Schedule H

Oral

• Immediate-release tablets: 5 mg, 10 mg

• Extended-release tablets: 5 mg, 10 mg

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indication: Type 2 Diabetes Mellitus (T2DM) — Monotherapy or Add-on Therapy

IMMEDIATE-RELEASE TABLETS

Parameter Recommendation

Starting dose 2.5–5 mg once daily, 30 minutes before breakfast

Titration Increase by 2.5–5 mg at weekly intervals based on glycaemic response

Usual maintenance dose 5–15 mg daily; if >10 mg/day, divide into twice daily dosing

Maximum dose 20 mg/day (doses above 20 mg offer limited additional benefit with increased hypoglycaemia risk)

Clinical Notes:

• Short half-life (~2–4 hours) results in lower overnight hypoglycaemia risk compared to longer-acting sulfonylureas

• Administer 30 minutes before meals for optimal absorption

• Efficacy diminishes as β-cell function declines in advanced T2DM

EXTENDED-RELEASE TABLETS

Parameter Recommendation

Starting dose 5 mg once daily with breakfast

Titration Increase by 5 mg at 1–2 week intervals based on response

Usual maintenance dose 5–10 mg once daily

Maximum dose 20 mg once daily

Clinical Notes:

• Must be swallowed whole; do not crush, chew, or break

• Provides smoother glycaemic control with once-daily dosing

• Ghost tablet may appear in stool (normal finding)

Secondary Indications — Adults (Off-label)

Indication Dose Notes

Maturity-Onset Diabetes of the Young (MODY) — HNF1A/HNF4A mutations Starting: 2.5–5 mg/day; titrate as per glycaemic response OFF-LABEL • Specialist only (Endocrinologist) • Requires genetic confirmation • Patients often highly sensitive to sulfonylureas — use lower doses • Based on Indian specialist practice and international MODY management consensus

PAEDIATRIC DOSING (Specialist Only)

Primary Indication

Not routinely recommended for paediatric T2DM

• Metformin remains the first-line oral agent for paediatric T2DM in India

• Not recommended below 18 years for standard T2DM management

Secondary Indications — Paediatrics (Off-label)

Indication Age Dosing Notes

MODY (HNF1A/HNF4A mutation-positive) ≥10 years Starting dose: 0.1–0.2 mg/kg/day (max initial: 5 mg/day) OFF-LABEL

Titration: Adjust every 1–2 weeks based on blood glucose monitoring Specialist only — Paediatric Endocrinologist

Usual maintenance: 0.2–0.4 mg/kg/day Requires genetic confirmation before initiation

Maximum dose: 0.6 mg/kg/day (not exceeding 20 mg/day) Based on Indian Paediatric Endocrine Society practice

Safety Monitoring:

• Stringent home blood glucose monitoring (minimum 3–4 times daily during initiation)

• Educate caregivers on hypoglycaemia recognition and management

• Regular meal timing essential

Age Restrictions:

• Not recommended in children <10 years

• Not recommended in infants — insufficient safety data

Dialysis Not recommended; drug not dialyzable; consider insulin as alternative

• Type 1 diabetes mellitus

• Diabetic ketoacidosis (with or without coma)

• Hyperosmolar hyperglycaemic state

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

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

• Severe hepatic impairment

• Pregnancy and lactation

• Elderly patients (increased hypoglycaemia susceptibility)

• Malnourished patients or those with irregular meal patterns

• Adrenal or pituitary insufficiency (reduced counter-regulatory response)

• Chronic alcoholism (impaired gluconeogenesis, erratic intake)

• Concurrent use of beta-blockers (may mask adrenergic hypoglycaemia symptoms)

• G6PD deficiency (theoretical risk of haemolysis — shared sulfonylurea class concern)

• Patients undergoing surgery or acute illness (consider temporary switch to insulin)

• Febrile illness or severe infection (may require temporary insulin coverage)

Parameter Details

Overall safety Not recommended — crosses placenta; associated with neonatal hypoglycaemia

Preferred alternatives Insulin is the preferred agent for glycaemic control in pregnancy; Metformin may be considered where insulin is not feasible

When it may be used Only if no safer alternative available and benefit clearly outweighs fetal risk — specialist decision

What to monitor Fetal growth (risk of macrosomia); neonatal blood glucose immediately after delivery; signs of neonatal hypoglycaemia

Preconception advice Discontinue glipizide and switch to insulin before planned conception or upon confirmation of pregnancy

Parameter Details

Compatibility Not recommended during breastfeeding

Preferred alternatives Insulin is safest; does not enter breast milk

Expected drug levels in milk Unknown — potential excretion into breast milk

What to monitor in infant Hypoglycaemia symptoms (poor feeding, lethargy, jitteriness, excessive sleepiness); adequate weight gain

Parameter Recommendation

Starting dose 2.5 mg/day

Titration Slower increments at 2-week intervals

Additional risks Higher hypoglycaemia risk due to: reduced renal reserve, irregular dietary intake, polypharmacy, impaired counter-regulatory hormonal response

