Metformin hydrochloride sustained-release tablets (III)

Pharmacological action: Metformin can reduce hepatic glucose production, inhibit intestinal absorption of glucose, and increase the uptake and utilization of glucose by peripheral tissues. It can improve insulin sensitivity by increasing the uptake and utilization of peripheral sugar. Toxicological action: Genetic toxicity The results of Ames test, mouse lymphocyte gene mutation test, human lymphocyte chromosome aberration test and mouse micronucleus test were all negative. Reproductive toxicity Male and female rats were given metformin hydrochloride at a dose of up to 600 mg/kg/day (equivalent to 3 times the maximum daily dose recommended by human clinical practice based on body surface area), and no effect on fertility was observed. Rats and rabbits were given metformin hydrochloride at a dose of up to 600 mg/kg/day (equivalent to 2 times and 6 times the maximum daily dose recommended by human clinical practice based on body surface area), and there was no teratogenic effect. The results of studies on lactating rats showed that metformin hydrochloride can be secreted into breast milk and can reach the level in plasma. Carcinogenicity Rats were given metformin 900 mg/kg/day for 104 weeks and mice were given metformin 1500 mg/kg/day for 91 weeks (these doses are equivalent to 4 times the maximum recommended clinical daily dose of metformin of 2000 mg calculated by body surface area). No evidence of metformin carcinogenicity was found in male and female mice. Metformin was also not found to be carcinogenic in male rats, but there was an increase in the occurrence of benign stromal uterine polyps in female rats at 900 mg/kg/day.

The main ingredient of this product is metformin hydrochloride. Chemical name: 1,1-dimethylbiguanide hydrochloride. Molecular formula: C4H11N5•HCl. Molecular weight: 165.63

This product is a white coated tablet, which appears white after removing the coating.

This product is used for adults with type 2 diabetes who have not responded to simple diet control and physical exercise. It can be used as a single drug or in combination with sulfonylureas or insulin.

The tablet must be swallowed whole and must not be crushed or chewed before taking. There is no fixed dose for this product to treat hyperglycemia in type 2 diabetes. The dose is adjusted individually according to efficacy and tolerance without exceeding the maximum recommended daily dose of 2500 mg. This product 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 adequately control the patient's blood sugar, it should be taken from a low dose and gradually increased. At the beginning of treatment and during dose adjustment (see recommended medication schedule), fasting blood sugar can be used to determine the treatment response of this product and determine the patient's minimum effective dose. Thereafter, glycated hemoglobin should be measured every three months. Whether used alone or in combination with sulfonylureas or 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. Recommended Dosage Plan: For adults with normal renal function (eGFR ≥ 90 mL/min/1.73 m2), the starting dose of this product is usually 500 mg once a day, taken with a glass of water at dinner. Depending on clinical needs, 1000 mg once a day can also be taken. The dose is increased by 500 mg per week to a maximum dose of 2500 mg, taken once a day with dinner. The results of a trial of patients treated with metformin hydrochloride tablets switching to metformin hydrochloride extended-release tablets suggest that patients receiving metformin hydrochloride tablets can safely switch to metformin hydrochloride extended-release tablets once a day at the same dose, up to 2500 mg once a day. After the switch, blood sugar should be closely monitored and the dose 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 2 weeks of switching, because chlorpropamide has a long retention time in the body, which can easily lead to overdose of the drug and hypoglycemia. Combined use with sulfonylureas: If patients do not respond to the maximum recommended dose of this product after four weeks, you should consider gradually adding a sulfonylurea oral hypoglycemic drug while maintaining the maximum dose of treatment, unless the patient has already failed to respond to sulfonylureas. Currently, there are only clinical and pharmacokinetic data on the interaction between metformin and glibenclamide (glyburide). When taking this product in combination with sulfonylureas, satisfactory blood sugar control can be achieved by adjusting the doses of both drugs. The risk of hypoglycemia caused by sulfonylureas persists and may even increase with combined treatment with this product, and appropriate prevention should be carried out. (See the package insert of the selected sulfonylurea drug). If patients cannot achieve satisfactory blood sugar control after 1 to 3 months of combined treatment with the maximum dose of this product and the maximum dose of oral sulfonylureas, consider changing the treatment method, including combining this product with insulin therapy or insulin alone. Combined use with insulin in adults: When starting to add this product, you can maintain the insulin dose. The starting dose of this product for patients treated with insulin should be 500 mg once a day. If the patient's response is insufficient, increase 500 mg after 1 week, and then increase 500 mg per week until satisfactory blood sugar control is achieved. The recommended maximum daily dose is 2500 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%-25%. Individualized adjustments should continue to be made based on the response to lower blood sugar or as directed by a doctor. Recommended use in patients with renal impairment: The patient's renal function should be assessed before administering this product, and should be assessed regularly thereafter. No dose adjustment is required for eGFR ≥ 60 mL/min/1.73 m2, and the dose should be reduced for eGFR 45~59 mL/min/l.73 m2. This product is not suitable for patients with a glomerular filtration rate below 45 mL/min/l.73 m2. Temporary discontinuation of medication in patients undergoing iodinated contrast imaging Patients with eGFR between 45 and 60 mL/min/l.73 m2 should stop taking this drug before or during iodinated contrast imaging, and patients with a history of liver damage, alcoholism, or heart failure should stop taking this drug before arterial perfusion iodinated contrast imaging. Reassess eGFR 48 hours after the end of the contrast imaging, and the medication can be restarted after renal function has recovered.

