Metformin Hydrochloride Extended Release Tablets

Pharmacological action Metformin is a type of hypoglycemic drug that improves glucose tolerance in patients with type 2 diabetes. It not only reduces basal blood sugar, but also reduces postprandial blood sugar. Its pharmacological mechanism of action is different from other types of oral hypoglycemic drugs. Metformin reduces hepatic gluconeogenesis, reduces glucose absorption in the small intestine, and improves insulin sensitivity by increasing the uptake and utilization of glucose by peripheral tissues. Unlike sulfonylureas, metformin does not cause hypoglycemia in patients with type 2 diabetes and normal people (except for special circumstances, see [Precautions]), nor does it cause hyperinsulinemia. Although metformin treatment may reduce fasting islet levels and plasma insulin response throughout the day, insulin secretion usually does not change. Toxicological studies have reported that the dosage of rats (taking the drug for 104 weeks) and mice (taking the drug for 91 weeks) reached 900 mg/kg/day and 1500 mg/kg/day, respectively, which is approximately equivalent to four times the maximum daily dose of 2000 mg recommended for humans based on body surface area. No carcinogenic effects of metformin were found in either male or female mice, nor in male rats, but the incidence of benign urinary polyps increased in female rats treated with metformin at 900 mg/kg/day. No mutagenic effects of metformin were found in in vitro tests such as the Ames test (S. typhimurium), the gene mutation test (mouse lymphoma cells), and the chromosome aberration test (human lymphocytes). The results of the in vivo micronucleus test in mice were also negative. The fertility of male and female rats was not affected when treated with metformin at a dose of 600 mg/kg/day, which is approximately three times the maximum recommended daily dose in humans when converted by body surface area. However, this product is not recommended for use by pregnant women unless necessary. Recent research results strongly suggest that abnormal blood sugar levels during pregnancy lead to a significantly increased incidence of congenital abnormalities. A large number of trials suggest that insulin should be used during pregnancy to keep blood sugar levels as close to normal as possible.

Active ingredient: Metformin hydrochloride.

This product is a special-shaped film-coated tablet, which appears white after removing the coating.

When using this product alone, it is recommended to combine it with diet and exercise therapy to achieve the effect of controlling blood sugar in non-insulin-dependent (type 2) diabetes. This product can also be used in combination with sulfonylurea hypoglycemic drugs or insulin to control blood sugar in type 2 diabetes patients.

There is no fixed dose for the treatment of hyperglycemia with this drug in type 2 diabetes. The dose must be individualized according to the effect and tolerance without exceeding the maximum recommended dose, i.e. 2000 mg/day. This drug is usually taken as a single dose with dinner. In order to reduce the occurrence of gastrointestinal complications and to use the minimum dose of the drug to control the patient's blood sugar, it should be taken from a small dose and gradually increased. At the beginning of treatment and during the dose adjustment period (see the recommended medication plan), fasting blood sugar can be used to determine the treatment response of this drug and determine the patient's minimum effective dose. Thereafter, glycated hemoglobin should be measured every three months. Whether used alone or in combination with sulfonylurea drugs and insulin, the goal of treatment is to use the lowest effective dose to reduce fasting blood sugar and glycated hemoglobin levels to normal or near normal levels. Monitoring blood sugar and glycated hemoglobin can determine primary failure and secondary failure. The former refers to the failure to effectively lower blood sugar after taking the maximum recommended dose of the drug, while the latter refers to the loss of satisfactory blood sugar-lowering effect after the initial effective period. For patients who usually control blood sugar well with diet alone but have temporary blood sugar elevation, short-term use of this drug is effective. Recommended Dosing Plan Adults - Usually, there is no clinically significant response at doses below 1500 mg/day. However, in order to reduce gastrointestinal adverse reactions, it is recommended to start with a small dose and gradually increase the dose. Usually the starting dose of metformin hydrochloride extended-release tablets is 500 mg, taken once a day with dinner. The dose is increased by 500 mg per week, up to a maximum dose of 2000 mg, taken once a day with dinner. If blood sugar is still not satisfactorily controlled with 2000 mg, once a day, you can consider switching to 1000 mg, twice a day for experimental treatment. If a larger amount of metformin is needed, the maximum dose of 2550 mg/day of metformin hydrochloride tablets should be used, taken in divided doses. A randomized trial of switching from metformin hydrochloride tablets to metformin hydrochloride extended-release tablets showed that patients receiving metformin hydrochloride tablets can safely switch to metformin hydrochloride extended-release tablets once a day at the same dose, up to 2000 mg once a day. Blood sugar should be closely monitored after the switch, and the dose should be adjusted accordingly. Switching from other hypoglycemic treatments Except for chlorpropamide, patients usually do not need a conversion period when switching from other oral hypoglycemic drugs to this product. Patients taking chlorpropamide should pay close attention to this product in the first two weeks of switching, because chlorpropamide stays in the body for a long time, which can easily lead to overdose of the drug and hypoglycemia. Combination with sulfonylureas If patients do not respond to the maximum recommended dose of this product after several weeks, they should consider gradually adding sulfonylurea oral hypoglycemic drugs while maintaining the maximum dose treatment, unless the patient has primary or secondary failure to sulfonylurea drugs. Currently, there are only clinical and pharmacokinetic data on the interaction between metformin and glibenclamide (glyburide). When taking this product in combination with sulfonylurea drugs, satisfactory blood sugar control can be achieved by adjusting the doses of the two drugs. The risk of hypoglycemia caused by sulfonylurea drugs continues to exist or even increases when combined with this product, and appropriate prevention should be carried out. (See the package insert of the selected sulfonylurea drug). If the patient still cannot satisfactorily control blood sugar after 1 to 3 months of combined treatment with the maximum dose of this product and the maximum dose of oral sulfonylurea drugs, consider changing the treatment method, including combining this product, insulin treatment or insulin alone. When combined with insulin in adults, the insulin dose can be maintained when starting to add this product. The starting dose of this product for patients treated with insulin should be 500 mg once a day. If the patient's response is not enough, increase 500 mg after 1 week, and then increase 500 mg every week until satisfactory blood sugar control is achieved. The recommended maximum daily dose is 2000 mg. When the fasting blood sugar of patients using this product in combination with insulin drops below 120 mg/dl, it is recommended to reduce the insulin dose by 10% to 25%. Or follow the doctor's advice. Individualized adjustments should continue to be made based on the response to lower blood sugar.

