Chlorpropamide: Difference between revisions

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|mechAction=C*hlorpropamide appears to lower the [[blood glucose]] acutely by stimulating the release of [[insulin]] from the [[pancreas]], an effect dependent upon functioning [[beta cells]] in the [[pancreatic islets]]. The mechanism by which chlorpropamide lowers blood [[glucose]] during long-term administration has not been clearly established. Extrapancreatic effects may play a part in the mechanism of action of oral [[sulfonylurea]] [[hypoglycemic drugs]]. While chlorpropamide is a [[sulfonamide]] derivative, it is devoid of antibacterial activity.
|mechAction=*Chlorpropamide appears to lower the [[blood glucose]] acutely by stimulating the release of [[insulin]] from the [[pancreas]], an effect dependent upon functioning [[beta cells]] in the [[pancreatic islets]]. The mechanism by which chlorpropamide lowers blood [[glucose]] during long-term administration has not been clearly established. Extrapancreatic effects may play a part in the mechanism of action of oral [[sulfonylurea]] [[hypoglycemic drugs]]. While chlorpropamide is a [[sulfonamide]] derivative, it is devoid of antibacterial activity.
|PD=*Chlorpropamide exerts a [[hypoglycemic effect]] in healthy subjects within one hour, becoming maximal at 3 to 6 hours and persisting for at least 24 hours. The potency of chlorpropamide is approximately 6 times that of [[tolbutamide]]. Some experimental results suggest that its increased duration of action may be the result of slower excretion and absence of significant deactivation.
|PD=*Chlorpropamide exerts a [[hypoglycemic effect]] in healthy subjects within one hour, becoming maximal at 3 to 6 hours and persisting for at least 24 hours. The potency of chlorpropamide is approximately 6 times that of [[tolbutamide]]. Some experimental results suggest that its increased duration of action may be the result of slower excretion and absence of significant deactivation.
|PK=*Chlorpropamide is absorbed rapidly from the gastrointestinal tract. Within one hour after a single oral dose, it is readily detectable in the blood, and the level reaches a maximum within 2 to 4 hours. It undergoes metabolism in humans and it is excreted in the urine as unchanged drug and as hydroxylated or hydrolyzed metabolites. The biological half-life of chlorpropamide averages about 36 hours. Within 96 hours, 80% to 90% of a single oral dose is excreted in the urine. However, long-term administration of therapeutic doses does not result in undue accumulation in the blood, since absorption and excretion rates become stabilized in about 5 to 7 days after the initiation of therapy.
|PK=*Chlorpropamide is absorbed rapidly from the gastrointestinal tract. Within one hour after a single oral dose, it is readily detectable in the blood, and the level reaches a maximum within 2 to 4 hours. It undergoes metabolism in humans and it is excreted in the urine as unchanged drug and as hydroxylated or hydrolyzed metabolites. The biological half-life of chlorpropamide averages about 36 hours. Within 96 hours, 80% to 90% of a single oral dose is excreted in the urine. However, long-term administration of therapeutic doses does not result in undue accumulation in the blood, since absorption and excretion rates become stabilized in about 5 to 7 days after the initiation of therapy.

Latest revision as of 17:05, 27 February 2015

Chlorpropamide
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alberto Plate [2]

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Overview

Chlorpropamide is a 1st generation sulfonylurea and hypoglycemic agent that is FDA approved for the treatment of type 2 diabetes mellitus. Common adverse reactions include hypoglycemia, diarrhea, hunger, loss of appetite, nausea and vomiting.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

  • There is no fixed dosage regimen for the management of type 2 diabetes with chlorpropamide or any other hypoglycemic agent. The patient’s blood glucose must be monitored periodically to determine the minimum effective dose for the patient; to detect primary failure, i.e., inadequate lowering of blood glucose at the maximum recommended dose of medication; and to detect secondary failure, i.e., loss of an adequate blood glucose lowering response after an initial period of effectiveness. Glycosylated hemoglobin levels may also be of value in monitoring the patient’s response to therapy.

Short-term administration of chlorpropamide may be sufficient during periods of transient loss of control in patients usually controlled well on diet.

