pms-Anagrelide
pms-Anagrelide Uses, Dosage, Side Effects, Food Interaction and all others data.
pms-Anagrelide is a platelet-reducing agent used to lower dangerously elevated platelet levels (i.e. to treat thrombocythemia) in patients with myeloproliferative neoplasms. It is an oral imidazoquinazoline that was first approved for use in the US in 1997. It appears to carry a better response rate than other thrombocythemia treatments (e.g. busulfan, hydroxyurea) and may be better tolerated.
pms-Anagrelide decreases platelet counts by suppressing transcription factors necessary for the synthesis and maturation of platelet-producing cells. The drug itself appears to have a relatively short residence time in the body necessitating twice or four times daily dosing. However, given that the pharmacological effect of anagrelide therapy is reliant on a gradual suppression of platelet-producing cells, it may take 7 to 14 days for its administration to be reflected in reduced platelet counts - for this reason any changes to anagrelide doses should not exceed 0.5 mg/day in any one week.
Evidence from animal studies suggests anagrelide may impair female fertility. Female patients of reproductive age should be advised of the potential for adverse effects on fertility prior to initiating therapy.
| Trade Name | pms-Anagrelide |
| Availability | Prescription only |
| Generic | Anagrelide |
| Anagrelide Other Names | Anagrelida, Anagrelide, Anagrelidum |
| Related Drugs | Agrylin, peginterferon alfa-2b |
| Type | |
| Formula | C10H7Cl2N3O |
| Weight | Average: 256.088 Monoisotopic: 254.996617275 |
| Groups | Approved |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | Canada, United States |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
pms-Anagrelide is a platelet-reducing agent used to treat thrombocythemia, and its related complications, secondary to myeloproliferative neoplasms.
pms-Anagrelide is indicated for the treatment of thrombocythemia, secondary to malignant neoplasms, to reduce platelet count and the associated risk of thrombosis. It is also beneficial in the amelioration of thrombocythemia symptoms including thrombo-hemorrhagic events.
pms-Anagrelide is also used to associated treatment for these conditions: Thrombocythemia
How pms-Anagrelide works
The exact mechanism by which anagrelide lowers platelet count is unclear. Evidence from human trials suggests a dose-related suppression of megakaryocyte maturation, the cells responsible for platelet production - blood drawn from patients receiving anagrelide showed a disruption to the post-mitotic phase of megakaryocyte development and a subsequent reduction in their size and ploidy. This may be achieved via indirect suppression of certain transcription factors required for megakaryocytopoeisis, including GATA-1 and FOG-1.
pms-Anagrelide is a known inhibitor of phosphodiesterase 3A (PDE3A), although its platelet-lowering effects appear unrelated to this inhibition. While PDE3 inhibitors, as a class, can inhibit platelet aggregation, this effect is only seen at higher anagrelide doses (i.e. greater than those required to reduce platelet count). Modulation of PDE3A has been implicated in causing cell cycle arrest and apoptosis in cancer cells expressing both PDE3A and SLFN12, and may be of value in the treatment of gastrointestinal stromal tumours.
Toxicity
The oral LD50 of anagrelide as reported in rats and mice is >1500mg/kg and >2500mg/kg, respectively. Symptoms of overdose may include hypotension, sinus tachycardia, and vomiting. As the therapeutic effect of anagrelide (i.e. platelet reduction) is dose-related, significant thrombocytopenia is expected in instances of overdose. Treatment of overdose should involve careful monitoring of platelet counts and complications such as bleeding. Employ symptomatic and supportive measures if clinically indicated.
Food Interaction
- Take with or without food. Co-administration with food slightly alters pharmacokinetics, but not to a clinically significant extent.
pms-Anagrelide Drug Interaction
Moderate: aspirin, aspirin, aspirin, aspirin, acetaminophen, acetaminophenUnknown: charcoal, charcoal, sodium iodide, sodium iodide, atorvastatin, atorvastatin, metoprolol, metoprolol, clopidogrel, clopidogrel, cyanocobalamin, cyanocobalamin, cholecalciferol, cholecalciferol
pms-Anagrelide Disease Interaction
Major: cardiac disease, liver disease, renal dysfunctionModerate: pulmonary dysfunction
Elimination Route
Following oral administration, the bioavailability of anagrelide is approximately 70%. Given on an empty stomach, the Cmax is reached within 1 hour (Tmax) of administration. Co-administration with food slightly lowers the Cmax and increases the AUC, but not to a clinically significant extent.
Half Life
The t1/2 of anagrelide and its active metabolite, 3-hydroxy anagrelide, are approximately 1.5 hours and 2.5 hours, respectively.
Elimination Route
Following metabolism, urinary excretion of metabolites appears to be the primary means of anagrelide elimination. Less than 1% of an administered dose is recovered in the urine as unchanged parent drug, while approximately 3% and 16-20% of the administered dose is recovered as 3-hydroxy anagrelide and RL603, respectively.
Innovators Monograph
You find simplified version here pms-Anagrelide
