Melbin

Melbin

metformin

Manufacturer:

Shiono Chemical

Distributor:

Main Life
Full Prescribing Info
Contents
Metformin hydrochloride.
Description
One MELBIN tablet contains 250 mg of metformin hydrochloride JP.
Size: 9.6 mm diameter, 5.4 mm thickness, 380 mg weight.
Identification code: MTR-250.
Chemical name: 1,1-Dimethylbiguanide monohydrochloride.
Molecular formula: C4H11N5·HCl.
Molecular weight: 165.62.
Metformin hydrochloride occurs as a white crystal or crystalline powder. It is soluble in water, sparingly soluble in acetic acid (100) and slightly soluble in ethanol (99.5).
Melting point: approximately 221°C (decomposition).
Excipients/Inactive Ingredients: Lactose hydrate, corn starch, hydroxylpropylcellulose, starch sodium glycolate, talc, magnesium stearate, hypromellose, macrogol.
Action
Pharmacology: Metformin hydrochloride is a hypoglycemic drug. Its mechanism of action is thought to promote signaling (transferring glucose transporter 4 to cell member through activation of AMP kinase or promoting combustion of fatty acid in liver or skeleton muscle cell, etc.) at after step of insulin receptor.
Pharmacokinetics: Bioequivalence test: Each tablet (metformin hydrochloride 250 mg) of MELBIN Tab 250 mg or a standard preparation was orally administered singly in healthy adult males under fasting by using cross-over method. The concentration of unchanged drug in blood plasma was measured. For drug kinetics parameters (AUC, Cmax) gained above, statistical analysis was performed by 90% confidence interval method.
The results indicated the parameters were in the range of log(0.8)-log(1.25) and could be verified for both drugs to be bioequivalent. (See Table 1 and figure.)

