SOLOSA Glimepiride 2mg Tablet 30's
RXDRUG-DRP-007
Discreet Packaging
FDA-registered Products
FDA-licensed Pharmacies
Indications/Uses
Non-insulin-dependent (type 2) diabetes mellitus, whenever blood glucose levels cannot be controlled adequately by diet, physical exercise and weight reduction alone.
Dosage/Direction for Use
General: In principle, the dosage of Glimepiride (Solosa) is governed by the desired blood glucose level. The dosage of glimepiride must be the lowest which is sufficient to achieve the desired metabolic control.
During treatment with Glimepiride (Solosa) glucose levels in blood and urine must be measured regularly. In addition, it is recommended that regular determinations of the proportion of glycated haemoglobin be carried out.
Mistakes, e.g. forgetting to take a dose, must never be corrected by subsequently taking a larger dose.
Measures for dealing with such mistakes (in particular forgetting a dose or skipping a meal) or situations where a dose cannot be taken at the prescribed time must be discussed and agreed between physician and patient beforehand.
Initial dose and dose titration: Usual initial dose: 1 mg Glimepiride (Solosa) once daily.
If necessary, the daily dose can be increased. It is recommended that the increase be guided by regular blood glucose monitoring, and that the dose be increased gradually, i.e. at intervals of one to two weeks and according to the following dose steps: 1 mg - 2 mg - 3 mg - 4 mg - 6 mg (- 8 mg).
Dose range in patients with well-controlled diabetes: Usual daily doses in patients with well controlled diabetes are 1 to 4 mg Glimepiride (Solosa). Daily doses of more than 6 mg are more effective only in a minority of patients.
Distribution of doses: Timing and distribution of doses are to be decided by the physician, taking into consideration the patient's current life-style.
Normally a single daily dose of Glimepiride (Solosa) is sufficient.
It is recommended that this dose be taken immediately before a substantial breakfast or if none is taken - immediately before the first main meal.
It is very important not to skip meals after the tablets have been taken.
As an improvement in control of diabetes is, in itself, associated with higher insulin sensitivity, glimepiride requirements may fall as treatment proceeds. To avoid hypoglycaemia timely dose reduction or cessation of Glimepiride (Solosa) therapy must therefore be considered.
Correction of dosage must also be considered, whenever the patient's weight changes; the patient's life-style changes; other factors arise which cause an increased susceptibility to hypoglycaemia or hyperglycaemia (see Precautions).
Duration of treatment: Treatment with Glimepiride (Solosa) is normally a long-term therapy.
Change-over from other oral antidiabetics to Glimepiride (Solosa): There is no exact dosage relationship between Glimepiride (Solosa) and other oral antidiabetics. When substituting Glimepiride (Solosa) for other oral antidiabetics, it is recommended that the procedure be the same as for initial dosage starting with daily doses of 1 mg. This applies even in cases where the patient is being switched from the maximum dose of another oral antidiabetic.
Consideration must be given to the potency and duration of action of the previous antidiabetic agent.
A break from medication may be required to avoid any summation of effects entailing a risk of hypoglycaemia.
Use with metformin: In patients not adequately controlled with the maximum daily dose of either glimepiride or metformin, combination therapy with both oral antidiabetic agents may be initiated. As the established therapy with either glimepiride or metformin progresses at the same dose level, the additional metformin or glimepiride treatment is started with a low dose, which 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.
Use with insulin: In patients not adequately controlled with the maximum daily dose of Glimepiride (Solosa), concomitant insulin therapy can be initiated. 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.
Special Populations: Children: Data are insufficient to recommend pediatric use of glimepiride (see Pharmacology: Pharmacodynamics and Pharmacokinetics under Actions).
Renal impairment: There is limited information available on the use of Glimepiride (Solosa) in renal insufficiency. Patients with impaired renal function may be more sensitive to the glucose-lowering effect of Glimepiride (Solosa) (see Pharmacology: Pharmacokinetics under Actions).
Administration: Glimepiride (Solosa) tablets must be swallowed without chewing with sufficient amounts of liquid (approx. ½ glass).
During treatment with Glimepiride (Solosa) glucose levels in blood and urine must be measured regularly. In addition, it is recommended that regular determinations of the proportion of glycated haemoglobin be carried out.
Mistakes, e.g. forgetting to take a dose, must never be corrected by subsequently taking a larger dose.
Measures for dealing with such mistakes (in particular forgetting a dose or skipping a meal) or situations where a dose cannot be taken at the prescribed time must be discussed and agreed between physician and patient beforehand.
Initial dose and dose titration: Usual initial dose: 1 mg Glimepiride (Solosa) once daily.
If necessary, the daily dose can be increased. It is recommended that the increase be guided by regular blood glucose monitoring, and that the dose be increased gradually, i.e. at intervals of one to two weeks and according to the following dose steps: 1 mg - 2 mg - 3 mg - 4 mg - 6 mg (- 8 mg).
Dose range in patients with well-controlled diabetes: Usual daily doses in patients with well controlled diabetes are 1 to 4 mg Glimepiride (Solosa). Daily doses of more than 6 mg are more effective only in a minority of patients.
