Label Changes for:
Agrylin (anagrelide hydrochloride) Capsules
Changes have been made to the ADVERSE REACTIONS sections of the safety label.
Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER)
Clinical Trial subsection
…Other less frequent adverse reactions (<1%) were:
- Cardiac disorders: Ventricular tachycardia, supraventricular tachycardia.
- Nervous system disorders: Hypoesthesia….
5 WARNINGS AND PRECAUTIONS
5.1 Cardiovascular Toxicity
- Added...Hepatic impairment increases anagrelide exposure and could increase the risk of QTc prolongation. Monitor patients with hepatic impairment for QTc prolongation and other cardiovascular adverse reactions. The potential risks and benefits of anagrelide therapy in a patient with mild and moderate hepatic impairment should be assessed before treatment is commenced. Reduce AGRYLIN dose in patients with moderate hepatic impairment. Use of AGRYLIN in patients with severe hepatic impairment has not been studied [see Dosage and Administration (2.3), Use in Specific Populations (8.6) and Clinical Pharmacology (12.2, 12.3)].
- Anagrelide increases the QTc interval of the electrocardiogram and increases the heart rate in healthy volunteers (see CLINICAL PHARMACOLOGY). Anagrelide should not be used in patients with known risk factors for QT interval prolongation, such as congenital long QT syndrome, a known history of acquired QTc prolongation, medicinal products that can prolong QTc interval and hypokalemia.
- In patients with heart failure, bradyarrhythmias, or electrolyte abnormalities, consider periodic monitoring with electrocardiograms (see CLINICAL PHARMACOLOGY and PRECAUTIONS, Laboratory Tests).
- In patients with cardiac disease, use Agrylin only when the benefits outweigh the risks.
- Hypotension: In 9 subjects receiving a single 5 mg dose of anagrelide, standing blood pressure fell an average of 22/15 mm Hg, usually accompanied by dizziness. Only minimal changes in blood pressure were observed following a dose of 2 mg.
Torsades de pointes and ventricular tachycardia have been reported with anagrelide treatment. Obtain a pre-treatment cardiovascular examination, including an ECG in all patients. During treatment with Agrylin, monitor patients for cardiovascular effects and evaluate as necessary.
Anagrelide is a phosphodiesterase 3 (PDE3) inhibitor and may cause vasodilation, tachycardia, palpitations, and congestive heart failure. Other drugs that inhibit PDE3 have caused decreased survival when compared with placebo in patients with Class III-IV congestive heart failure. In patients with cardiac disease, use Agrylin only when the benefits outweigh the risks.
- Cases of torsades de pointes, ventricular tachycardia
- Bleeding: Use of concomitant anagrelide and aspirin increased major hemorrhagic events in a postmarketing study. Assess the potential risks and benefits for concomitant use of anagrelide with aspirin, particularly in patients with a high risk profile for hemorrhage.
- Drug Interactions: Analyses of an ongoing observational study in patients with ET suggest the rate of major hemorrhagic events (MHEs) in patients treated with anagrelide is higher than in those subjects treated with another cytoreductive treatment. The majority of the major hemorrhagic events occurred in patients who were also receiving concomitant anti-aggregatory treatment (primarily, aspirin). Therefore, the potential risks of the concomitant use of anagrelide with aspirin should be assessed, particularly in patients with a high risk profile for hemorrhage, before treatment is initiated
- tubulointerstitial nephritis added
- In two clinical interaction studies in healthy subjects, co-administration of single-dose anagrelide 1mg and aspirin 900mg or repeat-dose anagrelide 1mg once daily and aspirin 75mg once daily showed greater ex vivo anti-platelet aggregation effects than administration of aspirin alone...
- Drug interaction studies have not been conducted with the other common medications used concomitantly with anagrelide in clinical trials which were acetaminophen, furosemide, iron, ranitidine, hydroxyurea, and allopurinol.