Class: Sulfonylureas
ATC Class: A10BB02
VA Class: HS502
CAS Number: 94-20-2
Brands: Diabinese
Introduction
Antidiabetic agent; sulfonylurea.189 a
Uses for Chlorpropamide
Diabetes Mellitus
Used as monotherapy as an adjunct to diet and exercise for management of type 2 (noninsulin-dependent) diabetes mellitus in patients whose hyperglycemia cannot be controlled with diet and exercise alone.189 a
Used as second-line therapy in combination with one or more other oral antidiabetic agents or insulin as an adjunct to diet and exercise in patients with type 2 diabetes mellitus in whom adequate glycemic control cannot be achieved with oral antidiabetic agent monotherapy.135 145 146 147 148 149 169 170 171 172 173 174 175 176 177 178 179 180
Alternative therapy in some type 2 diabetic patients being treated with insulin or other antidiabetic agent(s).189 a Useful in combination with insulin to improve glycemic control and/or decrease insulin dosage in some type 2 diabetic patients.135 145 146 150 151 153 154 155 156 157 158
Not effective as sole therapy in patients with type 1 diabetes mellitus or diabetic acidosis, ketosis, or coma; 101 103 106 insulin is necessary.101 102 106 (See Contraindications under Cautions.)
Not routinely recommended in hospitalized patients with diabetes mellitus.122 Long duration of action precludes rapid dosage adjustments.122 Increased risk of hypoglycemia in hospitalized diabetic patients with irregular eating patterns.122
Chlorpropamide Dosage and Administration
General
Adjust dosage according to severity of disease, tolerance, and blood glucose determinations.189 a
Monitor regularly (e.g., blood glucose concentrations) to determine minimum effective dosage and to detect primary failure or secondary failure.189 a (See Loss of Glycemic Control under Cautions.)
Monitor glycosylated hemoglobin (HbA1c) to determine patient’s continued response to therapy.189
Administration of loading dose is not recommended.189 a
During transfer from insulin therapy, patients should test their blood glucose concentrations ≥3 times daily.189 (See Advice to Patients.) Early hypoglycemia (≤24 hours) following transfer from intermediate or long-acting insulins usually results from insulin carry-over rather than from chlorpropamide.189 a In some patients, consider hospitalization during transition period.189 a
Administration
Oral Administration
Administer orally as a single daily dose each morning with breakfast.189 a May administer in 2 divided doses if GI intolerance occurs.189 a
Dosage
Adults
Diabetes Mellitus
Initiation
Oral
Initially, 250 mg daily.189 a
Initial Dosage in Patients Transferred from Other Oral Antidiabetic Agents
Oral
Initially, 250 mg daily.189 a May abruptly discontinue the other oral antidiabetic agent.189 a
Initial Dosage in Patients Transferred from Insulin
Oral
Insulin requirements ≤40 units daily: Initially, 250 mg daily.189 a Abruptly discontinue insulin.189 a
Insulin requirements >40 units daily: Initially, 250 mg daily; reduce daily insulin dosage by 50% for first few days.189 a Subsequently, adjust insulin dosage according to therapeutic response.189 a
Titration and Maintenance Dosage
Oral
5–7 days after initiating therapy, titrate dosage in increments or decrements of ≤50–125 mg daily at 3- to 5-day intervals to achieve adequate glycemic control; more frequent dosage adjustments usually undesirable.189
Usual maintenance dosage is 100–500 mg daily.189 a Patients not responding to 500 mg daily are unlikely to respond to higher dosages.189 a
Prescribing Limits
Adults
Diabetes Mellitus
Oral
Maximum 750 mg daily.189 a
Special Populations
Hepatic Impairment
Use conservative initial and maintenance dosages to avoid hypoglycemia.189 (See Hepatic Impairment under Cautions.)
Renal Impairment
Use conservative initial and maintenance dosages to avoid hypoglycemia.189 (See Renal Impairment under Cautions.)
Geriatric Patients
Initially, 100–125 mg daily.189 Use conservative initial and maintenance dosages to avoid hypoglycemia.189 (See Geriatric Use under Cautions.)
