anagrelide (Agrylin)

Dosing and uses of Agrylin (anagrelide)

• Adult
• Pediatric

 

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%)