Date of approval: XXXX XXXX, XXXX
Date of revision: XXXX XXXX XXXX
Gliclazide tablets instructions
Please read the instructions carefully and use under the guidance of a physician
Drug Name]
Generic name: Gliclazide Tablets
English name: Gliclazide Tablets
Hanyu Pinyin：Gelieqite Pian
Ingredients
The main ingredient of this product is: Gliclazide. Its chemical name is: 1-(3-azabicyclo[3.3.0]octyl)-3-tosylurea.
Chemical structure formula.
Molecular formula: C15H21N3O3S
Molecular weight: 323.41
Properties]: This product is a white or off-white tablet.
Indications】For adult type 2 diabetic patients whose blood glucose level is not sufficiently controlled by diet control, physical exercise and weight reduction alone.
Specification】80mg
Dosage】Orally.
The initial dosage is 40~80mg (half tablet~1 tablet) once, 1~2 times a day, later adjusted to 80mg~240mg (1~3 tablets) a day, divided into 2~3 doses according to blood glucose level, after the blood glucose is controlled, the daily maintenance dosage will be changed. Reduce the dosage for geriatric patients.
[Adverse Reactions].
Based on clinical experience with gliclazide, the following adverse reactions have been reported.
The most common adverse reaction to gliclazide is hypoglycemia.
As with other sulfonylureas, treatment with gliclazide may result in hypoglycemia if meals are irregularly timed, especially if they are not eaten. Possible symptoms of hypoglycemia include: headache, intense hunger, nausea, vomiting, fatigue, sleep disturbance, agitation, aggressive behavior, inattention, decreased consciousness, slowed reaction, depression, confusion, visual and speech disturbances, aphasia, tremor, light paralysis, sensory disturbances, dizziness, feelings of helplessness, loss of self-control, delirium, convulsions, superficial breathing, bradycardia, drowsiness and loss of consciousness, which may lead to coma and death.
In addition, adrenergic counter-regulatory symptoms may occur: sweating, moist skin, anxiety, tachycardia, hypertension, palpitations, angina pectoris and arrhythmias.
Usually, the symptoms disappear after the intake of carbohydrates (sugar). However, artificial sweeteners are not effective. Experience with other sulfonylureas suggests that hypoglycemia may occur even after the above measures have taken effect.
If hypoglycemic symptoms are severe or prolonged, immediate medical attention or even hospitalization is required, even if the symptoms are temporarily controlled after sugar intake.
Gastrointestinal disorders including abdominal pain, nausea, vomiting, dyspepsia, diarrhea and constipation have been reported and taking gliclazide with breakfast may avoid or alleviate these adverse effects.
Very rarely, the following adverse reactions have been reported.
-Dermal and subcutaneous tissue disorders: rash, pruritus, urticaria, angioedema, erythema, maculopapular rash, maculopapular reactions (e.g., Stevens-Johnson syndrome and toxic epidermal necrolysis), and drug rash with eosinophilia and systemic symptoms (drug hypersensitivity syndrome, DRESS).
-Hematologic and lymphatic system disorders: less likely to produce changes in hematologic indicators. May include anemia, leukopenia, thrombocytopenia, and granulocytopenia, usually reversible after discontinuation of the drug.
-Hepatobiliary disorders: elevated liver enzyme levels (AST, ALT, alkaline phosphatase), hepatitis (rare).
If cholestatic jaundice develops, treatment should be discontinued. The above symptoms usually disappear after discontinuation of the drug.
-Visual disturbances
Transient visual disturbances may occur at the start of treatment due to changes in blood glucose levels.
The following adverse reactions have been observed with other sulfonylureas during clinical use.
Erythrocytopenia, granulocyte deficiency, hemolytic anemia, pancytopenia, allergic vasculitis, hyponatremia, elevated liver enzyme levels or even impaired liver function (e.g., cholestasis and jaundice) and reversible sulfonylurea-induced hepatitis or, in isolated cases, life-threatening liver failure.
[Contraindications] The following conditions should be contraindicated.
1. hypersensitivity to any component of this product, other sulfonylureas or sulfonamides.
2. patients with clearly diagnosed type 1 diabetes mellitus (insulin-dependent).
3. diabetic patients with prodromal diabetes coma, coma or ketoacidosis.
4. patients with hepatic or renal insufficiency.
5. patients treated with miconazole (a drug used to treat fungal infections).
6. Contraindicated in nursing mothers (see [Pregnancy and Nursing Mothers]).
Precautions]
1. Hypoglycemia.
(1) This product should be taken as prescribed only if the patient is likely to maintain a regular diet (including breakfast). Late meal times, inadequate food intake, or low carbohydrate content of ingested foods can increase the risk of hypoglycemia, so regular carbohydrate intake is important.
(2) Low-calorie diet, prolonged or strenuous exercise, alcohol consumption or the combination of hypoglycemic drugs are more likely to cause hypoglycemia, so care should be taken to prevent hypoglycemic reactions.