Distribution of doses: Timing and distribution of doses are to be decided by the physician, taking into consideration the patient's current life-style.
Normally a single daily dose of Glimepiride (Solosa) is sufficient.
It is recommended that this dose be taken immediately before a substantial breakfast or if none is taken - immediately before the first main meal.
It is very important not to skip meals after the tablets have been taken.
As an improvement in control of diabetes is, in itself, associated with higher insulin sensitivity, glimepiride requirements may fall as treatment proceeds. To avoid hypoglycaemia timely dose reduction or cessation of Glimepiride (Solosa) therapy must therefore be considered.
Correction of dosage must also be considered, whenever the patient's weight changes; the patient's life-style changes; other factors arise which cause an increased susceptibility to hypoglycaemia or hyperglycaemia (see Precautions).
Duration of treatment: Treatment with Glimepiride (Solosa) is normally a long-term therapy.
Change-over from other oral antidiabetics to Glimepiride (Solosa): There is no exact dosage relationship between Glimepiride (Solosa) and other oral antidiabetics. When substituting Glimepiride (Solosa) for other oral antidiabetics, it is recommended that the procedure be the same as for initial dosage starting with daily doses of 1 mg. This applies even in cases where the patient is being switched from the maximum dose of another oral antidiabetic.
Consideration must be given to the potency and duration of action of the previous antidiabetic agent.
A break from medication may be required to avoid any summation of effects entailing a risk of hypoglycaemia.
Use with metformin: In patients not adequately controlled with the maximum daily dose of either glimepiride or metformin, combination therapy with both oral antidiabetic agents may be initiated. As the established therapy with either glimepiride or metformin progresses at the same dose level, the additional metformin or glimepiride treatment is started with a low dose, which 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.
Use with insulin: In patients not adequately controlled with the maximum daily dose of Glimepiride (Solosa), concomitant insulin therapy can be initiated. 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.
Special Populations: Children: Data are insufficient to recommend pediatric use of glimepiride (see Pharmacology: Pharmacodynamics and Pharmacokinetics under Actions).
Renal impairment: There is limited information available on the use of Glimepiride (Solosa) in renal insufficiency. Patients with impaired renal function may be more sensitive to the glucose-lowering effect of Glimepiride (Solosa) (see Pharmacology: Pharmacokinetics under Actions).
Administration: Glimepiride (Solosa) tablets must be swallowed without chewing with sufficient amounts of liquid (approx. ½ glass).
Overdosage
Signs and Symptoms: Acute overdosage as well as long-term treatment with too high a dose of glimepiride may lead to severe life-threatening hypoglycaemia.
Management: As soon as an overdose of Glimepiride (Solosa) has been discovered, a physician must be notified without delay.
The patient must immediately take sugar, if possible in the form of glucose, unless a physician has already undertaken responsibility for treating the overdose.
Careful monitoring is essential until the physician is confident that the patient is out of danger. It must be remembered that hypoglycaemia may recur after initial recovery.
Admission to hospital may sometimes be necessary even as a precautionary measure. In particular, significant overdoses and severe reactions with signs such as loss of consciousness or other serious neurological disorders are medical emergencies and require immediate treatment and admission to hospital.
If, for example, the patient is unconscious, an intravenous injection of concentrated glucose solution is indicated (for adults starting with 40 ml of 20% solution, for example). Alternatively in adults, administration of glucagon, e.g. in doses of 0.5 to 1 mg i.v., s.c. or i.m., may be considered.
In particular when treating hypoglycaemia due to accidental intake of Glimepiride (Solosa) in infants and young children, the dose of glucose given must be very carefully adjusted in view of the possibility of producing dangerous hyperglycaemia, and must be controlled by close monitoring of blood glucose.
Patients who have ingested life-threatening amounts of Glimepiride (Solosa) require detoxification (e.g. by gastric lavage and medicinal charcoal).
After acute glucose replacement has been completed it is usually necessary to give an intravenous glucose infusion in lower concentration so as to ensure that the hypoglycaemia does not recur. The patient's blood glucose level should be carefully monitored for at least 24 hours. In severe cases with a protracted course, hypoglycaemia, or the danger of slipping back into hypoglycaemia, may persist for several days.
Management: As soon as an overdose of Glimepiride (Solosa) has been discovered, a physician must be notified without delay.
The patient must immediately take sugar, if possible in the form of glucose, unless a physician has already undertaken responsibility for treating the overdose.
Careful monitoring is essential until the physician is confident that the patient is out of danger. It must be remembered that hypoglycaemia may recur after initial recovery.
Admission to hospital may sometimes be necessary even as a precautionary measure. In particular, significant overdoses and severe reactions with signs such as loss of consciousness or other serious neurological disorders are medical emergencies and require immediate treatment and admission to hospital.
If, for example, the patient is unconscious, an intravenous injection of concentrated glucose solution is indicated (for adults starting with 40 ml of 20% solution, for example). Alternatively in adults, administration of glucagon, e.g. in doses of 0.5 to 1 mg i.v., s.c. or i.m., may be considered.
In particular when treating hypoglycaemia due to accidental intake of Glimepiride (Solosa) in infants and young children, the dose of glucose given must be very carefully adjusted in view of the possibility of producing dangerous hyperglycaemia, and must be controlled by close monitoring of blood glucose.