  • The total daily dosage is generally taken at a single time each morning with breakfast. Occasionally cases of gastrointestinal intolerance may be relieved by dividing the daily dosage. A loading or priming dose is not necessary and should not be used.
Initial Therapy
  • The mild to moderately severe, middle-aged, stable type 2 diabetes patient should be started on 250 mg daily. In elderly patients, debilitated or malnourished patients, and patients with impaired renal function or impaired hepatic function, the initial and maintenance dosing should be conservative to avoid hypoglycemic reactions. Older patients should be started on smaller amounts of chlorpropamide, in the range of 100 mg to 125 mg daily.
  • No transition period is necessary when transferring patients from other oral hypoglycemic agents to chlorpropamide. *The other agent may be discontinued abruptly and chlorpropamide started at once. In prescribing chlorpropamide, due consideration must be given to its greater potency.
  • Many mild to moderately severe, middle-aged, stable type 2 diabetes patients receiving insulin can be placed directly on the oral drug and their insulin abruptly discontinued. For patients requiring more than 40 units of insulin daily, therapy with chlorpropamide may be initiated with a 50% reduction in insulin for the first few days, with subsequent further reductions dependent upon the response.
  • During the initial period of therapy with chlorpropamide, hypoglycemic reactions may occasionally occur, particularly during the transition from insulin to the oral drug. Hypoglycemia within 24 hours after withdrawal of the intermediate or long-acting types of insulin will usually prove to be the result of insulin carry-over and not primarily due to the effect of chlorpropamide.
  • During the insulin withdrawal period, the patient should self-monitor glucose levels at least 3 times daily. If they are abnormal, the physician should be notified immediately. In some cases, it may be advisable to consider hospitalization during the transition period.
  • Five to 7 days after the initial therapy, the blood level of chlorpropamide reaches a plateau. Dosage may subsequently be adjusted upward or downward by increments of not more than 50 mg to 125 mg at intervals of 3 to 5 days to obtain optimal control. More frequent adjustments are usually undesirable.
Maintenance Therapy
  • Most moderately severe, middle-aged, stable type 2 diabetes patients are controlled by approximately 250 mg daily. Many investigators have found that some milder diabetics do well on daily doses of 100 mg or less. Many of the more severe diabetics may require 500 mg daily for adequate control. Patients who do not respond completely to 500 mg daily will usually not respond to higher doses. Maintenance doses above 750 mg daily should be avoided.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Chlorpropamide in adult patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Chlorpropamide in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

There is limited information regarding Chlorpropamide FDA-Labeled Indications and Dosage (Pediatric) in the drug label.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Chlorpropamide in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Chlorpropamide in pediatric patients.

Contraindications

Chlorpropamide tablets are contraindicated in patients with:

Warnings

Special Warning on Increased Risk of Cardiovascular Mortality

  • 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. This warning is based on the study conducted by the University Group Diabetes Program (UGDP), a long-term prospective clinical trial designed to evaluate the effectiveness of glucose-lowering drugs in preventing or delaying vascular complications in patients with non-insulin-dependent diabetes. The study involved 823 patients who were randomly assigned to one of four treatment groups (Diabetes, 19 [supp 2]:747-830, 1970).
  • UGDP reported that patients treated for 5 to 8 years with diet plus a fixed dose of tolbutamide (1.5 grams per day) had a rate of cardiovascular mortality approximately 2½ times that of patients treated with diet alone. A significant increase in total mortality was not observed, but the use of tolbutamide was discontinued based on the increase in cardiovascular mortality, thus limiting the opportunity for the study to show an increase in overall mortality. Despite controversy regarding the interpretation of these results, the findings of the UGDP study provide an adequate basis for this warning. The patient should be informed of the potential risks and advantages of chlorpropamide and of alternative modes of therapy.
  • Although only one drug in the sulfonylurea class (tolbutamide) was included in this study, it is prudent from a safety standpoint to consider that this warning may also apply to other oral hypoglycemic drugs in this class, in view of their close similarities in mode of action and chemical structure.

Adverse Reactions

Clinical Trials Experience

Postmarketing Experience

There is limited information regarding Chlorpropamide Postmarketing Experience in the drug label.

Drug Interactions

There is limited information regarding Chlorpropamide Drug Interactions in the drug label.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): C

  • Animal reproductive studies have not been conducted with chlorpropamide. It is also not known whether chlorpropamide can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Chlorpropamide should be given to a pregnant woman only if the potential benefits justify the potential risk to the patient and fetus.
  • Because data suggest that abnormal blood glucose levels during pregnancy are associated with a higher incidence of congenital abnormalities, many experts recommend that insulin be used during pregnancy to maintain blood glucose levels as close to normal as possible.


Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Chlorpropamide in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Chlorpropamide during labor and delivery.

Nursing Mothers

  • An analysis of a composite of two samples of human breast milk each taken 5 hours after ingestion of 500 mg of chlorpropamide by a patient revealed a concentration of 5 mcg/mL. For reference, the normal peak blood level of chlorpropamide after a single 250 mg dose is 30 mcg/mL. Therefore, it is not recommended that a woman breast-feed while taking this medication.

Pediatric Use

  • Safety and effectiveness in children have not been established.

Geriatic Use

There is no FDA guidance on the use of Chlorpropamide in geriatric settings.

Gender

There is no FDA guidance on the use of Chlorpropamide with respect to specific gender populations.

Race

There is no FDA guidance on the use of Chlorpropamide with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Chlorpropamide in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Chlorpropamide in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Chlorpropamide in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Chlorpropamide in patients who are immunocompromised.

Administration and Monitoring

Administration

There is limited information regarding Chlorpropamide Administration in the drug label.

Monitoring

There is limited information regarding Chlorpropamide Monitoring in the drug label.

IV Compatibility

There is limited information regarding the compatibility of Chlorpropamide and IV administrations.