Common adverse reactions of this product include diarrhea, nausea, bloating, fatigue, indigestion, abdominal discomfort and headache. Some patients stopped taking the drug due to diarrhea. Other rare cases include abnormal stool, constipation, abdominal pain, bloating, hypoglycemia, myalgia, dizziness, abnormal nails, rash, increased sweating, abnormal taste, chest discomfort, chills, flu symptoms, hot flashes, palpitations, weight loss, etc. Metformin can reduce the absorption of vitamin B12, but rarely causes anemia. The incidence of lactic acidosis in patients treated with metformin hydrochloride is very low, usually in patients with obvious renal dysfunction. If any adverse events and/or adverse reactions outside of this instruction manual occur after taking this product, please contact your doctor.

Patients with the following diseases are contraindicated to use metformin hydrochloride: 1. Kidney disease or renal insufficiency caused by cardiovascular failure, acute myocardial infarction and sepsis (such as blood creatinine level ge; 1.5mg/dl (male), ge; 1.4mg/dl (female) or abnormal creatinine clearance). 2. Congestive heart failure requiring drug treatment, and other serious cardiopulmonary diseases. 3. Patients who have received radiotherapy including parenteral administration of iodinated contrast agents should suspend the use of metformin hydrochloride, because the use of such products can cause acute changes in renal function. 4. Known allergies to metformin hydrochloride and any ingredients in this product. 5. Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma. 6. Severe infection and trauma, major surgical operations, clinical hypotension and hypoxia, etc. 7. Alcoholism. 8. Uncorrected vitamin B12 and folic acid deficiency.

Precautions for children: The safety and efficacy of this product for children have not been established and it is not recommended for use. Precautions for pregnancy and lactation: This product is not recommended for pregnant women. Breastfeeding women should use this product with caution. If it must be used, breastfeeding should be stopped. Precautions for the elderly: When elderly patients over 65 years old use metformin, they should be cautious and have their renal function checked regularly. The maximum dose is usually not used. It is not recommended for patients over 80 years old unless their creatinine clearance test shows that their renal function is not reduced.

1. Single-dose combined use of metformin and glibenclamide did not change the pharmacokinetic parameters of metformin. 2. When metformin was used in combination with furosemide (furosemide), the AUC of metformin increased, but renal clearance did not change; at the same time, the Cmax and AUC of furosemide decreased, the terminal half-life shortened, and renal clearance did not change. 3. Cationic drugs secreted by the renal tubules (such as amiloride, digoxin, morphine, procainamide, quinidine, quinine, ranitidine, triamterene, trimethoprim and vancomycin) may theoretically compete with metformin for the renal tubular transport system and interact with each other. Therefore, it is recommended to closely monitor and adjust the dose of this product and/or interacting drugs. 4. When metformin was used in combination with cimetidine, the plasma and whole blood AUC of metformin increased, but when the two drugs were used alone, no change in the elimination half-life of metformin was observed. The pharmacokinetics of cimetidine did not change. 5. If you are taking certain drugs that may cause blood sugar to rise at the same time, such as thiazides or other diuretics, glucocorticoids, phenothiazines, thyroid preparations, estrogen, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blockers and isoniazid, you should monitor blood sugar closely, and pay close attention to the occurrence of hypoglycemia after these drugs are discontinued. 6. Metformin does not bind to plasma proteins. Therefore, drugs that are highly bound to proteins, such as salicylates, aminobenzenesulfonic acid, chloramphenicol, probenecid, etc., are less likely to interact with sulfonylureas, which are mainly bound to serum proteins. 7. Except for chlorpropamide, patients usually do not need a conversion period when switching from other oral hypoglycemic drugs to this product. Patients taking chlorpropamide should pay close attention to the first 2 weeks of switching to this product, because chlorpropamide has a long retention in the body, which can easily lead to overdose of the drug and hypoglycemia. 8. When healthy people take nifedipine and metformin together as a single dose, the peak plasma concentration and area under the plasma concentration-time curve of metformin increase by 20% and 9% respectively, and the excretion in urine increases, but the Tmax and half-life are not affected. 9. Metformin increases the anticoagulant tendency of warfarin. 10. The combination of resin drugs and this product can reduce the absorption of metformin.

Keep away from light, in a cool and dry place.

0.5 g (calculated as C4H11N5HCl)

24 months.

CHIA TAI Tianqing Pharmaceutical Group Co., Ltd.

• Founded in:

  1997-04-16

• Address:

  No. 369, Yuzhou South Road, Lianyungang City, Jiangsu Province

• Tax NO.:

  91320000608398264T

• Registered Funds:

  890 million yuan

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