Yes

Antidiabetic Agent (Sulfonylurea)

Control blood sugar in adult onset, noninsulin-dependent diabetes (type 2)

C

Clinical effects on the fetus: Crosses the placenta. Hypoglucemia; ear defects reported; other malformations reported but may have been secondary to poor maternal glucose control/diabetes. Insulin is the drug of choice for the control of diabetes mellitus during pregnancy.

Breast-feeding/lactation: Crosses into breast milk

Cross-sensitivity may exist with other hypoglycemics or sulfonamides; do not use with type 1 diabetes or with severe renal, hepatic, thyroid, or other endocrine disease

Patients should be properly instructed in the early detection and treatment of hypoglycemia; long half-life may complicate recovery from excess effects

Because of chlorpropamide's long half-life, duration of action, and the increased risk for hypoglycemia, it is not considered a hypoglycemic agent of choice in the elderly; see Pharmacodynamics/Kinetics

The administration of oral hypoglycemic drugs has been reported to be associated with increased cardiovascular mortality as compared to treatment with diet alone or diet plus insulin

At higher dosages, sulfonylureas may block the ATP-sensitive potassium channels, which may correspond to an increased risk of cardiovascular events. In May, 2000, the National Diabetes Center issued a warning to avoid the use of sulfonylureas at higher dosages (chlorpropamide daily doses >100 mg).

>10%:

Central nervous system: Headache, dizziness

Gastrointestinal: Anorexia, constipation, heartburn, epigastric fullness, nausea, vomiting, diarrhea

1% to 10%: Dermatologic: Skin rash, urticaria, photosensitivity

<1%: Edema, hypoglycemia, hyponatremia, SIADH, blood dyscrasias, aplastic anemia, hemolytic anemia, bone marrow suppression, thrombocytopenia, agranulocytosis, cholestatic jaundice

Symptoms of overdose include low blood glucose levels, tingling of lips and tongue, tachycardia, convulsions, stupor, coma

Antidote is glucose; intoxications with sulfonylureas can cause hypoglycemia and are best managed with glucose administration (oral for milder hypoglycemia or by injection in more severe forms); prolonged effects lasting up to 1 week may occur with this agent

Decreased effect: Thiazides and hydantoins (eg, phenytoin) decrease chlorpropamide effectiveness may increase blood glucose

Increased toxicity:

Increases alcohol-associated disulfiram reactions

Increases oral anticoagulant effects

Salicylates may increase chlorpropamide effects may decrease blood glucose

Sulfonamides may decrease sulfonylureas clearance

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

Peak effect: Oral: Within 6-8 hours

Distribution: V_d: 0.13-0.23 L/kg; appears in breast milk

Protein binding: 60% to 90%

Metabolism: Extensive (~80%) in the liver

Half-life: 30-42 hours; prolonged in the elderly or with renal disease

End-stage renal disease: 50-200 hours

Time to peak serum concentration: Within 3-4 hours

Elimination: 10% to 30% excreted in the urine as unchanged drug

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

Adults: 250 mg/day in mild to moderate diabetes in middle-aged, stable diabetic

Elderly: 100-125 mg/day in older patients

Subsequent dosages may be increased or decreased by 50-125 mg/day at 3- to 5-day intervals

Maintenance dose: 100-250 mg/day; severe diabetics may require 500 mg/day; avoid doses >750 mg/day

At higher dosages, sulfonylureas may block the ATP-sensitive potassium channels, which may correspond to an increased risk of cardiovascular events. In May, 2000, the National Diabetes Center issued a warning to avoid the use of sulfonylureas at higher dosages (chlorpropamide daily doses >100 mg); see Warnings/Precautions.

Dosing adjustment/comments in renal impairment: Cl_cr <50 mL/minute: Avoid use

Hemodialysis: Removed with hemoperfusion

Peritoneal dialysis: Supplemental dose is not necessary

Dosing adjustment in hepatic impairment: Dosage reduction is recommended. Conservative initial and maintenance doses are recommended in patients with liver impairment because chlorpropamide undergoes extensive hepatic metabolism.

