Schedule H

Subcutaneous

• Exenatide immediate-release prefilled pen: 5 mcg/dose (1.2 mL pen delivering 60 doses)

• Exenatide immediate-release prefilled pen: 10 mcg/dose (2.4 mL pen delivering 60 doses)

• Exenatide extended-release suspension for injection: 2 mg single-dose pen/vial (availability limited)

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

Type 2 Diabetes Mellitus (T2DM)

Patient selection: As adjunct to diet and exercise in adults with T2DM not adequately controlled on metformin, sulfonylurea, thiazolidinedione, or combinations thereof; may also be used with basal insulin.

Formulation 1: Immediate-Release (Twice Daily)

Parameter Recommendation

Starting dose 5 mcg subcutaneously twice daily

Titration After minimum 4 weeks, if tolerated and glycaemic control inadequate, increase to 10 mcg twice daily

Usual maintenance dose 5–10 mcg twice daily

Maximum dose 10 mcg twice daily (20 mcg/day total)

Administration guidance:

• Inject within 60 minutes before morning and evening meals (at least 6 hours apart)

• Do not administer after meals

• Inject in abdomen, thigh, or upper arm; rotate injection sites

Formulation 2: Extended-Release (Once Weekly)

Parameter Recommendation

Starting dose 2 mg subcutaneously once weekly

Titration Not applicable — fixed dose

Usual maintenance dose 2 mg once weekly

Maximum dose 2 mg once weekly

Administration guidance:

• May be administered at any time of day, with or without food

• Administer on same day each week; may change day if last dose was given ≥3 days prior

• If switching from immediate-release: discontinue twice-daily dosing, then initiate weekly formulation

Secondary Indications — Adults (Off-label)

1. Obesity / Weight Management (without T2DM) — OFF-LABEL

Parameter Details

Indication Obesity (BMI ≥30 kg/m²) or overweight with comorbidities in patients without diabetes

Dose 2 mg SC once weekly (extended-release formulation)

Duration Long-term; discontinue if <5% weight loss at 12 weeks

Specialist only Yes — Endocrinology or Obesity Medicine clinic

Evidence basis RCTs demonstrate modest weight loss (2–4 kg); liraglutide or semaglutide preferred for obesity in current practice

Note: Exenatide is not CDSCO-approved for obesity; other GLP-1 agonists (semaglutide, liraglutide) have stronger evidence and regulatory approval for weight management.

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

Not approved for paediatric use in India.

Secondary Indications — Paediatrics (Off-label)

Type 2 Diabetes Mellitus (Age ≥10 years) — OFF-LABEL

Parameter Details

Minimum age 10 years

Formulation Extended-release only

Starting dose 2 mg SC once weekly

Titration Not applicable — fixed dose

Maximum dose 2 mg once weekly

Specialist only Yes — Paediatric Endocrinology supervision mandatory

Evidence basis US FDA approved for ≥10 years based on paediatric trials; not CDSCO-approved in India

Safety monitoring (paediatrics):

• HbA1c every 3 months

• Growth parameters (height, weight) at each visit

• Gastrointestinal tolerance assessment

• Renal function monitoring

• Signs of pancreatitis

Age restriction: Not recommended below 10 years. Immediate-release (twice-daily) formulation NOT recommended in paediatric population due to limited data and hypoglycaemia risk.

Clinical note: GI adverse effects (vomiting, diarrhoea) may precipitate volume depletion and acute kidney injury; monitor hydration status and renal function in all patients.

Note: Exenatide is primarily cleared by renal mechanisms; hepatic metabolism plays a minor role.

• Personal or family history of medullary thyroid carcinoma (MTC)

• Multiple endocrine neoplasia syndrome type 2 (MEN 2)

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

• History of pancreatitis (acute or chronic)

• Known hypersensitivity to exenatide or any excipient

• Diabetic ketoacidosis

• Type 1 diabetes mellitus

• History of gallbladder disease or cholelithiasis (GLP-1 agonists may increase gallstone risk)

• Gastroparesis or significant gastrointestinal motility disorders

• Concurrent use with insulin or sulfonylureas (increased hypoglycaemia risk — dose reduction of insulin/SU required)

• Elderly patients (increased GI sensitivity)

• Patients at risk for dehydration (monitor hydration with GI symptoms)

• History of angioedema with other GLP-1 agonists

• Patients with thyroid nodules (clinical monitoring recommended)

Parameter Details

Risk category Not recommended — insufficient human data; animal studies show developmental toxicity at high doses

Preferred alternatives Insulin therapy (basal-bolus or premixed as appropriate); metformin in select cases under specialist guidance

When to use Only if potential benefit clearly outweighs risk; specialist (Maternal-Fetal Medicine + Endocrinology) supervision required

Monitoring Maternal glycaemic control, fetal growth ultrasonography

Recommendation: Discontinue exenatide before planned conception or upon confirmation of pregnancy.

