Agrylin Special Precautions

Cardiovascular Toxicity: Torsades de pointes and ventricular tachycardia have been reported with AGRYLIN. 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.
AGRYLIN increases the QTc interval of the electrocardiogram and increases the heart rate in healthy volunteers [see Pharmacology: Pharmacodynamics under Actions].
Do not use AGRYLIN 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 [see Drugs that Prolong QT under Interactions].
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 AGRYLIN 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. Avoid use of AGRYLIN in patients with severe hepatic impairment.
In patients with heart failure, bradyarrhythmias, or electrolyte abnormalities, consider periodic monitoring with electrocardiograms [see Pharmacology: Pharmacodynamics under Actions].
AGRYLIN 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 [see PDE3 Inhibitors under Interactions].
In patients with cardiac disease, use AGRYLIN only when the benefits outweigh the risks.
Pulmonary Hypertension: Cases of pulmonary hypertension have been reported in patients treated with AGRYLIN. Evaluate patients for signs and symptoms of underlying cardiopulmonary disease prior to initiating and during AGRYLIN therapy [see Clinical Trials Experience under Adverse Reactions].
Bleeding Risk: Use of concomitant AGRYLIN and aspirin increased major hemorrhagic events in a postmarketing study. Assess the potential risks and benefits for concomitant use of AGRYLIN with aspirin, since bleeding risks may be increased. Monitor patients for bleeding, including those receiving concomitant therapy with other drugs known to cause bleeding (e.g., anticoagulants, PDE3 inhibitors, NSAIDs, antiplatelet agents, selective serotonin reuptake inhibitors) [see Aspirin and Drugs that Increase Bleeding Risk under Interactions; Pharmacology: Pharmacokinetics under Actions].
Pulmonary Toxicity: Interstitial lung diseases (including allergic alveolitis, eosinophilic pneumonia and interstitial pneumonitis) have been reported to be associated with the use of AGRYLIN in postmarketing reports. Most cases presented with progressive dyspnea with lung infiltrations. The time of onset ranged from 1 week to several years after initiating AGRYLIN. If suspected, discontinue AGRYLIN and evaluate. Symptoms may improve after discontinuation [see Adverse Reactions].
Hepatic Impairment: Hepatic metabolism is the major route of anagrelide clearance. Exposure to anagrelide is increased 8-fold in patients with moderate hepatic impairment [see Pharmacology: Pharmacokinetics under Actions] and dose reduction is required [see Dose Modifications for Hepatic Impairment under Dosage & Administration]. Use of AGRYLIN in patients with severe hepatic impairment has not been studied. Avoid use of AGRYLIN in patients with severe hepatic impairment. The potential risks and benefits of AGRYLIN therapy in a patient with mild and moderate hepatic impairment should be assessed before treatment is commenced. Assess hepatic function before and during AGRYLIN treatment [see Cardiovascular Toxicity as previously mentioned].
Use in Children: The safety and effectiveness of AGRYLIN have been established in pediatric patients 7 years of age and older. There are no data for pediatric patients less than 7 years of age. Use of AGRYLIN in these pediatric patients is supported by evidence from adequate and well-controlled studies of AGRYLIN in adults with additional pharmacokinetic, pharmacodynamic, and safety data in 18 pediatric patients aged 7 through 16 years with thrombocythemia secondary to ET [see Recommended Starting Dosage under Dosage & Administration; Pharmacology: Pharmacokinetics and Pharmacology: Pharmacodynamics: Clinical Studies under Actions].
There were no apparent trends or differences in the types of adverse events observed between the pediatric patients compared with those of the adult patients [see Clinical Trials Experience under Adverse Reactions].
Use in the Elderly: Of the 942 subjects in clinical studies of AGRYLIN, 42.1% were 65 years and over, while 14.9% were 75 years and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in response between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.