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Pronunciation
(an AG gre lide)
Generic Available (U.S.)
Yes
Index Terms
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Use: Labeled Indications
Treatment of thrombocythemia associated with myeloproliferative disorders (eg, chronic myelogenous leukemia, essential thrombocythemia, polycythemia vera, myeloid metaplasia with myelofibrosis, or other myeloproliferative disorder) to reduce the risk of thrombosis and reduce associated symptoms (including thrombo-hemorrhagic events)
Pregnancy Risk Factor
C
Pregnancy Considerations
Teratogenic effects were not observed in animal studies; however, decreased pup survival was noted. Use of anagrelide during pregnancy is limited. The manufacturer recommends effective contraception in women of childbearing potential. Use during pregnancy only if potential benefit to mother outweighs possible risk to the fetus.
Lactation
Excretion in breast milk unknown/not recommended
Contraindications
Severe hepatic impairment
Warnings/Precautions
Concerns related to adverse effects:
• Pulmonary disorders: Interstitial lung disease (including allergic alveolitis, eosinophilic pneumonia, and interstitial pneumonitis) has been associated with use. Onset is from 1 week to several years, usually presenting with progressive dyspnea with lung infiltrations; symptoms usually improve after discontinuation.
• Renal abnormalities: Renal abnormalities (including renal failure) have been observed with anagrelide use; may be associated with pre-existing renal impairment, although dosage adjustment due to renal insufficiency was not required. Monitor closely in patients with renal insufficiency.
Disease-related concerns:
• Cardiovascular disease: Use with caution in patients with known or suspected heart disease; tachycardia, palpitation, vasodilation, orthostatic hypotension, and heart failure have been reported. Pretreatment cardiovascular evaluation and careful monitoring during treatment is recommended.
• Hepatic impairment: Use with caution in patients with mild-to-moderate hepatic impairment; dosage reduction and careful cardiovascular monitoring are required for moderate impairment; use is contraindicated in severe hepatic impairment. Monitor liver function prior to and during treatment.
Adverse Reactions
>10%:
Cardiovascular: Palpitation (26%), edema (21%)
Central nervous system: Headache (44%), dizziness (15%), pain (15%)
Gastrointestinal: Diarrhea (26%), nausea (17%), abdominal pain (16%)
Neuromuscular & skeletal: Weakness (23%)
Respiratory: Dyspnea (12%)
1% to 10%:
Cardiovascular: Peripheral edema (9%), chest pain (8%), tachycardia (8%), angina, arrhythmia, HF, hypertension, postural hypotension, syncope, thrombosis, vasodilatation
Central nervous system: Fever (9%), malaise (6%), amnesia, chills, confusion, depression, insomnia, migraine, nervousness, somnolence
Dermatologic: Rash (8%), pruritus (6%), alopecia, bruising, photosensitivity, urticaria
Endocrine & skeletal: Dehydration
Gastrointestinal: Flatulence (10%), vomiting (10%), anorexia (8%), dyspepsia (5%), aphthous stomatitis, constipation, eructation, gastritis, GI distress, GI hemorrhage, melena
Genitourinary: Dysuria
Hematologic: Thrombocytopenia (9%; grades 3/4: 5%), anemia, hemorrhage
Neuromuscular & skeletal: Back pain (6%), paresthesia (6%), arthralgia, leg cramps, myalgia
Ocular: Amblyopia, diplopia, visual field abnormality
Otic: Tinnitus
Renal: Renal abnormality (2%), renal failure (1%), hematuria
Respiratory: Pharyngitis (7%), cough (6%), asthma, bronchitis, epistaxis, pneumonia, rhinitis, sinusitis
Miscellaneous: Flu-like syndrome, lymphadenopathy
<1%, postmarketing, and/or case reports: Atrial fibrillation, cardiomegaly, cardiomyopathy, cerebrovascular accident, complete heart block, gastric/duodenal ulceration, hepatotoxicity, interstitial lung disease (allergic alveolitis, eosinophilic pneumonia, interstitial pneumonitis); leukocyte count increased, liver enzymes (ALT, AST) increased, MI, pancreatitis, pericarditis, pericardial effusion, pleural effusion, pulmonary fibrosis, pulmonary hypertension, pulmonary infiltrates, seizure, tubulointerstitial nephritis
Metabolism/Transport Effects
None known.
