General

High Alert Medication: This medication bears a heightened risk of causing significant patient harm when it is used in error.

Pronunciation
klor-PROE-pa-mide

Trade Name(s)

• Apo-Chlorpropamide [Canada]

• Diabinese

• Novo-Propamide [Canada]

Pregnancy Category
Category C

Ther. class.
antidiabetics

Pharm. class.
sulfonylureas

Indications

Control of blood sugar in type 2 diabetes mellitus when diet therapy fails. Requires some pancreatic function

Unlabelled Use(s):
Management of neurogenic diabetes insipidus

Action

• Lowers blood sugar by stimulating the release of insulin from the pancreas and increasing the sensitivity to insulin at receptor sites

• May also decrease hepatic glucose production

Therapeutic Effect(s):
Lowering of blood sugar in diabetic patients

Pharmacokinetics

Absorption: Well absorbed after oral administration

Distribution: 0.13–0.23 L/kg; enters breast milk

Metabolism and Excretion: Mostly metabolized by the liver; 10–30% excreted in urine as unchanged drug

Protein Binding: 60–90%

Half-life: 36 hr

TIME/ACTION PROFILE (hypoglycemic activity)

ROUTE	ONSET	PEAK	DURATION
PO	60 min	3–6 hr	24 hr

Contraindication/Precautions

Contraindicated in:

• Hypersensitivity

• Cross-sensitivity with sulfonamides (including thiazide diuretics) may occur

• Type 1 diabetics

• Diabetic coma or ketoacidosis

• Severe renal or hepatic disease

• Uncontrolled infection, serious burns, or trauma

• Lactation: Discontinue or bottle feed

Use Cautiously in:

• Severe cardiovascular disease

• Hepatic or renal impairment (increased risk of hypoglycemia)

• Infection, stress, or changes in diet may alter requirements for control of blood sugar

• Impaired thyroid, pituitary, or adrenal function

• Malnutrition, high fever, prolonged nausea, or vomiting

• OB: Safety not established; insulin recommended during pregnancy

• Geri: Prolonged half-life in geriatric patients may cause hypoglycemia, dosage reduction may be required. Appears on Beers list.

Adverse Reactions/Side Effects

CNS: anorexia, dizziness, headache.

GI: constipation, diarrhea, drug-induced hepatitis, increased appetite, nausea, vomiting.

Derm: photosensitivity, rash, pruritis, urticaria.

Endo: hypoglycemia, syndrome of inappropriate antidiuretic hormone (SIADH) secretion.

F and E: hyponatremia.

Hemat: APLASTIC ANEMIA, agranulocytosis, eosinophilia, hemolytic anemia, leukopenia, pancytopenia, thrombocytopenia.

Misc: disulfiram-like reaction.

*CAPITALS indicates life-threatening.
*italic indicates most frequent.

Interactions

Drug-Drug

• Ingestion of alcohol may result in disulfiram-like reaction

• Effectiveness may be decreased by concurrent use of diuretics, calcium channel blockers, corticosteroids, phenothiazines, hormonal contraceptives, estrogens, thyroid agents, phenytoin, nicotinic acid, adrenergics, and isoniazid

• Alcohol, androgens (testosterone), chloramphenicol, fluoroquinolones, MAO inhibitors, miconazole, NSAIDs), probenecid, salicylates, sulfonamides, and warfarin may increase the risk of hypoglycemia

• Concurrent use with warfarin may alter the response to both agents (may increase effects of both; close monitoring recommended during any changes in dosage)

• Beta blockers may alter the response to oral hypoglycemic agents (increase or decrease requirements; nonselective agents may cause prolonged hypoglycemia)

Drug-Natural Products
Glucosamine may worsen hypoglycemia. Fenugreek, chromium, and coenzyme Q-10 may produce additive hypoglycemic effects

Route/Dosage

• PO (Adults): 250 mg once daily, initially; may increase dose by 50–125 mg/day at 3–5 day intervals. Maximum daily dose is 750 mg.
Older, debilitated or malnourished patients—initiate therapy with 100–125 mg once daily; may increase dose by 50–125 mg/day at 3–5 day intervals. Maximum daily dose is 750 mg.
Antidiuretic dose—100–250 mg/day.

Hepatic Impairment

• PO (Adults): initiate therapy with 100–125 mg/day.

Renal Impairment

• PO (Adults CCr >= 50 ml/min): initiate therapy with 100–125 mg once daily.

