Anagrelide

Pronunciation: an-AGG-reh-lide
Class: Antiplatelet agent

Trade Names

Anagrelide
- Capsules 1 mg

Agrylin
- Capsules 0.5 mg

Gen-Anagrelide (Canada)
PMS-Anagrelide (Canada)
Sandoz Anagrelide (Canada)

Pharmacology

Studies support a hypothesis of dose-related reduction in platelet production resulting from a decrease in megakaryocyte hypermaturation.

Slideshow: View Frightful (But Dead Serious) Drug Side Effects

Pharmacokinetics

Absorption

Food decreased C max 14% but increased AUC 20%.

Metabolism

Two major metabolites (RL603 and 3-hydroxyanagrelide).

Elimination

More than 70% of dose recovered in urine. Plasma t ½ is 1.3 h.

Special Populations

Hepatic Function Impairment

AUC increased 8-fold with moderate hepatic function impairment.

Indications and Usage

Thrombocythemia (caused by myeloproliferative disorders) to reduce elevated platelet count and risk of thrombosis events; to relieve associated symptoms, including thrombohemorrhagic events.

Contraindications

Severe hepatic function impairment.

Dosage and Administration

Thrombocythemia
Adults (initial dose)

PO 0.5 mg 4 times daily or 1 mg twice daily for at least 7 days. Titrate to minimum effective dose to reduce and maintain platelet count less than 600,000/mcL. Avoid dosage increases more than 0.5 mg/day in any 1 wk period (max, 10 mg/day or 2.5 mg/dose).

Children (initial dose)

PO 0.5 mg/day for at least 7 days. Titrate to minimum effective dose to reduce and maintain platelet count less than 600,000/mcL. Avoid dosage increases more than 0.5 mg/day in any 1 wk period (max, 10 mg/day or 2.5 mg/dose).

Hepatic Function Impairment
Adults and children (initial dose)

PO 0.5 mg/day for at least 7 days. Avoid dosage increases more than 0.5 mg/day in any 1-wk period.

General Advice

  • Administer without regard to meals. Administer with food if GI upset occurs.
  • If a dose is missed, skip that dose and administer next dose at regularly scheduled time. Do not double the dose to catch up.

Storage/Stability

Store at controlled room temperature (59° to 86°F).

Drug Interactions

CYP1A2 inhibitors (eg, fluvoxamine)

Anagrelide plasma concentrations, theoretically, may be elevated, increasing the pharmacologic effects and adverse reactions.

CYP1A2 substrates (eg, theophylline)

Plasma levels of drugs metabolized by CYP1A2 may be elevated, theoretically increasing the pharmacologic effects and adverse reactions.

Cyclic AMP PDE III substrates (eg, cilostazol, milrinone)

Because anagrelide inhibits cyclic AMP PDE III, the effects of drugs that are substrates for cyclic AMP PDE III theoretically may be exacerbated.

Sucralfate

May reduce the oral absorption of anagrelide.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Palpitations (26%); chest pain, tachycardia (8%); angina pectoris, arrhythmia, CV disease, heart failure, hemorrhage, hypertension, postural hypotension, syncope, thrombosis, vasodilation (1% to less than 5%).

CNS

Headache (44%); asthenia (23%); dizziness (15%); paresthesia (6%); amnesia, confusion, depression, insomnia, nervousness, somnolence (1% to less than 5%).

Dermatologic

Rash (including urticaria [8%]); pruritus (6%); alopecia, skin disease (1% to less than 5%).

EENT

Pharyngitis (7%); abnormal vision, amblyopia, diplopia, epistaxis, rhinitis, tinnitus, visual field abnormality (1% to less than 5%).

GI

Diarrhea (26%); nausea (17%); abdominal pain (16%); flatulence, vomiting (10%); anorexia (8%); dyspepsia (5%); aphthous stomatitis, constipation, eructation, gastritis, GI distress or hemorrhage, melena (1% to less than 5%).

Genitourinary

Dysuria, hematuria (1% to less than 5%).

Hematologic-Lymphatic

Anemia, ecchymosis, lymphadenopathy, thrombocytopenia (1% to less than 5%).

Lab Tests

Elevated liver enzymes (1% to less than 5%).

Metabolic-Nutritional

Edema (21%); peripheral edema (9%); dehydration (1% to less than 5%).

Musculoskeletal

Back pain (6%); arthralgia, leg cramps, myalgia (1% to less than 5%).

Respiratory

Dyspnea (12%); cough (6%); asthma, bronchitis, pneumonia, respiratory disease, sinusitis (1% to less than 5%).

Miscellaneous

Pain (15%); fever (9%); malaise (6%); chills, flu-like symptoms, photosensitivity (1% to less than 5%).

Precautions

Monitor

Evaluate platelet counts every 2 days during first week of treatment and then at least weekly thereafter until maintenance dosage is reached. Frequently monitor blood counts (WBC, hemoglobin), liver function (liver enzymes), and renal function (serum creatinine, BUN) while platelet count is being lowered (usually during first 2 wk of treatment). Closely monitor patients with known or suspected heart disease, renal insufficiency, or hepatic function impairment.


Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy not established for patients younger than 6 yr of age.

Renal Function

Use with caution; closely monitor patients.

Hepatic Function

Contraindicated in patients with severe hepatic function impairment. Assess potential benefits vs risk of therapy in patients with mild to moderate hepatic function impairment; dose reduction required in patients with moderate hepatic function impairment; carefully monitor patients for CV effects.

CV

Use with caution in patients with known or suspected heart disease. May cause vasodilation, tachycardia, palpitations, and heart failure. Evaluate CV status before starting therapy and carefully monitor patients during treatment.

Thrombocytopenia

May occur but promptly recovers upon discontinuation of therapy.

Overdosage

Symptoms

Thrombocytopenia, which potentially can cause bleeding, and cardiac and CNS toxicity.

Patient Information

  • Advise patient that dose of medication may be adjusted to obtain max benefit.
  • Advise patient that each dose may be taken without regard to meals but to take with food if stomach upset occurs.
  • Advise patient that if a dose is missed to skip that dose then take the next one at the regularly scheduled time. Caution patient to never double the dose to catch up.
  • Instruct patient not to change dose or stop taking unless advised by health care provider.
  • Instruct patient to notify health care provider immediately if any of the following occur: bleeding or unusual bruising, unexplained shortness of breath or difficulty breathing, palpitations, rapid or irregular heart beat, swelling of the feet or ankles.
  • Advise patient to notify health care provider if persistent diarrhea, nausea or stomach pain, frequent vomiting, intolerable headache, or other unexplained feelings or symptoms occur.
  • Ensure women of childbearing potential are not pregnant when therapy is started and that effective contraception is being used during therapy.

Copyright © 2009 Wolters Kluwer Health.

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