Schedule H

Oral

• Tablets: 10 mg, 25 mg

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Type 2 Diabetes Mellitus (T2DM)

(As monotherapy or in combination with other antidiabetics)

Parameter Recommendation

Starting dose 10 mg once daily in the morning

Titration May increase to 25 mg once daily after 4–12 weeks if additional glycaemic control required

Usual maintenance dose 10–25 mg once daily

Maximum dose 25 mg once daily

Key Clinical Notes:

• Can be used as first-line, add-on, or combination therapy

• Reduces HbA1c by approximately 0.5–0.8%

• When combined with insulin or sulfonylureas, consider reducing their dose to minimize hypoglycaemia risk

• Not recommended for initiation if eGFR <30 mL/min/1.73m² (for glycaemic indication)

1. Heart Failure with Reduced Ejection Fraction (HFrEF)

(NYHA Class II–IV; with or without diabetes)

Parameter Recommendation

Starting dose 10 mg once daily

Titration Not applicable

Usual maintenance dose 10 mg once daily

Maximum dose 10 mg once daily

Key Clinical Notes:

• Indicated in diabetic and non-diabetic patients with HFrEF

• Reduces cardiovascular mortality and heart failure hospitalization (EMPEROR-Reduced trial)

• Can be initiated in patients with eGFR ≥20 mL/min/1.73m²

• Concurrent loop diuretic use may require dose adjustment due to additive volume depletion

1. Chronic Kidney Disease (CKD)

(With or without diabetes; albuminuric CKD)

Parameter Recommendation

Starting dose 10 mg once daily

Titration Not applicable

Usual maintenance dose 10 mg once daily

Maximum dose 10 mg once daily

Key Clinical Notes:

• Recommended for CKD with eGFR ≥20 mL/min/1.73m² and uACR ≥30 mg/g

• Slows progression of kidney disease and reduces risk of cardiovascular events

• Once initiated, may continue even if eGFR falls below 20 mL/min/1.73m² until dialysis or transplant

• Not for use in ESRD or patients on dialysis

Secondary Indications – Adults Only (Off-label)

Indication Dose Duration Notes

Type 1 Diabetes Mellitus (adjunct to insulin) 10 mg once daily Chronic OFF-LABEL; Specialist endocrinologist only; Evidence: EASE trials showing HbA1c and weight reduction; Significantly increased risk of diabetic ketoacidosis — requires strict patient education and ketone monitoring

Heart Failure with Preserved Ejection Fraction (HFpEF) 10 mg once daily Chronic OFF-LABEL; Specialist cardiology only; Evidence: EMPEROR-Preserved trial; May benefit selected patients with HFpEF

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

Type 2 Diabetes Mellitus (Age ≥10 years)

Parameter Recommendation

Starting dose 10 mg once daily

Titration May increase to 25 mg once daily after ≥4 weeks if additional glycaemic control needed

Usual maintenance dose 10–25 mg once daily

Maximum dose 25 mg once daily

Key Clinical Notes:

• Use only under paediatric endocrinologist supervision

• Assess baseline renal function and volume status before initiation

• Monitor for genital mycotic infections and educate on hygiene

Safety Monitoring:

• Renal function at baseline and periodically

• Blood glucose and HbA1c

• Volume status and blood pressure

• Signs of ketoacidosis (especially during intercurrent illness)

Secondary Indications – Paediatric Doses (Off-label)

Not applicable — No established off-label paediatric indications for heart failure or CKD in children.

Minimum age limit: Not recommended below 10 years of age. Use in children <10 years is not supported by evidence.

Dialysis Contraindicated Contraindicated

Additional Notes:

• For glycaemic indication, efficacy significantly reduced at eGFR <45 mL/min/1.73m²

• Cardiorenal benefits persist at lower eGFR levels

Impairment Level Recommendation

Mild (Child-Pugh A) No dose adjustment required

Moderate (Child-Pugh B) Use with caution; no dose adjustment but monitor closely

Severe (Child-Pugh C) Avoid use — limited data; increased risk of volume depletion and altered drug metabolism

• Type 1 Diabetes Mellitus (per CDSCO label — absolute contraindication)

• History of diabetic ketoacidosis

• eGFR <20 mL/min/1.73m² for initiation (cardiorenal indications) or <30 mL/min/1.73m² (glycaemic indication)

• End-stage renal disease or patients on dialysis

• Known hypersensitivity to empagliflozin or any excipient

• Severe volume depletion or dehydration

• Active urinary tract infection or urosepsis

• Elderly patients with low oral intake or at risk of dehydration

• History of recurrent genitourinary infections

• Concurrent use with insulin or sulfonylureas (increased hypoglycaemia risk — consider dose reduction)

• Patients with hypotensive tendency or on antihypertensives

• Perioperative period — discontinue 3 days before major surgery; resume when oral intake adequate

• Acute illness (fever, vomiting, diarrhoea) — consider temporary discontinuation

• Lower limb complications in patients with diabetes (monitor foot care)

• Pilots, drivers, or those in occupations requiring alertness — counsel regarding ketoacidosis risk

Parameter Recommendation

Safety status Not recommended — potential fetal renal toxicity and oligohydramnios (animal data; limited human data)

Preferred alternatives Insulin (standard of care); Metformin may be used in early pregnancy under specialist guidance

When it may be used Not recommended at any stage of pregnancy

Monitoring If inadvertently exposed — discontinue immediately; monitor fetal growth and amniotic fluid volume

Parameter Recommendation

Compatibility Not recommended during breastfeeding

Preferred alternatives Insulin; Metformin (compatible with breastfeeding)

Expected milk levels Excreted in animal milk; human data not available

Infant monitoring If used — monitor infant for signs of dehydration, poor feeding, reduced urine output