Patients who have ingested life-threatening amounts of Glimepiride (Solosa) require detoxification (e.g. by gastric lavage and medicinal charcoal).
After acute glucose replacement has been completed it is usually necessary to give an intravenous glucose infusion in lower concentration so as to ensure that the hypoglycaemia does not recur. The patient's blood glucose level should be carefully monitored for at least 24 hours. In severe cases with a protracted course, hypoglycaemia, or the danger of slipping back into hypoglycaemia, may persist for several days.
Administration
Should be taken on an empty stomach: Take immediately before meal. Do not chew.
Contraindications
Glimepiride (Solosa) must not be used: In patients hypersensitive to glimepiride, other sulfonylureas, other sulfonamides, or any of the excipients of Glimepiride (Solosa); in pregnant women; in breast-feeding women.
No experience has been gained concerning the use of Glimepiride (Solosa) in patients with severe impairment of liver function and in dialysis patients. In patients with severe impairment of hepatic function, change-over to insulin is indicated, not least to achieve optimal metabolic control. Glimepiride (Solosa) is not suitable for the treatment of insulin-dependent (type 1) diabetes mellitus (e.g., for the treatment of diabetics with a history of ketoacidosis), of diabetic ketoacidosis, or of diabetic precoma or coma.
No experience has been gained concerning the use of Glimepiride (Solosa) in patients with severe impairment of liver function and in dialysis patients. In patients with severe impairment of hepatic function, change-over to insulin is indicated, not least to achieve optimal metabolic control. Glimepiride (Solosa) is not suitable for the treatment of insulin-dependent (type 1) diabetes mellitus (e.g., for the treatment of diabetics with a history of ketoacidosis), of diabetic ketoacidosis, or of diabetic precoma or coma.
Warnings
In exceptional stress situations (e.g. trauma, surgery, febrile infections) blood glucose regulation may deteriorate, and a temporary change to insulin may be necessary to maintain good metabolic control.
Special Precautions
In the initial weeks of treatment, the risk of hypoglycaemia may be increased and necessitates especially careful monitoring.
Factors favouring hypoglycaemia include: Unwillingness or (more commonly in older patients) incapacity of the patient to co-operate; undernourishment, irregular mealtimes or skipped meals; imbalance between physical exertion and carbohydrate intake; alterations of diet; consumption of alcohol, especially in combination with skipped meals; impaired renal function; severe impairment of liver function; overdosage with Glimepiride (Solosa); 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 corticoadrenal insufficiency); concurrent administration of certain other medicines (see Interactions); treatment with Glimepiride (Solosa) in the absence of any indication.
If such risk factors for hypoglycaemia are present, it may be necessary to adjust the dosage of Glimepiride (Solosa) or the entire therapy. This also applies whenever illness occurs during therapy or the patient's lifestyle changes.
Those symptoms of hypoglycaemia which reflect the body's adrenergic counter-regulation (see Adverse Reactions) may be milder or absent where hypoglycaemia develops gradually, in the elderly, and where there is autonomic neuropathy or where the patient is receiving concurrent treatment with beta-blockers, clonidine, reserpine, guanethidine or other sympatholytic drugs.
Hypoglycaemia can almost always be promptly controlled by immediate intake of carbohydrates (glucose or sugar).
It is known from other sulfonylureas that, despite initially successful countermeasures, hypoglycaemia may recur. Patients must, therefore, remain under close observation.
Severe hypoglycaemia further requires immediate treatment and follow-up by a physician and, in some circumstances, in-patient hospital care.
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 non-sulfonylurea alternative should be considered.
Driving a Vehicle or Performing Other Hazardous Tasks: Alertness and reactions may be impaired due to hypo- or hyperglycaemia, especially when beginning or after altering treatment or when Glimepiride (Solosa) is not taken regularly. This may, for example, affect the ability to drive or to operate machinery.
Factors favouring hypoglycaemia include: Unwillingness or (more commonly in older patients) incapacity of the patient to co-operate; undernourishment, irregular mealtimes or skipped meals; imbalance between physical exertion and carbohydrate intake; alterations of diet; consumption of alcohol, especially in combination with skipped meals; impaired renal function; severe impairment of liver function; overdosage with Glimepiride (Solosa); 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 corticoadrenal insufficiency); concurrent administration of certain other medicines (see Interactions); treatment with Glimepiride (Solosa) in the absence of any indication.
If such risk factors for hypoglycaemia are present, it may be necessary to adjust the dosage of Glimepiride (Solosa) or the entire therapy. This also applies whenever illness occurs during therapy or the patient's lifestyle changes.
Those symptoms of hypoglycaemia which reflect the body's adrenergic counter-regulation (see Adverse Reactions) may be milder or absent where hypoglycaemia develops gradually, in the elderly, and where there is autonomic neuropathy or where the patient is receiving concurrent treatment with beta-blockers, clonidine, reserpine, guanethidine or other sympatholytic drugs.
Hypoglycaemia can almost always be promptly controlled by immediate intake of carbohydrates (glucose or sugar).
It is known from other sulfonylureas that, despite initially successful countermeasures, hypoglycaemia may recur. Patients must, therefore, remain under close observation.
