Schedule H

Oral

• Tablets: 2.5 mg, 5 mg

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

Type 2 Diabetes Mellitus (Monotherapy or Combination Therapy)

Parameter Details

Starting dose 2.5 mg once daily with breakfast

Titration Increase by 2.5 mg every 1–2 weeks based on fasting blood glucose response

Usual maintenance dose 5–10 mg/day (single morning dose or divided with meals)

Maximum dose 15 mg/day (doses >10 mg/day should be divided into 2 doses with meals)

Clinical Notes:

• Not first-line therapy; used when metformin is contraindicated or not tolerated

• Administer with meals to reduce hypoglycaemia risk

• Higher hypoglycaemia risk compared to other sulfonylureas (gliclazide, glimepiride)

• Consider safer alternatives in elderly and renal impairment

Secondary Indications – Adults Only (Off-label)

Not applicable — No established off-label indications with Indian specialist support.

PAEDIATRIC DOSING (Specialist Only)

Primary Indications

Neonatal Diabetes Mellitus (Monogenic Forms — KATP Channel Mutations)

Parameter Details

Starting dose 0.1 mg/kg/day in 1–2 divided doses

Titration Increase gradually by 0.1 mg/kg/day every 3–7 days based on glycaemic response

Usual maintenance dose 0.2–0.5 mg/kg/day in 2–3 divided doses

Maximum dose 0.8 mg/kg/day (rarely exceeded)

Clinical Notes:

• Specialist indication only — Paediatric Endocrinologist supervision mandatory

• Initiate in hospital or specialised diabetes centre

• May allow transition from insulin in genetically confirmed cases

• Tablets may be crushed or compounded suspension used

Safety Monitoring:

• Baseline: Genetic testing for KCNJ11/ABCC8 mutations, blood glucose, renal function, LFTs

• During initiation: Frequent blood glucose monitoring (4–6 times daily)

• Monitor for hypoglycaemia signs, potassium levels, feeding patterns

• Long-term: HbA1c every 3 months; growth parameters

Age Restriction: This indication applies primarily to neonates and infants with confirmed monogenic diabetes. NOT RECOMMENDED for Type 2 diabetes in children/adolescents below 18 years.

Secondary Indications – Paediatrics (Off-label)

Not applicable — Glibenclamide is not recommended for Type 2 diabetes in paediatric population due to high hypoglycaemia risk. Metformin is preferred first-line in adolescent T2DM.

Key Point: Glibenclamide has active metabolites that accumulate in renal impairment, making it the LEAST preferred sulfonylurea in CKD. Consider gliclazide or glipizide as safer alternatives.

Caution: Hepatic metabolism is impaired; hypoglycaemia may be prolonged and severe.

• Hypersensitivity to glibenclamide, other sulfonylureas, or sulfonamides

• Type 1 diabetes mellitus

• Diabetic ketoacidosis (with or without coma)

• Diabetic pre-coma

• Severe renal impairment (eGFR <30 mL/min/1.73m²)

• Severe hepatic impairment

• Pregnancy (especially second and third trimesters)

• Concomitant use with bosentan (increased risk of hepatotoxicity and reduced efficacy of both drugs)

• Elderly patients — significantly higher hypoglycaemia risk; consider alternatives

• Irregular meal timing or poor nutritional intake — increased hypoglycaemia risk

• Alcohol consumption — potentiates hypoglycaemic effect

• Adrenal or pituitary insufficiency — enhanced sensitivity to glucose-lowering effects

• Hypothyroidism — altered drug metabolism

• G6PD deficiency — risk of haemolytic anaemia

• Cardiovascular disease — severe hypoglycaemia may precipitate ischaemic events

• Patients on fasting regimens (religious or medical) — high hypoglycaemia risk

• Concurrent use with β-blockers — may mask hypoglycaemia symptoms

Aspect Details

Overall safety Avoid — crosses placenta; risk of neonatal hypoglycaemia and macrosomia

Preferred alternatives Insulin (first-line for gestational and pre-existing T2DM)

When it may be used Not recommended; very limited use in early first trimester if insulin unavailable under specialist supervision only

Pre-conception advice Discontinue and switch to insulin before conception

Monitoring if exposed Maternal blood glucose; fetal growth (serial USG); amniotic fluid volume; neonatal blood glucose after delivery

Aspect Details

Compatibility Not recommended; excreted in breast milk

Expected levels in milk Low, but risk of infant hypoglycaemia cannot be excluded

Preferred alternatives Insulin (first-line); Metformin (considered safer in lactation)

If use unavoidable Monitor infant for signs of hypoglycaemia (irritability, lethargy, poor feeding, jitteriness), feeding adequacy, weight gain

Aspect Recommendation

Starting dose 1.25–2.5 mg once daily with breakfast

Titration Slower; increase dose every 2–4 weeks

Maximum dose Consider limiting to 10 mg/day

Additional risks Prolonged and severe hypoglycaemia, falls, cognitive impairment, reduced awareness of hypoglycaemia, impaired renal clearance

Considerations Avoid if eGFR <45 mL/min/1.73m² or multiple comorbidities; consider gliclazide or DPP-4 inhibitors as safer alternatives

Monitoring Frequent blood glucose monitoring; renal function every 3–6 months

Key Point: Glibenclamide is generally NOT preferred in elderly patients due to high hypoglycaemia risk. Gliclazide MR or DPP-4 inhibitors are safer alternatives.

