Thromboreductin

Anagrelide Instructions

Common name: Anagrelide

Trade name: Anagrelide

Full names: anagrelide, anagrelide hydrochloride, chloroquine imidazolone, Agrylin, Anagrelide

Indications:

The US FDA has approved it for the treatment of essential thrombocythemia and polycythemia vera complicated by thrombocytosis. However, it can also be used for other myeloproliferative diseases such as myelofibrosis and myelodysplastic syndromes accompanied by elevated platelets.

Usage and dosage:

Adults: Anagrelide hydrochloride: Initial dose: 1 mg/day, administered in 2 divided doses, for 1 week, and then increase the dose by no more than 0.5 mg/day every week until the platelet count is at normal levels. Routine maintenance dose: 1-3mg/day. Maximum dose: 10 mg/day and 2.5 mg/dose.
Children: Initial dose: 0.5mg/day. Maintenance dose: same as adults. Maximum dose: 10 mg/day and 2.5 mg/dose.
Liver Impairment: Moderate to severe liver impairment: Avoid use.

Adverse reactions:

1. Cardiovascular system: fatigue, palpitations, edema, and individual heart rhythm disorders.
2. Digestive system: abdominal pain, nausea, and bloating, the incidence rate is about 10%. Liver transaminases are elevated.
3. Respiratory system: shortness of breath, pulmonary fibrosis and pulmonary infiltration.
4. Nervous system: headache (the incidence can reach half in Asia), dizziness, weakness, blurred vision or serious impact on vision.

Contraindications:

1. It is prohibited for those allergic to Anguining.
2. It is contraindicated for women who are pregnant or expect to become pregnant.
3. People with severe cardiovascular, liver and kidney diseases should use with caution.

Precautions:

Use with caution in patients with cardiovascular disease, children and lactating women. May cause liver and kidney damage, liver or kidney function needs to be monitored. Platelet counts should be performed every 2 days during the first week of treatment and at least weekly thereafter until maintenance dose.

Storage:

15-25℃, protected from light.

Mechanism of action:

Anagrelide is a cyclic adenosine monophosphate phosphodiesterase III inhibitor. At high concentrations, it can inhibit platelet production and aggregation. This drug was originally used to inhibit platelet aggregation and has anti-thrombotic effects, but in recent years, it has been found to have a platelet-lowering effect when used at low doses. The mechanism of action may be to affect the differentiation and maturation of megakaryocytes in the later stages of the cell cycle (after mitosis), thereby reducing platelet production. It does not affect the synthesis of DNA and RNA and the proliferation and division of megakaryocytes, so it has no potential carcinogenicity.

Efficacy and safety:

In a non-controlled study on 546 patients with essential thrombocythemia and a platelet count higher than 900×109/L, it was found that after an average of 65 weeks of treatment with this product, more than 70% of the patients had their platelet count reduced to 50% of the pre-treatment level or lower than 600×109/L, and the efficacy lasted for 4 years. A study was conducted on the combined use of anagrelide in addition to conventional treatment in 12 patients with chronic myelogenous leukemia. All patients were treated with hydroxyurea, and some were treated with alpha-interferon (alone or in combination with hydroxyurea), busulfan, or melphalan. Before using anagrelide, the platelet count was (970~3600)×109/L (average 2000×109/L), and 7 patients had bleeding and coagulation complications. After treatment, the platelet count of all patients dropped to less than 600×109/L (median was 343×109/L), and bleeding and coagulation symptoms disappeared. The median dose of anagrelide was 1.9 mg daily. The results show that anagrelide has significant antiplatelet effects. For patients with chronic myelogenous leukemia, anagrelide is a useful adjunct when conventional treatments fail to control thrombocytosis. 942 patients with thrombocytosis were treated with anagrelide, including 113 patients with polycythemia vera. The average dosage was 2.4 mg per day. The total effective rate was 74%, including 66% complete remission and 8% partial remission. The time for complete remission ranged from 17 to 25 days. The clinical efficacy of anagrelide was observed in 48 patients with essential thrombocythemia. Among them, 41 patients had a history of thrombosis or bleeding complications, 16 patients did not receive any treatment, 15 patients were treated with hydroxyurea, and the other 17 patients were treated with multiple drugs. Before anagrelide treatment, the patient's platelet count was (850~3100) × 109/L. After treatment, 87% had complete remission, and 13% had partial remission or ineffectiveness. About 10% of patients stopped treatment due to adverse reactions, and most patients had been treated for 7 years (the average dosage was 2.5 mg per day). The results showed that anagrelide not only reduced the number of platelets, but also reduced the occurrence of thrombotic complications.