Renal Impairment

• PO (Adults CCr < 50 ml/min): Avoid use.

Availability

• Tablets: 100 mg, 250 mg

Assessment

• Observe patient for signs and symptoms of hypoglycemic reactions (sweating, hunger, weakness, dizziness, tremor, tachycardia, anxiety). The long half-life of chlorpropamide increases the risk of recurrent hypoglycemia. Monitor patients who experience a hypoglycemic episode closely for 3–5 days

• Assess patient for allergy to sulfonamides

Lab Test Considerations

• Serum glucose and glycosylated hemoglobin should be monitored periodically throughout therapy to evaluate effectiveness of treatment

» Monitor CBC periodically throughout therapy. Notify physician or other health care professional promptly if decrease in blood counts occurs

» May cause an increase in ASTand LDH

» Monitor urine periodically for glucose, ketones, and protein

» Serum sodium levels and plasma osmolarity should be monitored periodically throughout therapy in patients taking chlorpropamide

Toxicity and Overdose

• Overdose is manifested by symptoms of hypoglycemia. Mild hypoglycemia may be treated with administration of oral glucose. Severe hypoglycemia should be treated with IV D50W followed by continuous IV infusion of more dilute dextrose solution at a rate sufficient to keep serum glucose at approximately 100 mg/dl

Potential Nursing Diagnoses

• Imbalanced nutrition: more than body requirements (Indications)

• Deficient knowledge, related to medication regimen (Patient/Family Teaching)

• Noncompliance (Patient/Family Teaching)

Implementation

• High Alert: Accidental administration of oral hypoglycemic agents to non-diabetic adults and children has resulted in serious harm or death. Before administering, confirm that patient is diabetic. Do not confuse chlorpropamide with chlorpromazine

• Patients stabilized on a diabetic regimen who are exposed to stress, fever, trauma, infection, or surgery may require administration of insulin

» Patients previously maintained on an insulin dosages of less than 40 units/day may be started on chlorpropamide. Insulin should be immediately discontinued. Patients taking greater than 40 units/day of insulin should have their insulin doses reduced by 50% daily for the first few days, then gradually reduced further, as necessary. Monitor serum glucose and urine ketones at least 3 times/day during conversion

• PO: May be administered once in the morning or divided into 2 doses (especially if patient experiences GI distress). Administer with meals to ensure best diabetic control and minimize gastric irritation. Do not administer after last meal of the day

» Tablets may be crushed and taken with fluids if patient has difficulty swallowing

Patient/Family Teaching

• Instruct patient to take medication at same time each day. If a dose is missed, take as soon as remembered unless almost time for next dose. Do not take if unable to eat

• Explain to patient that this medication controls hyperglycemia but does not cure diabetes. Therapy is long-term

• Review signs of hypoglycemia and hyperglycemia with patient. If hypoglycemia occurs, advise patient to take a glass of orange juice or 2–3 tsp of sugar, honey, or corn syrup dissolved in water and to notify health care professional

• Encourage patient to follow prescribed diet, medication, and exercise regimen to prevent hypoglycemic or hyperglycemic episodes. Caution patient to avoid skipping meals

• Instruct patient in proper testing of serum glucose and urine ketones. These tests should be closely monitored during periods of stress or illness and health care professional notified if significant changes occur

• May occasionally cause dizziness. Caution patient to avoid driving or other activities requiring alertness until response to medication is known

• Caution patient to avoid other medications, especially aspirin and alcohol, while on this therapy without consulting health care professional

• Concurrent use of alcohol may cause a disulfiram-like reaction (abdominal cramps, nausea, flushing, headaches, and hypoglycemia)

• Insulin is the preferred method of controlling blood sugar during pregnancy. Counsel female patients to use a form of contraception other than oral contraceptives and to notify health care professional promptly if pregnancy is planned or suspected

• Caution patient to use sunscreen and protective clothing to prevent photosensitivity reactions

• Advise patient to inform health care professional of medication regimen before treatment or surgery

• Advise patient to carry a form of sugar (sugar packets, candy) and identification describing disease process and medication regimen at all times

• Advise patient to notify health care professional promptly if unusual weight gain, weakness, sore throat, rash, or unusual bleeding or bruising occurs

• Emphasize the importance of routine follow-up examinations

Evaluation/Desired Outcomes

Control of blood glucose levels without the appearance of hypoglycemic or hyperglycemic episodes

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