Severe hypoglycaemia further requires immediate treatment and follow-up by a physician and, in some circumstances, in-patient hospital care.
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 non-sulfonylurea alternative should be considered.
Driving a Vehicle or Performing Other Hazardous Tasks: Alertness and reactions may be impaired due to hypo- or hyperglycaemia, especially when beginning or after altering treatment or when Glimepiride (Solosa) is not taken regularly. This may, for example, affect the ability to drive or to operate machinery.
Use In Pregnancy & Lactation
Pregnancy: Glimepiride (Solosa) must not be taken during pregnancy. Otherwise there is risk of harm to the child. The patient must change over to insulin during pregnancy.
Patients planning a pregnancy must inform their physician.
It is recommended that such patients change over to insulin.
Lactation: To prevent possible ingestion with the breast milk and possible harm to the child, Glimepiride (Solosa) must not be taken by breast-feeding women. If necessary the patient must change over to insulin, or must stop breast-feeding.
Patients planning a pregnancy must inform their physician.
It is recommended that such patients change over to insulin.
Lactation: To prevent possible ingestion with the breast milk and possible harm to the child, Glimepiride (Solosa) must not be taken by breast-feeding women. If necessary the patient must change over to insulin, or must stop breast-feeding.
Adverse Reactions
Metabolism and nutrition disorders: As a result of the blood-glucose-lowering action of Glimepiride (Solosa), hypoglycaemia may occur, which based on what is known of other sulfonylureas - may also be prolonged.
Possible symptoms of hypoglycaemia include headache, ravenous hunger, nausea, vomiting, lassitude, sleepiness, disordered sleep, restlessness, aggressiveness, impaired concentration, impaired alertness and reactions, depression, confusion, speech disorders, aphasia, visual disorders, tremor, pareses, 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.
The symptoms nearly always subside when hypoglycaemia is corrected.
Eye disorders: Especially at the start of treatment, there may be temporary visual impairment due to the change in blood glucose levels.
The cause is a temporary alteration in the turgidity and hence the refractive index of the lens, this being dependent on blood glucose level.
Gastrointestinal disorders: Occasionally, gastrointestinal symptoms such as nausea, vomiting, sensations of pressure or fullness in the epigastrium, abdominal pain and diarrhoea may occur.
In isolated cases, there may be hepatitis, elevation of liver enzyme levels and/or cholestasis and jaundice, which may progress to life-threatening liver failure but can regress after withdrawal of Glimepiride (Solosa).
Dysgeusia (frequency not known).
Blood and lymphatic system disorders: Changes in the blood picture may occur: Rarely, thrombocytopenia and, in isolated cases, leucopenia, haemolytic anaemia, erythrocytopenia, granulocytopenia, agranulocytosis or pancytopenia may develop. Cases of severe thrombocytopenia with platelet count less than 10,000/μl and thrombocytopenic purpura have been reported in post-marketing experience (frequency not known).
Skin and subcutaneous tissue disorders: Alopecia (frequency not known).
General disorders: Occasionally, allergic or pseudoallergic reactions may occur, e.g. in the form of itching, urticaria or rashes. Such mild reactions may develop into serious reactions with dyspnoea and a fall in blood pressure, sometimes progressing to shock. In the event of urticaria a physician must therefore be notified immediately.
In isolated cases, a decrease in serum sodium concentration and allergic vasculitis or hypersensitivity of the skin to light may occur.
Investigations: Glimepiride, like all sulfonylureas, can cause weight gain (frequency not known).
Possible symptoms of hypoglycaemia include headache, ravenous hunger, nausea, vomiting, lassitude, sleepiness, disordered sleep, restlessness, aggressiveness, impaired concentration, impaired alertness and reactions, depression, confusion, speech disorders, aphasia, visual disorders, tremor, pareses, 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.
The symptoms nearly always subside when hypoglycaemia is corrected.
Eye disorders: Especially at the start of treatment, there may be temporary visual impairment due to the change in blood glucose levels.
The cause is a temporary alteration in the turgidity and hence the refractive index of the lens, this being dependent on blood glucose level.
Gastrointestinal disorders: Occasionally, gastrointestinal symptoms such as nausea, vomiting, sensations of pressure or fullness in the epigastrium, abdominal pain and diarrhoea may occur.
In isolated cases, there may be hepatitis, elevation of liver enzyme levels and/or cholestasis and jaundice, which may progress to life-threatening liver failure but can regress after withdrawal of Glimepiride (Solosa).
Dysgeusia (frequency not known).
Blood and lymphatic system disorders: Changes in the blood picture may occur: Rarely, thrombocytopenia and, in isolated cases, leucopenia, haemolytic anaemia, erythrocytopenia, granulocytopenia, agranulocytosis or pancytopenia may develop. Cases of severe thrombocytopenia with platelet count less than 10,000/μl and thrombocytopenic purpura have been reported in post-marketing experience (frequency not known).
Skin and subcutaneous tissue disorders: Alopecia (frequency not known).
