Schedule H

Oral

• Tablets: 100 mg, 250 mg

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indication: Type 2 Diabetes Mellitus (T2DM)

Initiation criteria: Mild to moderate T2DM not adequately controlled by diet and lifestyle modifications alone

Parameter Recommendation

Starting dose 100–250 mg once daily with breakfast

Titration Increase by 50–125 mg every 3–5 days based on fasting blood glucose response

Usual maintenance dose 100–500 mg once daily

Maximum dose 750 mg/day (use with extreme caution; rarely required)

Clinical Notes:

• Very long half-life (24–72 hours) significantly increases risk of prolonged and severe hypoglycaemia

• Most suitable in patients with regular, predictable meal patterns

• Once-daily dosing possible due to prolonged duration of action

• Largely obsolete in current practice — safer alternatives (gliclazide, glimepiride) strongly preferred

• Ineffective in patients with absolute insulin deficiency

Secondary Indications – Adults (Off-label)

Not applicable.

No established off-label indications in current Indian clinical practice.

PAEDIATRIC DOSING (Specialist Only)

Not recommended in paediatric populations.

Chlorpropamide is not routinely used in children or adolescents due to:

• High risk of prolonged hypoglycaemia

• Very long half-life making dose adjustment difficult

• Availability of safer alternatives (metformin as first-line; glibenclamide for specific monogenic diabetes subtypes)

Primary Indication: Not applicable

No approved paediatric indication in India.

Secondary Indications – Paediatrics (Off-label)

Parameter Details

Indication Monogenic diabetes (e.g., certain KCNJ11/ABCC8 mutations) — OFF-LABEL

Use Specialist paediatric endocrinologist only

Starting dose 0.5–1 mg/kg/day orally once daily

Titration Gradual; based on glucose response

Maximum dose 500 mg/day

Evidence basis Limited case series; extrapolated from adult data; glibenclamide generally preferred for sulfonylurea-responsive monogenic diabetes

Safety Monitoring:

• Frequent blood glucose monitoring (minimum 4 times daily during initiation)

• Watch for signs of hypoglycaemia — confusion, sweating, irritability, drowsiness

• Caregiver education essential

• Not recommended below 2 years of age under any circumstances

Mild impairment (eGFR 60–89) Start at lower dose (100 mg); titrate cautiously; frequent glucose monitoring

Severe impairment (eGFR <30) Contraindicated

Haemodialysis Contraindicated — drug and metabolites not adequately removed

Clinical Note: Prefer short-acting sulfonylureas (glipizide) or gliclazide MR in patients with any degree of renal impairment.

• Type 1 diabetes mellitus

• Diabetic ketoacidosis or hyperosmolar hyperglycaemic state

• Known hypersensitivity to chlorpropamide, other sulfonylureas, or sulfonamides

• Severe renal impairment (eGFR <30 mL/min)

• Severe hepatic impairment

• Acute porphyria

• Pregnancy

• Lactation

• Concurrent use with bosentan (hepatotoxicity risk)

• Elderly patients (very high risk of prolonged hypoglycaemia)

• Irregular meal patterns or unreliable food intake

• Adrenal or pituitary insufficiency

• G6PD deficiency (theoretical haemolysis risk)

• Alcohol use (disulfiram-like reaction; enhanced hypoglycaemia)

• Mild-to-moderate renal impairment

• Cardiovascular disease (hypoglycaemia may mimic or mask ischaemic symptoms)

• Patients on multiple antidiabetic agents

• Intercurrent illness, surgery, or periods of physiological stress

Parameter Details

Risk Statement Contraindicated in pregnancy

Concern Crosses placenta; prolonged half-life increases risk of severe neonatal hypoglycaemia; potential teratogenicity not excluded

Preferred Alternative Insulin (regular insulin, NPH, or rapid-acting analogues as per obstetric protocol)

If inadvertent exposure Discontinue immediately; switch to insulin; inform obstetrician

Monitoring Fasting and postprandial glucose; fetal growth monitoring; neonatal blood glucose at delivery

Parameter Details

Compatibility Not recommended during breastfeeding

Concern Excreted in breast milk; prolonged half-life increases risk of neonatal hypoglycaemia

Drug levels in milk Low to moderate (but clinically significant due to long half-life)

Preferred Alternative Insulin; metformin may be considered under specialist guidance

Infant Monitoring (if inadvertently used) Feeding pattern, lethargy, jitteriness, weight gain, blood glucose if symptomatic

Parameter Recommendation

Starting dose 100 mg/day or lower

Titration Very slow; increase at intervals of 7–14 days only

Special Risks Prolonged and severe hypoglycaemia; falls; confusion; reduced renal reserve; impaired hepatic metabolism

Monitoring Daily SMBG during titration; caregiver education essential

Clinical Note: Chlorpropamide is particularly hazardous in elderly patients due to its very long half-life. Gliclazide MR or low-dose glimepiride are strongly preferred alternatives.

