AGRYLIN
Clinical safety rating
cautionComprehensive clinical and safety monograph for AGRYLIN (AGRYLIN).
Comprehensive clinical and safety monograph for AGRYLIN (AGRYLIN).
Essential thrombocythemia (ET) to reduce elevated platelet counts and the risk of thrombotic complications
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. |
| Molecular Weight | 440.52 |
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 | Avoid use during first trimester due to risk of fetal harm based on animal studies and limited human data. |
| 2nd trimester | Use only if potential benefit justifies risk to fetus; may cause fetal harm. |
| 3rd trimester | Use only if potential benefit justifies risk to fetus; may cause fetal harm near term. |
Clinical note
Comprehensive clinical and safety monograph for AGRYLIN (AGRYLIN).
| Placental transfer | Anagrelide crosses the placenta based on animal studies; no data in humans, but expected to transfer. |
| Breastfeeding | Anagrelide is present in breast milk; due to potential for serious adverse effects in nursing infants, breastfeeding is not recommended during treatment. |
| Lactation Rating | L5 - Contraindicated |
| 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. |
| 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. |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to anagrelide or any excipientSevere hepatic impairment
| 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. |
| 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. |
Loading safety data…