Schedule H

Oral

• Tablets: 0.5 mg, 1 mg, 2 mg

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Type 2 Diabetes Mellitus

As monotherapy or in combination with metformin, thiazolidinediones, or DPP-4 inhibitors (not with sulfonylureas).

Drug-Naïve Patients or Those Near Glycaemic Target:

Parameter Recommendation

Starting dose 0.5 mg orally before each main meal (15–30 minutes before eating)

Titration Double the dose at weekly intervals based on postprandial glucose response

Usual maintenance dose 0.5–4 mg before each main meal

Maximum dose 4 mg per meal; 16 mg per day

Patients Previously on Oral Antidiabetics or with Marked Hyperglycaemia:

Parameter Recommendation

Starting dose 1 mg orally before each main meal

Titration Increase at weekly intervals based on glucose response

Usual maintenance dose 1–4 mg before each main meal

Maximum dose 4 mg per meal; 16 mg per day

Clinical Notes:

• Administer 15–30 minutes before each main meal (typically 2–4 times daily)

• If a meal is skipped, the corresponding dose must be omitted

• If an extra meal is taken, an extra dose may be given

• Primarily targets postprandial hyperglycaemia

• Do not combine with sulfonylureas — overlapping mechanism increases hypoglycaemia risk

• Flexible dosing suits patients with irregular meal patterns

Secondary Indications – Adults (Off-label, if any)

Not applicable.

• No established off-label indications in Indian clinical practice

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

NOT APPROVED for use in children and adolescents below 18 years.

• Safety and efficacy not established in paediatric population

• Indian regulatory sources (CDSCO, NFI) do not list paediatric indications

Secondary Indications – Paediatrics (Off-label, if any)

Not applicable.

• No off-label paediatric indications supported by Indian practice or published data

Not recommended below age 18 years except under specialist supervision in tertiary centres.

Note: Repaglinide is primarily hepatically metabolised, making it relatively safer in renal impairment compared to renally-excreted sulfonylureas.

• Type 1 diabetes mellitus

• Diabetic ketoacidosis (with or without coma)

• Known hypersensitivity to repaglinide or any excipient

• Concurrent use with gemfibrozil (potent CYP2C8 inhibitor — severe hypoglycaemia risk)

• Severe hepatic impairment

• Elderly patients — increased sensitivity to hypoglycaemia; start low and titrate slowly

• Hepatic dysfunction — impairs drug metabolism; risk of prolonged hypoglycaemia

• Renal impairment — delayed clearance of active metabolites

• Irregular meal patterns — dose must be linked to meals; missed meals require dose omission

• Transitioning from sulfonylureas — avoid overlapping therapy; allow washout period

• Adrenal or pituitary insufficiency — increased hypoglycaemia susceptibility

• Malnourished or debilitated patients — higher hypoglycaemia risk

• Febrile illness, surgery, trauma — may require temporary switch to insulin

Parameter Details

Risk Category Limited human data; animal studies show embryotoxicity at high doses

Recommendation Avoid use during pregnancy

Preferred Alternatives Insulin is the preferred agent for glycaemic control in pregnancy (ICMR, FOGSI guidelines); Metformin acceptable in selected cases

When May Be Used Only if insulin is not feasible and potential benefit clearly outweighs risk; requires endocrinologist and obstetrician supervision

Monitoring Maternal blood glucose (fasting and postprandial); fetal growth surveillance; neonatal glucose monitoring at birth

Parameter Details

Compatibility Not recommended due to lack of human data

Drug Levels in Milk Unknown; excretion in human milk not studied

Preferred Alternatives Insulin or metformin (better characterised safety profile in lactation)

Infant Monitoring If inadvertent exposure, monitor infant for hypoglycaemia signs (poor feeding, lethargy, jitteriness, seizures) and adequate weight gain

Parameter Recommendation

Starting dose 0.5 mg before meals

Titration Slower titration (every 2 weeks); target lowest effective dose

Special Risks Increased susceptibility to hypoglycaemia; hypoglycaemia may present atypically (confusion, falls); polypharmacy increases interaction risk

Monitoring Assess renal and hepatic function before and during therapy; regular glucose monitoring; assess for falls risk

Interacting Drug Mechanism / Effect Recommendation

Gemfibrozil Potent CYP2C8 inhibitor; increases repaglinide AUC by 8-fold Contraindicated — severe hypoglycaemia risk

Clopidogrel CYP2C8 inhibitor; increases repaglinide exposure Avoid combination; if unavoidable, reduce repaglinide dose and monitor glucose closely