Interacting Drug Effect Mechanism/Management

Alcohol Disulfiram-like reaction (flushing, nausea, palpitations); enhanced hypoglycaemia Avoid alcohol completely

Bosentan Increased hepatotoxicity; reduced sulfonylurea efficacy Contraindicated combination

Rifampicin Reduced chlorpropamide efficacy CYP enzyme induction; use alternative antidiabetic during ATT

Warfarin Enhanced anticoagulant effect Protein-binding displacement; monitor INR closely

High-dose salicylates Potentiated hypoglycaemic effect Protein-binding displacement; monitor glucose

Sulfonamide antibiotics Additive hypoglycaemia risk Similar chemical structure; use with caution

Interacting Drug Effect Management

Beta-blockers (non-selective) Mask tachycardia warning sign of hypoglycaemia Prefer cardioselective agents; patient education

Thiazide diuretics May reduce hypoglycaemic effect Monitor glucose; may need dose adjustment

NSAIDs Enhanced hypoglycaemic effect Protein-binding displacement; monitor glucose

Isoniazid May impair glycaemic control Monitor glucose during ATT

Fluoroquinolones Unpredictable glycaemic effects Monitor glucose

Azole antifungals Increased chlorpropamide levels CYP2C9 inhibition; monitor for hypoglycaemia

ACE inhibitors May enhance hypoglycaemic effect Monitor glucose

• Hypoglycaemia (dose-related; may be prolonged)

• Nausea, anorexia

• Headache

• Facial flushing (with alcohol)

• Metallic taste

• Photosensitivity

• Weight gain

• Dizziness

Adverse Effect Clinical Notes

Prolonged severe hypoglycaemia May persist for 24–72 hours; requires hospitalisation, IV dextrose, monitoring

SIADH and hyponatraemia Notable with chlorpropamide; monitor sodium in elderly and those on diuretics

Cholestatic jaundice Rare; discontinue immediately if jaundice occurs

Agranulocytosis / leukopenia Rare; discontinue if unexplained fever, sore throat, infection

Thrombocytopenia Rare haematological toxicity

Severe cutaneous reactions Stevens-Johnson syndrome (rare); discontinue immediately

Aplastic anaemia Very rare; monitor CBC if prolonged use

During titration Daily SMBG; symptoms of hypoglycaemia; serum sodium weekly in high-risk patients

Long-term HbA1c every 3 months; renal and hepatic function every 6 months; serum sodium periodically; CBC annually

As needed LFTs if hepatic symptoms; CBC if haematological symptoms

Patient Education: Essential counselling on recognition and management of hypoglycaemia; strict avoidance of alcohol; regular meal timing.

Note: Chlorpropamide is an older first-generation sulfonylurea with very limited current usage. Availability in India is declining.

• Diabinese (Pfizer) — verify current availability

• Generic formulations may be available through select distributors

Prescribers should confirm local availability before prescribing. Many pharmacies may not routinely stock this medication.

• Not included in NLEM 2022

• Not routinely stocked in government hospitals

• Limited availability in private pharmacies due to shift towards newer agents

1. Obsolete in modern practice: Chlorpropamide is largely replaced by safer alternatives (gliclazide, glimepiride, glipizide) and should be considered only when other options are unavailable.

1. Prolonged hypoglycaemia risk: The very long half-life (24–72 hours) makes hypoglycaemia potentially life-threatening, especially in elderly or renally impaired patients. Hospital admission may be required for management.

1. Unique SIADH risk: Among sulfonylureas, chlorpropamide has the highest risk of causing SIADH and hyponatraemia — monitor sodium levels, particularly in elderly patients.

1. Absolute alcohol avoidance: Warn patients about disulfiram-like reaction (flushing, nausea, tachycardia) even with small amounts of alcohol.

1. Switching precaution: When switching from chlorpropamide to another antidiabetic, allow 2–3 day washout period before starting new agent to avoid overlapping hypoglycaemic effects.

1. Not for irregular meals: Only prescribe to patients with predictable, regular meal patterns due to prolonged action.

chlorpropamide; sulfonylurea; first-generation sulfonylurea; type 2 diabetes; hypoglycaemia risk; SIADH; hyponatraemia; elderly-avoid; renal-avoid; hepatic-caution; pregnancy-contraindicated; alcohol-interaction; Schedule H; not-in-NLEM

RxIndia v1.0 — 10 Jan 2025

• CDSCO approved prescribing information

• Indian Pharmacopoeia (IP)

• NLEM 2022 (not listed)

• API Textbook of Medicine

• ICMR Guidelines for Management of Type 2 Diabetes

• Harrison's Principles of Internal Medicine

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• Standard Indian endocrinology clinical practice