AGRYLIN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for AGRYLIN (AGRYLIN).
Agrylin (anagrelide) inhibits cyclic nucleotide phosphodiesterase III (PDE3) and reduces platelet production by interfering with megakaryocyte maturation and proliferation, likely via inhibition of cyclic AMP phosphodiesterase and modulation of intracellular calcium levels.
| Metabolism | Primarily metabolized by CYP1A2 to the active metabolite 3-hydroxyanagrelide, and to a lesser extent by CYP2C19 and CYP2D6. |
| Excretion | Renal: 80% (primarily unchanged drug), Biliary/Fecal: 5% |
| Half-life | Terminal elimination half-life: 1.3–1.5 days (31–36 hours) in patients with ET; allows twice-daily dosing. |
| Protein binding | 82–88% bound to plasma proteins (primarily albumin). |
| Volume of Distribution | 30–36 L (approximately 0.45–0.5 L/kg for a 70 kg adult); indicates extensive tissue distribution. |
| Bioavailability | Oral: 65–80% (median 73%) |
| Onset of Action | Oral: 4–7 days to achieve initial platelet reduction; full effect by 10–14 days. |
| Duration of Action | Platelet count returns to baseline within 5–10 days after discontinuation; effect persists for duration of therapy. |
Adults: 0.5 mg orally once or twice daily, increased by 0.5 mg every 2 weeks to maintain platelet count <600,000/µL. Maximum dose: 10 mg/day.
| Dosage form | CAPSULE |
| Renal impairment | No specific GFR-based recommendations; use with caution in renal impairment (CrCl <50 mL/min) and monitor closely. |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B or C: Reduce initial dose by 50% and titrate cautiously. |
| Pediatric use | Children ≥7 years: 0.5 mg orally once or twice daily; adjust based on platelet response. Maximum: 10 mg/day. Not established for <7 years. |
| Geriatric use | No specific adjustment; start at lower end of dosing range (0.5 mg twice daily) and monitor renal function and platelet counts closely. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for AGRYLIN (AGRYLIN).
| Breastfeeding | It is not known whether anagrelide is excreted in human milk. No M/P ratio is available. Due to potential for serious adverse reactions in breastfed infants (e.g., thrombocytopenia, cardiovascular effects), advise women not to breastfeed during treatment and for at least 7 days after last dose. |
| Teratogenic Risk | Pregnancy Category C. Anagrelide is not recommended in pregnancy. Animal studies have shown embryotoxicity and teratogenicity (e.g., increased fetal resorptions, skeletal anomalies) at doses less than the human therapeutic dose. There are no adequate and well-controlled studies in pregnant women. Use only if potential benefit justifies potential risk to fetus. First trimester: Avoid due to organogenesis risk. Second and third trimesters: Unknown risks; consider alternative therapy. |
■ FDA Black Box Warning
None
| Serious Effects |
["Severe hepatic impairment","Known hypersensitivity to anagrelide or any component of the formulation"]
| Precautions | ["Cardiovascular risks: increased risk of ventricular tachycardia, QTc prolongation, and heart failure; use caution in patients with known cardiac disease.","Hematologic effects: monitor complete blood counts regularly due to risk of anemia, leukopenia, or thrombocytopenia.","Hepatic impairment: reduce dose in patients with moderate to severe hepatic impairment.","Renal impairment: use with caution in severe renal impairment."] |
| Food/Dietary | Grapefruit and grapefruit juice should be avoided as they may increase anagrelide plasma concentrations. No other specific dietary restrictions; however, maintain adequate hydration to reduce risk of crystalluria. |
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| Fetal Monitoring | Monitor complete blood count (CBC) with platelet count every 2 days during first week of therapy, then weekly until maintenance dose established. Assess liver function tests and renal function periodically. Monitor for signs of hemorrhage or thrombosis. In pregnancy, consider fetal ultrasound to assess for possible anomalies if exposure occurs. |
| Fertility Effects | Anagrelide has not been formally studied for fertility effects in humans. In animal studies, no impairment of fertility was observed. However, its effect on spermatogenesis or oogenesis is unknown. |
| Clinical Pearls | Agrylin (anagrelide) is a phosphodiesterase III inhibitor used to reduce platelet counts in essential thrombocythemia. Monitor platelet count weekly during titration; target <600,000/µL. Avoid in patients with severe hepatic impairment (Child-Pugh C). Use with caution in cardiac disease due to risk of QT prolongation and arrhythmias. Anagrelide may increase bleeding risk, especially when combined with anticoagulants or NSAIDs. Discontinue 4-5 days before elective surgery. |
| Patient Advice | Take exactly as prescribed; do not skip doses or double up. · Report any signs of bleeding (easy bruising, nosebleeds, black/tarry stools) or palpitations immediately. · Avoid NSAIDs like ibuprofen and aspirin unless directed by your doctor. · Do not consume grapefruit or grapefruit juice while taking this medication. · Inform all healthcare providers (including dentists) that you are on anagrelide. · Store at room temperature away from moisture and heat. |