Debilitated or Malnourished Patients
Use conservative initial and maintenance dosages to avoid hypoglycemia.189
Pituitary or Adrenal Insufficiency
Use conservative initial and maintenance dosages to avoid hypoglycemia.189
Cautions for Chlorpropamide
Contraindications
Known hypersensitivity to chlorpropamide or any ingredient in formulation.189
Diabetic ketoacidosis with or without coma.189 a
Monotherapy for type 1 diabetes mellitus.189 a
Warnings/Precautions
Warnings
Cardiovascular Effects
Increased cardiovascular mortality reported with certain other antidiabetic agents (i.e., tolbutamide, phenformin).111 189 d However, ADA considers benefits of intensive glycemic control with insulin or sulfonylureas to outweigh the risks overall.112 115 128
General Precautions
Hypoglycemia
Possible severe hypoglycemia, especially in geriatric, debilitated, or malnourished patients and those with adrenal, pituitary, hepatic, or renal insufficiency.189 a d Increased risk of hypoglycemia with strenuous exercise, alcohol ingestion, insufficient caloric intake, or concurrent drug use (e.g., other antidiabetic agents, agents that enhance hypoglycemic effects).189 d (See Specific Drugs under Interactions.)
Higher incidence of hypoglycemia at therapeutic dosages with chlorpropamide than other sulfonylureas;c may result from prolonged duration of action.c d (See Duration under Pharmacokinetics.)
Hypoglycemia may be difficult to recognize in geriatric patients and those receiving β-adrenergic blocking agents.189
Appropriate patient selection and careful dosing and instructions are important to avoid chlorpropamide-induced hypoglycemia.189
Hypoglycemia may result in coma, seizures, or other neurologic impairment.189 a d
If hypoglycemia occurs, immediately reevaluate patient and adjust insulin or chlorpropamide dosage.a Monitor patient for 24–48 hours;189 may require hospitalization and IV glucose.189 a Carefully supervise dose and give frequent feedings for ≥3–5 days.189
Loss of Glycemic Control
Possible loss of glycemic control during periods of stress (e.g., fever, trauma, infection, surgery).101 102 105 106 189 May require use of insulin and/or temporary discontinuance of chlorpropamide.189 a
Efficacy of therapy may decrease over time (secondary failure); evaluate patients at regular intervals.189 a
Assess patient for adequate adjustment of dose and adherence to diet before attributing inadequate response to secondary failure of the drug.189
Manufacturer recommends discontinuance of chlorpropamide if loss of satisfactory glycemic control develops.189 ADA and other clinicians recommend addition of other oral antidiabetic agents or insulin.127 146 173 175 184 185 186 191 192 (See Diabetes Mellitus under Uses.)
Specific Populations
Pregnancy
Category C.189
Prolonged (4–10 days), severe hypoglycemia reported in some neonates born to women receiving a sulfonylurea at delivery;189 more frequent with long-acting sulfonylureas (e.g., chlorpropamide).189 Discontinue drug ≥1 month before expected delivery date to minimize the risk of neonatal hypoglycemia.189
Many experts recommend the use of insulin during pregnancy.189
Lactation
Distributed into milk.189 Use not recommended.189
Pediatric Use
Safety and efficacy not established.189
Geriatric Use
Safety and efficacy not established.189 Increased risk of hypoglycemia and/or hyponatremia; hypoglycemia may be difficult to recognize.189 d Cautious dosing recommended.189 (See Geriatric Patients under Dosage and Administration.)
Hepatic Impairment
Diminished gluconeogenic capacity and increased risk of hypoglycemia; conservative dosing recommended.189 a (See Hepatic Impairment under Dosage and Administration.)
Monitor liver function frequently during chlorpropamide initiation.a
Renal Impairment
Increased risk of hypoglycemia; conservative dosing recommended.189 a (See Renal Impairment under Dosage and Administration.)
Common Adverse Effects
Hypoglycemia,111 189 a nausea,189 a weight gain.111 142 143 144
Interactions for Chlorpropamide
Metabolized mainly by CYP2C9.c (See Elimination under Pharmacokinetics.)
