MIRADON
Clinical safety rating: caution
Comprehensive clinical and safety monograph for MIRADON (MIRADON).
MIRADON (anagrelide) inhibits cyclic nucleotide phosphodiesterase and the release of arachidonic acid from phospholipids, possibly by inhibiting phospholipase A2. It also suppresses megakaryocyte maturation and platelet production.
| Metabolism | Hepatic metabolism primarily via CYP1A2, with minor contributions from CYP3A4 and CYP2C19. |
| Excretion | Renal excretion of unchanged drug accounts for 60-70% of the administered dose. Fecal/biliary excretion accounts for 20-25%, with the remainder as oxidative metabolites. Up to 10% is eliminated as glucuronide conjugates. |
| Half-life | Terminal elimination half-life is 8-12 hours in adults with normal renal function. In patients with creatinine clearance <30 mL/min, half-life may extend to 20-30 hours. The half-life supports twice-daily dosing in most patients. |
| Protein binding | Approximately 85-90% bound to serum albumin. Binding is saturable at high concentrations. |
| Volume of Distribution | Volume of distribution is 1.2-1.5 L/kg, indicating extensive extravascular distribution and tissue penetration. |
| Bioavailability | Oral bioavailability is 75-85% due to first-pass metabolism. Bioavailability is reduced by 20-30% when taken with high-fat meals. |
| Onset of Action | Oral: Onset of clinical effect occurs within 1-2 hours after a single dose, with peak effect at 3-4 hours. |
| Duration of Action | Duration of action is 12-14 hours after oral administration, supporting twice-daily dosing. Clinical effect may persist longer in patients with hepatic impairment. |
2.5 mg orally twice daily (total daily dose 5 mg)
| Dosage form | TABLET |
| Renal impairment | GFR 30-50 mL/min: reduce to 2.5 mg once daily; GFR <30 mL/min: contraindicated |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: not recommended |
| Pediatric use | Not established; safety and efficacy in pediatric patients have not been studied |
| Geriatric use | No specific dose adjustment recommended; monitor renal function closely due to age-related decline |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for MIRADON (MIRADON).
| Breastfeeding | Not known if excreted in human milk; risk to nursing infant cannot be excluded. M/P ratio not available. Use caution; consider discontinuing nursing or drug. |
| Teratogenic Risk | Insufficient data in pregnant women; animal studies are inadequate. Risk cannot be excluded. Use only if maternal benefit justifies potential fetal risk. No specific trimester risks identified. |
| Fetal Monitoring |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypersensitivity to anagrelide or any component. Severe hepatic impairment. Pre-existing bleeding diathesis.
| Precautions | Cardiovascular toxicity: risk of QT prolongation, ventricular tachycardia, and cardiac arrest. Thrombocytopenia and bleeding risk. Hepatic impairment: dose adjustment required. Renal impairment: caution due to limited data. |
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| Monitor for signs of bleeding or thrombosis in mother and fetus. Regular fetal ultrasound for growth and development if used during pregnancy. |
| Fertility Effects | No specific human data on fertility effects. Animal studies not evaluated. |