Interacting Drug Effect Recommendation

Bosentan Increased hepatotoxicity risk; reduced efficacy of both drugs Contraindicated — do not co-administer

Miconazole (oral gel/systemic) Severe enhancement of hypoglycaemic effect (CYP2C9 inhibition) Avoid combination

Fluconazole CYP2C9 inhibitor; increases glibenclamide levels Avoid if possible; if essential, reduce glibenclamide dose and monitor closely

Rifampicin Strong CYP2C9/3A4 inducer; significantly reduces glibenclamide efficacy Avoid combination or monitor glucose very closely; may need substantial dose increase

Sulfonamide antibiotics (co-trimoxazole) Displacement from protein binding; enhanced hypoglycaemic effect Avoid if possible; monitor blood glucose closely

Interacting Drug Effect Recommendation

Warfarin Glibenclamide may enhance anticoagulant effect Monitor INR closely; adjust warfarin dose as needed

β-blockers (propranolol, atenolol) May mask hypoglycaemia symptoms (tachycardia, tremor) Counsel patient on alternative symptoms; prefer cardioselective β-blockers

ACE inhibitors May enhance hypoglycaemic effect Monitor blood glucose

NSAIDs (ibuprofen, diclofenac) May displace from protein binding; enhanced effect Monitor blood glucose

Isoniazid May reduce glycaemic control (hyperglycaemic effect) Monitor glucose; may need glibenclamide dose adjustment

Clarithromycin, Ciprofloxacin May enhance sulfonylurea effect Monitor blood glucose closely

Corticosteroids Counteract hypoglycaemic effect Monitor blood glucose; may need to increase glibenclamide dose during steroid therapy

Pioglitazone Additive glucose-lowering effect Monitor for hypoglycaemia

Alcohol Potentiates hypoglycaemia; disulfiram-like reaction possible Counsel patient to limit alcohol intake

• Hypoglycaemia (common and dose-related; more frequent than with other sulfonylureas)

• Weight gain (typically 2–4 kg)

• Nausea

• Epigastric fullness

• Headache

• Dizziness

• Skin rash

• Pruritus

Adverse Effect Action Required

Severe hypoglycaemia May require hospitalisation; IV dextrose administration; can be prolonged (12–72 hours); observation required

Cholestatic jaundice Rare; discontinue immediately; hepatology evaluation

Hepatitis Rare; discontinue and evaluate liver function

Haemolytic anaemia Especially in G6PD deficiency; discontinue immediately

Aplastic anaemia / Agranulocytosis Very rare; discontinue immediately; haematology referral

Thrombocytopenia Rare; discontinue and monitor

Stevens-Johnson Syndrome / TEN Very rare; immediate discontinuation; dermatology referral

Hyponatraemia (SIADH) Rare; discontinue if severe

Phase Parameters Frequency

Baseline FPG, HbA1c, renal function (creatinine, eGFR), LFTs, CBC, body weight Before initiation

After initiation FPG, PPG, symptoms of hypoglycaemia 1–2 times weekly for first 2–4 weeks

After dose change FPG Within 1 week

Stable long-term therapy HbA1c Every 3 months

Stable long-term therapy Renal function, LFTs Every 6 months

Stable long-term therapy Body weight At each visit

Elderly / CKD patients Blood glucose, renal function More frequently

Patient Education: All patients must be counselled on recognition and management of hypoglycaemia symptoms.

Single-ingredient formulations:

• Daonil (Sanofi)

• Euglucon (Abbott)

• Semi-Daonil (Sanofi) — 2.5 mg

• Glynase (Various)

• Gliben (Various generics)

Fixed-Dose Combinations:

Note: Glibenclamide is included in NLEM 2022; NPPA price-controlled formulation. Widely available in government supply at subsidised rates.

1. Not preferred sulfonylurea: Glibenclamide has the highest hypoglycaemia risk among sulfonylureas due to its long half-life and active metabolites. Gliclazide or glimepiride are preferred alternatives in most clinical scenarios.

1. Avoid in CKD: Active metabolites accumulate in renal impairment; gliclazide is the preferred sulfonylurea in mild-to-moderate CKD.

1. Avoid in elderly: High risk of prolonged and severe hypoglycaemia in elderly patients. Consider DPP-4 inhibitors or gliclazide MR as safer alternatives.

1. Hypoglycaemia education: Always counsel patients on recognising and treating hypoglycaemia. Advise carrying glucose tablets/sugar. Warn about alcohol consumption.

1. Neonatal diabetes niche: Glibenclamide has a unique role in KATP channel mutations (neonatal diabetes) where it can replace insulin — this is a specialist indication only.

1. Consistent meal timing: Emphasise importance of regular meal patterns. Avoid prescribing to patients with erratic eating schedules or those observing prolonged fasts.

Type 2 diabetes; sulfonylurea; hypoglycaemia-high-risk; NLEM India; neonatal diabetes; renal-avoid; elderly-avoid; second-generation sulfonylurea; KATP channel

RxIndia v1.0 — 25 Jan 2025

• CDSCO Approved Product Database

• Indian Pharmacopoeia (latest edition)

• National List of Essential Medicines (NLEM) 2022

• API Textbook of Medicine

• ICMR Guidelines for Management of Type 2 Diabetes (2023)

• AIIMS Pharmacology Protocols

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• Indian Paediatric Endocrinology Guidelines (for neonatal diabetes)

• IAP Drug Formulary