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Cytoreductive — Essential Thrombocythaemia Pregnancy: Contraindicated — teratogenic in animal studies; effective contraception required

Anagrelide

Brand names: Xagrid

Adult dose

Dose: 0.5 mg twice daily (starting dose); titrate by 0.5 mg/day every week based on platelet count
Route: Oral
Frequency: Twice or four times daily
Max: 10 mg/day (individual dose max 2.5 mg)
Second-line cytoreductive therapy in essential thrombocythaemia (ET), particularly in younger patients or those intolerant of hydroxycarbamide. Target platelet count <600 × 10⁹/L (ideally <400). Not first-line — PT-1 trial showed inferior outcomes vs hydroxycarbamide + aspirin.

Paediatric dose

Dose: Seek specialist opinion mg/kg
Route: Oral
Frequency: Twice daily (starting)
Max: Not established
Limited paediatric data; specialist paediatric haematology use only

Dose adjustments

Renal

No dose adjustment required in mild-moderate renal impairment; avoid in severe renal impairment

Hepatic

Reduce dose in moderate hepatic impairment; avoid in severe

Paediatric weight-based calculator

Limited paediatric data; specialist paediatric haematology use only

Clinical pearls

  • PT-1 trial (Harrison et al. NEJM 2005): anagrelide + aspirin inferior to hydroxycarbamide + aspirin in high-risk ET (higher rate of arterial thrombosis, major haemorrhage, and myelofibrosis transformation)
  • Mechanism: phosphodiesterase III inhibition → reduces megakaryocyte maturation and platelet production
  • Cardiac monitoring required before and during treatment — echo recommended at baseline for patients with cardiac disease
  • Common in young patients with ET to avoid hydroxycarbamide (leukaemogenic potential concerns) — despite PT-1 results, used selectively
  • Headache is very common on initiation — usually resolves after 1–2 weeks; paracetamol for symptom relief
  • Echocardiogram recommended at baseline — cardiac failure and cardiomyopathy are rare but serious complications

Contraindications

  • Severe hepatic impairment
  • Severe renal impairment
  • Severe cardiac failure
  • Pregnancy

Side effects

  • Palpitations (common — PDE3 inhibition)
  • Headache
  • Fluid retention
  • Anaemia
  • Diarrhoea
  • Nausea
  • Tachycardia
  • Cardiac failure (rare — cardiomyopathy)

Interactions

  • Sucralfate — reduces absorption
  • Milrinone/other PDE3 inhibitors — additive effects

Monitoring

  • Platelet count (weekly until stable, then every 3 months)
  • FBC
  • Renal function
  • LFTs
  • Cardiac monitoring (ECG, echo)

Reference: BNFc; BNF 90; PT-1 Trial (Harrison et al. NEJM 2005); BSH ET Guidelines 2010 (updated 2018); NICE guidance. Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

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