Schedule H

Oral

• Tablets (Immediate Release): 40 mg, 80 mg

• Tablets (Modified Release): 30 mg, 60 mg

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

Type 2 Diabetes Mellitus (Monotherapy or Combination Therapy)

A. Immediate Release (IR) Formulations

Parameter Details

Starting dose 40–80 mg once daily with breakfast

Titration Increase by 40–80 mg at intervals of ≥1 week based on glycaemic response

Usual maintenance dose 80–160 mg/day in 1–2 divided doses (with meals)

Maximum dose 320 mg/day (doses >160 mg/day should be divided)

Clinical Notes:

• Administer with meals to reduce hypoglycaemia risk

• Elderly or hepatic impairment: Start at 40 mg once daily

• Divide doses when total daily dose exceeds 160 mg

B. Modified Release (MR) Formulations

Parameter Details

Starting dose 30 mg once daily with breakfast

Titration Increase by 30 mg at intervals of 2–4 weeks based on glycaemic targets

Usual maintenance dose 30–90 mg once daily

Maximum dose 120 mg once daily

Clinical Notes:

• Tablets must be swallowed whole; do not crush, chew, or split

• Single daily dosing improves compliance

• MR and IR formulations are NOT dose-equivalent

• 30 mg MR ≈ 80 mg IR in terms of glycaemic effect (approximate equivalence)

Combination Therapy Options:

Combination Regimen Gliclazide Dose Clinical Notes

Add-on to Metformin Standard dosing as above Most common combination; synergistic effect

Add-on to DPP-4 inhibitor Standard dosing as above Generally well tolerated

Add-on to SGLT2 inhibitor Standard dosing as above May need lower gliclazide dose

Add-on to Insulin Consider dose reduction Increased hypoglycaemia risk; specialist supervision advised

Secondary Indications – Adults Only (Off-label)

Not applicable — No established off-label indications.

Note: The ADVANCE trial demonstrated microvascular benefits (including reduced nephropathy and retinopathy progression) with intensive glucose control using gliclazide MR-based regimen, but this represents optimised glycaemic control rather than a specific off-label indication for microvascular complications.

PAEDIATRIC DOSING (Specialist Only)

Primary Indications

Not applicable — Gliclazide is NOT APPROVED for use in patients below 18 years of age. Safety and efficacy have not been established in the paediatric population.

Secondary Indications – Paediatrics (Off-label)

Indication Dose Notes

Type 2 Diabetes in adolescents (≥10 years) Gliclazide MR 30 mg once daily; titrate cautiously to maximum 60–90 mg/day OFF-LABEL; Specialist only (Paediatric Endocrinologist); Very limited evidence; metformin preferred as first-line

Safety Monitoring:

• Baseline: FPG, HbA1c, renal function, LFTs

• Follow-up: Blood glucose monitoring; HbA1c every 3 months

• Monitor for hypoglycaemia symptoms, especially with irregular meals

• Growth parameters

Age Restriction: NOT RECOMMENDED below 10 years. Extremely limited data in paediatric population; use only under paediatric endocrinologist supervision when metformin and lifestyle measures have failed.

Key Point: Gliclazide is considered the safest sulfonylurea in mild-to-moderate CKD due to hepatic metabolism and inactive metabolites. However, hypoglycaemia risk increases with declining renal function.

Caution: Sulfonylureas are hepatically metabolised; hepatic impairment prolongs drug half-life and increases hypoglycaemia risk.

• Hypersensitivity to gliclazide, other sulfonylureas, or sulfonamides

• Type 1 diabetes mellitus

• Diabetic ketoacidosis (with or without coma)

• Diabetic pre-coma

• Severe renal impairment (eGFR <15 mL/min/1.73m²)

• Severe hepatic impairment

• Pregnancy

• Lactation

• Concomitant use with miconazole (oral gel or systemic) — risk of severe hypoglycaemia

• Elderly patients — higher risk of prolonged hypoglycaemia; start low

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

• Adrenal or pituitary insufficiency — enhanced hypoglycaemic effect

• Alcohol consumption — may potentiate hypoglycaemia

• Glucose-6-phosphate dehydrogenase (G6PD) deficiency — haemolytic anaemia risk

• Cardiovascular disease — severe hypoglycaemia may precipitate ischaemic events

• Patients on β-blockers — may mask hypoglycaemia symptoms

• Acute illness, surgery, or stress — may require temporary switch to insulin

Aspect Details

Overall safety Contraindicated; gliclazide crosses placenta; risk of neonatal hypoglycaemia

Preferred alternatives Insulin (first-line for gestational and pre-existing T2DM); Metformin may be continued under specialist guidance in early pregnancy

When it may be used Should not be used during pregnancy

Pre-conception advice Discontinue gliclazide and switch to insulin before conception or as soon as pregnancy confirmed

Monitoring if exposed Fetal growth monitoring; neonatal blood glucose monitoring after delivery

Aspect Details

Compatibility Not recommended; unknown if excreted in human milk

Expected levels in milk Unknown; sulfonylureas may pass into milk in small amounts

