No

Platelet Aggregation Inhibitor

Agent for essential thrombocythemia (ET); treatment of thrombocytopenia secondary to myeloproliferative disorders

C

Clinical effects on the fetus: The relative risks must be weighed carefully in relation to the potential benefits. Animal reproduction studies have shown an adverse effect on the fetus when anagrelide was administered during pregnancy. There are no adequate and well-controlled studies in humans; however, the potential benefits may warrant the use of this drug in pregnant women despite the potential risks.

Hypersensitivity to anagrelide

Anagrelide should be used with caution in patients with known or suspected heart disease, and only if the potential benefits of therapy outweigh the potential risks. Thrombocytopenia appears to be the main dose-limiting side effect of anagrelide; palpitations, orthostatic hypotension, and headache have also been reported. Caution is warranted when anagrelide is used in patients with reduced renal function or hepatic dysfunction.

Cardiovascular: Palpitations (27.2%), chest pain (7.8%), tachycardia (7.3%), orthostatic hypotension, CHF, cardiomyopathy, myocardial infarction (rare), complete heart block, angina, and atrial fibrillation, hypertension, pericardial perfusion (rare)

Central nervous system: Headache (44%), dizziness (14.7%), bad dreams, impaired concentration ability

Hematologic: Anemia, thrombocytopenia, ecchymosis and lymphadenoma have been reported rarely

Respiratory: Pleural effusion

Single oral doses of anagrelide at 2500, 1500, and 200 mg/kg in mice, rats, and monkeys, respectively, were not lethal. Symptoms of acute toxicity include decreased motor activity in mice and rats and softened stools and decreased appetite in monkeys. There are no reports of human overdosage with anagrelide. Platelet reduction from anagrelide therapy is dose-related; therefore, thrombocytopenia, which can potentially cause bleeding, is expected from overdosage.

Should overdosage occur, cardiac and central nervous system toxicity can also be expected. In the case of overdosage, close clinical supervision of the patient is required; this especially includes monitoring of the platelet count for thrombocytopenia. Dosage should be decreased or stopped, as appropriate, until the platelet count returns to within the normal range.

There is a single case report that suggests sucralfate may interfere with anagrelide absorption

Anagrelide appears to inhibit cyclic nucleotide phosphodiesterase and the release of arachidonic acid from phospholipase, possibly by inhibiting phospholipase A2. It also causes a dose-related reduction in platelet production, which results from decreased megakaryocyte hypermaturation. The drug disrupts the postmitotic phase of maturation.

Duration: 6-24 hours

Metabolism: In the liver

Half-life, plasma: 1.3 hours

Peak serum concentrations: Oral: 1 hour

Elimination: <1% of dose appears unchanged in urine

Adults: Oral: 0.5 mg 4 times/day or 1 mg twice daily

Elderly: There are no special requirements for dosing in the elderly

Food: No clinically significant effect on absorption

Anagrelide therapy requires close supervision of the patient. Because of the positive inotropic effects and side effects of anagrelide, a pretreatment cardiovascular examination is recommended along with careful monitoring during treatment; while the platelet count is being lowered (usually during the first 2 weeks of treatment), blood counts (hemoglobin, white blood cells), liver function test (AST, ALT) and renal function (serum creatinine, BUN) should be monitored.

Thrombocythemia: 60-300 ng/mL

May impair ability to concentrate and produce bad dreams

May cause hypotension which may be exacerbated by psychotropics; may cause heart block; use caution with TCAs

No information available to require special precautions

No effects or complications reported

Before using this drug, tell your physician your entire medical history, including any allergies (especially drug allergies), heart, kidney, or liver disease. Limit alcohol intake, as it may aggravate side effects. To avoid dizziness and lightheadedness when rising from a seated or lying position, get up slowly. This medication should be used only when clearly needed during pregnancy. Discuss the risks and benefits with your physician. It is not known whether this drug is excreted into breast milk. It is recommended to discontinue the drug or not to breast-feed, taking into account the risk to the infant. Tell your physician and pharmacist of all nonprescription and prescription medications you may use, especially sucralfate. Do not share this medication with others. Laboratory tests will be done to monitor the effectiveness and possible side effects of this drug.

Capsule: 0.5 mg, 1 mg

Anagrelide Study Group, "Anagrelide, a Therapy for Thrombocythemic States: Experience in 577 Patients," Am J Med, 1992, 92:69-76.

"Anagrelide, A Therapy for Thrombocythemic States: Experience in 577 Patients. Anagrelide Study Group," Am J Med, 1992, 92(1):69-76.

Chintagumpala MM, Kennedy LL, and Steuber CP, "Treatment of Essential Thrombocythemia With Anagrelide," J Pediatr, 1995, 127(3):495-8.

Petitt RM, Silverstein MN, and Petrone ME, "Anagrelide for Control of Thrombocythemia in Polycythemia and Other Myeloproliferative Disorders," Semin Hematol, 1997, 34(1):51-4.

Silverstein MN, et al, "Anagrelide: A New Drug for Treating Thrombocytosis," N Engl J Med, 1988, 318:1292-4.

Spencer CM and Brogden RN, "Anagrelide. A Review of Its Pharmacodynamic and Pharmacokinetic Properties, and Therapeutic Potential in the Treatment of Thrombocythaemia," Drugs, 1994, 47(5):809-22.