General disorders: Occasionally, allergic or pseudoallergic reactions may occur, e.g. in the form of itching, urticaria or rashes. Such mild reactions may develop into serious reactions with dyspnoea and a fall in blood pressure, sometimes progressing to shock. In the event of urticaria a physician must therefore be notified immediately.
In isolated cases, a decrease in serum sodium concentration and allergic vasculitis or hypersensitivity of the skin to light may occur.
Investigations: Glimepiride, like all sulfonylureas, can cause weight gain (frequency not known).
Drug Interactions
Based on experience with Glimepiride (Solosa) and on what is known of other sulfonylureas, the following interactions must be considered: Glimepiride is metabolized by cytochrome P450 2C9 (CYP2C9). This should be taken into account when glimepiride is coadministered with inducers (e.g. rifampicin) or inhibitors (e.g. fluconazole) of CYP 2C9.
Potentiation of the blood-glucose-lowering effect and, thus, in some instances hypoglycaemia may occur when one of the following drugs is taken, for example: insulin and other, oral antidiabetics; ACE inhibitors; anabolic steroids and male sex hormones; chloramphenicol; coumarin derivatives; cyclophosphamide; disopyramide; fenfluramine; fenyramidol; fibrates; fluoxetine; guanethidine; ifosfamide; MAO inhibitors; miconazole; fluconazole; para-aminosalicylic acid; pentoxifylline (high dose parenteral); phenylbutazone; azapropazone; oxyphenbutazone; probenecid; quinolones; salicylates; sulfinpyrazone; clarithromycin; sulfonamide antibiotics; tetracyclines; tritoqualine; trofosfamide.
Weakening of the blood-glucose-lowering effect and, thus raised blood glucose levels may occur when one of the following drugs is taken, for example: acetazolamide; barbiturates; corticosteroids; diazoxide; diuretics; epinephrine (adrenaline) and other sympathomimetic agents; glucagon; laxatives (after protracted use); nicotinic acid (in high doses); oestrogens and progestogens; phenothiazines; phenytoin; rifampicin; thyroid hormones.
H2 receptor antagonists, beta-blockers, clonidine and reserpine may lead to either potentiation or weakening of the blood-glucose-lowering effect.
Under the influence of sympatholytic drugs such as beta-blockers, clonidine, guanethidine and reserpine, the signs of adrenergic counter-regulation to hypoglycaemia may be reduced or absent.
Both acute and chronic alcohol intake may potentiate or weaken the blood-glucose-lowering action of Glimepiride (Solosa) in an unpredictable fashion.
The effect of coumarin derivatives may be potentiated or weakened.
Bile acid sequestrant: Colesevelam binds to glimepiride and reduces glimepiride absorption from the gastro-intestinal tract. No interaction was observed when glimepiride was taken at least 4 hours before colesevelam. Therefore glimepiride should be administered at least 4 hours prior to colesevelam.
Potentiation of the blood-glucose-lowering effect and, thus, in some instances hypoglycaemia may occur when one of the following drugs is taken, for example: insulin and other, oral antidiabetics; ACE inhibitors; anabolic steroids and male sex hormones; chloramphenicol; coumarin derivatives; cyclophosphamide; disopyramide; fenfluramine; fenyramidol; fibrates; fluoxetine; guanethidine; ifosfamide; MAO inhibitors; miconazole; fluconazole; para-aminosalicylic acid; pentoxifylline (high dose parenteral); phenylbutazone; azapropazone; oxyphenbutazone; probenecid; quinolones; salicylates; sulfinpyrazone; clarithromycin; sulfonamide antibiotics; tetracyclines; tritoqualine; trofosfamide.
Weakening of the blood-glucose-lowering effect and, thus raised blood glucose levels may occur when one of the following drugs is taken, for example: acetazolamide; barbiturates; corticosteroids; diazoxide; diuretics; epinephrine (adrenaline) and other sympathomimetic agents; glucagon; laxatives (after protracted use); nicotinic acid (in high doses); oestrogens and progestogens; phenothiazines; phenytoin; rifampicin; thyroid hormones.
H2 receptor antagonists, beta-blockers, clonidine and reserpine may lead to either potentiation or weakening of the blood-glucose-lowering effect.
Under the influence of sympatholytic drugs such as beta-blockers, clonidine, guanethidine and reserpine, the signs of adrenergic counter-regulation to hypoglycaemia may be reduced or absent.
Both acute and chronic alcohol intake may potentiate or weaken the blood-glucose-lowering action of Glimepiride (Solosa) in an unpredictable fashion.
The effect of coumarin derivatives may be potentiated or weakened.
Bile acid sequestrant: Colesevelam binds to glimepiride and reduces glimepiride absorption from the gastro-intestinal tract. No interaction was observed when glimepiride was taken at least 4 hours before colesevelam. Therefore glimepiride should be administered at least 4 hours prior to colesevelam.
Storage
Store below 30°C. Protect from humidity.
Action
Pharmacology: Pharmacodynamics: Mode of Action: Both in healthy persons and in patients with type 2 diabetes mellitus, glimepiride decreases blood glucose concentrations, mainly by stimulating insulin release from pancreatic beta cells. This effect is based predominantly on an improved responsiveness of the pancreatic beta cells to the physiological glucose stimulus. While achieving an equivalent reduction in blood glucose, the administration of low doses of glimepiride to animals and healthy volunteers causes the release of smaller amounts of insulin compared with glibenclamide. These fact points to the existence of extrapancreatic (insulin-sensitizing and insulin-mimetic) effects of glimepiride.
