Agrylin

anagrelide hydrochloride

Agrylin, Xagrid (UK)

Pharmacologic class: Hematologic drug

Therapeutic class: Antiplatelet drug

Pregnancy risk category C

Action

Unclear. May reduce platelet production by decreasing megakaryocytic hypermaturation, thereby decreasing platelet count and inhibiting platelet aggregation (at higher doses).

Availability

Capsules: 0.5 mg, 1 mg

Indications and dosages

Essential thrombocythemia

Adults: 0.5 mg P.O. q.i.d. or 1 mg P.O. b.i.d. for 1 week. Adjust as needed to lowest effective dosage that maintains platelet count below 600,000/mm3. Maximum dosage is 10 mg daily or 2.5 mg as a single dose.

Dosage adjustment

• Hepatic or renal disease

Contraindications

• Prolonged exposure to sunlight

• Women who are or may become pregnant

Precautions

Use cautiously in:

• renal, hepatic, or cardiac dysfunction

• pregnant or breastfeeding patients

• children younger than age 16.

Administration

• Give 1 hour before or 2 hours after meals.

Adverse reactions

CNS: amnesia, confusion, depression, dizziness, drowsiness, weakness, headache, syncope, insomnia, migraine, nervousness, pain, paresthesia, malaise, seizures, cerebrovascular accident

CV: angina, chest pain, hypertension, palpitations, orthostatic hypotension, peripheral edema, vasodilation, arrhythmias, tachycardia, heart failure, hemorrhage, myocardial infarction, cardiomyopathy, cardiomegaly, atrial fibrillation, complete heart block, pericarditis

EENT: amblyopia, abnormal or double vision, visual field abnormalities, tinnitus, epistaxis, rhinitis, sinusitis

GI: nausea, vomiting, diarrhea, constipation, abdominal pain, melena, gastric or duodenal ulcers, dyspepsia, aphthous stomatitis, anorexia, flatulence, gastritis, pancreatitis, GI hemorrhage

GU: painful urination, hematuria

Hematologic: lymphadenoma, bleeding tendency, anemia, thrombocytopenia

Metabolic: dehydration

Musculoskeletal: leg cramps; joint, back, muscle, neck pain

Respiratory: bronchitis, dyspnea, pneumonia, respiratory disease, asthma, pulmonary infiltrates, pulmonary fibrosis, pulmonary hypertension

Skin: bruising, pruritus, rash, alopecia, urticaria, skin disease, photosensitivity reaction

Other: chills, fever, flulike symptoms, edema

Interactions

Drug-drug. Sucralfate: interference with anagrelide absorption

Drug-diagnostic tests. Hemoglobin, platelets: decreased values

Hepatic enzymes: elevated values

Drug-food. Any food: decreased drug bioavailability

Drug-herbs. Evening primrose oil, feverfew, garlic, ginger, ginkgo biloba, ginseng, grapeseed: increased antiplatelet effect

Patient monitoring

See Watch for signs and symptoms of vasodilation, heart failure, and arrhythmias in patients with cardiovascular disease.

• For first 2 weeks, monitor CBC and liver and kidney function test results.

• Monitor platelet count regularly until maintenance dosage is established.

• Check regularly for adverse reactions, especially bleeding tendency.

• Monitor blood pressure for orthostatic hypertension.

Patient teaching

• Instruct patient to take drug 1 hour before or 2 hours after meals.

• Tell patient that drug may cause a temporary blood pressure decrease if he sits or stands up suddenly. Tell him to rise slowly and carefully.

See Instruct patient to report unusual bleeding or bruising or difficulty breathing.

See Tell patient to avoid prolonged exposure to sunlight.

• Caution patient to avoid driving and other hazardous activities until he knows how drug affects concentration, alertness, and vision.

• Inform patient using hormonal contraceptives that drug may interfere with contraceptive efficacy. Advise her to use alternative birth control method.

• Tell patient to avoid activities that may cause injury. Tell him to use soft toothbrush and electric razor to avoid gum and skin injury.

• Advise patient to minimize GI upset by eating small, frequent servings of food and drinking plenty of fluids.

• Notify patient that he'll undergo regular blood testing during therapy.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, foods, and herbs mentioned above.

anagrelide

(a-na-gre-lide) anagrelide,

Agrylin

(trade name)

Classification

Therapeutic: platelet reducing agent
Pregnancy Category: C

Indications

Treatment of thrombocythemia secondary to myeloproliferative disorders.

Action

Decreases maturation of megakaryocytes (platelet precursors).

Therapeutic effects

Reduction in platelet count with reduced risk of complications associated with thrombocythemia (thrombosis).

Pharmacokinetics

Absorption: Well absorbed after oral administration.Distribution: Unknown.Metabolism and Excretion: Extensively metabolized; <1% excreted unchanged in urine.Half-life: 1.3 hr.

Time/action profile (↓ in platelet count)

ROUTEONSETPEAKDURATION
PO7–14 days4–12 wk4 days†
†Increase in platelet count after discontinuation

Contraindications/Precautions

Contraindicated in: Hypersensitivity; Severe hepatic impairment; Lactation: Potential toxic effects in infant.Use Cautiously in: Cardiovascular, renal or mild to moderate hepatic impairment (monitor closely during treatment); Obstetric / Pediatric: Has been used safely in pregnant women and children <16 yr.