Click on icon to see table/diagram/image


Click on icon to see table/diagram/image

The concentration in blood plasma and parameters of AUC, Cmax and etc. are possibly different, depending on test conditions for choice of test subject, number of times or interval-time in sampling body fluid, etc.
Dissolution behavior: It has been verified that MELBIN Tab 250 mg conformed to the dissolution specification of metformin hydrochloride tablets established in Japan Pharmaceutical Codex Part 3.
Indications/Uses
Non-insulin dependent (type II) diabetes mellitus.
MELBIN Tablet is indicated only in cases where either of the following treatments is not adequately effective: dietetic therapy and exercise therapy per se; dietetic therapy and exercise therapy with sulfonylurea agents.
Dosage/Direction for Use
Initially, 500 mg of metformin hydrochloride is orally administered daily in 2-3 divided doses after meals normally.
Maintenance dosage should be decided according to individual response to the initial treatment. The maximum daily dosage should be 750 mg.
Overdosage
Symptoms: Overdose may induce lactic acidosis. (See Lactic acidosis under Adverse Reactions.)
Treatment: Appropriate measures such as correction of acidosis (intravenous injection of sodium bicarbonate, etc.), fluid infusion (forced diuresis) and hemodialysis should be taken.
Contraindications
This drug is contraindicated in the following patients.
Patients with any of the following conditions: Predisposition to lactic acidosis.
History of lactic acidosis.
Impaired renal function (including mild disorders): Decreases renal excretion of this drug.
Dialytic patients (including peritoneal dialytic patients): High blood level may persist.
Impaired hepatic function: Impairs lactate metabolic capacity in the liver.
Patients with serious disorders in cardiovascular or pulmonary function (shock, cardiac failure, cardiac infarction, pulmonary embolism, etc.), or other conditions that are apt to cause hypoxemia: Increases production of lactate.
Excessive alcohol intake: Impairs lactate metabolic capacity in the liver.
Patients with gastrointestinal disorders of diarrhea or vomit, etc. which are concerned about dehydration illness or dehydration conditions.
Elderly patients (see Use in Elderly under Precautions).
Patients with severe ketosis, diabetic coma or pre-diabetic coma, type-1 diabetes: It is essential to remedy immediately hyperglycemia by using infusion solution or insulin.
Patients with severe infection before or after an operation, or with serious external wounds: As it is desired to control blood glucose with insulin injection, it is unsuitable to administer this. And it is to predispose lactic acidosis.
Patients suffering from malnutrition, inanition, marasmus, pituitary dysfunction or adrenal dysfunction: Low blood glucose may occur.
Pregnant women, or women suspected of being pregnant: See Use in Pregnancy & Lactation.
Patients with a history of hypersensitivity to any component of this drug or to biguanide preparations.
Warnings
Serious lactic acidosis may occur and death cases are reported.
Do not administer to patients who are predisposed to lactic acidosis. (See Contraindications.)
Pay attention particularly to dosage, administration and precautions concerning use.
Special Precautions
Careful administration: MELBIN Tablet should be administered with caution in the following patients.
Patients with any of the following conditions [predisposition to lactic acidosis and hypoglycaemia]: Irregular or insufficient meal intake [hypoglycaemia may occur], Strenuous muscular exercise [hypoglycaemia may occur], Infections [lactic acidosis may occur], Co-administration with drugs indicated in Interactions [lactic acidosis may occur], Patients under administration of other diabetes drug (see Interactions and Adverse Reactions).
Important Precautions: Severe lactic acidosis or severe and prolonged hypoglycaemia may occasionally occur in patients receiving metformin. Therefore, due attention should be paid to patients engaged in work on elevated scaffolds or patients driving motor vehicles, etc. during medication. The patients and their family members should be fully informed of precautions concerning lactic acidosis and hypoglycaemia.
In patients examined with iodinated contrast medium, co-administration may induce lactic acidosis. Therefore, MELBIN Tablet should be withdrawn temporarily before examination (except for emergency examination). For 48 hours after administration of iodinated contrast medium, MELBIN Tablet should not be administered. Attention should be paid to the patients' health condition when administration of MELBIN Tablet is resumed. (See Interactions.)
Hypoglycemia symptom may occur. Therefore attend administration to patients who engage in high-place work or drive, etc. The attentions for hypoglycaemia symptom should be paid to patients and their families.
Lactic acidosis may occur by dehydration. Administration should be discontinued and proper treatments should be taken when dehydration appears.
Take account of use only to patients to whom the diagnosis of diabetes is established. Take notice there are disorders which have abnormal glucose tolerance and positive sugar urine similar to diabetes (renal diabetes, abnormal thyroid function, etc.).
Renal excretion of this drug decreases and the blood level of this drug increases in patients with kidney dysfunction. Take sufficient care of kidney function and condition of patients and to study for the acceptance of administration before start of administration or during administration. Use the values of eGFR and serum creatinine as a reference to evaluate for kidney functions.
Other Precautions: It is reported that hypoglycaemia is predisposed to occur by administering angiotensin-converting enzyme inhibitors during treatments with insulin or oral anti-hyperglycemic drugs.
Use in Elderly: Elderly patients generally have impaired renal and hepatic functions, etc. It is contraindicated for administration to the elderly since certain conditions are predisposed to lactic acidosis.
Use in Children: Safety in premature infants, neonates, nursing infants, infants or children has not been established.
Use In Pregnancy & Lactation
Administration to pregnant women, parturient women, nursing women, etc: This drug should not be administered to pregnant women or women suspected of being pregnant. "In animal tests (rats, rabbits), it was observed to transition into a fetus and reported that there were teratogenic actions in partial test animals. And pregnant women are predisposed to lactic acidosis."
Administration of this drug should be avoided to nursing women. Breast-feeding should be discontinued when administration should not be discontinued.
Adverse Reactions
For this drug, the investigation of usage results, etc. is not performed to make incidence of adverse reactions.
Clinically significant adverse reactions (Incidence unknown): Lactic acidosis: Lactic acidosis (showing increase of blood lactate value, increase of lactic acid/pyruvate ratio, decrease of blood pH, etc.) tends to have a poor prognosis. Clinical symptoms generally appeared are diverse, and gastrointestinal symptom, feeling of malaise, muscle ache and hyperpnea, etc. are often observed. Therefore administration of this drug should be discontinued immediately and necessary examinations should be conducted when these symptoms are observed. When lactic acidosis is strongly suspected, appropriate treatment should be promptly taken even before the results of blood lactate determination becomes available.
Hypoglycemia: Careful observation of the condition of patients is required through administration as hypoglycaemia may occur. Patients should normally be given sucrose when hypoglycemic symptoms (initial symptoms: feeling of weakness, severe hunger sensation and sweating, etc.) occur. Patients should be given glucose when hypoglycemic symptoms occur by co-administration with α-glycosidase inhibitors (Acarbose, Voglibose and Miglitol).
Hepatic function disorder and jaundice: Hepatic function disorder and jaundice with marked increase, etc. of AST (GOT), ALT (GPT), Al-P, γ-GTP and bilirubin may occur. Accordingly, close observation should be conducted and if abnormality is observed, appropriate measures such as discontinuation of administration should be taken.
Rhabdomyolysis: Rhabdomyolysis which is characterized by muscle ache, sense of exhaust, CK (CPK) increase, myoglobin increase in blood or urine may occur. In this case, administration should be discontinued and suitable treatments should be taken.
Other adverse reactions: If any of the following adverse reactions occurs, appropriate measures including dose reduction or discontinuation of administration should be taken as necessary. (See Table 2.)

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Drug Interactions
Precautions for co-administration (This product should be administered with care when co-administered with the following drugs.) (See Table 3.)

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Caution For Usage
At dispensing of drug: For drugs that are dispensed in press-through package (PTP), instruct patients to remove the drug from the PTP sheet prior to use.
It is reported that when PTP sheet is swallowed, the sharp corners of the sheet may puncture the esophageal mucosa, resulting in severe complications such as mediastinitis, etc.
Storage
Store at room temperature.
MIMS Class
ATC Classification
A10BA02 - metformin ; Belongs to the class of biguanides. Used in the treatment of diabetes.
Presentation/Packing
Tab 250 mg (white film-coated tablet) x 100's.
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