Schedule H

Intravenous (IV), Subcutaneous (SC)

• Prefilled syringe/vial for injection: 10 mcg, 20 mcg, 30 mcg, 40 mcg, 60 mcg, 100 mcg, 200 mcg, 300 mcg, 500 mcg

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Anaemia Associated with Chronic Kidney Disease (CKD)

For patients on dialysis and non-dialysis

Parameter Recommendation

Starting dose 0.45 mcg/kg SC or IV once weekly OR 0.75 mcg/kg SC every 2 weeks

Titration Adjust dose by 25% every 4 weeks based on Hb response; reduce or hold if Hb rises >1 g/dL in 2 weeks or exceeds 11 g/dL

Usual maintenance dose 0.45–1.5 mcg/kg/week SC or IV

Maximum dose Doses exceeding 1.5 mcg/kg/week are not generally recommended

Key Clinical Notes:

• Target Hb: 10–11.5 g/dL — avoid normalising Hb to ≥13 g/dL (increases cardiovascular risk)

• Iron stores must be adequate before and during therapy (ferritin >100 ng/mL, TSAT >20%)

• SC route preferred for non-dialysis CKD; IV route suitable during haemodialysis sessions

• Conversion from epoetin alfa: refer to conversion table (approximately 200 IU epoetin = 1 mcg darbepoetin)

1. Anaemia Due to Chemotherapy in Non-Myeloid Malignancies

Parameter Recommendation

Starting dose 500 mcg SC every 3 weeks OR 2.25 mcg/kg SC once weekly

Titration Evaluate Hb response after 4–6 weeks; reduce or interrupt if Hb >12 g/dL or rises >1 g/dL in 2 weeks

Usual maintenance dose Individualised based on response

Maximum dose Not well-defined; use lowest effective dose

Key Clinical Notes:

• Initiate only if Hb <10 g/dL and chemotherapy is ongoing

• Discontinue 6 weeks after completion of chemotherapy

• Not indicated for anaemia due to other causes in cancer patients

• Ensure iron repletion

Secondary Indications — Adults (Off-label)

Indication Dose Duration Evidence Basis Remarks

Pre-operative anaemia (elective orthopaedic surgery) 300 mcg SC every other day × 3 doses before surgery, plus on day of surgery Short-term perioperative Indian pre-operative protocols in select centres OFF-LABEL. Specialist only. Used to reduce transfusion requirements.

Low-risk myelodysplastic syndromes (symptomatic anaemia) 0.45–0.75 mcg/kg/week SC Long-term as tolerated International protocols; limited Indian data OFF-LABEL. Haematologist supervision only.

PAEDIATRIC DOSING (Specialist Only)

Primary Indications

Anaemia Associated with Chronic Kidney Disease

• Minimum age: ≥1 year

Weight Starting Dose Route Frequency

All weights 0.45 mcg/kg SC or IV Once weekly

Parameter Recommendation

Starting dose 0.45 mcg/kg SC or IV once weekly

Titration Adjust dose every 4 weeks based on Hb response; do not adjust more frequently

Usual maintenance dose Individualised to maintain Hb 10–11.5 g/dL

Maximum dose Not established; use lowest effective dose

Safety Monitoring:

• Haemoglobin every 1–2 weeks initially, then monthly

• Blood pressure at each visit

• Iron status (ferritin, TSAT) monthly until stable

• Monitor growth parameters

Secondary Indications — Paediatric Doses (Off-label)

• Chemotherapy-induced anaemia in children: NOT well supported by Indian data

• Use only under paediatric haematology/nephrology specialist supervision

• Not recommended below 1 year of age except under specialist supervision

CKD Stage 1–5 (non-dialysis) No dose adjustment; drug is therapeutically indicated

Haemodialysis No dose adjustment; IV administration during dialysis session is convenient

Peritoneal dialysis No dose adjustment; SC route preferred

Note: Response may vary with degree of renal impairment; dose titration based on Hb response.

• Uncontrolled hypertension

• Known hypersensitivity to darbepoetin alfa, other ESAs, or any excipient

• Pure red cell aplasia (PRCA) following prior ESA therapy

• Known hypersensitivity to mammalian cell-derived products

• Poorly controlled hypertension — may worsen; optimise BP control before and during therapy

• History of thromboembolic events — increased risk, especially with Hb >12 g/dL

• Rapid Hb rise (>1 g/dL in 2 weeks) — increases thrombosis and hypertension risk

• Iron deficiency — suboptimal response; ensure adequate iron stores

• Active malignancy — potential for tumour progression (use cautiously in cancer patients)

• History of seizures — particularly in CKD with rapid Hb correction

• Cardiovascular disease — higher risk of adverse outcomes with aggressive Hb targets

Parameter Details

Safety category Limited human data; animal studies do not indicate direct teratogenicity

When it may be used May be considered if benefit outweighs risk, particularly in CKD-associated anaemia; specialist supervision advised

Preferred alternatives No clearly preferred ESA; darbepoetin or epoetin may be used based on clinical judgment

What to monitor Maternal blood pressure, haemoglobin response, signs of pre-eclampsia, fetal growth