Adverse Reactions/Side Effects

Central nervous system

  • seizures (life-threatening)
  • dizziness (most frequent)
  • headache (most frequent)
  • malaise

Ear, Eye, Nose, Throat

  • abnormal vision

Respiratory

  • eosinophilic pneumonia (life-threatening)
  • interstitial pneumonitis (life-threatening)
  • pulmonary fibrosis (life-threatening)
  • pulmonary hypertension (life-threatening)
  • cough
  • dyspnea (most frequent)
  • pharyngitis

Cardiovascular

  • cerebrovascular accident (life-threatening)
  • complete heart block (life-threatening)
  • HF (life-threatening)
  • MI (life-threatening)
  • torsade de pointes (life-threatening)
  • ventricular tachycardia (life-threatening)
  • chest pain (most frequent)
  • edema (most frequent)
  • palpitations (most frequent)
  • angina
  • atrial fibrillation
  • pericarditis
  • pericardial effusion
  • orthostatic hypotension
  • tachycardia

Gastrointestinal

  • GI bleeding (life-threatening)
  • hepatotoxicity (life-threatening)
  • pancreatitis (life-threatening)
  • abdominal pain (most frequent)
  • diarrhea (most frequent)
  • flatulence (most frequent)
  • anorexia
  • constipation
  • dyspepsia
  • nausea
  • vomiting

Genitourinary

  • renal failure (life-threatening)
  • dysuria
  • hematuria

Dermatologic

  • alopecia
  • pruritis
  • rash

Hematologic

  • anemia

Musculoskeletal

  • arthralgia
  • back pain
  • myalgia
  • weakness (most frequent)

Neurologic

  • paresthesia

Miscellaneous

  • fever

Interactions

Drug-Drug interaction

Absorption may be ↓ by sucralfate.Fluvoxamine may ↑ blood levels.May ↑ blood levels of theophylline.May ↑ effects of milrinone and cilostazol.Concurrent use with aspirin may ↑ risk of bleeding.

Route/Dosage

Oral (Adults) 0.5 mg 4 times daily or 1 mg twice daily; may be ↑ weekly by 0.5 mg/day (not to exceed 10 mg/day or 2.5 mg as a single dose).Oral (Children) 0.5 mg daily; may be ↑ weekly by 0.5 mg/day (not to exceed 10 mg/day or 2.5 mg as a single dose.

Hepatic Impairment

Oral (Adults) Initiate at 0.5 mg daily; may be ↑ weekly by 0.5 mg/day.

Availability (generic available)

Capsules: 0.5 mg, 1 mg

Nursing implications

Nursing assessment

  • Monitor BP during initial therapy and periodically thereafter. May cause hypotension, especially upon standing.
  • Assess cardiovascular status and obtain at ECG before initiation of therapy and periodically during therapy. May cause vasodilation, tachycardia, palpitations, and heart failure. Close cardiovascular monitoring is required for patients with moderate hepatic impairment.
  • Monitor for signs and symptoms of interstitial lung diseases (progressive dyspnea with lung infiltrations). May occur from 1 week to several years after initiating anagrelide. Symptoms usually improve after discontinuation of anagrelide.
  • Lab Test Considerations: Monitor platelet count every 2 days during first wk of therapy and weekly until maintenance dose is reached. Platelet count usually begins to drop within 7–14 days.
    • Monitor AST and ALT prior to and periodically during therapy.
    • Monitor hemoglobin, WBC, BUN, and serum creatinine during the first 2 wk of therapy.

Potential Nursing Diagnoses

Ineffective tissue perfusion (Indications)
Deficient knowledge, related to medication regimen (Patient/Family Teaching)

Implementation

  • Dose should be reduced to the lowest possible to maintain platelet count of <600,000/mcl. Most patients experience an adequate response at a dose of 1.5–3 mg/day.
    • Interruption of therapy is usually followed by an increase in platelet count within 4 days.
  • Oral: May be taken without regard to food.

Patient/Family Teaching

  • Instruct patient to take medication as directed.
  • May cause dizziness. Caution patient to avoid driving or other activities requiring alertness until response to medication is known. Caution patient to stand slowly.
  • Instruct patient to limit alcohol intake as it may worsen the side effects of anagrelide.
  • Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
  • Advise patient to use contraception during therapy and to notify health care professional if pregnancy is planned or suspected, or if breastfeeding. May cause fetal harm.

Evaluation/Desired Outcomes

  • Maintenance of platelet count at <600,000/mcl or decrease of ≥50% from baseline. Initial response is expected in 7–14 days with complete response in 4–12 wks.

anagrelide

A cytoreductive agent used to manage essential thrombocythaemia and thrombocythaemia due to myeloproliferative disorders (e.g., CML, polycythemia vera) to reduce platelets, risk of thrombosis and other symptoms. It is generally regarded as a second-line therapy compared to hydroxyurea.

Agrylin®

Anagrelide, see there.