Schedule H

Oral

⚠️ LIMITED/NOT AVAILABLE in India — Tolazamide is a first-generation sulfonylurea that is not commonly marketed in India. Current CDSCO listings and major pharmaceutical distributors do not routinely stock this medication. Second-generation sulfonylureas (glimepiride, gliclazide) are standard practice.

If available (verify locally):

• Tablets: 100 mg, 250 mg

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indication: Type 2 Diabetes Mellitus (T2DM)

Initiation criteria: Patients with T2DM not adequately controlled by diet and lifestyle modifications alone

Parameter Recommendation

Starting dose 100–250 mg once daily with breakfast

Titration Increase by 100 mg at weekly intervals based on fasting blood glucose response

Usual maintenance dose 250–500 mg/day (once daily or in divided doses)

Maximum dose 1000 mg/day (in 2–3 divided doses if >500 mg/day)

Clinical Notes:

• Intermediate duration of action among first-generation sulfonylureas

• Higher risk of prolonged hypoglycaemia compared to second-generation agents

• Largely obsolete in current Indian practice — glimepiride or gliclazide strongly preferred

• Once-daily dosing suitable for doses ≤500 mg; split doses for higher amounts

• Ineffective in patients with absolute insulin deficiency (Type 1 DM, pancreatic diabetes)

Secondary Indications – Adults (Off-label)

Not applicable.

No established off-label indications in Indian clinical practice.

PAEDIATRIC DOSING (Specialist Only)

Not recommended in paediatric populations (below 18 years).

• No safety or efficacy data established in children or adolescents

• Not approved for paediatric use in India or internationally

• Safer alternatives available: Metformin (first-line in adolescent T2DM); insulin for Type 1 DM

Primary Indication

Not applicable — no approved paediatric indication.

Secondary Indications – Paediatrics (Off-label)

Not applicable.

Use in children should not be attempted. If sulfonylurea therapy is specifically required for monogenic diabetes, glibenclamide under paediatric endocrinologist supervision is the agent of choice.

Mild impairment (eGFR 60–89) Use with caution; start at 100 mg/day; monitor glucose closely

Moderate impairment (eGFR 30–59) Avoid if possible; if essential, use lowest dose with frequent monitoring

Severe impairment (eGFR <30) Avoid use — significant risk of prolonged hypoglycaemia due to accumulation of active metabolites

Haemodialysis Avoid use — not significantly dialysable

Clinical Note: Prefer short-acting agents (glipizide) or gliclazide in patients with renal impairment.

• Type 1 diabetes mellitus

• Diabetic ketoacidosis (DKA) or hyperosmolar hyperglycaemic state

• Known hypersensitivity to tolazamide, other sulfonylureas, or sulfonamide derivatives

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

• Severe hepatic impairment

• Pregnancy

• Lactation

• Concurrent use with bosentan (hepatotoxicity risk)

• Acute porphyria

• Elderly patients (significantly increased hypoglycaemia risk)

• G6PD deficiency (theoretical haemolysis risk with sulfonamide structure)

• Adrenal or pituitary insufficiency

• Irregular meal patterns or unreliable food intake

• Fasting states (religious fasting, pre-operative)

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

• Combination with other antidiabetic agents (additive hypoglycaemia risk)

• Patients with sulfonamide allergy (cross-reactivity possible, though uncommon)

• Mild-to-moderate renal or hepatic impairment

• Intercurrent illness, surgery, or physiological stress

Parameter Details

Risk Statement Contraindicated in pregnancy

Concern Crosses placenta; may cause prolonged fetal and neonatal hypoglycaemia; potential teratogenic effects not excluded

Preferred Alternative Insulin (regular insulin, NPH, or rapid-acting analogues 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 May be excreted in breast milk; risk of neonatal hypoglycaemia

Drug levels in milk Low to moderate (limited data)

Preferred Alternative Insulin; metformin may be considered under specialist guidance

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

Parameter Recommendation

Starting dose 100 mg/day

Titration Very slow; increase at intervals of 10–14 days only

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

Monitoring Daily SMBG during titration; caregiver education essential

Clinical Note: First-generation sulfonylureas are particularly hazardous in elderly patients. Gliclazide MR or low-dose glimepiride are strongly preferred alternatives.

