Schedule H

Oral

• Tablets: 2.5 mg, 5 mg

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

Type 2 Diabetes Mellitus (T2DM)

Used as monotherapy when diet and exercise fail to achieve glycaemic control, or as add-on therapy with metformin, sulfonylureas, thiazolidinediones, or insulin in adults with inadequate control on existing agents.

Standard Adult Dosing:

Parameter Recommendation

Starting dose 5 mg once daily (with or without food)

Titration Not typically required

Usual maintenance dose 5 mg once daily

Maximum dose 5 mg once daily

Dose Modifications:

Clinical Scenario Dose

Co-administration with strong CYP3A4/5 inhibitors (ketoconazole, ritonavir, clarithromycin) 2.5 mg once daily

Moderate to severe renal impairment (eGFR <45 mL/min/1.73m²) 2.5 mg once daily

End-stage renal disease on haemodialysis 2.5 mg once daily (administer post-dialysis not mandatory)

Clinical Notes:

• Not indicated for Type 1 diabetes mellitus or diabetic ketoacidosis

• Associated with lower hypoglycaemia risk compared to sulfonylureas when used as monotherapy

• Weight-neutral agent

• Discontinue if pancreatitis suspected

Secondary Indications — Adults (Off-label)

Not applicable — No validated off-label indications per current Indian guidelines.

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

Not applicable — Saxagliptin is not approved for use in patients below 18 years of age.

Secondary Indications — Paediatrics (Off-label)

Not applicable — Safety and efficacy data in paediatric population are not established.

Statement: Use in children and adolescents is not recommended. Any consideration for use must be under direct supervision of a paediatric endocrinologist in exceptional clinical trial settings only.

• Saxagliptin and its active metabolite are partially cleared renally

• Monitor renal function periodically during therapy

• No dose adjustment based on proteinuria alone

• Known hypersensitivity to saxagliptin or any component of the formulation

• History of severe hypersensitivity reaction (anaphylaxis, angioedema, exfoliative skin conditions) to any DPP-4 inhibitor

• Type 1 diabetes mellitus

• Diabetic ketoacidosis (current or history of)

• History of pancreatitis — discontinue promptly if acute pancreatitis develops

• Heart failure (particularly NYHA Class III–IV) — observed increase in hospitalisation for heart failure in clinical trials

• Concomitant use with strong CYP3A4/5 inhibitors — dose reduction required

• Use with insulin or sulfonylureas — increased hypoglycaemia risk; may need to reduce dose of secretagogue/insulin

• Hepatic impairment — limited data; avoid in severe cases

• Elderly patients with reduced renal reserve

Parameter Recommendation

Safety Category Limited human data; animal studies suggest no major teratogenicity

Preferred Alternative Insulin is the preferred antidiabetic in pregnancy

Use in Pregnancy Only if clearly needed and benefits outweigh potential risks; requires specialist input

Monitoring Maternal glycaemic control; fetal growth assessment

Parameter Recommendation

Breastfeeding Compatibility Not recommended due to insufficient safety data

Excretion in Milk Unknown in humans; expected to be low based on molecular characteristics

Preferred Alternatives Insulin or metformin (if oral agent required)

Infant Monitoring Not established; avoid use unless essential

• Starting dose: 5 mg once daily if renal function preserved; 2.5 mg once daily if eGFR <45

• Slower dose escalation not typically required as titration is not routine

• Increased susceptibility to infections (UTI, URTI)

• Higher risk of hypoglycaemia when combined with insulin or sulfonylureas

• Assess renal function before initiating and periodically thereafter

• Consider frailty and polypharmacy before prescribing

Interacting Drug/Class Effect Management

Strong CYP3A4/5 inhibitors (ketoconazole, itraconazole, ritonavir, nelfinavir, clarithromycin) Significantly increased saxagliptin plasma levels Reduce saxagliptin dose to 2.5 mg once daily

Insulin Additive hypoglycaemic effect Consider reducing insulin dose; monitor blood glucose closely

Sulfonylureas (glimepiride, gliclazide) Additive hypoglycaemic effect Consider reducing sulfonylurea dose

Interacting Drug/Class Effect Management

Rifampicin (strong CYP3A4 inducer) Reduced saxagliptin efficacy Monitor glycaemic control; may need alternative DPP-4 inhibitor or different antidiabetic class

Diltiazem, verapamil Moderate CYP3A4 inhibition; increased saxagliptin exposure Monitor for adverse effects; dose adjustment usually not required

Erythromycin Moderate CYP3A4 inhibition Monitor for increased saxagliptin effect

ACE inhibitors Potentially increased risk of angioedema Monitor for angioedema symptoms

• Upper respiratory tract infection

• Nasopharyngitis

• Headache

• Urinary tract infection

• Peripheral oedema

• Diarrhoea

• Gastroenteritis

Adverse Effect Clinical Consideration

Acute pancreatitis Rare; discontinue immediately if persistent severe abdominal pain occurs

Severe hypersensitivity reactions Anaphylaxis, angioedema, urticaria, exfoliative skin reactions; discontinue permanently

Heart failure exacerbation Increased hospitalisation observed; use with caution in NYHA III–IV

Severe hypoglycaemia Primarily when combined with secretagogues or insulin

Severe arthralgia May develop weeks to months after initiation; discontinue if disabling joint pain occurs

Bullous pemphigoid Rare; discontinue if blistering skin lesions develop

Baseline:

• Fasting plasma glucose, HbA1c

• Serum creatinine, eGFR

• Liver function tests (if hepatic impairment suspected)

• Clinical assessment for heart failure symptoms

After Initiation / Dose Change:

• Blood glucose monitoring (especially if combined with insulin/sulfonylureas)

• Watch for symptoms of pancreatitis, hypersensitivity, or hypoglycaemia

Long-term:

• HbA1c every 3–6 months

• Renal function (eGFR) every 6–12 months

• Periodic assessment for infections, especially in elderly

• Monitor for heart failure symptoms

• Onglyza® (AstraZeneca)

• Saxa® (USV)

• Glyx-C® (Eris Lifesciences)

• Saxaday® (Micro Labs)

• Not currently under NPPA price control as individual molecule

• Prices vary across brands and pharmacy channels

• Government supply availability limited

• Consider alternative DPP-4 inhibitors (sitagliptin, linagliptin) in patients with established heart failure or high cardiovascular risk, given SAVOR-TIMI 53 trial findings showing increased heart failure hospitalisation

• Linagliptin may be preferred over saxagliptin in patients with fluctuating renal function as it requires no renal dose adjustment

• Discontinue promptly and do not rechallenge if pancreatitis is suspected

• No additional glycaemic benefit when combined with GLP-1 receptor agonists — avoid this combination

• When initiating with sulfonylureas, consider proactive dose reduction of sulfonylurea to prevent hypoglycaemia

• Saxagliptin is weight-neutral — suitable option when weight gain is a concern

saxagliptin; type 2 diabetes; DPP-4 inhibitor; oral antidiabetic; weight-neutral; renal-adjustment; heart-failure-caution; CYP3A4 substrate; incretin-based therapy

RxIndia v1.0 — 10 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 (2023)

• AIIMS Drug Formulary

• Manufacturer product inserts (Onglyza®, Glyx-C®)

• Goodman & Gilman's The Pharmacological Basis of Therapeutics, 13th Edition

• SAVOR-TIMI 53 Trial (N Engl J Med 2013) — for heart failure risk data