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Standard Commodity Classification No. of Japan DEAMELIN®·S Tablets 250 mg
Powerful drug and Prescription drug Note) This product should be stored at room temperature. Date of listing in the NHI reimbursement price Expiration date
This product should be used before the expiration Note) Caution: Use only as directed by a physician
WARNINGS
DOSAGE AND ADMINISTRATION
This product may induce a serious and prolonged hypo- The usual dosage of this product for oral use is 125 to 250 mg glycemia. Read the sections of “DOSAGE AND of Glyclopyramide daily, and as required, may be increased to ADMINISTRATION” and “PRECAUTIONS” carefully determine a maintenance dose, with the upper limit of 500 mg This product should be orally administered once daily before or after breakfast, or twice daily before or after breakfast and CONTRAINDICATIONS (This product is contraindicat-
ed in the following patients.)
(1) Patients with severe ketosis, diabetic coma or precoma, and insulin-dependant diabetes [Insulin must be applied.] PRECAUTIONS
(2) Patients with serious hepatic or renal dysfunction [Hypo- 1. Careful Administration (This product should be admin-
istered with care in the following patients.)
(3) Patients with severe infections, pre- or post-operation, (1) Patients with hepatic or renal dysfunction and serious injury [Insulin must be applied.] (2) Patients with a possible episode of hypoglycemia, or the (4) Patients with gastrointestinal disorders, such as diarrhea (5) Patients with a history of hypersensitivity to any of 2) Pituitary malfunction or adrenal insufficiency ingredients of this product or sulfonamide preparations 3) Malnutrition, starvation, irregular intakes of meals, and (6) Pregnant or possibly pregnant women (See the section of “Use during Pregnancy, Delivery or Lactation.”) 4) Heavy muscular exercise 5) Excessive alcohol intake 6) Elderly patients (See the section of “Use in the DESCRIPTION
Product description
7) Coadministration of this product with a drug enhancing hypoglycemia, as shown in the section of “Drug Interac-tions” 2.Important Precautions
(1) This product should be administered to just the patients with an established diagnosis of diabetes. Attention should be paid to the diseases showing diabetes-like symptoms (e.g., renal glycosuria, geriatric oligosaccharidoses and thyroid dysfunction), such as abnormal glucose tolerance (2) This product should be administered only after diet and exercise therapies failed to manage diabetes properly. (3) Administration of this product should be started at a low dose, and the clinical response be investigated by regular INDICATIONS
examinations for blood and urine sugar, with the doses Insulin-independent diabetes mellitus (when symptoms cannot gradually increased. If the response is poor, this product should be immediately switched with another therapy. (4) Since the cases in which administration may not be required, the dose must be reduced, or little or no clinical response may be induced by noncompliance with treatment of patients or complicated infections may occur during the period of treatment, attention should be paid to dietary intake, change in body weight, blood glucose and the presence or absence of infections to judge continuation of administration, dosage, and selection of drugs. (5) Since this product may cause serious and prolonged
hypoglycemia, patients should be cautioned against
engaging in potentially hazardous activities requiring alertness, such as operating machines, working in heights, or driving cars. In addition, the patients and their families should be adequately informed of precautions concerning Sensitivity to insulin in the peripheral 3. Drug Interactions
Precautions for Coadministration (This product should be
administered with care when coadministered with the
inhibited, and its renal excretion is delayed. following drugs.)
(1) Drugs enhancing hypoglycemic action
Hypoglycemic symptoms, such as weakness, highly hungry feeling, diaphoresis, palpitation, tremor, headache, sensory abnormality, anxiety, excitement, nervousness, decreased mental concentration, mental disorder, dis- (2) Drugs reducing hypoglycemic action
turbed consciousness, and convulsions may develop owing to an increase in hypoglycemic action. Hyperglycemic symptoms, such as nausea, vomiting, dehydration, and acetone smell in exhalation may When this product is coadministered with any of the develop owing to a decrease in hypoglycemic action. following drugs, patients’ conditions should be adequate- ly monitored including plasma glucose and the dosage of When this product is coadministered with any of the this product or coadministered drug should be adjusted following drugs, patients’ conditions should be ade- with care if necessary. If any of hypoglycemic symptoms quately monitored including plasma glucose. is observed, sucrose should be usually administered. Separately, if any of hypoglycemic symptoms is
Mechanism and Risk Factors
observed by coadministration of the product with an
-glucosidase inhibitor (acarbose or voglibose, etc.),
glucose should be administered.
