Mircera

Approved Indications

• Anemia associated with chronic kidney disease (CKD):
• In adult patients on dialysis
• In adult patients not on dialysis

Clinically Accepted Off-label Uses

• Anemia due to chemotherapy in adult cancer patients with non-myeloid malignancies
• Anemia associated with zidovudine treatment in HIV-infected patients (select cases)
• Preoperative anemia in patients refusing blood transfusion (e.g., Jehovah’s Witnesses)
• Anemia of prematurity (investigational and specialist-supervised protocols)

Route of Administration: Subcutaneous (SC) or Intravenous (IV) injection

Adults (CKD-related Anemia)

• Dialysis Patients:
• Initial dose: 0.6 mcg/kg body weight once every 2 weeks, SC or IV
• Maintenance: After hemoglobin is stabilized, may switch to once-monthly (1.2 mcg/kg) regimen
• Dose adjustments:
• Increase by 25% if Hb rises <1 g/dL after 4 weeks
• Decrease by 25% if Hb rises >2 g/dL in 4 weeks or Hb >12 g/dL
• Discontinue if Hb exceeds 13 g/dL
• Non-Dialysis Patients:
• Initial: 0.6 mcg/kg SC every 2 weeks
• Maintenance: Once stable, convert to monthly dosing
• Same dose adjustment rules apply

Pediatrics

• Safety and efficacy not established in children below 18 years

Elderly

• Use adult dosing; monitor closely for hypertension and thrombotic risk

Special Populations

• Renal Impairment: No dose adjustment required; indicated for use
• Hepatic Impairment: No specific data; use with caution and monitor

Methoxy Polyethylene Glycol-Epoetin Beta is a continuous erythropoiesis receptor activator (CERA). It binds to and activates the erythropoietin receptor on erythroid progenitor cells in the bone marrow, initiating a signaling cascade (primarily via JAK2-STAT5 pathway) that promotes proliferation and differentiation of red blood cell precursors. The pegylation of the molecule extends its half-life, allowing sustained erythropoietic activity and less frequent dosing.

• Absorption: Slow and sustained after subcutaneous injection; peak plasma concentration at ~48–72 hours
• Bioavailability: ~50% (subcutaneous)
• Distribution: Volume of distribution ~0.1 L/kg
• Metabolism: Catabolized by receptor-mediated uptake; not via CYP450 system
• Elimination: Primarily via reticuloendothelial system; negligible renal clearance
• Half-life:
• IV: ~134 hours
• SC: ~139 hours
• Steady-state: Achieved after 6–8 weeks of regular dosing

Pregnancy

• FDA Pregnancy Category C
• Animal studies show no fetal harm, but human data are insufficient
• Use only if potential benefit justifies the risk to the fetus

Lactation

• Unknown if excreted in human milk; minimal systemic absorption in infants expected
• Use cautiously in breastfeeding mothers

Summary

• Use in pregnancy and lactation only when clearly indicated. Data remain limited; monitoring advised.

• Class: Erythropoiesis-Stimulating Agent (ESA)
• Subclass: Continuous Erythropoiesis Receptor Activator (CERA)
• Generation: Long-acting, pegylated erythropoietin analog

• Known hypersensitivity to Methoxy PEG-Epoetin Beta or formulation components
• Uncontrolled hypertension
• Pure red cell aplasia (PRCA) following prior ESA use
• Active malignancy not undergoing curative chemotherapy
• Hemoglobin levels >13 g/dL (risk of thromboembolic events)

• Hypertension: Common; monitor BP regularly
• Cardiovascular Risks: Elevated hemoglobin (>12 g/dL) linked to stroke, MI, DVT
• Thromboembolic Events: Risk increases with higher Hb targets or rapid rise
• PRCA: May develop neutralizing antibodies; discontinue permanently if suspected
• Seizures: Reported in early therapy, especially in CKD patients
• Iron Deficiency: Ensure adequate iron status before and during treatment
• Cancer Risk: Possible acceleration of tumor growth; use only in chemo-induced anemia
• Monitoring Required:
• Hemoglobin (every 2–4 weeks)
• Blood pressure
• Iron parameters (TSAT, ferritin)
• Reticulocyte count (in unexplained non-response)

Common Adverse Effects

• Cardiovascular: Hypertension, thromboembolic events
• Neurologic: Headache, dizziness
• Musculoskeletal: Muscle cramps, back pain, arthralgia
• Injection Site: Pain, redness, swelling
• Others: Flu-like symptoms, fatigue, edema

Serious and Rare Adverse Effects

• Pure red cell aplasia (PRCA)
• Seizures
• Stroke, myocardial infarction
• Anaphylaxis or severe hypersensitivity
• Thrombocytopenia
• Hypertensive crisis

Onset & Severity:

• Side effects generally mild to moderate
• PRCA and serious thrombosis typically delayed onset
• Dose-dependent risk for hypertension and thrombotic events

• Drug-Drug
• No significant interactions with CYP450 drugs
• ACE inhibitors/ARBs: May blunt erythropoietic response
• Immunosuppressants: May alter immune-mediated PRCA risk
• Drug-Food
• No known food interactions
• Drug-Alcohol
• No direct interaction, but alcohol may exacerbate hypertension or liver dysfunction
• Mechanism
• Not metabolized by CYP enzymes (no CYP3A4 involvement)

• KDIGO 2024:
• Emphasizes individualized Hb target (avoid >11 g/dL); focus on patient safety over normalization
• FDA 2023 Advisory:
• Updated safety labeling for cardiovascular and thrombotic risks
• EMA 2022:
• Reaffirmed long-term safety of once-monthly dosing regimen
• NCCN Guidelines 2023:
• Methoxy PEG-Epoetin Beta remains recommended for chemotherapy-induced anemia under ESA protocol

• Temperature: Store at 2°C to 8°C (refrigerated)
• Light Protection: Keep in original carton to protect from light
• Freezing: Do not freeze. Discard if accidentally frozen
• Handling:
• Do not shake
• Bring to room temperature before use
• Single-use only; discard unused portion
• Special Considerations: No reconstitution needed; prefilled syringes ready for administration