Moreover, compared to other sulfonylureas, glimepiride has less effect on the cardiovascular system. It reduces platelet aggregation (animal and in vitro data) and leads to a marked reduction in the formation of atherosclerotic plaques (animal data).
Insulin release: Like all sulfonylureas, glimepiride regulates insulin secretion by interacting with the ATP-sensitive potassium channel in the beta cell membrane. Unlike other sulfonylureas, glimepiride binds specifically to a 65 kDa protein located in the membrane of the beta cell. This interaction of glimepiride with its binding protein determines the probability of the ATP-sensitive potassium channel being open or closed.
Glimepiride closes the potassium channel. This induces depolarization of the beta cell and results in opening of voltage-sensitive calcium channels and influx of calcium into the cell. Finally, the rise in intracellular calcium concentration activates the release of insulin through exocytosis.
Glimepiride associates with and dissociates from its binding protein much more rapidly and, hence, frequently than glibenclamide. It is assumed that this characteristic high exchange rate of glimepiride with the binding protein is responsible for its pronounced glucose sensitizing effect and for protecting the beta cells from desensitization and premature exhaustion.
Insulin-sensitizing effect: Glimepiride augments the normal action of insulin on peripheral glucose uptake (human and animal data).
Insulin-mimetic effects: Glimepiride mimics the action of insulin on peripheral glucose uptake and hepatic glucose output.
Peripheral glucose uptake occurs by transport into the muscle and fat cells. Glimepiride directly increases the number of glucose transport molecules in the plasma membranes of muscle and fat cells. The increased influx of glucose causes an activation of the glycosylphosphatidylinositol-specific phospholipase C. As a result, cellular cAMP levels decrease, causing a reduction in activity of protein kinase A; this in turn results in a stimulation of the metabolism of the glucose.
Glimepiride inhibits hepatic glucose output by increasing the concentration of fructose-2,6 bisphosphate which inhibits gluconeogenesis.
Effects on platelet aggregation and formation of atherosclerotic plaques: Glimepiride reduces platelet aggregation in vitro and in vivo. This effect is probably the result of a selective inhibition of cyclooxygenase, which is responsible for the formation of thromboxane A, an important endogenous platelet aggregation factor.
Glimepiride significantly reduces the formation of atherosclerotic plaques in animals. The underlying mechanism has still to be elucidated.
Cardiovascular effects: Through ATP-sensitive potassium channels (see as previously mentioned), sulfonylureas also affect the cardiovascular system. Compared with conventional sulfonylureas, glimepiride has significantly less effect on the cardiovascular system (animal data). This may be explained by the specific nature of its interaction with the binding protein of the ATP-sensitive potassium channel.
Pharmacodynamic Characteristics: In healthy persons, the minimum effective oral dose is approx. 0.6 mg. The effect of glimepiride is dose-dependent and reproducible. The physiological response to acute physical exercise, i.e., reduction of insulin secretion, is still present under glimepiride.
There was no significant difference in effect regardless of whether the drug was given 30 minutes or immediately before a meal. In diabetic patients, good metabolic control over 24 hours can be achieved with one single dose. Moreover, in a clinical study, good metabolic control was even achieved in 12 out of 16 patients with renal insufficiency (creatinine clearance 4 to 79 ml/min).
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: In patients not adequately controlled with the maximum dosage of either glimepiride or metformin, combination therapy with both oral antidiabetic agents can be initiated.
The improvement in metabolic control in conjunction with combination treatment as compared to treatment with either medicinal product alone has been verified in two studies.
Combination therapy with insulin: In patients not adequately controlled with the maximum dosage 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.
Clinical Efficacy/Clinical Studies: 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 randomized children (8-17 years of age) with type 2 diabetes. Both glimepiride and metformin exhibited a significant decrease from baseline in HbA1c.
No significant difference was observed between treatment groups. Glimepiride failed to demonstrate noninferiority to metformin.
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.
Pharmacokinetics: The absolute bioavailability of glimepiride is complete. Food intake has no relevant influence on absorption. Maximum serum concentrations (Cmax) are reached approx. 2.5 hours after oral intake (309 ng/ml during multiple dosing of 4 mg daily), and there is a linear relationship between dose and both Cmax and AUC (area under the time/concentration curve). 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). 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 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 cumulation.
Pharmacokinetics in five non-diabetic patients after bile duct surgery were similar to those in healthy persons.
Special populations: Gender: Pharmacokinetics were similar in males and females.
Elderly: Pharmacokinetics were similar in young and elderly (above 65 years) patients.
Paediatric Patients: A study evaluating the pharmacokinetics, safety, and tolerability of a 1 mg single dose of glimepiride in 30 paediatric patients (aged 10 to 17 years) with type 2 diabetes showed mean AUC(0-last), Cmax and t1/2 similar to that previously observed in adults.
