Schedule H

Subcutaneous (SC), Intravenous (IV)

• Injection: 2000 IU/0.5 mL pre-filled syringe

• Injection: 4000 IU/1 mL pre-filled syringe

• Injection: 5000 IU/1 mL vial

• Injection: 10,000 IU/1 mL pre-filled syringe

• Injection: 40,000 IU/1 mL pre-filled syringe

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

▶ 1. Anaemia Associated with Chronic Kidney Disease (CKD) — Dialysis Patients

Parameter Recommendation

Starting dose 50–100 IU/kg IV or SC, three times weekly

Titration Increase by 25% if Hb rise <1 g/dL after 4 weeks; decrease by 25% if Hb rise >2 g/dL in 4 weeks or Hb approaches 11 g/dL

Usual maintenance dose 75–300 IU/kg/week divided in 2–3 doses

Maximum dose 300 IU/kg/week

Key Clinical Notes:

• IV route preferred in haemodialysis patients (administered during dialysis session)

• Target Hb: 10–11 g/dL; do not exceed 11.5 g/dL

• Ensure adequate iron stores before initiation (ferritin >100 ng/mL, TSAT >20%)

• Reduce dose rather than withhold when Hb approaches target

▶ 2. Anaemia Associated with Chronic Kidney Disease (CKD) — Non-Dialysis Patients

Parameter Recommendation

Starting dose 50–100 IU/kg SC, once or twice weekly

Titration Increase by 25% if Hb rise <1 g/dL after 4 weeks; decrease by 25% if Hb rise >2 g/dL in 4 weeks

Usual maintenance dose 75–150 IU/kg/week in 1–2 divided doses

Maximum dose 300 IU/kg/week

Key Clinical Notes:

• SC route preferred for non-dialysis CKD (better bioavailability, prolonged half-life)

• Target Hb: 10–11 g/dL

• Monitor blood pressure at each visit — hypertension common

• Initiate ESA when Hb <10 g/dL with CKD symptoms

▶ 3. Chemotherapy-Induced Anaemia (Non-Myeloid Malignancies)

Thrice-Weekly Regimen:

Parameter Recommendation

Starting dose 150 IU/kg SC three times weekly

Titration Increase to 300 IU/kg three times weekly if Hb rise <1 g/dL after 4 weeks

Usual maintenance dose 150–300 IU/kg SC three times weekly

Maximum dose 300 IU/kg three times weekly

Once-Weekly Regimen (Alternative):

Parameter Recommendation

Starting dose 40,000 IU SC once weekly

Titration Increase to 60,000 IU weekly if Hb rise <1 g/dL after 4 weeks

Usual maintenance dose 40,000–60,000 IU SC once weekly

Maximum dose 60,000 IU once weekly

Key Clinical Notes:

• Initiate when Hb <10 g/dL and chemotherapy ongoing or planned for ≥2 more months

• Discontinue if no response (Hb rise <1 g/dL) after 8 weeks at maximum dose

• Avoid use in curative-intent chemotherapy regimens (potential tumour progression)

• Target Hb: Lowest level to avoid transfusion; do not exceed 12 g/dL

▶ 4. Reduction of Allogeneic Blood Transfusion — Elective Orthopaedic Surgery

Regimen A (Daily for 15 days):

Parameter Recommendation

Starting dose 300 IU/kg/day SC

Titration Not applicable

Usual maintenance dose 300 IU/kg/day SC for 10 days pre-operatively, on day of surgery, and 4 days post-operatively (total 15 doses)

Maximum dose 300 IU/kg/day

Regimen B (Weekly):

Parameter Recommendation

Starting dose 600 IU/kg SC once weekly

Titration Not applicable

Usual maintenance dose 600 IU/kg SC weekly × 3 weeks pre-operatively + on day of surgery (total 4 doses)

Maximum dose 600 IU/kg/week

Key Clinical Notes:

• Indicated only for patients with baseline Hb 10–13 g/dL undergoing elective major orthopaedic surgery with expected significant blood loss

• Thromboprophylaxis recommended due to increased thromboembolic risk

• Ensure adequate iron supplementation throughout

Secondary Indications — Adults (Off-label)

Indication Dose Duration Notes

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

▶ 1. Anaemia Associated with Chronic Kidney Disease (Dialysis and Non-Dialysis)

Parameter Recommendation

Starting dose 50 IU/kg IV or SC three times weekly

Titration Increase by 25% every 4 weeks if Hb rise <1 g/dL; decrease by 25% if Hb rises >2 g/dL in 4 weeks