(3) Hypoglycemia may occur after taking sulfonylureas. Severe and prolonged cases may occur. Hospitalization for several days may be required to control blood glucose.
(4) Patients must be carefully selected for dosing and given clear instructions to reduce the risk of hypoglycemic episodes.
(5) Factors that increase the risk of hypoglycemia.
-patient refusal or (especially in elderly patients) non-cooperation.
-Malnutrition, irregular diet, non-feeding, fasting or recipe changes.
-imbalance between physical activity and carbohydrate intake
-renal insufficiency.
-severe hepatic insufficiency.
-Overdose of this product.
-certain endocrine disorders: thyroid disorders, hypopituitarism and adrenal insufficiency.
-Concurrent administration of certain other drugs.
2. hepatic and renal insufficiency: the pharmacokinetic and/or pharmacodynamic parameters of gliclazide may be altered in patients with hepatic insufficiency or severe renal failure, resulting in prolonged hypoglycemic effects, which should be treated appropriately.
3. Patient information: The dangers of hypoglycemia, its symptoms and treatment, and the causes of hypoglycemia should be clearly explained to patients and their families. Patients should be informed of the importance of following dietary recommendations, engaging in regular exercise, and monitoring blood glucose levels regularly.
4. Poor blood glucose control.
Blood glucose control in patients receiving antidiabetic therapy may be affected by any of the following factors: St. John’s Wort (Kanzai) preparations, fever, trauma, infection, or undergoing surgery.
In some cases, such as stressful situations such as infection, trauma, surgery and ketoacidosis and non-ketotic hyperosmolar diabetic coma, treatment should be switched to insulin.
Decreased efficacy of all oral hypoglycemic agents, including gliclazide, after longer periods of administration may occur as a result of increased severity of diabetes or failure to respond to treatment with the drug, a phenomenon called secondary failure and should be distinguished from primary failure, which is when a drug proves ineffective as first-line therapy for a given patient. Appropriate dose adjustments and monitoring of diet must be considered before classifying a patient’s treatment as a secondary failure.
5. Blood glucose abnormalities.
Glucose disturbances, including hypoglycemia and hyperglycemia, have been reported in patients with diabetes mellitus treated with combination fluoroquinolones, particularly in elderly patients. Close monitoring of blood glucose in all patients taking both this product and fluoroquinolones is recommended.
6. Laboratory Tests.
Should be taken under the supervision of a physician. Patients must be checked regularly for blood glucose and urine sugar. Measurement of glycated hemoglobin levels (or fasting intravenous glucose values) is recommended in the assessment of glycemic control. Self-monitoring of blood glucose levels may also be useful.
7. Patients with galactose intolerance, lactase deficiency, or a rare genetic condition of glucose-galactose malabsorption should not take this product.
8. Treatment of patients with hereditary glucose-6-phosphate dehydrogenase (G6PD) deficiency with sulfonylureas can lead to hemolytic anemia. Because gliclazide is a sulfonylurea, it should be used with caution in patients with G6PD deficiency and a non-sulfonylurea should be considered as an alternative.
9. When used in combination with anticoagulants, coagulation tests should be done regularly.
[For pregnant and lactating women].
Animal experiments and clinical observations have shown that sulfonylurea hypoglycemic agents can be teratogenic and can be secreted from breast milk, so this product should not be used by pregnant women and nursing mothers.
Use in children
It is not clear.
For Elderly]
The dosage should be reduced appropriately.
Drug Interactions
The risk of hypoglycemia may be increased by the use of the following drugs.
Combination application is prohibited
-Miconazole (systemic route of administration, oral mucosal gel): increases the hypoglycemic effect and may cause hypoglycemic symptoms, even coma.
Combinations are not recommended
-Phenylbutazone (systemic route of administration): increases the hypoglycemic effect of sulfonylureas (replaces their binding to plasma proteins and/or reduces their elimination). Use of other anti-inflammatory drugs is preferable, otherwise patients need to be warned and the importance of performing glucose self-monitoring needs to be emphasized. Dose adjustments should be made after treatment with anti-inflammatory drugs, if necessary.
-Alcohol: increases the hypoglycemic response (by suppressing the compensatory response) and may lead to hypoglycemic coma. Alcohol consumption or use of alcohol-containing drugs should be avoided while taking medication.
Caution is needed for combination application
The hypoglycemic effect may be enhanced by taking one of the following drugs and therefore hypoglycemia may occur in some cases.
Other antidiabetic agents (insulin, acarbose, metformin, thiazolidinediones, DPP-4 inhibitors, GLP-1 receptor agonists), beta-blockers, fluconazole, angiotensin-converting enzyme inhibitors (captopril, enalapril), H2 receptor antagonists, MAOIs (monoamine oxidase inhibitors), clarithromycin, nonsteroidal anti-inflammatory drugs (especially salicylates) sulfonamide antimicrobials, bicoumarins anticoagulants, benzodiazepines, tetracyclines, chloramphenicol, dicyclohexyl piperidine and clofibrate.
