Drug information of chlorpropamide


chlorpropamide

Drug group: blood sugar

chlorpropamide is an anti diabetic agent from Sulfonylurea category, that is used for Management of blood sugar in type 2 diabetes mellitus (noninsulin dependent, NIDDM) as an adjunct to diet and exercise to lower blood glucose

Mechanism of effect

Stimulates insulin release from the pancreatic beta cells; reduces glucose output from the liver; insulin sensitivity is increased at peripheral target sites

Pharmacodynamic

Chlorpropamide, a second-generation sulfonylurea antidiabetic agent, is used with diet to lower blood glucose levels in patients with diabetes mellitus type II. Chlorpropamide  is twice as potent as the related second-generation agent glipizide.

Pharmacokinetics

Onset of action: 1 hour

Peak effect: 3-6 hours

Duration: 24 hours

Absorption: Rapid

Metabolism: Extensively hepatic (~80%), primarily via CYP2C9; forms metabolites

Half-life elimination: ~36 hours; prolonged in elderly or with renal impairment

End-stage renal disease: 50-200 hours

Excretion: Urine (unchanged drug and as hydroxylated or hydrolyzed metabolites)

Dosage

Adult

Type 2 diabetes: Oral: The dosage of chlorpropamide is variable and should be individualized based upon the patient's response

Initial dose: 250 mg daily in mild-to-moderate diabetes in middle-aged, stable diabetic patients

 

Titration: After 5-7 days of initiation, subsequent daily dosages may be increased or decreased by 50-125 mg at 3- to 5-day intervals

 

Maintenance dose: 100-250 mg daily; severe patients with diabetes may require 500 mg daily; avoid doses >750 mg daily

Dosing: Geriatric

 

Reduce initial dose to 100 to 125 mg/day in older patients; after 5 to 7 days of initiation, subsequent daily dosages may be increased or decreased by 50 to 125 mg at 3- to 5-day intervals (slower upward titration may be appropriate in older patients).

Dosing: Renal Impairment

No specific dosage adjustment provided in manufacturer’s labeling

Dosing: Hepatic Impairment

No specific dosage adjustment provided in manufacturer’s labeling; conservative initial and maintenance doses are recommended in patients with liver impairment since chlorpropamide undergoes extensive hepatic metabolism.

Alerts

  • Cardiovascular mortality : Product labeling states oral hypoglycemic drugs may be associated with an increased cardiovascular mortality as compared to treatment with diet alone or diet plus insulin.
  • Hypoglycemia: All sulfonylurea drugs are capable of producing severe hypoglycemia. Hypoglycemia is more likely to occur when caloric intake is deficient, after severe or prolonged exercise, when ethanol is ingested, or when more than one glucose-lowering drug is used.
  • It is also more likely in elderly patients, malnourished patients and in patients with impaired renal or hepatic function; use with caution. Autonomic neuropathy, advanced age, and concomitant use of beta-blockers or other sympatholytic agents may impair the patient’s ability to recognize the signs and symptoms of hypoglycemia; use with caution.
  • Sulfonamide (“sulfa”) allergy:. In cases where prior reactions were severe (Stevens-Johnson syndrome/TEN), some clinicians choose to avoid exposure to these classes.
  • Glucose-6-phosphate dehydrogenase (G6PD) deficiency: Patients with G6PD deficiency may be at an increased risk of sulfonylurea-induced hemolytic anemia; Use with caution and consider a nonsulfonylurea alternative in patients with G6PD deficiency.
  • Stress-related states: It may be necessary to discontinue therapy and administer insulin if the patient is exposed to stress (fever, trauma, infection, surgery).
  • Long half-life: Patients should be properly instructed in the early detection and treatment of hypoglycemia
  • Secondary failure: Loss of efficacy may be observed following prolonged use as a result of the progression of type 2 diabetes mellitus which results in continued beta cell destruction. In patients who were previously responding to sulfonylurea therapy, consider additional factors which may be contributing to decreased efficacy (eg, inappropriate dose, nonadherence to diet and exercise regimen). If no contributing factors can be identified, consider discontinuing use of the sulfonylurea due to secondary failure of treatment. Additional antidiabetic therapy (eg, insulin) will be required.

Points of recommendation

  • Administer once daily with breakfast.
  • Daily dose may be divided to reduce GI upset.
  • Patients that are NPO or require decreased caloric intake may need doses held to avoid hypoglycemia.

Pregnancy level

C


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