Mechanism and Risk Factors
Drugs improving insulin Insulin action is enhanced. Cortisol secretion, sugar availability in (2) Other Adverse Reactions
0.1≤ < 5%
Incidence unknown
5. Use in the Elderly
This product should be administered to elderly patients with care for hypoglycemia, with a low starting dose and frequent [Since elderly patients often have reduced physiological functions, hypoglycemia may frequently occur.] 6. Use during Pregnancy, Delivery or Lactation
4. Adverse Reactions
(1) This product should not be administered to pregnant or This product has not been investigated (Drug-use results surveys, etc.) to determine the incidence of adverse [Sulfonylurea preparations have been reported to cross reactions. The incidence data on the product have therefore the placenta to induce hypoglycemia in newborns and been collected from investigations until approval and the (2) Use of this product is not recommended in lactating Out of a total of 975 cases, 53 cases (5.44%) had adverse reactions (including laboratory test abnormalities). The most [Other sulfonylurea preparations have been reported to common reactions included 23 events (2.36%) of hypoglycemia, eight (0.82%) of anorexia, and four (0.41%) 7. Overdosage
each of abdominal discomfort, increased AST (GOT) and (1) Signs or symptoms:
increased ALT (GPT) (the results of reevaluation). Overdosage of this product may induce hypoglycemia. Adverse reactions with their incidences unknown are also (See the heading of “Hypoglycemia” in the section of (1) Clinically significant adverse reactions
(2) Treatment:
1) Hypoglycemia (2.36%)
1) For the patients who can ingest food, in general, Weakness, heavy hungry feeling, diaphoresis, palpita- sucrose should be orally given after administration of tion, tremor, headache, sensory abnormality, anxiety, this product, and glucose after coadministration of this excitement, nervousness, decreased mental concentra- product with an α-glucosidase inhibitor (acarbose or tion, mental disorder, disturbed consciousness, and/or convulsions may occur. If such a symptom occur, 2) For the patients with disturbed consciousness, 20 mL of administration should be discontinued with appropriate a 50% glucose solution should be intravenously ad- therapeutic measures taken. Since mental disorder and ministered, and as required, a 5% glucose solution disturbed consciousness may mainly develop when should be instilled to retain euglycemia. hypoglycemia deteriorates gradually, attention should 3) Glucagon may also be administered as a hyperglycemic As appropriate measures of hypoglycemia, sucrose 8. Precautions Concerning Use
should be usually given after administration of this Precautions regarding dispensing: For the drug that is
product alone, and glucose after coadministration of dispensed in a press-through package (PTP), patients should this product with an -glucosidase inhibitor (acarbose be instructed to remove the drug from the package prior to 2) Aplastic anemia and agranulocytosis (incidence
[It has been reported that if the PTP sheet is swallowed, its sharp corners may puncture the esophageal mucosa, result- Since aplastic anemia and agranulocytosis may occur, ing in serious complications such as mediastinitis.) patients should be adequately monitored. If such an 9. Other Precautions
abnormality is observed, administration should be (1) It has been reported that a long-term use of a sulfonylurea discontinued with appropriate measures taken. preparation (tolbutamide at a daily dose of 1.5 g) induced significantly higher mortality from cardiovascular disorder (2) It has been reported that administration of an angiotensin converting enzyme inhibitor is likely to induce hypogly- cemia during treatment with insulin or an oral hypoglyce- PACKAGING
DEAMELIN·S Tablets 250 mg
100 tablets (10 tablets x 10), 500 tablets (10 tablets x 50) PHARMACOKINETICS
and 1000 tablets (10 tablets x 100) in press-through 1. Plasma Concentrations1)
When a tablet of this product was orally given to male beagle dogs, the plasma concentrations reached the peak of REFERENCES
70.7 g/mL after 3.3 hours, with the biological half-life of 1) Uchida H., Comparative absorption study of glyclopyramide 2. Metabolism and Excretion2)
2) Abe Y. et al., The Clinical Report, 11, 1639 (1977) When Glyclopyramide at a single dose of 11 mg/body was 3) Oda T. et al., The Journal of Therapy, 47, 843 (1965) orally given to rats, the major metabolite excreted in urine 4) Irikura T. et al., J. Pharmaceutical Soc. Jpn., 85, 104 (1965) within 24 hours was the unchanged form, and an excretion ratio of the form to its metabolite REQUEST FOR LITERATURE SHOULD BE
p-chlorobenzenesulfonamide was 27:1. The ratio in bile,
MADE TO:
A request for in-house data mentioned in the References can
however, was 2.5:1. N-acetyl-p-chlorobenzenesulfonamide was also excreted as a minor metabolite. Overall, the Kyorin Pharmaceutical Co, Ltd. Drug Information Center metabolites including the unchanged form were mainly 6, Kanda surugadai 4-chome, Chiyoda-ku, Tokyo 101-8311, excreted in the urine, and the amount excreted in both urine and feces within 24 hours accounted for 80% of the dose. 9:00 to 17:00 (Monday through Friday exclusive of national PHARMACOLOGY
When Glyclopyramide at a dose of 150 mg/kg was orally given to rabbits, the time to reach the peak of the plasma concentrations coincided with that to reach trough of the Manufactured and Marketed by:
Kyorin Pharmaceutical Co., Ltd.
glucose levels, with about 1 hour after dosing. In addition, a 6, Kanda Surugadai 4-chome, Chiyoda-ku, Tokyo 101- 8311, dose response of Glyclopyramide at doses of 12.5 to 100 mg in rats was linear at 1 hour, and the hypoglycemic effect was 2.66 times as high as that of tolbutamide.3),4)
PHYSICOCHEMISTRY
Nonproprietary name:
Chemical name:
N-(p-Chlorobenzenesulfonyl)-N’-pyrrolidinourea Molecular formula:
Molecular weight:
Structural formula:
Melting point:
Description:
Glyclopyramide occurs as a white crystalline powder, with no odor. It is soluble in dimethylformamide, slightly soluble in acetone and chloroform, and practically insoluble in water, ethanol (95%), and diethylether. It is soluble in sodium hydroxide and ammonia solutions. Partition coefficient:

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