Renal Impairment: In a single-dose, open-label study conducted in 15 patients with renal impairment, glimepiride (3 mg) was administered to 3 groups of patients with different levels of mean creatinine clearance (CLcr); (Group I, CLcr=77.7 mL/min, n=5), (Group II, CLcr=27.4 mL/min, n=3), and (Group III, CLcr=9.4 mL/min, n=7). Glimepiride was found to be well tolerated in all 3 groups. 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.
Results from a multiple-dose titration study conducted in 16 NIDDM patients with renal impairment using doses ranging from 1-8 mg daily for 3 months were consistent with the results observed after a single dose. All patients with a CLcr less than 22 mL/min had adequate control of their glucose levels with a dosage regimen of only 1 mg daily. Overall, no additional risk of cumulation is to be assumed in such patients.
It is not known if glimepiride is dialyzable.
Toxicology: Non-Clinical Safety Data: Chronic Toxicity: In subchronic and chronic toxicity studies in rats, mice and dogs, a decline in serum glucose as well as a degranulation of the beta cells of the pancreas were noted; these were shown to be, in principle, reversible and are regarded as signs of the pharmacodynamic effect. In a chronic toxicity study in dogs, two of the animals receiving the highest dose (320 mg/kg body weight) developed cataracts. In vitro studies in the bovine lens and investigations in rats demonstrated no cataractogenic or co-cataractogenic potential.
Carcinogenicity: Lifetime studies in rats revealed no carcinogenic potential. In mice, there was an increased incidence of islet cell hyperplasia and of islet cell adenomas; these are regarded as resulting from the chronic stimulation of the beta cells. Glimepiride did not show any mutagenic or genotoxic effects.
Impairment of Fertility: Reproduction toxicology: Administration to rats revealed no effects on fertility, course of pregnancy or delivery. Fetuses delivered by caesarean section were slightly retarded in growth. In spontaneously born progeny whose mothers had been treated with high doses, anomalies of the humerus, femur, shoulder and hip joint were observed. Oral administration in the late phase of pregnancy and/or during lactation led to increased numbers of fetal deaths and to the same limb deformities. Glimepiride had no recognizable effects on the rearing, physical development, functional and learning behaviour, memory or fertility of the progeny.
In animals, glimepiride is excreted into milk.
Glimepiride is ingested by the offspring in breast milk; high doses given to mother rats cause hypoglycaemia in suckling young rats.
Malformations (e.g. eye malformations, fissures, and bone anomalies) occurred in rats and rabbits, and in rabbits only - the numbers of abortions and intrauterine deaths were increased.
All reproduction toxicology findings are probably due to the pharmacodynamic effects of excessive doses and are not substance-specific.
Moreover, compared to other sulfonylureas, glimepiride has less effect on the cardiovascular system. It reduces platelet aggregation (animal and in vitro data) and leads to a marked reduction in the formation of atherosclerotic plaques (animal data).
Insulin release: Like all sulfonylureas, glimepiride regulates insulin secretion by interacting with the ATP-sensitive potassium channel in the beta cell membrane. Unlike other sulfonylureas, glimepiride binds specifically to a 65 kDa protein located in the membrane of the beta cell. This interaction of glimepiride with its binding protein determines the probability of the ATP-sensitive potassium channel being open or closed.
Glimepiride closes the potassium channel. This induces depolarization of the beta cell and results in opening of voltage-sensitive calcium channels and influx of calcium into the cell. Finally, the rise in intracellular calcium concentration activates the release of insulin through exocytosis.
Glimepiride associates with and dissociates from its binding protein much more rapidly and, hence, frequently than glibenclamide. It is assumed that this characteristic high exchange rate of glimepiride with the binding protein is responsible for its pronounced glucose sensitizing effect and for protecting the beta cells from desensitization and premature exhaustion.
Insulin-sensitizing effect: Glimepiride augments the normal action of insulin on peripheral glucose uptake (human and animal data).
Insulin-mimetic effects: Glimepiride mimics the action of insulin on peripheral glucose uptake and hepatic glucose output.
Peripheral glucose uptake occurs by transport into the muscle and fat cells. Glimepiride directly increases the number of glucose transport molecules in the plasma membranes of muscle and fat cells. The increased influx of glucose causes an activation of the glycosylphosphatidylinositol-specific phospholipase C. As a result, cellular cAMP levels decrease, causing a reduction in activity of protein kinase A; this in turn results in a stimulation of the metabolism of the glucose.
Glimepiride inhibits hepatic glucose output by increasing the concentration of fructose-2,6 bisphosphate which inhibits gluconeogenesis.
Effects on platelet aggregation and formation of atherosclerotic plaques: Glimepiride reduces platelet aggregation in vitro and in vivo. This effect is probably the result of a selective inhibition of cyclooxygenase, which is responsible for the formation of thromboxane A, an important endogenous platelet aggregation factor.
Glimepiride significantly reduces the formation of atherosclerotic plaques in animals. The underlying mechanism has still to be elucidated.
Cardiovascular effects: Through ATP-sensitive potassium channels (see as previously mentioned), sulfonylureas also affect the cardiovascular system. Compared with conventional sulfonylureas, glimepiride has significantly less effect on the cardiovascular system (animal data). This may be explained by the specific nature of its interaction with the binding protein of the ATP-sensitive potassium channel.
