Schedule H

Oral

• Tablet: 5 mg

• Tablet: 15 mg

• Tablet (FDC with Metformin): 5 mg/500 mg, 5 mg/1000 mg, 15 mg/500 mg, 15 mg/1000 mg

• Tablet (FDC with Sitagliptin): 5 mg/100 mg, 15 mg/100 mg

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

Type 2 Diabetes Mellitus — in adults for glycaemic control

May be used as monotherapy (when metformin is unsuitable) or in combination with other antidiabetic agents including metformin, sulfonylureas, DPP-4 inhibitors, or insulin.

Parameter Recommendation

Starting dose 5 mg once daily in the morning, with or without food

Titration If additional glycaemic control required and 5 mg tolerated, increase to 15 mg once daily after 4–12 weeks

Usual maintenance dose 5–15 mg once daily

Maximum dose 15 mg/day

Clinical notes Morning dosing preferred to minimize nocturia; assess renal function before initiation — do not initiate if eGFR <45 mL/min/1.73 m²; glycaemic efficacy reduced as eGFR declines; provides modest weight reduction (2–3 kg) and blood pressure lowering (3–5 mmHg systolic)

When used with Metformin (FDC):

Parameter Recommendation

Starting dose Ertugliflozin 5 mg + Metformin (at previously tolerated metformin dose) once or twice daily

Titration May increase ertugliflozin component to 15 mg based on glycaemic response

Maximum dose Ertugliflozin 15 mg/day + Metformin 2000 mg/day

Combination with Sulfonylurea or Insulin:

Parameter Recommendation

Starting dose 5 mg once daily

Titration Increase to 15 mg once daily if needed

Clinical notes Consider reducing sulfonylurea or insulin dose to minimize hypoglycaemia risk

Secondary Indications — Adults (Off-label)

Indication Dose Duration Specialist Status Evidence Basis

Heart Failure with Reduced Ejection Fraction (OFF-LABEL) 5–15 mg once daily Long-term Specialist only (Cardiology/Endocrinology) SGLT2 class effect demonstrated in DAPA-HF, EMPEROR trials; VERTIS CV showed HF hospitalization benefit but not primary endpoint; ertugliflozin NOT specifically approved for HF in India unlike dapagliflozin/empagliflozin

Chronic Kidney Disease with T2DM (OFF-LABEL) 5–15 mg once daily Long-term Specialist only (Nephrology) Emerging data from VERTIS RENAL; less robust evidence than dapagliflozin (DAPA-CKD) or empagliflozin (EMPA-KIDNEY); not Indian guideline recommended specifically for CKD

PAEDIATRIC DOSING (Specialist Only)

Primary Indications

Not applicable — Ertugliflozin is NOT approved for use in children or adolescents below 18 years of age. Safety and efficacy have not been established in the paediatric population.

Secondary Indications — Paediatrics (Off-label)

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

Age Restriction: Not recommended below 18 years of age. Use only in exceptional research settings under paediatric endocrinologist supervision with institutional ethics approval.

Note: Unlike dapagliflozin/empagliflozin, ertugliflozin does NOT have robust evidence for renal protection independent of glycaemic control.

• Known hypersensitivity to ertugliflozin or any excipient

• Type 1 diabetes mellitus

• Diabetic ketoacidosis (DKA) — current or history of recurrent DKA

• Severe renal impairment (eGFR <30 mL/min/1.73 m²) or end-stage renal disease (ESRD)

• Patients on dialysis

• Pregnancy

• Lactation

• Moderate renal impairment (eGFR 30–45) — reduced efficacy; increased risk of adverse effects

• Volume depletion or hypotension risk — especially elderly patients, those on diuretics, or with low blood pressure

• Recurrent urinary tract infections or genitourinary infections

• Risk of euglycaemic diabetic ketoacidosis — particularly perioperatively, during prolonged fasting, acute illness, or reduced carbohydrate intake

• Frail, malnourished, or elderly patients — higher risk of volume depletion

• History of foot ulcers or peripheral vascular disease — possible increased amputation risk (class concern)

• Osteoporosis or fracture risk — potential increased bone fracture risk

• Concurrent use with insulin or sulfonylureas — hypoglycaemia risk

Parameter Recommendation

Risk category Not recommended; potential fetal renal toxicity based on mechanism of action; limited human data

Preferred alternatives Insulin (first choice for all trimesters); metformin (acceptable under specialist guidance)

When it may be used Should NOT be used during pregnancy — discontinue if pregnancy is detected

What to monitor If inadvertent exposure occurs: amniotic fluid volume (oligohydramnios risk), fetal renal function, fetal growth

Parameter Recommendation

Compatibility Not compatible — avoid use during breastfeeding

Expected drug levels in milk Unknown; potential risk of infant renal effects

Preferred alternatives Insulin (no systemic absorption in infant); metformin (low milk levels, generally acceptable)

What to monitor in infant If inadvertent exposure: hydration status, urine output, feeding adequacy, weight gain

Parameter Recommendation

Starting dose 5 mg once daily

Titration Slow and cautious — assess volume status and renal function before dose escalation

Key risks Increased susceptibility to volume depletion, orthostatic hypotension, falls, dehydration; higher incidence of genitourinary infections; reduced renal reserve may limit efficacy and increase adverse effects

Monitoring Assess eGFR before initiation and periodically; monitor for signs of dehydration (dizziness, weakness); ensure adequate fluid intake

