Anagrelide Dosing for Thrombocytosis
Start anagrelide at 0.5 mg four times daily (or 1 mg twice daily) in adults, with dose titration by no more than 0.5 mg/day per week to achieve platelet counts below 600,000/μL, ideally between 150,000-400,000/μL, with most patients responding at 1.5-3.0 mg/day. 1
Starting Dose
Adults:
- The FDA-approved starting dose is 0.5 mg four times daily or 1 mg twice daily 1
- A lower starting dose of 0.5 mg/day may be preferable as it results in fewer adverse events (particularly palpitations), lower discontinuation rates, and comparable platelet-lowering effects compared to starting at 1.0 mg/day 2
- Continue the starting dose for at least one week before titration 1
Pediatric Patients:
- Start at 0.5 mg daily 1
Dose Titration Strategy
- Increase dose by no more than 0.5 mg/day in any one week 1
- Target platelet count: below 600,000/μL, ideally between 150,000-400,000/μL 1
- Maximum dose: 10 mg/day or 2.5 mg in a single dose 1
- Most patients achieve adequate response at 1.5-3.0 mg/day 1, 3
- The median maintenance dose in clinical practice is typically 2-2.5 mg/day 3, 4, 5
Time to Response
- Platelet counts typically begin to respond within 7-14 days at the proper dosage 1, 3, 4
- Time to complete response (platelet count ≤600,000/μL) ranges from 4-12 weeks 1
- If therapy is interrupted, platelet counts start to rise within 4 days and return to baseline in 1-2 weeks 1, 3
Monitoring Requirements
During Titration:
- Monitor platelet counts every 2 days during the first week 1
- Then monitor at least weekly until maintenance dosage is reached 1
Maintenance Phase:
- Monitor platelet counts monthly or as necessary 1
- Obtain pre-treatment cardiovascular examination including ECG in all patients 1
- Monitor complete blood counts, hepatic and renal function, and electrolytes throughout therapy 1
Special Populations
Moderate Hepatic Impairment (Child-Pugh score 7-9):
- Start at 0.5 mg/day 1
- Monitor frequently for cardiovascular events 1
- After one week of tolerance, may increase dose by no more than 0.5 mg/day per week 1
Severe Hepatic Impairment:
- Avoid use of anagrelide 1
Common Pitfalls to Avoid
- Do not increase dose by more than 0.5 mg/day in any one week, as this increases cardiovascular adverse events including tachycardia, palpitations, and headache 1, 2
- Do not start at doses higher than 1 mg twice daily without considering that lower starting doses (0.5 mg/day) provide comparable efficacy with better tolerability 2
- Do not discontinue monitoring after achieving target platelet count, as maintenance therapy is required indefinitely and platelet counts can rebound rapidly 1, 3
- Anagrelide has no effect on platelet function at therapeutic doses, so antiplatelet agents may need to be added separately if thrombosis risk requires additional management 4
Mechanism and Specificity
- Anagrelide selectively suppresses megakaryocyte maturation and decreases platelet production without affecting erythroid and myeloid progenitor cells 3, 6
- This specificity distinguishes it from other cytoreductive agents like hydroxyurea, interferon-alpha, and alkylating agents that suppress all cell lines 3, 6