Protein-bound Drugs
Potential pharmacokinetic interaction (increased hypoglycemic effect because of displacement of chlorpropamide from binding sites on proteins).189 a (See Specific Drugs under Interactions.)
Close observation recommended when initiating or discontinuing concomitant therapy with a highly protein-bound drug.189 a
Specific Drugs
Drug
|
Interaction
|
Comments
|
|---|
Alcohol
|
Disulfiram-like reactions reported189 a
Moderate-to-large amounts of alcohol may increase the risk of hypoglycemia189
|
If intolerant, attempt therapy with another sulfonylurea agenta
|
Antifungals, oral azoles (i.e., fluconazole, miconazole)
|
Increased plasma concentrations of sulfonylureas and hypoglycemic effect182 183 189
|
Not known whether interaction occurs with IV, topical, or vaginal miconazole189
|
Anticoagulants, oral
|
Possible potentiation of hypoglycemic effects189 a
|
Observe closely for hypoglycemia or loss of glycemic control when concurrent therapy initiated or discontinued189
|
Barbiturates
|
May prolong action of barbiturates189 a
|
Use concurrently with caution189 a
|
β-Adrenergic blocking agents
|
Possible potentiation of hypoglycemic effects189
Signs of hypoglycemia may be masked by β-adrenergic blocking agents189
|
Observe closely for hypoglycemia or loss of glycemic control when concurrent therapy is initiated or discontinued189
|
Calcium-channel blocking agents
|
Potential for decreased hypoglycemic effect189
|
Observe closely for loss of glycemic control or hypoglycemia when concurrent therapy is initiated or discontinued189
|
Chloramphenicol
|
Possible potentiation of hypoglycemic effects189
|
Observe closely for hypoglycemia when concurrent therapy is initiated or discontinued189
|
Contraceptives, oral
|
Potential for decreased hypoglycemic effect189
|
Observe closely for loss of glycemic control or hypoglycemia when concurrent therapy is initiated or discontinued189
|
Corticosteroids
|
Potential for decreased hypoglycemic effect189
|
Observe closely for loss of glycemic control or hypoglycemia when concurrent therapy is initiated or discontinued189
|
Diuretics
|
Potential for decreased hypoglycemic effect189
|
Observe closely for loss of glycemic control or hypoglycemia when concurrent therapy is initiated or discontinued189
|
Estrogens
|
Potential for decreased hypoglycemic effect189
|
Observe closely for loss of glycemic control or hypoglycemia when concurrent therapy is initiated or discontinued189
|
Isoniazid
|
Potential for decreased hypoglycemic effect189
|
Observe closely for loss of glycemic control or hypoglycemia when concurrent therapy is initiated or discontinued189
|
MAO inhibitors
|
Possible potentiation of hypoglycemic effects189
|
Observe closely for hypoglycemia or loss of glycemic control when concurrent therapy is initiated or discontinued189
|
Niacin
|
Potential for decreased hypoglycemic effect189
|
Observe closely for loss of glycemic control or hypoglycemia when concurrent therapy is initiated or discontinued189
|
NSAIAs
|
Possible displacement of chlorpropamide from plasma proteins and potentiation of hypoglycemic effects189
|
Observe closely for hypoglycemia or loss of glycemic control when concurrent therapy initiated or discontinued189
|
Phenothiazines
|
Potential for decreased hypoglycemic effect189
|
Observe closely for loss of glycemic control or hypoglycemia when concurrent therapy is initiated or discontinued189
|
Phenytoin
|
Potential for decreased hypoglycemic effect189
|
Observe closely for loss of glycemic control or hypoglycemia when concurrent therapy is initiated or discontinued189
|
Probenecid
|
Possible potentiation of hypoglycemic effects189
|
Observe closely for hypoglycemia or loss of glycemic control when concurrent therapy initiated or discontinued189
|
Salicylates
|
Possible displacement of chlorpropamide from plasma proteins and potentiation of hypoglycemic effects189
|
Observe closely for hypoglycemia or loss of glycemic control when concurrent therapy initiated or discontinued189
|
Sulfonamides
|
Possible displacement of chlorpropamide from plasma proteins and potentiation of hypoglycemic effects189
|
Observe closely for hypoglycemia or loss of glycemic control when concurrent therapy initiated or discontinued189
|
Sympathomimetic agents
|
Potential for decreased hypoglycemic effect189
|