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

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

Aspect Recommendation

Starting dose 40 mg IR once daily OR 30 mg MR once daily

Titration Slower; increase dose every 2–4 weeks

Maximum dose Consider limiting to 160 mg/day (IR) or 90 mg/day (MR)

Additional risks Prolonged hypoglycaemia, falls, cognitive impairment, fractures (due to neuroglycopenia), reduced awareness of hypoglycaemia

Monitoring More frequent blood glucose monitoring; renal function assessment

Considerations Consider DPP-4 inhibitors or SGLT2 inhibitors as alternatives with lower hypoglycaemia risk

Key Point: MR formulation preferred in elderly due to smoother pharmacokinetic profile and once-daily dosing.

Interacting Drug Effect Recommendation

Miconazole (oral gel/systemic) Severe enhancement of hypoglycaemic effect Contraindicated — do not co-administer

Fluconazole CYP2C9 inhibitor; increases gliclazide levels Avoid if possible; if essential, monitor blood glucose closely and consider dose reduction

Phenylbutazone Displaces gliclazide from protein binding; inhibits metabolism Avoid combination

Alcohol (acute excess) Potentiates hypoglycaemic effect Counsel patient; avoid binge drinking

Interacting Drug Effect Recommendation

Clarithromycin, Ciprofloxacin May enhance sulfonylurea effect Monitor blood glucose closely

Warfarin Gliclazide may potentiate anticoagulant effect Monitor INR closely; adjust warfarin dose if needed

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

Rifampicin CYP2C9 inducer; may reduce gliclazide efficacy Monitor glycaemic control; may need dose adjustment

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

NSAIDs (high dose) May potentiate hypoglycaemic effect Monitor blood glucose

ACE inhibitors May enhance hypoglycaemic effect Monitor; usually clinically insignificant

Metformin Additive glucose-lowering effect Generally safe; standard combination

Thiazolidinediones Additive effect; may increase weight gain and oedema Monitor weight and fluid status

• Hypoglycaemia (most common, dose-related)

• Weight gain (typically 2–4 kg)

• Nausea

• Abdominal discomfort

• Diarrhoea or constipation

• Headache

• Dizziness

Adverse Effect Action Required

Severe hypoglycaemia May require hospitalisation; IV dextrose administration; adjust dose or discontinue

Cholestatic jaundice Rare; discontinue and evaluate liver function

Hepatitis Rare; discontinue immediately

Haemolytic anaemia Rare; especially in G6PD deficiency; discontinue

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

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

Thrombocytopenia Rare; discontinue and monitor

Phase Parameters Frequency

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

After initiation FPG, symptoms of hypoglycaemia Within 1–2 weeks

After dose change FPG 1 week after each dose adjustment

Stable long-term therapy HbA1c Every 3 months

Stable long-term therapy FPG, PPG Periodically (monthly or as clinically indicated)

Stable long-term therapy Renal function, body weight Every 6–12 months

Elderly / CKD patients Blood glucose, renal function More frequently

Single-ingredient formulations:

• Diamicron, Diamicron MR (Serdia/Servier)

• Reclazide (Intas)

• Glycinorm (Abbott)

• Glizid, Glizid M (Panacea Biotec)

• Glyclazide (Various generics)

• Dianorm (Torrent)

• Glynase MR (Pfizer — Note: Not to be confused with glibenclamide brand)

Fixed-Dose Combinations:

Note: Gliclazide is included in NLEM 2022; NPPA price-controlled formulations available. Widely available in government supply.

1. Safest sulfonylurea in CKD: Gliclazide is hepatically metabolised to inactive metabolites, making it the preferred sulfonylurea in mild-to-moderate renal impairment (avoid glibenclamide in CKD).

1. Hypoglycaemia prevention: Always counsel patients on consistent meal timing. Hypoglycaemia risk is highest with erratic eating patterns, elderly patients, and those on multiple glucose-lowering agents.

1. MR vs IR formulations: MR formulations provide smoother glycaemic control with once-daily dosing, improving compliance and potentially reducing hypoglycaemia risk. Preferred in elderly patients.

1. Dose equivalence caution: MR and IR formulations are NOT interchangeable on a mg-for-mg basis. Approximately 30 mg MR ≈ 80 mg IR.

1. Weight gain management: Sulfonylureas cause weight gain (2–4 kg average). Consider combination with metformin or SGLT2 inhibitors if weight is a concern.

1. Sick day rules: Advise patients to temporarily withhold gliclazide during acute illness with reduced oral intake to prevent hypoglycaemia. Switch to insulin if hospitalised or during critical illness.

Type 2 diabetes; sulfonylurea; gliclazide MR; hypoglycaemia risk; NLEM India; renal-safer sulfonylurea; elderly-caution; weight gain; second-generation sulfonylurea

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 (2022)

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

• AIIMS New Delhi Internal Medicine Protocols

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• ADVANCE Trial (N Engl J Med 2008) — for microvascular outcomes data