Cyclosporine Inhibits OATP1B1 and CYP3A4; increases repaglinide levels Avoid or use with extreme caution; significant hypoglycaemia risk

Clarithromycin / Ketoconazole / Itraconazole CYP3A4 inhibitors; increase repaglinide levels Monitor closely for hypoglycaemia; consider dose reduction

Rifampicin Potent CYP3A4 and CYP2C8 inducer; decreases repaglinide levels by 50–80% Avoid combination; loss of glycaemic efficacy

Interacting Drug Mechanism / Effect Recommendation

Beta-blockers (especially non-selective) May mask hypoglycaemia symptoms (tachycardia, tremor) Use cardioselective beta-blockers when possible; counsel patient about hypoglycaemia awareness

Thiazide diuretics / Corticosteroids Counter-regulatory effects may reduce glycaemic efficacy Monitor blood glucose; may need repaglinide dose adjustment

NSAIDs Protein binding displacement may enhance hypoglycaemic effect Monitor for hypoglycaemia

Metformin Additive hypoglycaemic effect Commonly combined; monitor glucose; adjust doses appropriately

Fenofibrate Milder CYP2C8 inhibition than gemfibrozil Can be used together with caution; monitor for hypoglycaemia

Trimethoprim Mild CYP2C8 inhibitor Monitor blood glucose during concurrent use

Deferasirox CYP2C8 inhibitor Monitor for increased hypoglycaemic effect

• Hypoglycaemia (especially with delayed or omitted meals)

• Weight gain (usually modest; less than with sulfonylureas)

• Headache

• Dizziness

• Nausea

• Diarrhoea

• Abdominal pain

• Upper respiratory tract infection

Adverse Effect Clinical Action

Severe hypoglycaemia May be life-threatening; requires immediate oral glucose or IV dextrose; hospitalisation may be necessary

Hepatotoxicity (rare) Discontinue if unexplained hepatic dysfunction; monitor LFTs

Hypersensitivity reactions (rash, urticaria, rarely angioedema) Discontinue immediately; supportive care

Cardiovascular events Monitor in patients with pre-existing cardiac disease

After initiation/dose change Self-monitoring of blood glucose (especially postprandial); assess for hypoglycaemia symptoms; review at 1–2 weeks

Long-term HbA1c every 3 months; periodic renal and hepatic function tests; weight monitoring; hypoglycaemia event review

Monotherapy:

• Novonorm (Novo Nordisk)

• Eurepa (Torrent)

• Repaglinide (Cipla)

• Regan (Glenmark)

• Raplin (Sun Pharma)

• Glinate (USV)

• Repace (Zydus)

Fixed-Dose Combinations:

• With Metformin: Novonorm M, Eurepa M

0.5 mg tablet ₹3–₹6

• Not included in NLEM; pricing not NPPA-controlled

• Cost varies across brands and regions

• Repaglinide is ideal for patients with irregular meal patterns — flexible "dose-with-meal" approach allows skipping dose when meal is skipped, reducing hypoglycaemia risk compared to longer-acting sulfonylureas

• Preferred secretagogue in moderate renal impairment where sulfonylureas (especially glibenclamide) are contraindicated — hepatic metabolism makes it relatively safer

• Always educate patients: no meal = no dose; if meal is skipped, dose must be omitted

• Gemfibrozil combination is absolutely contraindicated — 8-fold increase in repaglinide exposure causes severe, prolonged hypoglycaemia

• Hypoglycaemia risk is lower than with glibenclamide but still significant — particularly in elderly, hepatic impairment, or when meals are delayed

• Short duration of action (4 hours) means less prolonged hypoglycaemia compared to sulfonylureas if it occurs

• Not effective for fasting hyperglycaemia — combines well with metformin (fasting) for comprehensive glucose control

Repaglinide; type 2 diabetes; meglitinide; insulin secretagogue; short-acting; postprandial hyperglycaemia; flexible dosing; hypoglycaemia-risk; hepatic-caution; renal-safe; Schedule H

RxIndia v1.0 — 26 Apr 2025

• CDSCO approved product information

• Indian Pharmacopoeia (IP)

• National Formulary of India (NFI) 2021

• API Textbook of Medicine — Diabetes Mellitus chapter

• ICMR Guidelines for Management of Type 2 Diabetes (2018)

• AIIMS Endocrinology Treatment Protocols

• Harrison's Principles of Internal Medicine

• Goodman & Gilman's: The Pharmacological Basis of Therapeutics