Usual maintenance dose 50–250 IU/kg/week divided in 2–3 doses

Maximum dose 300 IU/kg/week

Key Clinical Notes:

• IV route for haemodialysis patients; SC route for peritoneal dialysis and non-dialysis CKD

• Target Hb: 10–12 g/dL (children may tolerate slightly higher targets than adults)

• Ensure iron repletion before and during therapy

• Higher weight-based doses often required in children compared to adults

Safety Monitoring (All Paediatric Indications):

• Haemoglobin: Every 2 weeks during titration, then monthly once stable

• Blood pressure: At each visit

• Iron studies (ferritin, TSAT): Monthly during initiation, then every 3 months

• Reticulocyte count: Baseline and at 4 weeks to assess response

⚠️ Not recommended in infants <1 year except under paediatric nephrology or haematology supervision with documented clinical rationale

Secondary Indications — Paediatrics (Off-label)

Indication Age Dose Duration Notes

Chemotherapy-Induced Anaemia — OFF-LABEL >5 years 600 IU/kg SC weekly (maximum 40,000 IU) OR 150 IU/kg SC three times weekly Until Hb stable or chemotherapy completed Specialist only (paediatric oncology); Evidence: International data; Indian tertiary centre experience

Anaemia of Prematurity — OFF-LABEL Preterm neonates 200–400 IU/kg SC three times weekly 2–6 weeks Specialist only (neonatology); Evidence: Meta-analyses show modest reduction in transfusions

Patient Category Route Preference Dosing Considerations

Haemodialysis IV preferred (administered via dialysis circuit) Standard dosing; give at end of dialysis session

Peritoneal dialysis SC preferred Standard dosing

• Known hypersensitivity to epoetin alfa, any excipient, or mammalian cell-derived products

• Uncontrolled hypertension

• Pure red cell aplasia (PRCA) following prior treatment with any erythropoietin

• Inability to receive adequate antithrombotic prophylaxis (for peri-operative indication)

• History of hypertension — ESA therapy commonly exacerbates or induces hypertension

• History of seizures or epilepsy — rapid Hb rise may lower seizure threshold

• History of thromboembolic events (stroke, MI, DVT, PE) — increased risk with ESA use

• Malignancy — avoid in curative-intent chemotherapy; potential tumour progression and reduced survival reported

• Functional iron deficiency — ensure adequate iron stores before and during therapy

• Cardiovascular disease — increased cardiovascular events reported with higher Hb targets (>12 g/dL)

• Sickle cell disease — may precipitate crisis

• Porphyria — potential exacerbation

• Aluminium overload in dialysis patients — may impair response

• Avoid rapid Hb rise (>2 g/dL in 4 weeks) — associated with increased thromboembolic risk

Aspect Details

Risk category Limited human data; animal studies inconclusive; use with caution

Safety statement May be considered if severe anaemia unresponsive to iron therapy and transfusion is not preferable

Preferred alternatives Oral/IV iron supplementation; blood transfusion if severe symptomatic anaemia

When to use Only if benefit clearly outweighs potential risk; obstetric haematology input advised

Monitoring Maternal blood pressure (ESA may cause/worsen hypertension); haemoglobin; fetal growth surveillance

Aspect Details

Compatibility Likely compatible with breastfeeding

Drug levels in milk Expected to be negligible (large molecular weight glycoprotein; poor oral bioavailability)

Preferred alternatives Iron supplementation is first-line for postpartum anaemia

Infant monitoring Routine monitoring only; no specific adverse effects expected

Aspect Recommendation

Starting dose Lower end of dose range (50 IU/kg three times weekly for CKD)

Titration Slower titration recommended; assess response every 4 weeks

Extra risks Higher incidence of hypertension; increased thromboembolic risk (stroke, MI); vascular access complications in dialysis patients; underlying cardiovascular disease may be exacerbated

Monitoring More frequent blood pressure monitoring; lower Hb target may be appropriate in high cardiovascular risk patients

Interacting Drug Mechanism / Effect Management

Cyclosporine Both bind to red blood cells; increased cyclosporine levels possible with rapid Hb rise Monitor cyclosporine levels closely during ESA initiation and dose changes

Androgens (nandrolone, testosterone) Additive erythropoietic effect Monitor Hb closely; increased polycythaemia risk

Interacting Drug Mechanism / Effect Management

Iron supplements (oral/IV) Essential for adequate ESA response; not an adverse interaction Co-administer to maintain ferritin >100 ng/mL and TSAT >20%

