Schedule H

Oral

• Tablets: 60 mg, 120 mg

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indication: Type 2 Diabetes Mellitus (Monotherapy or in combination with Metformin)

Parameter Recommendation

Starting dose 60 mg orally, three times daily (before each main meal)

Titration Increase to 120 mg TID based on glycaemic response after 1–2 weeks

Usual maintenance dose 120 mg three times daily (before breakfast, lunch, and dinner)

Maximum dose 120 mg TID (360 mg/day)

Clinical Notes:

• Administer 1–30 minutes before each main meal

• Meal-dependent mechanism — stimulates rapid, short-duration insulin release

• If a meal is skipped, the corresponding dose must also be skipped to prevent hypoglycaemia

• Particularly useful for targeting postprandial glucose excursions

• Commonly used as add-on to metformin when postprandial hyperglycaemia persists

Secondary Indications — Adults (Off-label)

Not applicable — No established off-label indications in Indian clinical practice.

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

Not approved for paediatric use.

Secondary Indications — Paediatrics (Off-label)

Not applicable.

Age Restriction:

• Not recommended below 18 years of age due to absence of safety and efficacy data in paediatric population

End-stage renal disease / Dialysis Not recommended — limited data available

• Type 1 diabetes mellitus

• Diabetic ketoacidosis (with or without coma)

• Known hypersensitivity to nateglinide or any excipient

• Severe hepatic impairment

• Concomitant use with other meglitinides (e.g., repaglinide) — pharmacological redundancy

• Elderly patients — increased susceptibility to hypoglycaemia

• Patients with irregular or unpredictable meal patterns

• Moderate renal or hepatic impairment

• Autonomic neuropathy — may mask hypoglycaemia symptoms

• Adrenal or pituitary insufficiency — impaired counter-regulatory response

• Not a substitute for insulin in insulin-dependent states

• Patients on concurrent hypoglycaemia-potentiating drugs

Parameter Details

Overall safety Not recommended — insufficient human safety data

Preferred alternatives Insulin is the preferred agent for glycaemic control during pregnancy

When it may be used Only if clearly indicated and benefits outweigh risks — specialist decision only

What to monitor Maternal blood glucose closely; fetal growth monitoring for macrosomia or growth restriction

Parameter Details

Compatibility Not recommended during breastfeeding

Preferred alternatives Insulin (does not enter breast milk); metformin under specialist guidance

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

What to monitor in infant Signs of hypoglycaemia (poor feeding, lethargy, jitteriness); adequate weight gain

Parameter Recommendation

Starting dose 60 mg TID (before meals)

Titration Slower titration advised; assess response before increasing dose

Additional risks Increased hypoglycaemia risk; risk of falls, confusion, and cognitive impairment from subclinical hypoglycaemia; altered renal reserve; irregular dietary habits common

Interacting Drug Effect Mechanism / Management

Gemfibrozil Significant increase in nateglinide exposure CYP2C9 inhibition — avoid combination

Rifampicin Reduced nateglinide efficacy CYP2C9/CYP3A4 induction — may require alternative antidiabetic or dose adjustment

Beta-blockers (non-selective) Masking of hypoglycaemia symptoms Use cardioselective beta-blockers preferentially; educate patient on neuroglycopenic symptoms

Miconazole (systemic/oral gel) Potentiation of hypoglycaemia CYP inhibition — avoid if possible; monitor glucose closely

Interacting Drug Effect Management

NSAIDs, Salicylates (high-dose) Increased hypoglycaemia risk Monitor blood glucose; adjust dose if needed

ACE inhibitors May enhance glucose-lowering effect Monitor blood glucose, especially during initiation

Clarithromycin Possible increase in nateglinide plasma levels Monitor for hypoglycaemia

Corticosteroids Hyperglycaemia; reduced nateglinide efficacy May need increased antidiabetic therapy during corticosteroid use

Thiazide diuretics May oppose antidiabetic action Monitor glycaemic control

Alcohol Potentiates hypoglycaemic risk Advise caution; avoid excess alcohol consumption

• Hypoglycaemia (especially with missed meals or delayed eating)

• Upper respiratory tract infections

• Flu-like symptoms

• Dizziness

• Back pain

• Arthralgia

Adverse Effect Notes

Severe hypoglycaemia May require IV dextrose administration and hospitalisation

Hepatotoxicity Rare; monitor LFTs if unexplained fatigue, nausea, or jaundice develops — discontinue if suspected

Hypersensitivity reactions Angioedema, urticaria, rash (rare) — discontinue immediately

Phase Parameters

Baseline Fasting blood glucose, postprandial glucose, HbA1c, renal function tests, liver function tests

Initiation / Titration Frequent glucose monitoring (fasting and postprandial) for first 1–2 weeks; reassess postprandial glucose 1–2 weeks after each dose change

Long-term HbA1c every 3 months; periodic renal and hepatic function tests if risk factors present

Ongoing Monitor for hypoglycaemia episodes, particularly with irregular meals or concurrent illness

• Glinate (Torrent Pharmaceuticals)

• Natelide (Dr. Reddy's Laboratories)

• Nategra (Sun Pharma)

• Nateglyn (USV)

• Natelin (Intas)

Note: Not included in NLEM 2022; not under NPPA price control. Prices vary across brands.

1. Target patient profile: Best suited for patients with predominantly postprandial hyperglycaemia with preserved fasting glucose; particularly useful when postprandial spikes remain despite metformin monotherapy

1. Meal-dependent dosing: The "no meal, no dose" rule is critical — always skip the dose if the corresponding meal is skipped to prevent hypoglycaemia

1. Comparison with sulfonylureas: Shorter duration of action compared to sulfonylureas results in fewer prolonged hypoglycaemic episodes; preferred in patients with erratic meal schedules

1. Limited HbA1c reduction: Provides modest HbA1c lowering (~0.5–1%); not suitable as primary agent when significant HbA1c reduction is required

1. Timing matters: Drug must be taken 1–30 minutes before meals for optimal effect; taking with or after meals reduces efficacy

1. Avoid in advanced diabetes: Not effective in insulin-deficient states or when β-cell function is significantly compromised

Nateglinide; Type 2 diabetes; meglitinide; glinide; oral antidiabetic; postprandial hyperglycaemia; hypoglycaemia-risk; elderly-caution; Schedule H India

RxIndia v1.0 — 25 Jan 2025

• CDSCO — Approved Formulations Database

• National Formulary of India (NFI)

• API Textbook of Medicine

• AIIMS Pharmacology and Internal Medicine Protocols

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• Harrison's Principles of Internal Medicine

• Indian Specialist Practice Guidelines — Diabetology