Interacting Drug Mechanism / Effect Action

Loop diuretics (furosemide, torsemide) Additive diuretic effect; increased risk of hypovolaemia and hypotension Use with caution; monitor volume status and blood pressure closely; may need to reduce diuretic dose

Thiazide diuretics (hydrochlorothiazide) Additive volume depletion risk Monitor for dehydration and hypotension; consider dose adjustment

Insulin Additive hypoglycaemic effect Monitor blood glucose closely; consider reducing insulin dose by 10–20% when initiating ertugliflozin

Sulfonylureas (glimepiride, gliclazide) Additive hypoglycaemic effect Monitor blood glucose; may need to reduce sulfonylurea dose

Lithium Increased renal lithium excretion due to natriuretic effect; may reduce lithium levels Monitor lithium levels closely; may need lithium dose adjustment

Interacting Drug Mechanism / Effect Action

ACE inhibitors / ARBs Additive hypotensive effect; theoretical additive renal effects Monitor blood pressure and renal function; generally can be used together with monitoring

NSAIDs (ibuprofen, diclofenac) May reduce diuretic/natriuretic effect; additive renal impairment risk in volume-depleted patients Avoid prolonged concurrent use; ensure adequate hydration

Rifampicin UGT enzyme induction; may reduce ertugliflozin exposure Monitor glycaemic control during concurrent TB treatment

Phenytoin / Carbamazepine Enzyme induction; may reduce ertugliflozin efficacy Monitor glycaemic response; may need dose adjustment

Digoxin Possible minor increase in digoxin levels Monitor digoxin levels if symptoms of toxicity occur

DPP-4 inhibitors (sitagliptin, vildagliptin) No pharmacokinetic interaction; commonly used together Monitor for additive genitourinary infection risk

• Genital mycotic infections (vulvovaginal candidiasis, balanitis) — more common in females

• Urinary tract infections

• Increased urination / polyuria

• Thirst / polydipsia

• Nasopharyngitis

• Headache

• Mild volume depletion symptoms (dizziness, orthostatic hypotension)

• Increased LDL cholesterol (modest elevation)

• Weight loss (therapeutic effect but may be concerning in underweight patients)

Adverse Effect Clinical Significance

Euglycaemic diabetic ketoacidosis May occur with normal or near-normal blood glucose; presents with nausea, vomiting, abdominal pain, fatigue, dyspnoea; discontinue immediately; requires hospitalization and IV fluids/insulin

Fournier's gangrene (necrotizing fasciitis of perineum) Rare but life-threatening; presents with genital/perineal pain, tenderness, erythema, fever; discontinue immediately; requires urgent surgical debridement and antibiotics

Severe hypovolaemia / hypotension May lead to syncope, falls, acute kidney injury; discontinue and rehydrate

Acute kidney injury Usually reversible with drug discontinuation and hydration; more common in elderly and those on diuretics/NSAIDs

Severe UTI / urosepsis / pyelonephritis Rare; requires discontinuation and appropriate antibiotic therapy

Lower limb amputation Class concern (more data with canagliflozin); increased risk in patients with peripheral vascular disease or prior amputation

Long-term maintenance HbA1c every 3 months; eGFR every 3–6 months (more frequently if borderline renal function); lipid profile annually; periodic assessment for ketoacidosis symptoms especially during acute illness

Special situations Withhold 3–4 days before elective surgery; monitor for DKA during acute illness, reduced oral intake, or perioperative period

Monotherapy:

• Steglatro (MSD/Organon)

Fixed-Dose Combinations:

Note: Ertugliflozin has limited availability in India compared to dapagliflozin and empagliflozin. Generic versions are emerging but availability may be variable.

NPPA Status: Not included in NLEM 2022; not currently under DPCO price control.

• Less CV/renal outcome data compared to alternatives — VERTIS CV showed non-inferiority for MACE but not superiority; dapagliflozin and empagliflozin have stronger evidence for CV and renal benefits; consider these alternatives if cardio-renal protection is the primary goal

• Morning dosing is essential — reduces nocturia and minimizes disruption to sleep; advise patients to take with breakfast

• Genital infections are the most common ADR — counsel on perineal hygiene; more common in females and uncircumcised males; usually responds to topical antifungals

• Perioperative management critical — withhold 3–4 days before elective surgery to prevent euglycaemic DKA; resume when patient is eating normally and clinically stable

• Do not use for weight loss indication — although weight loss occurs, drug is not approved or safe for non-diabetic weight management

• Educate patients on DKA symptoms — nausea, vomiting, abdominal pain, excessive thirst, confusion; advise to seek immediate care if these occur, especially during illness

Ertugliflozin; SGLT2 inhibitor; gliflozin; type 2 diabetes; oral antidiabetic; glycosuria; weight loss; genital infection risk; DKA risk; renal-caution; Schedule H

RxIndia v1.0 — 22 Apr 2025

• CDSCO — Approved drug information

• Indian Pharmacopoeia / National Formulary of India

• API Textbook of Medicine

• ICMR Guidelines for Management of Type 2 Diabetes

• RSSDI Clinical Practice Guidelines

• AIIMS Pharmacology Handbook

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

• Harrison's Principles of Internal Medicine

• VERTIS CV Trial (off-label evidence for cardiovascular outcomes)

• Indian manufacturer package inserts (Steglatro, Steglujan)