AGRYLIN SIDE EFFECTS
- Generic Name: anagrelide
- Brand Name: Agrylin
- Drug Class: Antiplatelet Agents, Hematologic
SIDE EFFECTS
The following clinically significant adverse reactions are discussed in greater detail in other sections of the labeling:
- Cardiovascular Toxicity.
- Pulmonary Hypertension.
- Bleeding Risk.
- Pulmonary Toxicity.
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Clinical Studies In Adult Patients
In three single-arm clinical studies, 942 patients diagnosed with myeloproliferative neoplasms of varying etiology (ET: 551; PV: 117; OMPN: 274) were exposed to AGRYLIN with a mean duration of approximately 65 weeks. Serious adverse reactions reported in these patients included the following: congestive heart failure, myocardial infarction, cardiomyopathy, cardiomegaly, complete heart block, atrial fibrillation, cerebrovascular accident, pericardial effusion, pleural effusion, pulmonary infiltrates, pulmonary fibrosis, pulmonary hypertension, and pancreatitis. Of the 942 patients treated with AGRYLIN, 161 (17%) were discontinued from the study because of adverse reactions or abnormal laboratory test results. The most common adverse reactions resulting in treatment discontinuation were headache, diarrhea, edema, palpitations, and abdominal pain.
The most frequently reported adverse reactions to AGRYLIN (in 5% or greater of 942 patients with myeloproliferative neoplasms) in clinical trials were listed in Table 1.
Table 1: Adverse Reactions Reported in Clinical Studies of AGRYLIN in at least 5% of Patients
| Adverse Reactions | AGRYLIN (N=942) (%) |
| Cardiac disorders | |
| Palpitations | 26% |
| Tachycardia | 8% |
| Chest pain | 8% |
| General disorders and administration siteconditions | |
| Asthenia | 23% |
| Edema | 21% |
| Pain | 15% |
| Fever | 9% |
| Peripheral edema | 9% |
| Malaise | 6% |
| Gastrointestinal disorders | |
| Diarrhea | 26% |
| Nausea | 17% |
| Abdominal pain | 16% |
| Vomiting | 10% |
| Flatulence | 10% |
| Anorexia | 8% |
| Dyspepsia | 5% |
| Respiratory, thoracic and mediastinal disorders | |
| Dyspnea | 12% |
| Cough | 6% |
| Skin and subcutaneous tissue disorders | |
| Rash | 8% |
| Pruritus | 6% |
| Musculoskeletal and connective tissue disorders | |
| Back pain | 6% |
| Nervous system disorders | |
| Headache | 44% |
| Dizziness | 15% |
| Paresthesia | 6% |
Adverse Reactions (frequency 1% to <5%) Included
General disorders and administration site conditions: Flu symptoms, chills.
Cardiac disorders: Arrhythmia, angina pectoris, heart failure, syncope.
Vascular disorders: Hemorrhage, hypertension, postural hypotension, vasodilatation.
Gastrointestinal disorders: Constipation, gastrointestinal hemorrhage, gastritis.
Blood and lymphatic system disorders: Anemia, thrombocytopenia, ecchymosis.
Hepatobiliary disorders: Elevated liver enzymes.
Musculoskeletal and connective tissue disorders: Arthralgia, myalgia.
Psychiatric disorders: Depression, confusion, nervousness.
Nervous system disorders: Somnolence, insomnia, amnesia, migraine headache.
Respiratory, thoracic and mediastinal disorders: Epistaxis, pneumonia.
Skin and subcutaneous tissue disorders: Alopecia.
Eye disorders: Abnormal vision, diplopia.
Ear and labyrinth disorders: Tinnitus.
Renal and urinary disorders: Hematuria, renal failure.
Other Less Frequent Adverse Reactions (<1%) Were
Cardiac disorders: Ventricular tachycardia, supraventricular tachycardia.
Nervous system disorders: Hypoesthesia.
Clinical Study In Pediatric Patients
The frequency of adverse reactions observed in pediatric patients was similar to adult patients. The most common adverse reactions observed in pediatric patients were fever, epistaxis, headache, and fatigue during the 3-month AGRYLIN treatment in the study. Episodes of increased pulse and decreased systolic or diastolic blood pressure beyond the normal ranges in the absence of clinical symptoms were observed. Other adverse reactions reported in these pediatric patients receiving AGRYLIN treatment were palpitations, headache, nausea, vomiting, abdominal pain, back pain, anorexia, fatigue, and muscle cramps.
Postmarketing Experience
The following adverse reactions have been identified during post-marketing use of AGRYLIN. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Cardiac disorders: Prinzmetal angina, Torsades de pointes.
Respiratory, thoracic and mediastinal disorders: Interstitial lung diseases (including allergic alveolitis, eosinophilic pneumonia, and interstitial pneumonitis).
Renal and urinary disorders: Tubulointerstitial nephritis.
Hepatobiliary disorders: Clinically significant hepatotoxicity (including symptomatic ALT and AST elevations and elevations greater than three times the ULN).
Other adverse reactions in pediatric patients reported in spontaneous reports and literature reviews include:
Blood and lymphatic system disorders: Anemia.
Skin and subcutaneous tissue disorders: Cutaneous photosensitivity.
Investigations: Elevated leukocyte count.
SRC: NLM .