Overdosage

  • Overdosage of sulfonylureas including chlorpropamide can produce hypoglycemia. Mild hypoglycemic symptoms without loss of consciousness or neurologic findings should be treated aggressively with oral glucose and adjustments in drug dosage and/or meal patterns. Close monitoring should continue until the physician is assured that the patient is out of danger. Severe hypoglycemic reactions with coma, seizure, or other neurological impairment occur infrequently, but constitute medical emergencies requiring immediate hospitalization. If hypoglycemic coma is diagnosed or suspected, the patient should be given a rapid intravenous injection of concentrated (50%) glucose solution. This should be followed by a continuous infusion of a more dilute (10%) glucose solution at a rate that will maintain the blood glucose at a level above 100 mg/dL. Patients should be closely monitored for a minimum of 24 to 48 hours since hypoglycemia may recur after apparent clinical recovery.

Pharmacology

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Chlorpropamide
Systematic (IUPAC) name
4-chloro-N-(propylcarbamoyl)benzenesulfonamide
Identifiers
CAS number 94-20-2
ATC code A10BB02
PubChem 2727
DrugBank DB00672
Chemical data
Formula Template:OrganicBox atomTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBox 
Mol. mass 276.74 g/mol
SMILES eMolecules & PubChem
Physical data
Melt. point 126–130 °C (259–266 °F)
Pharmacokinetic data
Bioavailability >90%
Protein binding 90%
Metabolism <1%
Half life 36 hours
Excretion Renal (glomerular filtration → reabsorption → tubular secretion)
Therapeutic considerations
Licence data

US

Pregnancy cat.

C(AU) C(US)

Legal status

Prescription Only (S4)(AU) ?(CA) POM(UK) [[Prescription drug|Template:Unicode-only]](US)

Routes Oral

Mechanism of Action

Structure

There is limited information regarding Chlorpropamide Structure in the drug label.

Pharmacodynamics

  • Chlorpropamide exerts a hypoglycemic effect in healthy subjects within one hour, becoming maximal at 3 to 6 hours and persisting for at least 24 hours. The potency of chlorpropamide is approximately 6 times that of tolbutamide. Some experimental results suggest that its increased duration of action may be the result of slower excretion and absence of significant deactivation.

Pharmacokinetics

  • Chlorpropamide is absorbed rapidly from the gastrointestinal tract. Within one hour after a single oral dose, it is readily detectable in the blood, and the level reaches a maximum within 2 to 4 hours. It undergoes metabolism in humans and it is excreted in the urine as unchanged drug and as hydroxylated or hydrolyzed metabolites. The biological half-life of chlorpropamide averages about 36 hours. Within 96 hours, 80% to 90% of a single oral dose is excreted in the urine. However, long-term administration of therapeutic doses does not result in undue accumulation in the blood, since absorption and excretion rates become stabilized in about 5 to 7 days after the initiation of therapy.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Studies with chlorpropamide have not been conducted to evaluate carcinogenic or mutagenic potential.

  • Rats treated with continuous chlorpropamide therapy for 6 to 12 months showed varying degrees of suppression of spermatogenesis at a dose level of 250 mg/kg (five times the human dose based on body surface area). The extent of suppression seemed to follow that of growth retardation associated with chronic administration of high-dose chlorpropamide in rats. The human dose of chlorpropamide is 500 mg/day (300 mg/M2). Six- and twelve-month toxicity work in the dog and rat, respectively, indicates the 150 mg/kg is well tolerated. Therefore, the safety margins based upon body-surface-area comparisons are 3 times human exposure in the rat and 10 times human exposure in the dog.

Clinical Studies

There is limited information regarding Chlorpropamide Clinical Studies in the drug label.

How Supplied

Chlorpropamide Tablets, USP are available containing either 100 mg or 250 mg of Chlorpropamide, USP.

The 100 mg tablets are green round, scored tablets debossed with MYLAN above the score and 197 below the score on one side of the tablet and 100 on the other side. They are available as follows:

  • NDC 0378-0197-01: bottles of 100 tablets
  • NDC 0378-0197-05: bottles of 500 tablets

The 250 mg tablets are green round, scored tablets debossed with MYLAN above the score and 210 below the score on one side of the tablet and 250 on the other side. They are available as follows:

  • NDC 0378-0210-01: bottles of 100 tablets
  • NDC 0378-0210-10: bottles of 1000 tablets

Storage

Store at 20° to 25°C (68° to 77°F). Protect from light.

Images

Drug Images

{{#ask: Page Name::Chlorpropamide |?Pill Name |?Drug Name |?Pill Ingred |?Pill Imprint |?Pill Dosage |?Pill Color |?Pill Shape |?Pill Size (mm) |?Pill Scoring |?NDC |?Drug Author |format=template |template=DrugPageImages |mainlabel=- |sort=Pill Name }}

Package and Label Display Panel

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Patient Counseling Information

There is limited information regarding Chlorpropamide Patient Counseling Information in the drug label.

Precautions with Alcohol

  • Alcohol-Chlorpropamide interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

Look-Alike Drug Names

There is limited information regarding Chlorpropamide Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.