Chlorpropamide - a First--Generation Sulfonylurea

A first-generation sulfonylurea called chlorpropamide was used in conjunction with diet and exercise to help individuals with  type 2 diabetes control their blood sugar levels. It is no longer advised for the treatment of individuals with type 2 diabetes mellitus  due to its prolonged duration of action and significant adverse effects. Additionally, it was infrequently used to treat central diabetic insipidus.

Chlorpropamide dose in Adults

Chlorpropamide dose in type 2 Diabetes mellitus:

    • 250 mg orally once a day or in two divided doses
    • Use the lowest possible dose in malnourished or debilitated patients
    • The dose may be adjusted after 5 to 7 days by increasing or decreasing it by 50 - 125 mg
    • The usual maintenance dose is 100 250 mg once a day or in divided doses.
    • Doses of more than 750 mg per day should be avoided.

Dosage of Chlorpropamide for Central (neurogenic) diabetes insipidus (off-label use) treatment:

  • 125 to 250 mg orally once or twice a day.
  • Higher doses should be avoided.

Chlorpropamide dose in Childrens

Not recommended for use in children.

Pregnancy Risk Factor C

  • ChlorpropamideCrosses the placental boundary
  • There have been adverse maternal and fetal effects, including prolonged and severe hypoglycemia.
  • Uncontrolled hyperglycemia can also lead to adverse outcomes. Therefore, it is important that blood sugar levels are maintained at normal levels during pregnancy.
  • Insulin is the best anti-diabetic agent during pregnancy. However, metformin or glyburide can be used.

Chlorpropamide use during Breastfeeding:

  • It is not recommended during breastfeeding.

Chlorpropamide dose in Renal disease:

  • For patients with kidney disease, the manufacturer has not offered any dose adjustment. 
  • Advanced renal disease should avoid it. If used in patients suffering from renal disease

The following are my recommendationsYou can also follow these steps:

    • CrCl of more than 50 mL/minute:
      • Reduce dose by half.
    •  CrCl of less than 50 mL/minute:
      • Avoid its use.
    • Hemodialysis, Peritoneal dialysis, or CRRT:
      • Avoid using chlorpropamide.

Chlorpropamide dose in Liver Disease:

  • Dose adjustment is not recommended.
  • However, it should still be done with caution as the drug undergoes extensive liver metabolism. 

Common Side Effects of Chlorpropamide include:

  • Central nervous system:
    • Disulfiram-like reaction
    • Headache
    • Dizziness
  • Dermatologic:
    • Maculopapular rash
    • Pruritus
    • Urticaria
    • Exfoliative dermatitis
    • Erythema multiforme
    • Skin photosensitivity
  • Endocrine & metabolic:
    • Hepatic porphyria
    • Weight gain
    • Hypoglycemia
    • SIADH (syndrome of inappropriate antidiuretic hormone secretion)
    • Porphyria cutanea tarda
  • Gastrointestinal:
    • Anorexia
    • Vomiting
    • Diarrhea
    • Nausea
    • Hunger
  • Hematologic & oncologic:
    • Aplastic anemia
    • Agranulocytosis
    • Eosinophilia
    • Pancytopenia
    • Leukopenia
    • Thrombocytopenia
    • Hemolytic anemia
  • Hepatic:
  • Cholestatic jaundice
  • Hepatitis
  • Hepatic failure

Contraindication to Chlorpropamide include:

  • Allergies to the formulation's ingredients, including chlorpropamide
  • Type 1 Diabetes Mellitus
  • Diabetic ketoacidosis

Warnings & Precautions

  • Cardiovascular mortality:
    • An increase in cardiovascular mortality has been linked to oral hypoglycemic medications.
    • Patients with an established cardiovascular disease should not be treated with chlorpropamide.
  • Hypoglycemia:
    • Hypoglycemia can be caused by any drug in the sulfonylurea class.
    • Avoid using sulfonylureas, especially chlorpropamide, in patients who are thin, debilitated, or have a long duration of action.
    • Sulfonylurea use should be monitored in individuals with renal impairment or hepatic dysfunction, elderly patients, beta-blocker users, and those with autonomic neuropathy.
  • Sulfonamide (“sulfa”) allergy:
    • Patients who have previously experienced sulfonamide allergies should use the medication with caution.
  • Glucose-6-phosphate dehydrogenase (G6PD) deficiency:
    • People who have had hemolytic anemia due to sulfonylurea in the past or those with G6PD deficiencies should be cautious about using this drug.
  • Stress-related states:
    • In the event of stress, trauma, infection, or an acute illness, patients should be switched to insulin.

Chlorpropamide: Drug Interaction

Note: Drug Interaction Categories:

  • Risk Factor C: Monitor When Using Combination
  • Risk Factor D: Consider Treatment Modification
  • Risk Factor X: Avoid Concomitant Use

Risk Factor C (Monitor therapy)

Ajmaline

Sulfonamides might make ajmaline more harmful or poisonous. In particular, there may be an elevated risk for cholestasis.

