolus followed by an infusion of a 10% solution keeping blood glucose under strict control.

Symptomatic treatment should then be performed.

In particular, in treating cases of hypoglycaemia due to accidental intake of Solosa by children and adolescents, the glucose dose must be carefully calculated to avoid causing dangerous hyperglycemia. Blood glucose must be closely monitored.

05.0 PHARMACOLOGICAL PROPERTIES

05.1 Pharmacodynamic properties

Pharmacotherapeutic group:

Hypoglycemic agents, excluding insulins: sulfonamides, urea derivatives.

ATC code: A10B B12.

Glimepiride is an orally active hypoglycemic substance belonging to the group of sulfonylureas. It can be used in non-insulin-dependent diabetes mellitus.

Glimepiride works primarily by stimulating insulin secretion by pancreatic beta cells. As with other sulfonylureas this effect is the result of an increased response of pancreatic beta cells to the physiological stimulation of glucose. Furthermore, glimepiride appears to have a pronounced extrapancreatic effect also hypothesized for other sulfonylureas.

Insulin secretion

Sulfonylureas regulate insulin secretion by blocking the ATP-sensitive potassium channel located in the membranes of beta cells. increased influx of calcium into cells.

This results in the release of insulin by exocytosis.

Glimepiride binds with a high exchange rate to a beta cell membrane protein associated with the ATP-sensitive potassium channel but at a different binding site than is usual for sulfonylureas.

Extrapancreatic activity

The extrapancreatic effects are, for example, an "increased sensitivity of peripheral tissues to insulin" and a reduction in its absorption by the liver.

The absorption of glucose from the blood by peripheral muscle cells and adipose tissue occurs by means of specific transport proteins located on the cell membranes. The transport of glucose in these tissues is the limiting factor in the use of glucose itself.

Glimepiride very rapidly increases the number of molecules active in glucose transport in the membrane of muscle cells and adipose tissue with the final result of increased glucose uptake.

Glimepiride increases the activity of phospholipase C specific for glycosyl-phosphatidyl-inositol which may be related to drug-induced lipogenesis and glycogenesis in isolated fat and muscle cells. Glimepiride inhibits glucose production in the liver by increasing the intracellular concentration of the fructose 2,6-bisphosphate which, in turn, inhibits gluconeogenesis.

General

In healthy people, the minimum effective oral dose is approximately 0.6 mg. The effect of glimepiride is dose-dependent and reproducible. The physiological response to strenuous exercise, such as reduced insulin secretion, is still present under glimepiride treatment.

There was no significant difference in therapeutic effect whether the drug is administered 30 minutes before or immediately before a meal. Good metabolic control for 24 hours can be achieved in diabetic patients with a once daily dose.

Although the hydroxyl metabolite of glimepiride causes a small but significant decrease in serum glucose in healthy people, it accounts for only a small part of the drug's overall effect.

Combined therapy with metformin

One study showed that in patients inadequately controlled on the maximum daily dose of metformin, combination therapy with glimepiride results in better metabolic control than metformin as the sole agent.

Combination therapy with insulin

Data on combination insulin therapy are limited. In patients who are not adequately controlled on the maximum dose of glimepiride, concomitant insulin treatment may be initiated. In two studies, combination therapy resulted in an improvement in metabolic control equal to that achieved with insulin alone; however, a lower mean insulin dose was required in combination therapy.

Special populations

Pediatric population

An active-controlled study (glimepiride up to 8 mg / day or metformin up to 2,000 mg / day) lasting 24 weeks was conducted in 285 children (8-17 years) with type II diabetes.

Both glimepiride and metformin showed a significant decrease in HbA 1c from baseline (glimepiride - 0.95 (eg 0.41); metformin - 1.39 (eg 0.40)). However, glimepiride did not meet the criteria of non-inferiority to metformin in mean change from baseline in HbA 1c. The difference between treatments was 0.44% in favor of metformin. The upper bound of the 95% confidence interval for the difference was not less than the 0.3% non-inferiority margin.

After treatment with glimepiride, no new safety concerns were identified in children compared to adults with type II diabetes mellitus. There are no long-term efficacy and safety data in pediatric patients.

05.2 Pharmacokinetic properties

Absorption: The bioavailability of glimepiride after oral administration is complete.

Food intake does not significantly affect absorption; only the absorption rate is slightly reduced. The maximum serum concentration (Cmax) is reached approximately 2.5 hours after oral intake (mean 0.3 mcg / ml for a multiple dose of 4 mg / day) and there is a linear relationship between the dose and the Cmax is the area under the concentration / time curve (AUC).

Distribution: Glimepiride has a very low volume of distribution (approximately 8.8 liters) and practically equivalent to the volume of distribution of albumin, high protein binding (> 99%) and a low clearance value (approximately 48 ml. /minute).

In animals, glimepiride is excreted in milk. Glimepiride crosses the placenta. The passage of the blood-brain barrier is limited.

Metabolism and Elimination: The half-life in serum, which is an important factor for serum concentrations during repeat-dose treatment, is approximately 5-8 hours. A little longer half-life values ​​were found after administration of high doses.

After a single dose of radiolabelled glimepiride 58% of the radioactivity was recovered in the urine and 35% in the faeces. The unchanged substance was not detected in the urine. Two metabolites, as a likely result of hepatic metabolism (major enzyme is CYP2C9), have been identified in both faeces and urine: a hydroxyl derivative and a carboxylic derivative. After oral administration of glimepiride the terminal half-lives of the two metabolites were 3-6 hours and 5-6 hours, respectively.