Parameter Recommendation

Starting dose 10 mg once daily

Titration Cautious; assess renal function and volume status before dose increase

Extra risks Orthostatic hypotension, dehydration, acute kidney injury, urinary tract infections, genital mycotic infections, falls

Special considerations Ensure adequate fluid intake; more frequent renal function monitoring; lower threshold to reduce or hold during intercurrent illness

Drug/Class Effect Management

Loop diuretics (furosemide, torsemide) Additive volume depletion; increased risk of hypotension and AKI Monitor volume status closely; may need to reduce diuretic dose

Thiazide diuretics Additive volume depletion and hypotension Monitor BP and hydration; adjust doses as needed

Insulin Increased risk of hypoglycaemia Reduce insulin dose by 10–20% when initiating empagliflozin

Sulfonylureas (glimepiride, gliclazide) Increased risk of hypoglycaemia Consider reducing sulfonylurea dose

Lithium Increased lithium clearance due to osmotic diuresis; risk of altered lithium levels Monitor serum lithium levels more frequently

Drug/Class Effect Management

ACE inhibitors / ARBs Additive hypotensive effect; potential additive effect on renal haemodynamics Monitor BP and renal function; generally beneficial combination

NSAIDs Risk of AKI, particularly in volume-depleted patients Avoid prolonged use; ensure adequate hydration

Rifampicin CYP/UGT induction may reduce empagliflozin plasma concentrations Monitor glycaemic control; may need dose adjustment

Digoxin Possible modest increase in digoxin levels Monitor digoxin levels and clinical response

Phenytoin, Carbamazepine Enzyme induction may reduce empagliflozin exposure Monitor glycaemic response

• Genital mycotic infections (vulvovaginal candidiasis, balanitis)

• Urinary tract infections

• Increased urination (polyuria, pollakiuria)

• Thirst

• Hypoglycaemia (when combined with insulin/sulfonylureas)

• Mild volume depletion symptoms (dizziness, postural hypotension)

• Increased haematocrit

• Mild dyslipidaemia (increased LDL-cholesterol)

Adverse Effect Clinical Action

Diabetic ketoacidosis (including euglycaemic DKA) Discontinue immediately; hospitalize; IV fluids and insulin therapy; may occur with normal or mildly elevated glucose

Fournier's gangrene (necrotizing fasciitis of perineum) Rare but serious; discontinue immediately; urgent surgical referral; IV antibiotics

Severe urinary tract infection / Urosepsis / Pyelonephritis Discontinue; appropriate antimicrobial therapy

Acute kidney injury Hold therapy; IV hydration; investigate cause; resume cautiously after recovery

Severe hypotension / Hypovolaemic shock Discontinue; IV fluid resuscitation

Lower limb amputation Increased risk noted in some SGLT2 inhibitor trials (less with empagliflozin); careful foot examination

After initiation (1–2 weeks) Blood pressure, volume status, symptoms of dehydration or hypotension

Short-term (4–12 weeks) HbA1c, renal function, electrolytes

Long-term HbA1c every 3 months; eGFR every 3–6 months (more frequently if CKD or elderly); periodic urinalysis; foot examination in diabetic patients

Special monitoring Ketone monitoring during acute illness, especially if nausea/vomiting; educate patients on DKA symptoms

• Jardiance® (Boehringer Ingelheim)

• Gibtulio® (Lupin)

• Empaglyn® (Sun Pharma)

• Empavac® (Sun Pharma)

• Glyxambi® (FDC: Empagliflozin + Linagliptin)

• Jardiance Met® (FDC: Empagliflozin + Metformin)

• Empaone® (Zydus)

FDCs available: Empagliflozin + Metformin; Empagliflozin + Linagliptin; Empagliflozin + Metformin + Linagliptin

• Under NLEM 2022: Yes (Empagliflozin 10 mg)

• NPPA price control: Applicable to 10 mg formulation

• Government supply: Limited; primarily available in private sector

• Cardiorenal dose is 10 mg: For HFrEF and CKD indications, use 10 mg only — higher dose (25 mg) does not provide additional cardiorenal benefit.

• Perioperative management: Discontinue empagliflozin 3 days before elective major surgery to reduce DKA risk; resume when patient is eating and drinking normally.

• Euglycaemic DKA awareness: Ketoacidosis can occur with near-normal glucose levels — maintain high index of suspicion in patients with nausea, vomiting, or malaise.

• Genital infection counselling: Proactively counsel on genital hygiene; higher risk in uncircumcised males and women with history of candidiasis.

• Volume status first: Do not initiate in volume-depleted patients; correct hydration status before starting therapy.

• Beneficial beyond glucose: Weight loss (~2–3 kg), blood pressure reduction (~3–5 mmHg), and uric acid lowering make empagliflozin particularly useful in metabolic syndrome.

empagliflozin; SGLT2 inhibitor; type 2 diabetes; heart failure; HFrEF; chronic kidney disease; CKD; NLEM India; cardiorenal protection; euglycaemic DKA; pregnancy-avoid

RxIndia v1.0 — 28 May 2025

• CDSCO Product Information – Empagliflozin

• Indian Pharmacopoeia / National Formulary of India (NFI) 2021

• NLEM 2022

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

• API Textbook of Medicine

• AIIMS Endocrinology Department Protocols

• KDIGO 2022 Clinical Practice Guideline for Diabetes Management in CKD (referenced in Indian nephrology consensus)

• EMPA-REG OUTCOME Trial (cardiovascular outcomes)

• EMPEROR-Reduced Trial (HFrEF indication)

• EMPA-KIDNEY Trial (CKD indication)