Pharmacodynamic Characteristics: In healthy persons, the minimum effective oral dose is approx. 0.6 mg. The effect of glimepiride is dose-dependent and reproducible. The physiological response to acute physical exercise, i.e., reduction of insulin secretion, is still present under glimepiride.
There was no significant difference in effect regardless of whether the drug was given 30 minutes or immediately before a meal. In diabetic patients, good metabolic control over 24 hours can be achieved with one single dose. Moreover, in a clinical study, good metabolic control was even achieved in 12 out of 16 patients with renal insufficiency (creatinine clearance 4 to 79 ml/min).
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: In patients not adequately controlled with the maximum dosage of either glimepiride or metformin, combination therapy with both oral antidiabetic agents can be initiated.
The improvement in metabolic control in conjunction with combination treatment as compared to treatment with either medicinal product alone has been verified in two studies.
Combination therapy with insulin: In patients not adequately controlled with the maximum dosage 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.
Clinical Efficacy/Clinical Studies: 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 randomized children (8-17 years of age) with type 2 diabetes. Both glimepiride and metformin exhibited a significant decrease from baseline in HbA1c.
No significant difference was observed between treatment groups. Glimepiride failed to demonstrate noninferiority to metformin.
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.
Pharmacokinetics: The absolute bioavailability of glimepiride is complete. Food intake has no relevant influence on absorption. Maximum serum concentrations (Cmax) are reached approx. 2.5 hours after oral intake (309 ng/ml during multiple dosing of 4 mg daily), and there is a linear relationship between dose and both Cmax and AUC (area under the time/concentration curve). 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). 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 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 cumulation.
Pharmacokinetics in five non-diabetic patients after bile duct surgery were similar to those in healthy persons.
Special populations: Gender: Pharmacokinetics were similar in males and females.
Elderly: Pharmacokinetics were similar in young and elderly (above 65 years) patients.
Paediatric Patients: A study evaluating the pharmacokinetics, safety, and tolerability of a 1 mg single dose of glimepiride in 30 paediatric patients (aged 10 to 17 years) with type 2 diabetes showed mean AUC(0-last), Cmax and t1/2 similar to that previously observed in adults.
Renal Impairment: In a single-dose, open-label study conducted in 15 patients with renal impairment, glimepiride (3 mg) was administered to 3 groups of patients with different levels of mean creatinine clearance (CLcr); (Group I, CLcr=77.7 mL/min, n=5), (Group II, CLcr=27.4 mL/min, n=3), and (Group III, CLcr=9.4 mL/min, n=7). Glimepiride was found to be well tolerated in all 3 groups. 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.
Results from a multiple-dose titration study conducted in 16 NIDDM patients with renal impairment using doses ranging from 1-8 mg daily for 3 months were consistent with the results observed after a single dose. All patients with a CLcr less than 22 mL/min had adequate control of their glucose levels with a dosage regimen of only 1 mg daily. Overall, no additional risk of cumulation is to be assumed in such patients.
It is not known if glimepiride is dialyzable.
Toxicology: Non-Clinical Safety Data: Chronic Toxicity: In subchronic and chronic toxicity studies in rats, mice and dogs, a decline in serum glucose as well as a degranulation of the beta cells of the pancreas were noted; these were shown to be, in principle, reversible and are regarded as signs of the pharmacodynamic effect. In a chronic toxicity study in dogs, two of the animals receiving the highest dose (320 mg/kg body weight) developed cataracts. In vitro studies in the bovine lens and investigations in rats demonstrated no cataractogenic or co-cataractogenic potential.
Carcinogenicity: Lifetime studies in rats revealed no carcinogenic potential. In mice, there was an increased incidence of islet cell hyperplasia and of islet cell adenomas; these are regarded as resulting from the chronic stimulation of the beta cells. Glimepiride did not show any mutagenic or genotoxic effects.
Impairment of Fertility: Reproduction toxicology: Administration to rats revealed no effects on fertility, course of pregnancy or delivery. Fetuses delivered by caesarean section were slightly retarded in growth. In spontaneously born progeny whose mothers had been treated with high doses, anomalies of the humerus, femur, shoulder and hip joint were observed. Oral administration in the late phase of pregnancy and/or during lactation led to increased numbers of fetal deaths and to the same limb deformities. Glimepiride had no recognizable effects on the rearing, physical development, functional and learning behaviour, memory or fertility of the progeny.
In animals, glimepiride is excreted into milk.
Glimepiride is ingested by the offspring in breast milk; high doses given to mother rats cause hypoglycaemia in suckling young rats.
Malformations (e.g. eye malformations, fissures, and bone anomalies) occurred in rats and rabbits, and in rabbits only - the numbers of abortions and intrauterine deaths were increased.
All reproduction toxicology findings are probably due to the pharmacodynamic effects of excessive doses and are not substance-specific.
MedsGo Class
Antidiabetic Agents
Features
Brand
Solosa
Full Details
Dosage Strength
2 mg
Drug Ingredients
- Glimepiride
Drug Packaging
Tablet 30's
Generic Name
Glimepiride
Dosage Form
Tablet
Registration Number
DRP-007
Drug Classification
Prescription Drug (RX)
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