Alternatives to consider DPP-4 inhibitors (e.g., sitagliptin, vildagliptin) may offer lower hypoglycaemia risk in vulnerable elderly patients

Monitoring More frequent blood glucose checks; educate caregivers on hypoglycaemia recognition

Interacting Drug Effect Mechanism / Management

Fluconazole, Miconazole Potentiated hypoglycaemia CYP2C9 inhibition — avoid or reduce glipizide dose; monitor glucose closely

Sulfonamide antibiotics Increased hypoglycaemia risk Displacement from protein binding + possible CYP inhibition

Clarithromycin, Erythromycin Enhanced hypoglycaemic effect CYP inhibition — monitor and reduce dose if needed

Rifampicin Reduced glipizide efficacy CYP2C9 induction; may require increased glipizide dose or alternative antidiabetic

MAO inhibitors Potentiated hypoglycaemia Avoid combination; if unavoidable, reduce glipizide dose and monitor intensively

Insulin / Other sulfonylureas Additive hypoglycaemia Avoid concomitant sulfonylurea use; if combining with insulin, use reduced doses of both

Interacting Drug Effect Management

NSAIDs (high-dose) Increased hypoglycaemia risk Monitor blood glucose; consider dose adjustment

Warfarin Possible potentiation of anticoagulant effect Monitor INR more frequently

ACE inhibitors May enhance hypoglycaemic response Monitor blood glucose, especially at initiation

Beta-blockers May mask adrenergic symptoms of hypoglycaemia Use cardioselective beta-blockers if possible; educate patient on neuroglycopenic symptoms

H2-receptor blockers (Ranitidine, Cimetidine) May increase sulfonylurea levels Monitor for hypoglycaemia

Isoniazid May increase blood glucose Monitor glycaemic control; may need glipizide dose adjustment

Corticosteroids Hyperglycaemia; reduced glipizide efficacy May require increased antidiabetic therapy during steroid use

• Hypoglycaemia (especially with missed meals, excessive dosing, renal impairment)

• Weight gain (typically 1–3 kg)

• Nausea, dyspepsia

• Headache

• Dizziness

Adverse Effect Notes

Severe hypoglycaemia May require IV dextrose, hospitalisation; can cause seizures, altered consciousness

Cholestatic jaundice Rare; discontinue drug immediately

Haematological reactions Leukopenia, thrombocytopenia, agranulocytosis (rare) — discontinue if suspected

Severe hypersensitivity Rash, urticaria, angioedema; Stevens-Johnson Syndrome (very rare) — discontinue immediately

Hyponatraemia SIADH-like effect (rare)

Phase Parameters

Baseline Fasting blood glucose, HbA1c, renal function (serum creatinine, eGFR), liver function tests

Initiation / Titration Fasting and postprandial blood glucose 2–3 times per week; assess for hypoglycaemia symptoms

Long-term HbA1c every 3 months until stable, then every 6 months; renal and hepatic function every 6–12 months

Ongoing Monitor for hypoglycaemia episodes, especially during illness, dose changes, or missed meals

• Minidiab (Pfizer)

• Glizen (USV)

• Glytop (Aristo)

• Dibizide (Micro Labs)

• Glipizide ER (multiple generic manufacturers)

• Glynase (Cadila — note: may also refer to glibenclamide in some contexts)

Note: Included in NLEM 2022; price controlled under DPCO by NPPA

1. Patient selection: Best suited for T2DM patients with preserved β-cell function and consistent meal patterns; less effective in advanced diabetes with β-cell exhaustion

1. Hypoglycaemia prevention: Always counsel patients on hypoglycaemia symptoms, importance of regular meals, and carrying glucose tablets/sugar

1. Switching from longer-acting sulfonylureas: When switching from glibenclamide or glimepiride, start glipizide at lower doses due to different duration of action

1. Extended-release advantages: Consider ER formulation for improved compliance (once-daily dosing) and potentially smoother glycaemic profile

1. Fasting situations: Advise dose reduction or omission during Ramadan fasting or medical procedures requiring fasting — high hypoglycaemia risk

1. Combination therapy: Commonly combined with metformin; when adding to metformin, start at lowest glipizide dose (2.5 mg) and titrate based on response

Glipizide; Type 2 diabetes; sulfonylurea; hypoglycaemia; oral antidiabetic; renal-adjustment; hepatic-caution; pregnancy-avoid; elderly-caution; NLEM India; low-cost diabetes

RxIndia v1.0 — 25 Jan 2025

• CDSCO approved prescribing information

• Indian Pharmacopoeia

• National List of Essential Medicines (NLEM) 2022

• API Textbook of Medicine

• ICMR Guidelines for Management of Type 2 Diabetes

• AIIMS Standard Treatment Guidelines

• Indian Paediatric Endocrine Society — MODY consensus

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• Harrison's Principles of Internal Medicine