The use of the following drugs may cause an increase in blood glucose levels
Combination application is not recommended
-Danazol: Danazol causes diabetic effects. If the use of this drug cannot be avoided, patients need to be warned and the importance of urine glucose and blood glucose self-monitoring needs to be emphasized. The dose of diabetic medication should be adjusted when using and discontinuing danazol therapy.
Combination applications require caution
-Thorazine (sedation): Treatment with high doses of chlorpromazine (daily doses >100 mg) increases blood glucose levels (decreases insulin release) and patients need to be warned and the importance of self-monitoring of blood glucose levels needs to be emphasized, especially during the start of treatment. Dose adjustments of diabetes treatment medications may be required during and after sedation therapy.
Glucocorticoids (systemic and topical routes of administration: intra-articular, transdermal and rectal preparations) and ticlopidine: blood glucose levels may be elevated and may be accompanied by ketosis (reduced tolerance to carbohydrates due to glucocorticoids). Patients need to be warned and the importance of self-monitoring of blood glucose levels needs to be emphasized, especially during the start of treatment. Dose adjustments of antidiabetic drugs may be required during and after glucocorticoid therapy.
-Litodrine, salbutamol, terbutaline (intravenous): due to beta-2 agonist effect can raise blood glucose levels. The importance of self-monitoring of blood glucose levels needs to be emphasized. Switch to insulin if necessary.
-St. John’s Wort (Kanzai) preparation: The use of St. John’s Wort preparation leads to a decrease in gliclazide exposure. The importance of self-monitoring of blood glucose levels needs to be emphasized.
Combination medications that require attention
-Fluoroquinolones: If this product and fluoroquinolones are used together, patients should be warned of the risk of abnormal blood glucose and the importance of self-monitoring of blood glucose levels should be emphasized.
Combination medications to consider
-Anticoagulant therapy (warfarin, etc.): Sulfonylureas may enhance anticoagulant effects during combination dosing and may require adjustment of anticoagulant dosage.
[Drug overdose].
Sulfonylurea overdose may lead to hypoglycemia.
Moderate hypoglycemic reactions, not accompanied by any loss of consciousness or neurological symptoms, must be corrected by carbohydrate intake, dose adjustment, and/or dietary changes. Strict monitoring should be continued until the physician determines that the patient is out of danger.
Severe hypoglycemic reactions, which may present with coma, convulsions or the development of other neurological disorders, should be treated as an internal medical emergency and require immediate hospitalization.
If a hypoglycemic coma is diagnosed or suspected, the patient should be quickly given an intravenous 50% glucose solution or intramuscular glucagon. The physician should monitor the patient closely and, depending on the subsequent condition, decide whether further monitoring is necessary.
Dialysis is not effective in these patients due to the strong binding of gliclazide to proteins.
Pharmacology and Toxicology]
Pharmacological effects
Gliclazide is a sulfonylurea oral hypoglycemic agent that stimulates insulin secretion from pancreatic beta cells, thereby lowering blood glucose levels. Gliclazide restores peak first-phase insulin secretion in response to glucose, increases second-phase insulin secretion, and significantly increases postprandial or glucose-induced insulin secretion response in patients with type 2 diabetes.
Gliclazide reduces microthrombosis through two mechanisms of action that may be related to diabetic vascular complications: (1) partial inhibition of platelet coagulation and adhesion and reduction of platelet activation markers (β-platelet globulin with thromboxane B2); and (2) modulation of endothelial fibrinolytic activity by increasing t-PA activity.
Toxicological studies
Genotoxicity tests did not reveal any abnormal reactions that could suggest harmful effects in humans. No teratogenicity was observed in reproductive toxicity tests, and fetal weight loss was observed at 25 times the maximum recommended human therapeutic dose. No carcinogenicity test was conducted.
Pharmacokinetics
It is rapidly absorbed in the gastrointestinal tract and reaches its peak plasma level in 3-4 hours, with a plasma protein binding rate of 92% and a half-life of 10-12 hours.
Storage】Store under shade and seal.
Package】Aluminum-plastic package, 60 tablets per box.
Expiration date】12 months
Execution Standard
Approval Number】State Drug Administration H44024979
Marketing authorization holder
Company Name: Guangdong South China Pharmaceutical Group Co.
Registered Address: West Lake Industrial Zone, Shilong Town, Dongguan City, Information Industry Park
Manufacturer
Drug manufacturer: Guangdong South China Pharmaceutical Group Co.
Production Address: West Lake Industrial Zone, Shilong Town, Dongguan City, Information Industry Park
Postal code: 523325
Telephone number: (0769) 86188305
Fax number: (0769) 86188080
Web address: www.hn-pharm.com