Alcohol (Ethyl)

Sulfonylureas may increase Alcohol's harmful or toxic effects (Ethyl). There could be a flushing reaction.

Alpha-Lipoic Acid May strengthen an anti-diabetic agent's hypoglycemic impact.
Aminolevulinic Acid (Topical) Aminolevulinic Acid's photosensitizing impact may be enhanced by photosensitizing agents (Topical).
Androgens

Can make blood glucose lowering medications more effective at lowering blood sugar. Danazol is an exception.

Antidiabetic Agents Possibly makes hypoglycemia-associated agents more effective.
Beta-Blockers

Sulfonylureas' hypoglycemic impact might be strengthened. Betablockers that are cardioselective  (such as acebutolol, atenolol, metoprolol, and penbutolol) may be less dangerous than those that are nonselective.  As the initial sign of hypoglycemia, tachycardia seems to be concealed by all beta-blockers. Beta-blockers used intravenously most likely carry a lesser risk than those used systemically. Exceptions: Metipranol; Levobunol.

Carbocisteine

Sulfonylureas may intensify Carbocisteine's harmful or hazardous effects.  Particularly, sulfonylureas may intensify the negative effects of the alcohol contained in liquid  formulations of medicines containing carbocisteine.

Chloramphenicol (Systemic) Sulfonylureas' metabolism might be slowed down.
Cimetidine Sulfonylureas' serum levels might rise.
Cyclic Antidepressants Sulfonylureas' hypoglycemic impact might be strengthened.
CYP3A4 Inducers (Strong) May lower the level of chlorproPAMIDE in the serum.
Dexketoprofen Sulfonamides' harmful or poisonous effects could be amplified.
Direct Acting Antiviral Agents (HCV) May strengthen an anti-diabetic agent's hypoglycemic impact.
Fibric Acid Derivatives Sulfonylureas' hypoglycemic impact might be strengthened.
Guanethidine May strengthen an anti-diabetic agent's hypoglycemic impact.
Herbs (Hypoglycemic Properties) May intensify the hypoglycemic effects of agents associated with hypoglycemia.
Hyperglycemia-Associated Agents May reduce an anti-diabetic agent's therapeutic efficacy.
Hypoglycemia-Associated Agents May increase other hypoglycemia-associated agents' hypoglycemic effects.
Hypoglycemia-Associated Agents The hypoglycemic effect of hypoglycemia-associated agents may be strengthened by antidiabetic agents.
Lumacaftor

May lower the serum level of CYP2C9 substrates (High Risk with Inhibitors or Inducers).  The serum concentration of CYP2C9 Substrates may rise when taking lumacaftor (High Risk with Inhibitors or Inducers).

Maitake Can make blood glucose lowering medications more effective at lowering blood sugar.
Miconazole (Oral)

Sulfonylureas' hypoglycemic impact might be strengthened.  The blood content of sulfonylureas may rise when using miconazole (Oral).

Monoamine Oxidase Inhibitors Can make blood glucose lowering medications more effective at lowering blood sugar.
Pegvisomant Can make blood glucose lowering medications more effective at lowering blood sugar.
Porfimer The photosensitizing effect of Porfimer may be strengthened by photosensitizing agents.
Probenecid

Sulfonylureas may lessen their ability to attach to proteins. Sulfonylurea serum levels may rise in response to probenecid.

Prothionamide Can make blood glucose lowering medications more effective at lowering blood sugar.
Quinolones

Can make blood glucose lowering medications more effective at lowering blood sugar.  Blood Glucose Lowering Agents' therapeutic impact may be lessened by quinolones.  In particular, the use of quinolones may result in a loss of blood sugar control if an agent is being used to treat diabetes.

RaNITIdine Sulfonylureas' serum levels might rise.
Rifapentine May lower the serum level of CYP2C9 substrates (High risk with Inducers).
Ritodrine May reduce an anti-diabetic agent's therapeutic efficacy.
Salicylates Can make blood glucose lowering medications more effective at lowering blood sugar.
Selective Serotonin Reuptake Inhibitors Can make blood glucose lowering medications more effective at lowering blood sugar.
Sulfonamide Antibiotics Sulfonylureas' hypoglycemic impact might be strengthened.
Thiazide and Thiazide-Like Diuretics May reduce an anti-diabetic agent's therapeutic efficacy.
Urinary Acidifying Agents ChlorproPAMIDE serum concentration can rise.
Verteporfin Verteporfin's photosensitizing effect may be strengthened by photosensitizing agents.
Vitamin K Antagonists (eg, warfarin)

The anticoagulant action of Vitamin K antagonists may be increased by sulfonylureas.  Sulfonylureas may have a greater hypoglycemia effect when used with vitamin K antagonists.

Voriconazole Sulfonylureas' serum levels might rise.

