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. |
| Molecular Weight | 1000 |
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 | Contraindicated due to teratogenicity; risk of fetal warfarin syndrome including nasal hypoplasia, stippled epiphyses, and CNS abnormalities. |
| 2nd trimester | Contraindicated; risk of fetal hemorrhage and placental abruption. |
| 3rd trimester | Contraindicated; risk of fetal hemorrhage, placental abruption, and maternal hemorrhage during delivery. |
Clinical note
Comprehensive clinical and safety monograph for MIRADON (MIRADON).
| Placental transfer | Crosses placenta; fetal serum levels approximate maternal levels; known to cause fetal hemorrhage and teratogenicity. |
| Breastfeeding | Excreted into breast milk in small amounts; not known to cause adverse effects in infants, but caution is advised due to potential for anticoagulation in the infant. Monitor for bleeding in the infant. |
■ FDA Black Box Warning
None.
| Serious Effects |
PregnancyActive bleedingHemorrhagic disordersRecent surgery with risk of bleedingSevere liver or kidney diseaseUncontrolled hypertensionInability to monitor prothrombin time
| 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. |
| Food/Dietary | Avoid grapefruit and grapefruit juice as they may increase drug levels and risk of QT prolongation. No other significant food interactions. |
| Clinical Pearls |
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| Lactation Rating |
| L3 (Moderately Safe) |
| 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 | 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. |
| MIRADON (anagrelide) is a phosphodiesterase 3 inhibitor used to reduce elevated platelet counts in essential thrombocythemia and other myeloproliferative disorders. Monitor platelet count weekly during dose titration and every 2-4 weeks thereafter. Avoid abrupt discontinuation; taper if possible. Use with caution in patients with hepatic or renal impairment. May cause QT prolongation; follow ECG before and during therapy. Concomitant use with aspirin increases bleeding risk. Dose adjustments needed if co-administered with CYP1A2 inhibitors (e.g., fluvoxamine) or inducers. |
| Patient Advice | Take MIRADON exactly as prescribed; do not change dose or stop without consulting your doctor. · Report any unusual bleeding, bruising, black/tarry stools, or blood in urine/vomit immediately. · Avoid aspirin, ibuprofen, and other NSAIDs unless directed by your doctor, as they increase bleeding risk. · Regular blood tests to monitor platelet counts and liver/kidney function are essential. · Notify your doctor if you experience palpitations, fainting, dizziness, or chest pain (signs of QT prolongation). · Store at room temperature; protect from light and moisture. |