anagrelide (Agrylin)
Classes: Antiplatelet Agents, Hematologic; PDE-3 Inhibitors; Phospholipase A2 Inhibitors
Dosing and uses of Agrylin (anagrelide)
Adult dosage forms and strengths
capsule
- 0.5mg
- 1mg
Thrombocythemia
Indicated for essential thrombocythemia and for thrombocythemia secondary to myeloproliferative disorders to decrease risk thrombosis and thrombo-hemorrhagic event
0.5 PO q6hr or 1 mg q12hr; increase PRN not more frequently than 0.5 mg/day/week
Not to exceed 10 mg/day or 2.5 mg/dose
Platelet count responds typically in 7-14 days; time to complete response is 4 to 12 weeks
Polycythemia Vera (Orphan)
Orphan indication sponsor
- Roberts Pharmaceutical Corp; Meridian Center II, 4 Industrial Way West; Eatontown, NJ 07724-2274
Hepatic Impairment
Moderate: Start with 0.5 mg/day for at least 1 week; increase PRN no more frequently than 0.5 mg/day/week
Severe: Contraindicated
Monitor
Platelet count
Pediatric dosage forms and strengths
capsule
- 0.5mg
- 1mg
Thrombocythemia
0.5 mg/day to 0.5 mg PO q6hr; adjust dose PRN no more frequently than 0.5 mg/day/week
Platelet count responds typically in 7-14 days; time to complete response is 4 to 12 weeks
Agrylin (anagrelide) adverse (side) effects
>10%
Headache (44%)
Palpitations (26%)
Diarrhea (26%)
Asthenia (23%)
Edema (21%)
Nausea (17%)
Abdominal pain (16%)
Dizziness (15%)
General pain (15%)
Dyspnea (12%)
1-10%
Flatulence (10%)
Vomiting (10%)
Fever (9%)
Edema (9%)
Rash (8%)
Chest pain (8%)
Anorexia (8%)
Tachycardia (8%)
Pharyngitis (7%)
Malaise (6%)
Cough (6%)
Paresthesia (6%)
Back pain (6%)
Pruritus (6%)
Confusion (1-5%)
Depression
Migraine
Myalgia
Nervousness
Photosensitivity
Arthralgia
Vision abnormalities
Angina
Arrhythmia
Cardiovascular disease
Heart failure
Hemorrhage
Hypertension
Postural hypotension
Syncope
Thrombosis
Vasodilation
Bronchitis
Rhinitis
Sinusitis
Constipation
Dyspepsia
Gastritis
Anemia
Elevated liver enzymes
Flu symptoms
Leg cramps
Dehydration
Postmarketing Reports
Interstitial lung diseases, including allergic alveolitis, eosinophilic pneumonia and interstitial pneumonitis
Hepatotoxicity
Tubulointerstitial nephritis
Supraventricular tachycardia (SVT)
Hypoesthesia
Torsades de pointes
Warnings
Contraindications
Severe hepatic impairment
Cautions
Caution in heart disease, renal impairment, mild-moderate hepatic impairment
Torsades de pointes and ventricular tachycardia reported; obtain pretreatment cardiovascular exam, including EKG, in all patients
Hepatic impairment increases anagrelide exposure and could increase risk of QTc prolongation; monitor patients with hepatic impairment for QTc prolongation and other cardiovascular adverse reactions
Increases QTc interval and heart rate in healthy volunteers; 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 cardiac disease, use only when benefits outweigh risks
In patients with heart failure, bradyarrhythmias, or electrolyte abnormalities, consider periodic ECG monitoring
Orthostatic hypotension reported with higher doses; minimal BP changes observed following 2 mg/dose
Coadministration with aspirin increases risk for major hemorrhagic event
Interstitial lung diseases (including allergic alveolitis, eosinophilic pneumonia and interstitial pneumonitis) reported to be associated with use of anagrelide in post-marketing reports; most cases presented with progressive dyspnea with lung infiltrations; time of onset ranged from 1 week to several years after initiating anagrelide; discontinue anagrelide if it occurs and evaluate; symptoms may improve after discontinuation
Monitor platelets, Hgb, WBC, LFTs, Cr, BUN for at least first 2 weeks
May induce highoutput heart failure by PDE4 inhibition (may be reversible upon discontinuation)
Pregnancy and lactation
Pregnancy category: C
Lactation: excretion in milk unknown/not recommended
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Agrylin (anagrelide)
Mechanism of action
Phosphodiesterase 3 (PDE3) inhibitor; inhibits nucleotide PDE and the release of arachidonic acid from phospholipase A2; reduces also platelet production by disrupting the maturation phase of megakaryocytes
Pharmacokinetics
Onset of action: Within 7-14 days (initial); 4-12 weeks (complete)
Peak plasma time: 1 hr
Duration: 6-24 hr
Metabolism: Extensive; partially through CYP1A2
Half-life: 1.3 hr
Excretion: Urine (<1%)
