Cardiovascular Safety of Anagrelide in Healthy Subjects: Effects of Caffeine and Food Intake on Pharmacokinetics and Adverse Reactions

  title={Cardiovascular Safety of Anagrelide in Healthy Subjects: Effects of Caffeine and Food Intake on Pharmacokinetics and Adverse Reactions},
  author={Manuel Mart{\'i}nez‐Sell{\'e}s and Tomas Datino and Lourdes M Figueiras-Graillet and J. Gustavo Vega Gama and Christopher Jones and Richard Arthur Franklin and Francisco Fern{\'a}ndez‐Avil{\'e}s},
  journal={Clinical Drug Investigation},
  pages={45 - 54}
BackgroundEssential thrombocythaemia (ET) is a rare clonal myeloproliferative disorder characterized by a sustained elevation in platelet count and megakaryocyte hyperplasia. Anagrelide is used in the treatment of ET, where it has been shown to reduce platelet count. Anagrelide is metabolized by cytochrome P450 (CYP) 1A2, and previous studies of the effect of food on the bioavailability and pharmacokinetics of anagrelide were conducted prior to the identification of the active metabolite, 3… 
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Both formulations of a novel anagrelide extended‐release (AER) formulation and its active metabolites were well tolerated, with a trend toward more frequently occurring adverse events after the CARP.
Effect of anagrelide on cardiac repolarization in healthy volunteers: a randomized, double‐blind, placebo‐ and positive‐controlled, thorough QT study
The increase in QTc interval met the definition for a positive thorough QT/QTc study only when HR was increasing rapidly, suggesting that the increased QTC may be related to the rapidly increasing HR rather than a direct effect of anagrelide plasma concentrations.
Anagrelide hydrochloride for essential thrombocythemia
Introduction: Essential thrombocytemia (ET) is a myeloproliferative neoplasm characterized by an elevated platelet count and an increased risk of thrombohemorrhagic events. Anagrelide hydrochloride
Ventricular tachyarrhythmia in a 78-year-old woman with essential thrombocythaemia
A 78-year-old woman with essential thrombocythaemia and recently started on anagrelide who presented with syncope and multiple bruises and facial trauma and found to have developed ventricular tachyarrhythmia is reported.
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The available evidence about the management of patients with myeloproliferative neoplasms, with a special focus on the side effects of drug therapies is reviewed.
A novel LC-ESI-MS/MS assay method for the determination of anagrelide in human plasma by using a solid phase extraction technique and its application to a pharmacokinetic study
A simple, rapid and sensitive liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) assay method has been developed and validated for the determination of anagrelide
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This brief review will discuss the current literature relating to the potential efficacy of caffeine to enhance muscular endurance and strength based performance, and provides evidence based recommendations for athletes and coaches to implement.
Hybrid System for Engagement Recognition During Cognitive Tasks Using a CFS + KNN Algorithm
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Adverse effects and benefits of two years of anagrelide treatment for thrombocythemia in chronic myeloproliferative disorders.
Side effects and toxic discontinuation rates were higher than in previous studies, probably because this is the first long-term prospective study of the feasibility and toxicity of anagrelide treatment.
Anagrelide: a review of its use in the management of essential thrombocythaemia.
The role of anagrelide in the management of high-risk patients with essential thrombocythaemia will ultimately depend on individual patient assessment and future clarification of the potential leukaemogenicity of hydroxycarbamide.
Successful rechallenge with anagrelide in a patient with anagrelide-associated cardiomyopathy
A patient with essential thrombocythaemia who developed anagrelide-associated cardiomyopathy was successfully rechallenged with the drug at a lower dose after 17 months of treatment.
Caffeine as a marker substrate for testing cytochrome P450 activity in human and rat.
Caffeine pharmacokinetics may be changed by drugs affecting the activity of CYP1A2 (human and rat) or CYP2C (rat) or by treatment with certain antidepressants or neuroleptics, therefore, patients taking caffeine-containing medicine or coffee drinkers taking drugs that interact with CYP 1A2 may require proper dosage adjustments upon caffeine ingestion and cessation.
Long-term use of anagrelide in young patients with essential thrombocythemia.
It is concluded that long-term treatment of ET with anagrelide is associated with decreased reporting of initial side effects and the development of mild-to-moderate anemia, and complete normalization of platelet counts may be needed to minimize residual thrombohemorrhagic risk during therapy.
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Compared the activities of anagrelide, BCH24426 and RL603 on the growth and differentiation of CD34+ haematopoietic progenitor cells in liquid culture and on the migration of differentiated megakaryocytes show the selectivity of these compounds against themegakaryocytic lineage.
Hydroxyurea compared with anagrelide in high-risk essential thrombocythemia.
Hydxyurea plus low-dose aspirin is superior to anagrelideplus low- dose aspirin for patients with essential thrombocythemia at high risk for vascular events.
Coffee Acutely Increases Sympathetic Nerve Activity and Blood Pressure Independently of Caffeine Content: Role of Habitual Versus Nonhabitual Drinking
Coffee and caffeine induced comparable increases in MSA and BP in nonhabitual coffee drinkers, whereas habitual coffee drinkers exhibited lack of BP increase despite MSA activation to coffee.
Anagrelide‐Induced Cardiomyopathy
A 48‐year‐old woman with polycythemia vera developed cardiotoxicity manifested by congestive heart failure and palpitations, which was suspected to be temporally related to titrating dosages of anagrelide.