According to foreign literature reports: During the initial treatment, the most common adverse reactions are nausea, vomiting, diarrhea, abdominal pain and loss of appetite, which can usually be relieved by themselves in most patients. The following adverse reactions may occur when taking metformin hydrochloride extended-release tablets. The frequency of adverse reactions is defined as follows: very common (≥10%); common (1%~10%, including 1%), occasional (0.1%~1%, including 0.1%), rare (0.01%~0.1%, including 0.01%), very rare (0.01%). In each frequency group, adverse reactions are arranged in order of decreasing severity. Metabolic and nutritional disorders: very rare: lactic acidosis (see [Precautions]) Long-term use of metformin may reduce the absorption of vitamin B12. This cause should be considered if the patient develops megaloblastic anemia. Nervous system abnormalities: common: taste disorders Gastrointestinal abnormalities: very common: gastrointestinal abnormalities such as nausea, vomiting, diarrhea, abdominal pain and loss of appetite. Most of these adverse reactions occur at the beginning of treatment, Most patients usually recover on their own. Slowly increasing the dose can improve gastrointestinal tolerance. Hepatobiliary dysfunction: Very rare: There are reports of individual cases of abnormal liver function tests or hepatitis that returned to normal after stopping metformin. Skin and subcutaneous tissue abnormalities: Very rare: Skin reactions such as erythema, itching, and urticaria. Other possible adverse reactions include: bloating, fatigue, dyspepsia, abdominal discomfort and headache, abnormal stool, constipation, abdominal distension, hypoglycemia, myalgia, dizziness, lightheadedness, abnormal nails, rash, increased sweating, chest discomfort, chills, flu symptoms, hot flashes, palpitations, weight loss, accidental injury, infection, rhinitis, etc. Adverse reactions reported with post-marketing metformin treatment include cholestasis, hepatocellular and mixed hepatocellular injury.

Severe renal failure (eGFR) Acute conditions that may affect renal function, such as dehydration, severe infection, shock; diseases that can cause tissue hypoxia (especially acute diseases or exacerbation of chronic diseases), such as decompensated heart failure, respiratory failure, recent myocardial infarction and shock; severe infection and trauma, major surgical operations, clinical hypotension and hypoxia, etc.; known allergy to metformin hydrochloride and any ingredient in this product; any acute metabolic acidosis, including lactic acidosis, diabetic ketoacidosis; prodromal stage of diabetic coma; liver dysfunction, acute alcoholism, alcoholism; uncorrected vitamin B12 and folic acid deficiency

Precautions for children: The safety and efficacy of this product for children (under 17 years old) have not been established and is not recommended for use. Precautions for pregnancy and lactation: Metformin is not recommended for patients who are planning to become pregnant or are already pregnant. However, insulin can be used to maintain blood sugar levels as close to normal as possible, thereby reducing the risk of fetal malformations. For lactating women, metformin can be excreted through breast milk. Breastfeeding is not recommended during metformin treatment. Precautions for the elderly: Because elderly patients may have impaired renal function, renal function should be checked regularly and the dose of metformin should be adjusted according to renal function.

1. The combined use of metformin and glibenclamide as a single dose did not change the pharmacokinetic parameters of metformin. The AUC and Cmax of the pharmacokinetic curve of glibenclamide decreased, but there was no fixed trend, which was of little clinical significance. 2. When metformin was used in combination with furosemide (furosemide), the AUC and Cmax 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, which may increase the risk of lactic acidosis. Therefore, it is recommended to closely monitor and adjust the dose of this product and/or interacting drugs. 4. When metformin is used in combination with cimetidine, the plasma and whole blood AUC of metformin increases, and no change in the elimination half-life of metformin is observed. The pharmacokinetics of cimetidine are unchanged. 5. If certain drugs that may cause hyperglycemia are taken at the same time, such as thiazides or other diuretics, glucocorticoids, phenothiazines, thyroid preparations, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blockers and isoniazid, blood sugar should be closely monitored, and after these drugs are discontinued, close attention should be paid to the occurrence of hypoglycemia. 6. Metformin does not bind to plasma proteins. Therefore, drugs that are highly bound to proteins, such as salicylates, sulfonamides, chloramphenicol, and probenecid, 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 two 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 use nifedipine and metformin together as a single dose, the Cmax and AUC 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 has the tendency to increase the anticoagulant effect of warfarin. 10. The combination of resin drugs and this product can reduce the absorption of metformin. 11. Experiments conducted in healthy subjects have shown that metformin and propranolol, as well as metformin and ibuprofen, do not affect each other's pharmacokinetics when administered as a single dose. 12. Topiramate or other carbonic anhydrase inhibitors (such as zonisamide, acetazolamide, dichlorphenamide) can cause a decrease in plasma bicarbonate, reduce the non-anion gap and metabolic acidosis. The combined use of these drugs with this product will increase the risk of lactic acidosis, and these patients should be monitored more closely. 13. Alcohol is known to affect the effect of metformin on lactic acid metabolism. Therefore, patients receiving this product should be warned to avoid excessive drinking.

Seal tightly, protect from light, and store in a dry place below 25℃.

0.5g: National Medicine Standard No. H20193408; 1.0g: National Medicine Standard No. H20193409

24 months

Qingdao BAHEAL Pharmaceutical Co., Ltd.

• Founded in:

  1990-02-07

• Address:

  No. 88, Taiji Road, Jimo District, Qingdao City, Shandong Province

• Tax NO.:

  91370200163570278P

• Registered Funds:

  98.3043 million yuan

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