Parameter Details

Compatibility Likely compatible with breastfeeding

Expected drug levels in milk Low; minimal systemic absorption expected

Preferred alternatives None if ESA is indicated

What to monitor in infant Adequate feeding, weight gain

• Starting dose: Same as younger adults

• Titration: Slower titration may be prudent; more frequent monitoring advisable

• Extra risks:

• Increased thromboembolic risk (stroke, MI, DVT)

• Higher prevalence of hypertension and cardiovascular disease

• Fluid overload with IV administration

• Reduced renal reserve — monitor function

• Monitoring: Blood pressure, haemoglobin, iron status, and cardiovascular symptoms at each visit

Interacting Drug(s) Effect Mechanism Management

Cyclosporine Additive hypertensive effect; potential for erythropoietin resistance Nephrotoxicity, altered erythropoiesis Monitor BP closely; adjust doses as needed

Androgens (nandrolone, testosterone) Enhanced erythropoietic response Additive stimulation of erythropoiesis Monitor Hb closely to avoid polycythaemia

Note: No absolute contraindications to concomitant use with other drugs, but vigilance required.

Interacting Drug(s) Effect Management

ACE inhibitors / ARBs May blunt erythropoietic response May require higher ESA doses; monitor Hb response

Iron preparations (oral or IV) Required for optimal ESA effectiveness Ensure adequate iron supplementation throughout therapy

Zidovudine (in HIV patients) Altered response to ESA Adjust ESA dose based on Hb monitoring

Anticoagulants (warfarin, heparin) Dose adjustment may be needed as haematocrit rises Monitor INR/aPTT; adjust anticoagulant dose as required

• Hypertension (most common)

• Headache

• Injection site pain or reaction

• Arthralgia / myalgia

• Peripheral oedema

• Nausea

• Fatigue

Adverse Effect Clinical Notes

Pure red cell aplasia (PRCA) Rare; due to anti-erythropoietin antibodies; requires permanent discontinuation of all ESAs

Thromboembolic events (DVT, PE, stroke, MI) Risk increases with aggressive Hb targets (>12 g/dL); use lowest effective dose

Seizures Risk elevated in CKD with rapid Hb rise; monitor BP and rate of Hb increase

Severe hypertension / Hypertensive encephalopathy Especially with rapid Hb correction; may require antihypertensive escalation or ESA discontinuation

Anaphylaxis / Severe allergic reactions Rare; discontinue immediately if suspected

Phase Parameter Frequency

Baseline Haemoglobin, haematocrit, blood pressure, serum ferritin, transferrin saturation (TSAT), serum creatinine, LFTs Before initiating therapy

After initiation/dose change Haemoglobin Every 1–2 weeks until stable

After initiation/dose change Blood pressure At each visit

After initiation/dose change Iron studies Monthly until stable

Long-term Haemoglobin Monthly once stable

Long-term Iron studies (ferritin, TSAT) Every 3 months

Long-term Reticulocyte count, Hb drop If PRCA suspected

Long-term Signs/symptoms of thromboembolism Ongoing clinical assessment

• Cresp (Dr Reddy's Laboratories)

• Dargen (Intas Pharmaceuticals)

• Darbecon (Lupin)

• Darbepoetin (Reliance Life Sciences)

• Darviz (Zydus Lifesciences)

• Aranix (Hetero)

Strength Approximate Price

20 mcg ₹900–1,200 per vial/PFS

40 mcg ₹1,500–1,800 per vial/PFS

100 mcg ₹2,500–3,500 per vial/PFS

200 mcg ₹4,500–5,500 per vial/PFS

• Prices vary by brand

• Not included in NLEM — not under NPPA price control

• Available in select government hospital supplies

1. Iron first: Always ensure adequate iron stores (ferritin >100 ng/mL, TSAT >20%) before and during ESA therapy — iron deficiency is the commonest cause of suboptimal response.

1. Avoid over-correction: Target Hb 10–11.5 g/dL; aiming for normal Hb (≥13 g/dL) increases stroke, MI, and mortality risk (supported by TREAT and CHOIR trials).

1. Hypertension vigilance: Blood pressure control is critical — hypertension is the most common complication and may necessitate dose reduction or temporary discontinuation.

1. Route selection: SC preferred for non-dialysis CKD (better bioavailability); IV convenient for haemodialysis patients during sessions.

1. Extended dosing advantage: Longer half-life of darbepoetin allows once-weekly or fortnightly dosing compared to epoetin alfa (thrice weekly) — improves compliance.

1. Hold in infection/inflammation: Inflammatory states cause ESA resistance; consider withholding therapy temporarily during active infections or inflammatory flares.

anaemia; ESA; CKD; erythropoietin; darbepoetin; dialysis; chemotherapy; oncology; nephrology; specialist-use

RxIndia v0.9 — 01 Apr 2025

• CDSCO approved product list

• Indian product inserts (Cresp, Darbecon)

• NFI 2021

• API Textbook of Medicine 2023

• AIIMS Nephrology and Oncology protocols

• Indian Society of Nephrology recommendations

• ICMR advisory on anaemia in CKD (2022)

• TREAT and CHOIR trials (for off-label and safety information)