Adult: In patients who are intolerant to or unresponsive to other therapy, and in thrombocythaemia secondary to myeloproliferative disorders: Initially, 1 mg daily in 2 divided doses. Alternatively, 2 mg daily in 2-4 divided doses. Maintain initial dose for at least 1 week, then titrate by not more than 0.5 mg daily at weekly intervals until the platelet count is maintained within normal range. Max: 2.5 mg/dose or 10 mg daily. Maintenance: 1-3 mg daily. Child: ≥7 years Initially, 0.5 mg daily for 1 week, increase in increments of 0.5 mg daily at weekly intervals until the platelet count is maintained within normal range. Usual maintenance dose: 2.5 mg/dose or 10 mg daily. Dosing recommendations may vary among individual products and between countries (refer to specific product guidelines).
Renal Impairment
CrCl (mL/min)
Dosage
<50
Contraindicated.
Hepatic Impairment
Moderate to severe: Contraindicated. Dosing recommendations may vary among individual products and between countries (refer to specific product guidelines).
Administration
May be taken with or without food.
Contraindications
Moderate to severe hepatic and renal (CrCl <50 mL/min) impairment.
Special Precautions
Patient with known risk factors for QT interval prolongation (e.g. congenital long QT syndrome, history of acquired QTc prolongation); hypokalaemia, suspected heart disease, class III or IV heart failure. Avoid abrupt withdrawal. Mild renal and hepatic impairment. Children. Pregnancy and lactation.
Adverse Reactions
Significant: Serious CV events (e.g. torsades de pointes, ventricular tachycardia, cardiomyopathy, cardiomegaly, palpitation, CHF); hypotension, dizziness (high doses); pulmonary hypertension, interstitial lung disease (including allergic alveolitis, eosinophilic pneumonia, interstitial pneumonitis); renal abnormalities (e.g. haematuria, renal failure). Blood and lymphatic system disorders: Anaemia. Cardiac disorders: Tachycardia, palpitation. Gastrointestinal disorders: Abdominal pain, flatulence, nausea, vomiting, diarrhoea. General disorders and administration site conditions: Fatigue. Metabolism and nutrition disorders: Fluid retention. Nervous system disorders: Headache. Skin and subcutaneous tissue disorders: Rash. Potentially Fatal: Increased risk of thrombotic complications (e.g. cerebral infarction) if treatment is discontinued abruptly or dose is substantially reduced.
This drug may cause dizziness, if affected, do not drive or operate machinery.
Monitoring Parameters
Perform CV evaluation (including ECG) before and during treatment. Assess for signs and symptoms of cardiopulmonary disease before and during treatment. Obtain platelet count (every 2 days during 1st week of treatment and weekly thereafter until reaching maintenance dose then continue after discontinuation of treatment); CBC with differential (before and during treatment); BUN and serum creatinine (before and during treatment); LFT (before and during treatment); serum electrolytes. Monitor blood pressure, heart rate; signs and symptoms of thrombosis or bleeding, and interstitial lung disease.
Overdosage
Symptoms: Sinus tachycardia, vomiting, hypotension. Management: Supportive treatment. Monitor platelet count for thrombocytopenia. Decrease or discontinue dose, if needed, until platelet count returns to normal range.
Drug Interactions
Exacerbation of inotropic effects with other phosphodiesterase (PDE) III inhibitors (e.g. milrinone, amrinone, enoximone, olprinone, cilostazol). Increased risk of bleeding with anticoagulants, SSRI, NSAIDs, antiplatelet agents. Increased risk of major haemorrhagic events with aspirin. Increased exposure with CYP1A2 inhibitors (e.g. fluvoxamine, enoxacin, ciprofloxacin). Decreased exposure with CYP1A2 inducers (e.g. omeprazole). May compromise absorption of oral contraceptives. Enhanced QTc-prolonging effect with drugs that prolong QTc interval (e.g. chloroquine, clarithromycin, haloperidol, methadone, amiodarone, moxifloxacin, disopyramide, pimozide, procainamide). May alter the exposure of CYP1A2 substrates (e.g. theophylline, ondansetron, fluvoxamine).
Action
Description: Mechanism of Action: Anagrelide is a cyclic adenosine monophosphate (cAMP) PDE III inhibitor which reduces platelet production and inhibits platelet aggregation at high concentrations. Onset: Initial: Within 7-14 days. Complete response: 4-12 weeks. Pharmacokinetics: Absorption: Well absorbed from the gastrointestinal tract. Delayed absorption with food. Time to peak plasma concentration: Approx 1 hour (fasted state). Metabolism: Extensively metabolised in the liver mainly by CYP1A2 into 2 major metabolites, 3-hydroxy anagrelide (active) and RL603 (inactive). Excretion: Via urine (<1% as unchanged drug, approx 3% as 3-hydroxy anagrelide, 16-20% as RL603). Elimination half-life: Approx 1.5 hours.
Chemical Structure
Anagrelide Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 135409400, Anagrelide. https://pubchem.ncbi.nlm.nih.gov/compound/Anagrelide. Accessed Nov. 22, 2023.
L01XX35 - anagrelide ; Belongs to the class of other antineoplastic agents. Used in the treatment of cancer.
References
Agrylin Capsule (Takeda Pharmaceuticals America, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 06/02/2023.Agrylin Capsule 0.5 mg (Takeda Malaysia Sdn Bhd). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 06/02/2023.Anagrelide 0.5 mg Hard Capsules (Accord Healthcare Limited). MHRA. https://products.mhra.gov.uk. Accessed 06/02/2023.Anon. Anagrelide. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 06/02/2023.Buckingham R (ed). Anagrelide Hydrochloride. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 06/02/2023.Joint Formulary Committee. Anagrelide. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 06/02/2023.Takeda New Zealand Limited. Agrylin 0.5 mg Hard Capsules data sheet 12 August 2022. Medsafe. http://www.medsafe.govt.nz. Accessed 06/02/2023.
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