A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Agrylin Side Effects, and Drug Interactions - Anagrelide
Agrylin Side Effects, and Drug Interactions - Anagrelide
SIDE EFFECTS
Analysis of the adverse events in a population
consisting of 942 patients diagnosed with myelo-proliferative diseases
of varying etiology (ET:
551; PV: 117; OMPD: 274) has shown that all disease
groups have the same adverse event profile. While most reported adverse
events during anagrelide therapy have been mild in intensity
and have decreased in frequency
with continued therapy, serious adverse events were reported in these
patients. These include the following: congestive heart
failure, myocardial infarction,
cardiomyopathy, cardiomegaly, complete heart
block, atrial fibrillation,
cerebrovascular accident, pericarditis,
pulmonary infiltrates, pulmonary
fibrosis, pulmonary hypertension,
pancreatitis, gastric/duodenal
ulceration, and seizure.
Of the 942 patients treated with anagrelide for a mean
duration of approximately
65 weeks, 161 (17%) were discontinued from the study because of adverse
events or abnormal laboratory
test results. The most common
adverse events for treatment
discontinuation were headache,
diarrhea, edema,
palpitation, and abdominal
pain. Overall, the occurrence rate
of all adverse events was 17.9 per
1,000 treatment days. The
occurrence rate of adverse events
increased at higher dosages of anagrelide.
The most frequently reported adverse reactions to anagrelide (in 5% or
greater of 942 patients with myeloproliferative
disease) in clinical trials were:
Headache
|
43.5%
|
Palpitations
|
26.1%
|
Diarrhea
|
25.7%
|
Asthenia
|
23.1%
|
Edema, other
|
20.6%
|
Nausea
|
17.1%
|
Abdominal Pain
|
16.4%
|
Dizziness
|
15.4%
|
Pain, other
|
15.0%
|
Dyspnea
|
11.9%
|
Flatulence
|
10.2%
|
Vomiting
|
9.7%
|
Fever
|
8.9%
|
Peripheral Edema
|
8.5%
|
Rash, including urticaria
|
8.3%
|
Chest Pain
|
7.8%
|
Anorexia
|
7.7%
|
Tachycardia
|
7.5%
|
Pharyngitis
|
6.8%
|
Malaise
|
6.4%
|
Cough
|
6.3%
|
Paresthesia
|
5.9%
|
Back Pain
|
5.9%
|
Pruritus
|
5.5%
|
Dyspepsia
|
5.2%
|
Adverse events with an incidence
of 1% to < 5% included:
Body as a Whole System: Flu symptoms, chills, photosensitivity.
Cardiovascular System: Arrhythmia, hemorrhage,
cardiovascular disease, angina
pectoris, heart failure, postural
hypotension, thrombosis,
vasodilatation, migraine,
syncope.
Digestive System: Constipation, GI
distress, GI hemorrhage, gastritis,
melena, aphthous
stomatitis, eructation.
Hemic & Lymphatic System: Anemia, thrombocytopenia,
ecchymosis, lymphadenopathy. Platelet counts below 100,000/L occurred
in 84 patients (ET: 35; PV: 9; OMPD: 40), reduction
below 50,000/L 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, hypertension,
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 O.P.
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.
DRUG
INTERACTIONS
Bioavailability studies evaluating
possible interactions between anagrelide and other drugs have not been
conducted. The most common medications used concomitantly with anagrelide
have been aspirin, acetaminophen, furosemide, iron,
ranitidine, hydroxyurea, and allopurinol. The most frequently used concomitant
cardiac medication has been
digoxin. Although, drug-to-drug interaction studies have not been conducted,
there is no clinical
evidence to suggest that
anagrelide interacts with any of these compounds.
There is a single case
report, which suggests that sucralfate
may interfere with anagrelide absorption.
Food has no
clinically significant effect on the bioavailability
of anagrelide.
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