Interacting Drug Effect Mechanism/Management

Bosentan Increased hepatotoxicity; reduced sulfonylurea efficacy Contraindicated combination

Fluconazole / Miconazole Significantly enhanced hypoglycaemic effect CYP2C9 inhibition; avoid or reduce tolazamide dose substantially

Clarithromycin Enhanced hypoglycaemia CYP inhibition; monitor closely

MAO inhibitors Potentiated hypoglycaemic effect Avoid combination

Disopyramide Additive hypoglycaemia Monitor glucose; may need dose reduction

Non-selective beta-blockers Mask warning signs of hypoglycaemia (tachycardia, tremor) Prefer cardioselective agents; patient education

Interacting Drug Effect Management

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

Thiazide diuretics Reduced hypoglycaemic effect Monitor glucose; may need dose adjustment

Corticosteroids Hyperglycaemic effect Monitor glucose; temporary dose increase may be needed

Warfarin Variable effect on anticoagulation Monitor INR closely

NSAIDs Enhanced hypoglycaemic effect Protein displacement; monitor glucose

Isoniazid May impair glycaemic control Monitor glucose during ATT

Alcohol Enhanced hypoglycaemia; possible disulfiram-like reaction Counsel patients; limit alcohol intake

Fluoroquinolones Unpredictable glycaemic effects Monitor glucose

• Hypoglycaemia (dose-related)

• Weight gain

• Nausea, epigastric discomfort

• Headache

• Dizziness

• Skin rash

• Photosensitivity

Adverse Effect Clinical Notes

Severe prolonged hypoglycaemia May require hospitalisation; IV dextrose; can cause coma, seizures

Cholestatic jaundice Rare; discontinue immediately if jaundice occurs

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

Aplastic anaemia Very rare; monitor CBC if symptoms develop

Stevens-Johnson Syndrome / TEN Rare; discontinue immediately if skin reaction occurs

SIADH and hyponatraemia Rare; monitor sodium in high-risk patients

During titration Daily SMBG; symptoms of hypoglycaemia

Long-term HbA1c every 3 months initially, then 3–6 months; weight monitoring; renal and hepatic function every 6–12 months

As needed LFTs if hepatic symptoms; CBC if haematological symptoms; serum sodium if SIADH suspected

Patient Education: Essential counselling on recognition and management of hypoglycaemia; importance of regular meals; sick day rules.

⚠️ NOT AVAILABLE in India — Tolazamide is not currently marketed or routinely available in India.

The brands previously mentioned in draft versions (Tolamide, Tolaz, Tolnat) could not be verified in current CDSCO listings or major pharmaceutical distributors.

Prescribers should use available alternatives:

• Glimepiride

• Gliclazide / Gliclazide MR

• Glipizide

NOT AVAILABLE in India — No current pricing data available as the drug is not marketed in India.

• Not included in NLEM 2022

• Not available in government supply

1. Not available in India: Tolazamide is essentially unavailable in the Indian market. This monograph is provided for academic completeness; prescribers should use glimepiride, gliclazide, or glipizide instead.

1. Historical context: First-generation sulfonylureas (tolazamide, tolbutamide, chlorpropamide) have been largely replaced by safer second-generation agents with better pharmacokinetic profiles.

1. If encountered in transferred care: Patients on tolazamide from other countries should be switched to an equivalent second-generation sulfonylurea with appropriate dose adjustment.

1. Intermediate duration: Among first-generation sulfonylureas, tolazamide has intermediate duration (shorter than chlorpropamide, longer than tolbutamide).

1. Cross-reactivity: Patients with documented sulfonamide antibiotic allergy may have cross-reactivity, though this is uncommon.

1. Switching guidance: If switching from tolazamide to glimepiride, consider approximate equivalence: tolazamide 250–500 mg ≈ glimepiride 1–2 mg (adjust based on response).

tolazamide; sulfonylurea; first-generation sulfonylurea; type 2 diabetes; hypoglycaemia risk; not-available-in-India; elderly-avoid; renal-caution; hepatic-caution; pregnancy-contraindicated; Schedule H; obsolete-drug

RxIndia v1.0 — 10 Jan 2025

• CDSCO approved formulation listings (drug not currently listed)

• Indian Pharmacopoeia / NFI 2021

• NLEM 2022 (not included)

• API Textbook of Medicine

• RSSDI Guidelines for Management of Type 2 Diabetes in India

• Harrison's Principles of Internal Medicine

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• Standard Indian endocrinology clinical practice