Alcohol: A disulfiram-like reaction characterized by flushing, headache, nausea, vomiting, sweating or tachycardia; avoid use. Inform patient of chlorpropamide-alcohol flush (facial reddening and an increase in facial temperature).

Food: Chlorpropamide may cause GI upset; take with food. Take at the same time each day; eat regularly and do not skip meals.

Glucose: Decreases blood glucose concentration; hypoglycemia may occur. Educate patients how to detect and treat hypoglycemia. Monitor for signs and symptoms of hypoglycemia. Administer glucose if necessary. Evaluate patient's diet and exercise regimen. May need to decrease or discontinue dose of sulfonylurea.

Sodium: Reports of hyponatremia and SIADH. Those at increased risk include patients on medications or who have medical conditions that predispose them to hyponatremia. Monitor sodium serum concentration and fluid status. May need to restrict water intake.

Fasting blood glucose, normal Hgb A_1c or fructosamine levels; monitor for signs and symptoms of hypoglycemia, (fatigue, sweating, numbness of extremities); monitor urine for glucose and ketones

Target range: Adults:

Glycosylated hemoglobin: <7%

Dizziness is common

Rare reports of agranulocytosis; use caution with clozapine and carbamazepine

No information available to require special precautions

Chlorpropamide-dependent diabetics (noninsulin dependent, Type 2) should be appointed for dental treatment in morning in order to minimize chance of stress-induced hypoglycemia

This medication is used to control diabetes; it is not a cure. Other components of treatment plan are important: follow prescribed diet, medication, and exercise regimen. Take exactly as directed, at the same time each day. Do not change dose or discontinue without consulting prescriber. Avoid alcohol while taking this medication; could cause severe reaction. Inform prescriber of all other prescription or OTC medications you are taking; do not introduce new medication without consulting prescriber. If you experience hypoglycemic reaction, contact prescriber immediately. Maintain regular dietary intake and exercise routine and always carry quick source of sugar with you. You may experience side effects during first weeks of therapy (headache, constipation or diarrhea, bloating or loss of appetite); consult prescriber if these persist. Report severe or persistent side effects, including fever, extended vomiting or flu-like symptoms, skin rash, easy bruising or bleeding, or change in color of urine or stool. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant. Do not breast-feed.

Patients who are anorexic or NPO may need to hold the dose to avoid hypoglycemia

Monitor fasting blood glucose, normal Hgb A, C, or fructosamine levels; monitor for signs and symptoms of hypoglycemia, (fatigue, sweating, numbness of extremities); monitor urine for glucose and ketones

Tablet: 100 mg, 250 mg

Arrigoni L, Fundak G, Horn J, et al, "Chlorpropamide Pharmacokinetics in Young Healthy Adults and Older Diabetic Patients," Clin Pharm, 1987, 6(2):162-4.

Erickson T, Arora A, Lebby TI, et al, "Acute Oral Hypoglycemic Ingestions," Vet Hum Toxicol, 1991, 33(3):256-8.

Forrest JAH, "Chlorpropamide Overdosage: Delayed and Prolonged Hypoglycemia," Clin Toxicol, 1974, 7(1):19-24.

Gordon MR, Flockhart D, Zawadzki JK, et al, "Hypoglycemia Due to Inadvertent Dispensing of Chlorpropamide," Am J Med, 1988, 85(2):271-2.

Graw RG and Clarke RR, "Chlorpropamide Intoxication - Treatment With Peritoneal Dialysis," Pediatrics, 1970, 45(1):106-8.

Seltzer HS, "Drug-Induced Hypoglycemia. A Review of 1418 Cases," Endocrinol Metab Clin North Am, 1989, 18(1):163-83.

"Standards of Medical Care for Patients With Diabetes Mellitus. American Diabetes Association," Diabetes Care, 1994, 17(6):616-23.