Parameter Details

Compatibility Not recommended — insufficient human data

Drug levels in milk Unknown in humans; animal studies suggest excretion in milk

Preferred alternatives Insulin (safe during lactation); metformin (low milk transfer, widely used)

Infant monitoring If inadvertent exposure occurs: monitor infant feeding, weight gain, gastrointestinal symptoms

Parameter Recommendation

Starting dose Same as adults (5 mcg BID or 2 mg weekly); however, consider starting with immediate-release to assess tolerability

Titration Slower titration recommended; extend observation period to ≥6 weeks before dose increase

Extra risks Increased GI sensitivity (nausea, vomiting); higher risk of dehydration and acute kidney injury; hypoglycaemia risk if combined with sulfonylureas or insulin

Monitoring Renal function every 3–6 months; hydration status; weight

Interacting Drug Mechanism / Effect Recommendation

Insulin Additive hypoglycaemia risk Reduce insulin dose by 10–20% when initiating exenatide; monitor closely

Sulfonylureas (glimepiride, gliclazide, glipizide) Additive hypoglycaemia risk Consider reducing sulfonylurea dose; monitor for hypoglycaemia

Oral contraceptives Delayed gastric emptying may reduce absorption Administer oral contraceptive at least 1 hour before exenatide injection

Warfarin Altered anticoagulant effect reported (delayed absorption, variable INR) Monitor INR frequently when initiating or adjusting exenatide

Narrow therapeutic index oral drugs (digoxin, levothyroxine, phenytoin) Delayed gastric emptying may alter absorption Administer at least 1 hour before exenatide; monitor drug levels/effect

Interacting Drug Effect Management

Metformin Generally synergistic; safe combination No dose adjustment; monitor GI tolerance

Paracetamol Delayed absorption (reduced Cmax, prolonged Tmax) No dose adjustment; clinical effect usually preserved

DPP-4 inhibitors (sitagliptin, vildagliptin) Redundant mechanism (both enhance incretin effect) Avoid combination — no additional benefit, increased cost

Antibiotics (doxycycline, ciprofloxacin) Possible delayed absorption Monitor for therapeutic efficacy; administer antibiotics at least 1 hour before exenatide if possible

Acarbose Additive GI effects Monitor for increased GI intolerance

• Nausea (20–40% — most common, often dose-limiting)

• Vomiting

• Diarrhoea

• Constipation

• Decreased appetite

• Dyspepsia

• Abdominal pain/discomfort

• Headache

• Dizziness

• Injection site reactions (pruritus, erythema, nodule formation with extended-release)

• Hyperhidrosis

Adverse Effect Clinical Action

Acute pancreatitis Discontinue immediately; do not rechallenge; supportive care

Acute kidney injury Usually secondary to dehydration from GI symptoms; discontinue if severe; rehydrate

Severe hypoglycaemia More common with concurrent insulin/SU; treat appropriately; reduce concomitant therapy dose

Angioedema / Anaphylaxis Discontinue permanently; emergency management

Thyroid C-cell tumours Theoretical risk (rodent studies); clinical relevance uncertain; avoid in patients with MTC history/risk

Severe GI intolerance May require discontinuation if persistent despite dose adjustment

Acute cholecystitis / Cholelithiasis Evaluate; surgical consultation if indicated

Long-term HbA1c every 3 months until stable, then every 6 months; renal function every 3–6 months (more frequently in elderly or at-risk); weight at each visit; persistent abdominal pain (pancreatitis surveillance); thyroid nodules (clinical exam annually)

• BYETTA (AstraZeneca) — 5 mcg and 10 mcg prefilled pens (immediate-release)

• BYDUREON (AstraZeneca) — 2 mg extended-release single-dose pen (limited availability)

Note: Extended-release formulation availability may be limited in India; confirm local availability before prescribing.

Notes:

• Not included in NLEM 2022

• Not price-controlled by NPPA

• Limited government hospital availability

• Cost may be a barrier to long-term adherence

1. Nausea management is key to adherence — counsel patients that nausea typically diminishes over 4–8 weeks; advise smaller meals and slower eating; do not escalate dose until GI symptoms resolve.

1. Weekly formulation improves compliance — consider extended-release for patients who struggle with twice-daily injections or have adherence issues; allows flexible dosing time.

1. Weight loss is a therapeutic advantage — prefer exenatide (or other GLP-1 agonists) over insulin or sulfonylureas in obese T2DM patients where weight reduction is a treatment goal.

1. Reduce sulfonylurea/insulin when adding exenatide — proactively reduce SU by 25–50% and basal insulin by 10–20% to prevent hypoglycaemia.

1. Not interchangeable with other GLP-1 agonists — exenatide, liraglutide, semaglutide, and dulaglutide have different pharmacokinetics and dosing; do not substitute unit-for-unit.

1. Extended-release injection site nodules are expected — reassure patients that subcutaneous nodules with Bydureon are benign and resolve over weeks.

exenatide; GLP-1 agonist; type 2 diabetes; incretin mimetic; weight loss; subcutaneous injection; renal-caution; pancreatitis-risk; not NLEM; endocrinology

RxIndia v0.9 — 11 Jun 2025

• CDSCO approved product information

• Indian Pharmacopoeia / National Formulary of India

• API Textbook of Medicine, 11th edition — Diabetes chapter

• ICMR Guidelines for Management of Type 2 Diabetes

• AIIMS Endocrinology Department Formulary

• RSSDI Clinical Practice Recommendations for Management of Type 2 Diabetes

• Harrison's Principles of Internal Medicine (pharmacology reference)

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• US FDA paediatric data (referenced for off-label paediatric use only)