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Pronunciation |
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(an
AG gre
lide) |
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U.S. Brand
Names |
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Agrylin™ |
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Generic
Available |
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No |
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Synonyms |
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Anagrelide Hydrochloride |
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Pharmacological Index |
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Platelet Aggregation Inhibitor |
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Use |
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Agent for essential thrombocythemia (ET); treatment of thrombocytopenia
secondary to myeloproliferative disorders |
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Pregnancy Risk
Factor |
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C |
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Pregnancy/Breast-Feeding
Implications |
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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. |
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Contraindications |
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Hypersensitivity to anagrelide |
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Warnings/Precautions |
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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. |
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Adverse
Reactions |
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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 |
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Overdosage/Toxicology |
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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.
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Drug
Interactions |
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There is a single case report that suggests sucralfate may interfere with
anagrelide absorption |
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Mechanism of
Action |
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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. |
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Pharmacodynamics/Kinetics |
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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 |
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Usual Dosage |
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Adults: Oral: 0.5 mg 4 times/day or 1 mg twice daily
Elderly: There are no special requirements for dosing in the elderly
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Dietary
Considerations |
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Food: No clinically significant effect on absorption |
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Monitoring
Parameters |
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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. |
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Reference Range |
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Thrombocythemia: 60-300 ng/mL |
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Mental Health: Effects
on Mental Status |
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May impair ability to concentrate and produce bad dreams |
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Mental Health:
Effects on Psychiatric
Treatment |
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May cause hypotension which may be exacerbated by psychotropics; may cause
heart block; use caution with TCAs |
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Dental Health: Local
Anesthetic/Vasoconstrictor
Precautions |
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No information available to require special precautions |
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Dental Health:
Effects on Dental Treatment |
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No effects or complications reported |
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Patient
Information |
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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. |
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Dosage Forms |
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Capsule: 0.5 mg, 1 mg |
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References |
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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. |
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