itis, eructation.
Hemic & Lymphatic System: Anemia, thrombocytopenia, ecchymosis, lymphadenopathy.
Platelet counts below 100,000/µL occurred in 84 patients (ET: 35; PV: 9; OMPD: 40), reduction below 50,000/µL occurred in 44 patients (ET: 7; PV: 6; OMPD: 31) while on anagrelide therapy. Thrombocytopenia promptly recovered upon discontinuation of anagrelide.
Hepatic System: Elevated liver enzymes were observed in 3 patients (ET: 2; OMPD: 1) during anagrelide therapy.
Musculoskeletal System: Arthralgia, myalgia, leg cramps.
Nervous System: Depression, somnolence, confusion, insomnia, nervousness, amnesia.
Nutritional Disorders: Dehydration.
Respiratory System: Rhinitis, epistaxis, respiratory disease, sinusitis, pneumonia, bronchitis, asthma.
Skin and Appendages System: Skin disease, alopecia.
Special Senses: Amblyopia, abnormal vision, tinnitus, visual field abnormality, diplopia.Urogenital System: Dysuria, hematuria.
Renal abnormalities occurred in 15 patients (ET: 10; PV: 4; OMPD: 1). Six ET, 4 PV and 1 with OMPD experienced renal failure (approximately 1%) while on anagrelide treatment; in 4 cases, the renal failure was considered to be possibly related to anagrelide treatment. The remaining 11 were found to have pre-existing renal impairment. Doses ranged from 1.5-6.0 mg/day, with exposure periods of 2 to 12 months. No dose adjustment was required because of renal insufficiency.
The adverse event profile for patients in three clinical trials on anagrelide therapy (in 5% or greater of 942 patients with myeloproliferative diseases) is shown in the following bar graph:
Postmarketing Reports
Cases of torsades de pointes, ventricular tachycardia, interstitial lung diseases (including allergic alveolitis, eosinophilic pneumonia and interstitial pneumonitis), tubulointerstitial nephritis and clinically significant hepatotoxicity have been reported (See WARNINGS, Cardiovascular,Interstitial Lung Diseases and PRECAUTIONS, Laboratory Tests).
OVERDOSAGEAcute Toxicity and Symptoms
Single oral doses of anagrelide hydrochloride at 2,500, 1,500 and 200 mg/kg in mice, rats and monkeys, respectively, were not lethal. Symptoms of acute toxicity were: decreased motor activity in mice and rats and softened stools and decreased appetite in monkeys.
There have been postmarketing case reports of intentional overdose with anagrelide hydrochloride. Reported symptoms include sinus tachycardia and vomiting. Symptoms resolved with conservative management. 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.
Management and Treatment
In 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.
DOSAGE AND ADMINISTRATIONTreatment with AGRYLIN ® Capsules should be initiated under close medical supervision. The recommended starting dosage of AGRYLIN ® for adult patients is 0.5 mg qid or 1 mg bid (2 capsules of 0.5 mg twice a day), which should be maintained for at least one week. Starting doses in pediatric patients have ranged from 0.5 mg per da |