Drug Interactions
Anticoagulants: Antiplatelet Agents may enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Antiplatelet Agents: May enhance the anticoagulant effect of other Antiplatelet Agents. Risk C: Monitor therapy
Collagenase (Systemic): Antiplatelet Agents may enhance the adverse/toxic effect of Collagenase (Systemic). Specifically, the risk of injection site bruising and/or bleeding may be increased. Risk C: Monitor therapy
Dasatinib: May enhance the anticoagulant effect of Antiplatelet Agents. Risk C: Monitor therapy
Drotrecogin Alfa (Activated): Antiplatelet Agents may enhance the adverse/toxic effect of Drotrecogin Alfa (Activated). Bleeding may occur. Management: When possible, avoid use of drotrecogin within 7 days of use of any IIb/IIIa antagonists, higher dose aspirin (more than 650 mg/day), or use of other antiplatelet agents. Risk D: Consider therapy modification
Glucosamine: May enhance the antiplatelet effect of Antiplatelet Agents. Risk C: Monitor therapy
Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Antiplatelet Agents. Bleeding may occur. Risk D: Consider therapy modification
Ibritumomab: Antiplatelet Agents may enhance the adverse/toxic effect of Ibritumomab. Both agents may contribute to impaired platelet function and an increased risk of bleeding. Risk C: Monitor therapy
MAO Inhibitors: May enhance the orthostatic hypotensive effect of Orthostatic Hypotension Producing Agents. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: May enhance the adverse/toxic effect of Antiplatelet Agents. An increased risk of bleeding may occur. Nonsteroidal Anti-Inflammatory Agents may diminish the cardioprotective effect of Antiplatelet Agents. This interaction is likely specific to aspirin, and not to other antiplatelet agents. Risk C: Monitor therapy
Omega-3-Acid Ethyl Esters: May enhance the antiplatelet effect of Antiplatelet Agents. Risk C: Monitor therapy
Pentosan Polysulfate Sodium: May enhance the adverse/toxic effect of Antiplatelet Agents. Specifically, the risk of bleeding may be increased by concurrent use of these agents. Risk C: Monitor therapy
Pentoxifylline: May enhance the antiplatelet effect of Antiplatelet Agents. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the antiplatelet effect of Antiplatelet Agents. Risk C: Monitor therapy
Rivaroxaban: Antiplatelet Agents may enhance the anticoagulant effect of Rivaroxaban. Management: Avoid concurrent use of clopidogrel with rivaroxaban unless the anticipated benefits outweigh the risks of bleeding. Avoid concurrent use of rivaroxaban with other antiplatelet agents whenever possible. Risk D: Consider therapy modification
Salicylates: Antiplatelet Agents may enhance the adverse/toxic effect of Salicylates. Increased risk of bleeding may result. Risk C: Monitor therapy
Thrombolytic Agents: Antiplatelet Agents may enhance the anticoagulant effect of Thrombolytic Agents. Risk C: Monitor therapy
Tositumomab and Iodine I 131 Tositumomab: Antiplatelet Agents may enhance the adverse/toxic effect of Tositumomab and Iodine I 131 Tositumomab. Specifically, the risk of bleeding-related adverse events may be increased. Risk C: Monitor therapy
Vitamin E: May enhance the antiplatelet effect of Antiplatelet Agents. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Ethanol: May increase CNS adverse effects.
Food: No clinically significant effect on absorption.
Herb/Nutraceutical: Avoid herbs with anticoagulant/antiplatelet properties (alfalfa, anise, bilberry, bladderwrack, bromelain, cat's claw, celery, chamomile, coleus, cordyceps, dong quai, evening primrose oil, fenugreek, feverfew, garlic, ginger, ginkgo biloba, ginseng [American], ginseng [Panax], ginseng [Siberian], grape seed, green tea, guggul, horse chestnut seed, horseradish, licorice, prickly ash, red clover, reishi, SAMe [S-adenosylmethionine], sweet clover, turmeric, white willow); may enhance the adverse effect of antiplatelets agents.
Storage
Store at 27°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from light.
Mechanism of Action
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 (disrupts the postmitotic phase of maturation).