Antihypertensives ESA may reduce antihypertensive efficacy due to hypertensive effect Monitor blood pressure; may need to increase antihypertensive doses

ACE inhibitors / ARBs May blunt erythropoietic response (reduced endogenous EPO, increased kininase activity) Monitor response; may require higher ESA doses

Myelosuppressive chemotherapy May reduce ESA response Adjust ESA dose based on Hb response; discontinue if no response after 8 weeks

• Hypertension (most common; dose-related)

• Injection site pain/reactions (SC route)

• Headache

• Arthralgia / myalgia

• Flu-like symptoms (fever, chills, malaise)

• Nausea

• Diarrhoea

• Oedema / peripheral swelling

• Rash

Adverse Effect Clinical Action

Pure Red Cell Aplasia (PRCA) Rare but serious; develops due to anti-erythropoietin antibodies; discontinue ESA permanently; do not switch to another ESA; investigate with reticulocyte count and anti-EPO antibodies; immunosuppressive therapy may be required

Thromboembolic events (stroke, MI, DVT, PE) Risk increased with rapid Hb rise or Hb >12 g/dL; discontinue if major event; thromboprophylaxis in high-risk patients

Severe hypertension / hypertensive encephalopathy May present with headache, confusion, seizures; discontinue temporarily; aggressive BP control; resume at lower dose once controlled

Seizures Usually with rapid Hb rise; manage seizure; slow Hb correction; lower target Hb

Anaphylaxis / severe allergic reactions Discontinue immediately; standard anaphylaxis management; do not rechallenge

Tumour progression (cancer patients) Reported in some studies; avoid in curative-intent regimens

During titration (first 2–3 months) Haemoglobin: every 2 weeks; blood pressure: at each visit; iron studies: monthly

Maintenance phase Haemoglobin: monthly (stable patients may extend to every 2–3 months); blood pressure: at each visit; iron studies: every 3 months

Long-term surveillance Monitor for PRCA (unexplained loss of efficacy with low reticulocyte count — check anti-EPO antibodies); regular cardiovascular assessment

Brand Name Manufacturer Notes

Eprex Johnson & Johnson Reference product

Erykine Intas Biosimilar

Vintor Torrent Biosimilar

Renocrit Zydus Biosimilar

Wepox Wockhardt Biosimilar

Epofit Intas Biosimilar

Epogen Ranbaxy Biosimilar

Note: Mircera (methoxy polyethylene glycol-epoetin beta) is a different long-acting ESA — not an epoetin alfa product.

NLEM Status Included in NLEM 2022 (4000 IU) Price regulated by NPPA

Government Supply Available through government dialysis centres and oncology units Often at significantly subsidised rates

• Iron status is critical: Most cases of ESA resistance are due to iron deficiency; ensure ferritin >100 ng/mL and TSAT >20% before and during therapy; consider IV iron if oral iron inadequate

• Avoid Hb overshoot: Target Hb 10–11 g/dL in CKD; exceeding 12 g/dL increases thromboembolic risk without additional benefit; reduce dose (don't stop) when Hb approaches target

• SC route is more efficient in non-dialysis CKD: Longer half-life and better bioavailability allow less frequent dosing and lower total weekly dose compared to IV route

• Hypertension is predictable: Check blood pressure before each injection; most patients require initiation or intensification of antihypertensive therapy during ESA use

• Evaluate non-responders systematically: Check iron status, folate, B12; rule out occult blood loss, haemolysis, infection, inflammation, aluminium toxicity, hyperparathyroidism, and PRCA

• In cancer patients, use judiciously: Limit to palliative chemotherapy settings; avoid in curative-intent regimens due to potential adverse outcomes

Epoetin alfa; ESA; erythropoietin; anaemia; CKD; dialysis; chemotherapy-induced anaemia; nephrology; haematology; injection; NLEM India; biosimilar; renal-safe; hypertension-risk; thromboembolic-risk; Schedule H

RxIndia v1.0 — 01 Jun 2025

• CDSCO approved product information

• Indian Pharmacopoeia

• NLEM India 2022

• API Textbook of Medicine, 11th Edition

• Indian Society of Nephrology — CKD Anaemia Management Guidelines

• AIIMS Nephrology and Haematology Treatment Protocols

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• Harrison's Principles of Internal Medicine

• KDIGO Anaemia Guidelines (supportive reference for dosing principles)

• International RCTs (for off-label indications: MDS, HIV-associated anaemia)