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P-selectin Inhibitor — Sickle Cell Disease Pregnancy: Avoid — limited data; effective contraception required; benefit vs risk discussion with haematology

Crizanlizumab

Brand names: Adakveo

Adult dose

Dose: 5 mg/kg
Route: IV infusion over 30 minutes
Frequency: Loading dose at week 0 and week 2, then every 4 weeks
Max: 5 mg/kg per dose
Indicated for prevention of vaso-occlusive crises (VOCs) in sickle cell disease in adults and children ≥16 years. Can be used with or without hydroxyurea. Premedicate if prior infusion reaction.

Paediatric dose

Dose: 5 mg/kg mg/kg
Route: IV infusion
Frequency: Loading doses at weeks 0 and 2, then every 4 weeks
Max: 5 mg/kg
Licensed in patients ≥16 years in UK (NICE TA663). Under 16 years — seek specialist paediatric haematology opinion

Dose adjustments

Renal

No dose adjustment required

Hepatic

No dose adjustment required

Paediatric weight-based calculator

Licensed in patients ≥16 years in UK (NICE TA663). Under 16 years — seek specialist paediatric haematology opinion

Clinical pearls

  • SUSTAIN trial: crizanlizumab 5 mg/kg significantly reduced median VOC rate vs placebo (1.63 vs 2.98 per year); benefit seen irrespective of hydroxyurea co-use
  • Mechanism: blocks P-selectin on activated platelets and endothelium, preventing neutrophil/red cell adhesion — the initiating step in vaso-occlusive cascade
  • NICE TA663 (2021): approved for adults and children ≥16 years with SCD and ≥3 VOCs in the preceding year
  • STAND trial (ongoing): evaluating higher dose 7.5 mg/kg — results pending
  • Slow the infusion rate or interrupt if infusion-related reaction occurs — most reactions mild and resolve with supportive care
  • Can be used in combination with hydroxycarbamide (hydroxyurea) — complementary mechanisms

Contraindications

  • Hypersensitivity to crizanlizumab

Side effects

  • Infusion-related reactions (arthralgia, myalgia, fever, chills, urticaria)
  • Nausea
  • Back/chest pain during infusion
  • Headache

Interactions

  • No clinically significant pharmacokinetic interactions identified

Monitoring

  • VOC frequency (patient diary)
  • Infusion reactions
  • LFTs and renal function at baseline

Reference: BNFc; BNF 90; SUSTAIN Trial (Ataga et al. NEJM 2017); NICE TA663; SPC Adakveo. Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

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