Comparison between single and repeated once daily dosing does not show significant differences in pharmacokinetics and intraindividual variations are also very limited. No relevant accumulation was observed.

Special populations

Pharmacokinetic data are similar in men and women as well as in young and elderly patients (aged over 65 years). In patients with low creatinine clearance, there is a trend towards increased clearance of glimepiride and a reduction in mean serum concentration; this is most likely the result of a more rapid elimination due to a reduction in the protein-bound share. Renal elimination of the two metabolites was impaired.

It can be assumed that there is no additional risk of accumulation in these patients.

Kinetic data in five non-diabetic patients undergoing bile duct surgery were similar to those of the healthy volunteer.

Pediatric population

A fed study of the pharmacokinetics, safety and tolerability of a single dose of glimepiride 1 mg in 30 pediatric patients (4 children aged 10-12 and 26 children aged 12-17 years) with type II diabetes showed mean values ​​of AUC (0-end) Cmax and T½ similar to those previously observed in adults.

05.3 Preclinical safety data

The observed preclinical effects are related to exposures that are sufficiently higher than the maximum ones in humans, indicating little relevance to clinical use, or are consequent to the pharmacodynamics of the molecule (hypoglycemia). This result is based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenesis, reproductive toxicity. In the latter (including embryotoxicity, teratogenesis and developmental toxicity), the adverse effects observed were considered to be secondary to the hypoglycemic effects induced by the drug in the mothers and offspring.

06.0 PHARMACEUTICAL INFORMATION

06.1 Excipients

Lactose monohydrate, sodium carboxymethyl starch (type A), magnesium stearate, microcrystalline cellulose, povidone 25000.

Solosa 1 mg: red iron oxide (E 172);

Solosa 2 mg: yellow iron oxide (E 172) and indigo carmine aluminum lake (E 132);

Solosa 3 mg: yellow iron oxide (E 172);

Solosa 4 mg: carmine indigo aluminum lake (E 132);

06.2 Incompatibility

Not relevant.

06.3 Period of validity

Solosa 1 mg, 2 mg, 3 mg, 4 mg: 3 years.

06.4 Special precautions for storage

Solosa 1 mg, 2 mg, 3 mg and 4 mg: Do not store above 30 ° C. Store in the original package in order to protect from moisture.

06.5 Nature of the immediate packaging and contents of the package

PVC / aluminum blister.

14, 15 (Solosa 1 mg only), 20, 28, 30, 50, 60, 90, 112, 120 and 280 tablets.

Not all pack sizes may be marketed.

06.6 Instructions for use and handling

No special instructions.

07.0 MARKETING AUTHORIZATION HOLDER

LABORATORI GUIDOTTI S.p.A. - Via Livornese, 897 - PISA - La Vettola

08.0 MARKETING AUTHORIZATION NUMBER

SOLOSA 1 mg:

- 14 tablets, AIC n. 032117335

- 20 tablets, AIC n. 032117095

- 28 tablets, AIC n. 032117347

- 30 tablets, AIC n. 032117107

- 50 tablets, AIC n. 032117119

- 60 tablets, AIC n. 032117121

- 90 tablets, AIC n. 032117133

- 112 tablets, AIC n. 032117350

- 120 tablets, AIC n. 032117145

- 280 tablets, AIC n. 032117362

SOLOSA 2 mg:

- 14 tablets, AIC n. 032117374

- 20 tablets, AIC n. 032117057

- 28 tablets, AIC n. 032117386

- 30 tablets, AIC n. 032117018

- 50 tablets, AIC n. 032117069

- 60 tablets, AIC n. 032117071

- 90 tablets, AIC n. 032117083

- 112 tablets, AIC n. 032117398

- 120 tablets, AIC n. 032117020

- 280 tablets, AIC n. 032117400

SOLOSA 3 mg:

- 14 tablets, AIC n. 032117412

- 20 tablets, AIC n. 032117158

- 28 tablets, AIC n. 032117424

- 30 tablets, AIC n. 032117160

- 50 tablets, AIC n. 032117172

- 60 tablets, AIC n. 032117184

- 90 tablets, AIC n. 032117196

- 112 tablets, AIC n. 032117436

- 120 tablets, AIC n. 032117208

- 280 tablets, AIC n. 032117448

SOLOSA 4 mg:

- 14 tablets, AIC n. 032117451

- 20 tablets, AIC n. 032117210

- 28 tablets, AIC n. 032117463

- 30 tablets, AIC n. 032117222

- 50 tablets, AIC n. 032117234

- 60 tablets, AIC n. 032117246

- 90 tablets, AIC n. 032117259

- 112 tablets, AIC n. 032117475

- 120 tablets, AIC n. 032117261

- 280 tablets, AIC n. 032117487

09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION

SOLOSA 1 mg: 22 September 2006/9 February 2010

SOLOSA 2 mg - 30 tablets: November 22, 1996 / February 9, 2010

SOLOSA 2 mg: packs of 14, 20, 28, 50, 60, 90, 112, 120 and 280 tablets: 22 September 2006/9 February 2010

SOLOSA 3 mg: 22 September 2006/9 February 2010

SOLOSA 4 mg: 22 September 2006/9 February 2010

10.0 DATE OF REVISION OF THE TEXT

11.0 FOR RADIO DRUGS, COMPLETE DATA ON THE INTERNAL RADIATION DOSIMETRY

12.0 FOR RADIO DRUGS, FURTHER DETAILED INSTRUCTIONS ON EXEMPORARY PREPARATION AND QUALITY CONTROL

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