Observe closely for loss of glycemic control or hypoglycemia when concurrent therapy is initiated or discontinued189
|
Thyroid agents
|
Potential for decreased hypoglycemic effect189
|
Observe closely for loss of glycemic control or hypoglycemia when concurrent therapy is initiated or discontinued189
|
Chlorpropamide Pharmacokinetics
Absorption
Bioavailability
Rapidly absorbed following oral administration; peak plasma concentrations attained within 2–4 hours.189 a b
Onset
In healthy individuals, hypoglycemic action begins ≤1 hour; maximal at 3–6 hours.189
Duration
In healthy individuals, hypoglycemic action persists for ≥24 hours;189 longest duration of action of the sulfonylureas.a d
Food
Food does not appear to affect absorption or bioavailability; decreases peak serum concentrations of drug.b
Special Populations
Following administration of a single dose in healthy elderly and young adult individuals, age did not affect pharmacokinetics of chlorpropamide.b
Distribution
Extent
Sulfonylureas are distributed into extracellular fluids.a
Chlorpropamide crosses the placenta and is distributed into milk.189 (See Pregnancy under Cautions.)
Plasma Protein Binding
Highly bound to plasma proteins.a
Elimination
Metabolism
Extensively metabolized, mainly by CYP2C9.c
Elimination Route
Excreted in urine (80–90%) mainly as metabolites.189 a c
Increased or decreased rate of elimination in alkaline or acidic urine, respectively.a c
Half-life
36 hours (range: 25–60 hours).189 a b c d
Special Populations
Renal or hepatic insufficiency may affect pharmacokinetics and increase the risk of serious hypoglycemic reactions.189
Metabolism influenced by CYP2C9 polymorphism; genetic differences in drug metabolism affect drug response.c
Stability
Storage
Oral
Tablets
<30°C.189
ActionsActions
Stimulates secretion of postprandial endogenous insulin from beta cells of pancreas.189 a d
Ineffective in absence of functioning beta cells.189 a
During prolonged administration, extrapancreatic effects (e.g., enhanced peripheral sensitivity to insulin, reduction of basal hepatic glucose production) contribute to hypoglycemic action.189 a
Advice to Patients
Inform patients of potential risks and advantages of chlorpropamide therapy and alternative forms of treatment.189
Importance of regular testing of blood glucose concentrations and HbA1c values.189
During insulin withdrawal, importance of testing blood glucose concentrations ≥3 times daily.189 Importance of patients immediately informing clinicians of abnormal results for appropriate adjustments in therapy, if necessary.189
Importance of adhering to diet and exercise regimen.101 102 107 110 189
Importance of hygiene and avoidance of infection.a
Advise patients about nature of diabetes mellitus, prevention and detection of complications, and importance of glycemic control.a
Importance of understanding primary and secondary failure to therapy.189
Risks of hypoglycemia.189 Importance of patients and responsible family members understanding symptoms and treatment of hypoglycemic reactions and identifying conditions that predispose to development of such reactions.189
Risk of alcohol intolerance (e.g., facial flushing).a
Advise patients to use caution while driving and operating machinery.189
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.189
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.189
Importance of informing patients of other important precautionary information.189 (See Cautions.)
Preparations
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Chlorpropamide
Routes
|
Dosage Forms
|
Strengths
|
Brand Names
|
Manufacturer
|
|---|
Oral
|
Tablets
|
100 mg*
|
Diabinese (scored)
|
Pfizer
|
| |
250 mg*
|
Diabinese (scored)
|
Pfizer
|
Comparative Pricing
This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 03/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.
ChlorproPAMIDE 100MG Tablets (MYLAN): 60/$30.99 or 180/$85.97
ChlorproPAMIDE 250MG Tablets (MYLAN): 60/$55.99 or 180/$145.98
Diabinese 250MG Tablets (PFIZER U.S.): 60/$79.99 or 180/$219.98
Disclaimer
This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.
The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.
AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions July 2008. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.
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