Pharmacodynamics/Kinetics
Onset of action: Initial: Within 7-14 days; complete response (platelets ≤600,000/mm3): 4-12 weeks
Duration: 6-24 hours; upon discontinuation, platelet count begins to rise within 4 days
Metabolism: Hepatic, partially via CYP1A2; to two major metabolites, RL603 and 3-hydroxy anagrelide
Half-life elimination, plasma: 1.3 hours
Time to peak, serum: 1 hour
Excretion: Urine (<1% as unchanged drug)
Dosage
Note: Maintain initial dose for ≥1 week, then adjust to the lowest effective dose to reduce and maintain platelet count <600,000/mm3 ideally to the normal range; the dose must not be increased by >0.5 mg/day in any 1 week; maximum dose: 10 mg/day or 2.5 mg/dose
Oral: Thrombocythemia:
Children: Initial: 0.5 mg/day (range: 0.5 mg 1-4 times/day)
Adults: Initial: 0.5 mg 4 times/day or 1 mg twice daily (most patients will experience adequate response at dose ranges of 1.5-3 mg/day)
Elderly: There are no special requirements for dosing in the elderly
Dosage adjustment in renal impairment: No adjustment required in renal insufficiency; monitor closely
Dosage adjustment in hepatic impairment:
Moderate impairment: Initial: 0.5 mg once daily; maintain for at least 1 week with careful monitoring of cardiovascular status; the dose must not be increased by >0.5 mg/day in any 1 week.
Severe impairment: Use is contraindicated
Administration: Oral
May be administered without regard to food.
Monitoring Parameters
Platelet count (every 2 days during the first week of treatment and at least weekly until the maintenance dose is reached; continue to monitor after cessation of treatment); CBC with differential (monitor closely during first 2 weeks of treatment), liver function (ALT and AST; baseline and during treatment), BUN, and serum creatinine (monitor closely during first weeks of treatment); blood pressure; cardiovascular exam (pretreatment; monitor during therapy). Monitor for thrombosis or bleeding.
Dietary Considerations
May be taken without regard to food.
Patient Education
May cause headache, dizziness, rash, pain or weakness, nausea, diarrhea, gas, or abdominal pain. Report signs of fluid retention (swelling of extremities, unusual weight gain), shortness of breath, unusual bleeding, heart palpitations, irregular heart beat, or chest pain.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Orthostatic hypotension
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May impair ability to concentrate and produce bad dreams
Mental Health: Effects on Psychiatric Treatment
May cause hypotension which may be exacerbated by psychotropics; may cause heart block; use caution with TCAs
Nursing: Physical Assessment/Monitoring
Perform careful cardiac assessment prior to and periodically during treatment.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, oral: 0.5 mg, 1 mg
Agrylin®: 0.5 mg
Pricing: U.S. (www.drugstore.com)
Capsules (Agrylin)
0.5 mg (50): $329.97
Capsules (Anagrelide HCl)
0.5 mg (30): $79.55
1 mg (50): $109.99
References
Doubek M, Brychtova Y, Doubek R, et al, “Anagrelide Therapy in Pregnancy: Report of a Case of Essential Thrombocythemia,” Ann Hematol, 2004, 83(11):726-7.
Harrison CN, Campbell PJ, Buck G, et al, “Hydroxyurea Compared With Anagrelide in High-Risk Essential Thrombocythemia,” N Engl J Med, 2005, 353(1):33-45.
Pescatore SL and Lindley C, “Anagrelide: A Novel Agent for the Treatment of Myeloproliferative Disorders,” Expert Opin Pharmacother, 2000, 1(3):537-46.
Steurer M, Gastl G, Jedrzejczak WW, et al, Anagrelide for Thrombocytosis in Myeloproliferative Disorders: A Prospective Study to Assess Efficacy and Adverse Event Profile,” Cancer, 2004, 101(10):2239-46.
Tefferi A and Vardiman JW, “Classification and Diagnosis of Myeloproliferative Neoplasms: The 2008 World Health Organization Criteria and Point-of-Care Diagnostic Algorithms,” Leukemia, 2008, 22(1):14-22.
International Brand Names
Lexi-Comp.com
Last full review/revision October 2011
Content last modified October 2011
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