Overview
11 DESCRIPTION Anagrelide hydrochloride, USP is a platelet-reducing agent. Its chemical name is 6,7-dichloro-1,5-dihydroimidazo[2,1-b]quinazolin-2(3H)-one monohydrochloride monohydrate. The molecular formula is C 10 H 7 Cl 2 N 3 O•HCl•H 2 O which corresponds to a molecular weight of 310.59. The structural formula is: Anagrelide hydrochloride is an off-white powder.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action The precise mechanism by which anagrelide reduces blood platelet count is unknown. In cell culture studies, anagrelide suppressed expression of transcription factors including GATA-1 and FOG-1 required for megakaryocytopoiesis, ultimately leading to reduced platelet production. 12.2 Pharmacodynamics In blood withdrawn from normal volunteers treated with anagrelide, a disruption was found in the postmitotic phase of megakaryocyte development and a reduction in megakaryocyte size and ploidy. At therapeutic doses, anagrelide does not produce significant changes in white cell counts or coagulation parameters, and may have a small, but clinically insignificant effect on red cell parameters.
Indications
- 1 INDICATIONS & USAGE Anagrelide capsules are indicated for the treatment of patients with thrombocythemia, secondary to myeloproliferative neoplasms, to reduce the elevated platelet count and the risk of thrombosis and to ameliorate associated symptoms including thrombo-hemorrhagic events. Anagrelide is a platelet reducing agent indicated for the treatment of thrombocythemia, secondary to myeloproliferative neoplasms, to reduce the elevated platelet count and the risk of thrombosis and to ameliorate associated symptoms including thrombo-hemorrhagic events. (1)
Common Doses
- 0.5 mg
- 1 mg
- 10 mg
- 2.5 mg
Dosage
2 DOSAGE & ADMINISTRATION The starting dose for adults is 0.5 mg four times a day or 1 mg twice a day. (2.1) The starting dose for pediatric patients is 0.5 mg per day. (2.1) Maintain the starting dose for at least one week and then titrate to maintain target platelet counts. (2.2) Do not exceed a dose increment of 0.5 mg/day in any one week. Do not exceed 10 mg/day or 2.5 mg in a single dose. (2.2) Moderate hepatic impairment: Start with 0.5 mg per day. (2.3) 2.1 Recommended Starting Dosage Adults: The recommended starting dosage of anagrelide capsules is 0.
Contraindications
- 4 CONTRAINDICATIONS None. None (4)
Side Effects
- 6 ADVERSE REACTIONS The following clinically significant adverse reactions are discussed in greater detail in other sections of the labeling: Cardiovascular Toxicity [see Warnings and Precautions (5.1)] Pulmonary Hypertension [see Warnings and Precautions (5.2)] Bleeding Risk [see Warnings and Precautions (5.3)] Pulmonary Toxicity [see Warnings and Precautions (5.4)] The most common adverse reactions (incidence ≥ 5%) are headache, palpitations, diarrhea, asthenia, edema, nausea, abdominal pain, dizziness, pain, dyspnea, cough, flatulence, vomiting, fever, peripheral edema, rash, chest pain,...
Interactions
- 7 DRUG INTERACTIONS Other PDE 3 inhibitors: Exacerbation of inotropic effects (7.2) Aspirin and Drugs that Increase Bleeding Risk: Increased risk of bleeding with concomitant use (7.3) 7.1 Drugs that Prolong QT Avoid use of anagrelide in patients taking medications that may prolong QT interval (including, but not limited to, chloroquine, clarithromycin, haloperidol, methadone, moxifloxacin, amiodarone, disopyramide, procainamide, and pimozide) [see Warnings and Precautions (5.1) and Clinical Pharmacology (12.2)] . 7.2 PDE3 Inhibitors Anagrelide is a phosphodiesterase 3 (PDE3) inhibitor.