Risk Factor D (Consider therapy modification)

Dabrafenib May decrease the serum concentration of CYP2C9 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP2C9 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects).
Dipeptidyl Peptidase-IV Inhibitors

Sulfonylureas' hypoglycemic impact might be strengthened. When starting treatment with a dipeptidyl peptidase-IV inhibitor, take into account lowering the dose of sulfonylurea and keep an eye out for hypoglycemia in the patients.

Enzalutamide

May lower the serum level of CYP2C9 substrates (High risk with Inducers).  Treatment: Enzalutamide should not be used concurrently with CYP2C9 substrates that have a limited therapeutic index.  Enzalutamide use, like with the use of any other CYP2C9 substrate, should be done with caution and under close observation.

Fluconazole

Sulfonylureas' serum levels might rise. Management: When possible, look for alternatives.  If fluconazole is started or the dose is increased, keep a cautious eye out  for any increased or decreased effects of sulfonylureas if the two medications are being used together.

Glucagon-Like Peptide-1 Agonists

Sulfonylureas' hypoglycemic impact might be strengthened. Management: When used with glucagonlike peptide-1 agonists, sulfonylurea dose reductions should be taken into account.

Metreleptin

Sulfonylureas' hypoglycemic impact might be strengthened. Management: To reduce the risk for hypoglycemia  when using metreleptin concurrently, sulfonylurea dosage changes (including possibly significant decreases) may be necessary.  Observe carefully.

MiFEPRIStone

May elevate CYP2C9 substrates' serum levels (High risk with Inhibitors).  Management: During and for two weeks after mifepristone treatment, use CYP2C9 substrates  at the lowest dose advised and keep a close eye out for any negative effects.

RifAMPin

May lower the level of sulfonylureas in the serum. Management: When possible, look for substitutions for these mixtures.  If rifampin is started or the dose is increased, keep a watchful eye out for  therapeutic effects of sulfonylureas that are lowered or amplified.

Sodium-Glucose Cotransporter 2 (SLGT2) Inhibitors

Sulfonylureas' hypoglycemic impact might be strengthened. When starting therapy with a sodium-glucose cotransporter 2 inhibitor, take into account lowering the dose of  sulfonylurea and keep an eye out for hypoglycemia in your patients.

Thiazolidinediones May enhance the hypoglycemic effect of Sulfonylureas. Management: Consider sulfonylurea dose adjustments in patients taking thiazolidinediones and monitor for hypoglycemia.

Risk Factor X (Avoid combination)

Aminolevulinic Acid (Systemic) Aminolevulinic Acid's photosensitizing impact may be enhanced by photosensitizing agents (Systemic).
Mecamylamine Sulfonamides may intensify Mecamylamine's harmful or hazardous effects.
Mitiglinide Sulfonylureas' harmful or hazardous effects could be increased.

Monitor:

  • Blood glucose
  • Glycated hemoglobin
  • Clinical features of hypoglycemia such as:
    • palpitations,
    • Sweating,
    • Blurred vision
    • Dizziness
    • Drowsiness

How to take Chlorpropamide?

  • It is consumed orally once day with breakfast.
  • To lessen gastrointestinal troubles, the dose can be divided.

Mechanism of action of Chlorpropamide:​​​​​​​

  • A first-generation Sulfonylurea called chlorpropamide encourages the release of insulin from pancreatic beta cells.
  • It can also decrease the production of glucose and increase insulin sensitivity at target sites.
  • Due to its prolonged duration of action, it is not advised for people with type 2 diabetes.

It isRapidly absorbedIt has been an

The beginning of actionWithin one hour. 

ThePeak effectIt can be seen in between 3 and 6 hours.

Duration of the actionIt lasts approximately 24 hours. The drug's 90% protein-bound component is extensively metabolized by the liver via CYP2C. 

It has a high hAlf-life Elimination of AboutIt takes 36 hours, which is longer for the elderly and patients with kidney impairment. End-stage renal disease is a condition that can lead to kidney failure. The half-lifeIt can reach 50-200 hours. It is mostly excreted through urine.

Chlorpropamide International brands:

  • Abemide
  • Adiaben
  • Anti-D
  • Arodoc C
  • Biodiabes
  • BPros
  • Chlormide
  • Chlorpropamid
  • Copamide
  • Dabinese
  • Diabemide
  • Diabenese
  • Diabezin
  • Diabines
  • Diabinese
  • Diabitex
  • Dibecon
  • Hypomide
  • Insogen
  • Litangen
  • Meldian
  • Mellitos C
  • Pamidin
  • Propamide
  • Trane

Chlorpropamide brands in Pakistan:

Chlorpropamide [Tabs 250 mg]

Chlorpropamide Geofman Pharmaceuticals
Dabwin Jinnah Pharmaceuticals
Diab-tus ZAFA Pharmaceuticals Laboratories (PVT) LTD.
Diabinese Pfizer Laboratories LTD.

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