Chlorpropamide + Phenformin

Usage

This combination of Chlorpropamide and Phenformin was previously used to treat type 2 diabetes mellitus, but it is no longer recommended due to the risk of serious side effects, particularly lactic acidosis associated with Phenformin. Phenformin has been withdrawn from many markets worldwide. Therefore, discussing this combination in detail for current clinical practice is not applicable. It’s crucial for Indian doctors to be aware of the outdated nature of this combination. Metformin, a safer biguanide, is now preferred in combination with other antidiabetic agents.

Pharmacological Classification:

• Chlorpropamide: Sulfonylurea (first-generation)
• Phenformin: Biguanide

Mechanism of Action (historical):

• Chlorpropamide: Stimulates insulin release from the pancreas.
• Phenformin: Decreases hepatic glucose production, increases insulin sensitivity, and may improve glucose uptake in peripheral tissues.

Alternate Names

This specific combination doesn’t have alternate names. The individual drugs do:

• Chlorpropamide: Diabinese (brand name)
• Phenformin: DBI, Meltrol (brand names – discontinued)

How It Works (historical)

Chlorpropamide:

• Pharmacodynamics: Binds to sulfonylurea receptors on pancreatic beta-cells, leading to closure of ATP-sensitive potassium channels, depolarization of the cell membrane, and calcium influx. This triggers insulin release.
• Pharmacokinetics: Orally administered, well-absorbed. Metabolized in the liver (CYP2C9), excreted primarily in the urine. Long half-life (approximately 36 hours).

Phenformin:

• Pharmacodynamics: Inhibits mitochondrial complex I, affecting gluconeogenesis and potentially enhancing peripheral glucose utilization. The exact mechanism remains partially unclear.
• Pharmacokinetics: Orally administered, well-absorbed. Not metabolized significantly, excreted primarily by the kidneys.

Dosage

This combination is no longer recommended due to the risk of lactic acidosis associated with Phenformin. No current dosage guidelines exist. Information provided here is purely for historical context.

Historical Dosage (Chlorpropamide):

• Adults: Initially 250 mg daily, adjusted as needed based on blood glucose; maximum 750 mg daily.
• Children: Not recommended.

Historical Dosage (Phenformin):

• Adults: 50-150 mg daily, divided into two or three doses.

Side Effects

Chlorpropamide: Hypoglycemia, gastrointestinal upset, skin reactions, hyponatremia (due to SIADH).

Phenformin: Lactic acidosis (rare but serious), gastrointestinal effects (metallic taste, nausea, vomiting, diarrhea), anorexia, vitamin B12 deficiency.

Contraindications

Chlorpropamide: Type 1 diabetes, diabetic ketoacidosis, severe renal or hepatic impairment, sulfonamide allergy.

Phenformin: Renal impairment, hepatic disease, heart failure, history of lactic acidosis, conditions predisposing to tissue hypoxia.

Drug Interactions

Both drugs have numerous potential drug interactions, including with alcohol, other antidiabetic medications, and certain antibiotics. Consult historical references for a complete list.

Pregnancy and Breastfeeding

Chlorpropamide: Contraindicated in pregnancy.

Phenformin: Contraindicated in pregnancy and breastfeeding.

Drug Profile Summary (historical and no longer clinically relevant)

Popular Combinations

Not applicable. This combination is no longer used.

Precautions

Not applicable. This combination is no longer used.

FAQs

Q1: What is the recommended dosage for Chlorpropamide + Phenformin?

A: This combination is obsolete and no longer recommended.

Q2: Why is Phenformin no longer used?

A: Due to the risk of lactic acidosis.

Q3: What is a safer alternative to this combination?

A: Metformin combined with other antidiabetic agents is now preferred.

Q4: What should I do if a patient is still taking this combination?

A: Discontinue Phenformin immediately and transition to a safer regimen.

Q5: What are the signs of lactic acidosis?

A: Nausea, vomiting, abdominal pain, rapid breathing, weakness, muscle pain, unusual sleepiness, dizziness, lightheadedness.

Q6: Are there any specific monitoring parameters for patients historically taking this combination?

A: Blood glucose, renal function, and signs of lactic acidosis.

Q7: What are the common side effects of Chlorpropamide?

A: Hypoglycemia and gastrointestinal upset.

Q8: What are the drug interactions of Chlorpropamide?

A: It can interact with alcohol, NSAIDs, sulfonamides, and anticoagulants.

Q9: What are the drug interactions of Phenformin?

A: Cimetidine and alcohol can interact with Phenformin.