Anagrelide Administration Research Articles

Aortic Valve and Arch Replacements in a High-Risk Patient with Essential Thrombocythemia

Reports of the clinical results of cardiac surgery in patients with Essential Thrombocythemia (ET) are rare. In addition, cases of aortic arch aneurysm in ET have not been previously reported. We present a successful aortic valve and arch replacements with the frozen elephant trunk technique using hypothermic circulatory arrest in an ET patient with grade 3 aortic regurgitation and arch aneurysms. Reducing platelet count via the administration of anagrelide and the careful balancing of antiplatelets and anticoagulants is essential in determining the outcome of surgery.

Cecal cancer with essential thrombocythemia treated by laparoscopic ileocecal resection: a case report

BackgroundEssential thrombocythemia (ET) is a myeloproliferative disorder characterized by thrombocytosis and a propensity for both thrombotic and hemorrhagic events. ET rarely occurs simultaneously with colorectal cancer. Here, we report a case of colorectal cancer in an ET patient treated using laparoscopic ileocecal resection.Case presentationA 40-year-old woman was admitted to our hospital after presenting with liver dysfunction. She had been previously diagnosed with ET; aspirin and anagrelide had been prescribed. Subsequent examination at our hospital revealed cecal cancer. Distant metastasis was absent; laparoscopic ileocecal resection was performed. Anagrelide was discontinued only on the surgery day. She was discharged on the seventh postoperative day without thrombosis or hemorrhage. However, when capecitabine and oxaliplatin were administered as adjuvant chemotherapy with continued anagrelide administration, she experienced hepatic dysfunction and thrombocytopenia; thus, anagrelide was discontinued. Five days later, her platelet count recovered. Subsequently, anagrelide and aspirin administration was resumed, without any adjuvant chemotherapy. Her liver function normalized gradually in 4 months. One-year post operation, she is well without tumor recurrence or new metastasis.ConclusionsTo our knowledge, this is the first report of laparoscopic colectomy performed on an ET patient receiving anagrelide. Our report shows that complications such as bleeding or thrombosis can be avoided by anagrelide administration. Contrastingly, thrombocytopenia due to anagrelide intake should be considered when chemotherapy that could cause bone marrow suppression is administered.

Efficacy and safety of anagrelide as a first-line drug in cytoreductive treatment-naïve essential thrombocythemia patients in a real-world setting.

ObjectiveThis study aimed to retrospectively assess the efficacy and safety of anagrelide in cytoreduction therapy‐naïve essential thrombocythemia (ET) patients in a real‐world setting.MethodData from 53 ET patients who received anagrelide as a first‐line therapy were reviewed for patient characteristics, antiplatelet status, cytoreduction status, therapeutic effects, adverse events, thrombohemorrhagic event development, progression to myelofibrosis or acute leukemia, and cause of death.ResultsThe rate of achieving a platelet count of <600 × 109/L during anagrelide monotherapy was 83.0%. Adverse events occurred in 32 of 53 patients, and tended to be slightly more severe in patients with cardiac failure; however, they were mostly tolerable. The therapeutic effect of anagrelide was consistent, regardless of genetic mutation profiles. The incidence of anemia as an adverse event was significantly higher in the CALR mutation‐positive group. Favorable platelet counts were also achieved in patients for whom hydroxyurea was introduced as a replacement for anagrelide or in addition to anagrelide because of unresponsiveness or intolerance to treatment.ConclusionIn Japanese cytoreduction therapy‐naïve ET patients, anagrelide administration as a first‐line therapy demonstrated favorable effects in reducing platelet counts, and its safety profile that was generally consistent with those in previous reports.

PB2222 EFFICACY AND SAFETY OF ANAGRELIDE AS A FIRST‐LINE DRUG IN CYTOREDUCTIVE TREATMENT‐NAÏVE ET PATIENTS IN A REAL WORLD SETTING

Background:The goal of treating essential thrombocythemia (ET) is to prevent the potential onset of thrombohemorrhagic events (THEs) and disease progression to myelofibrosis (MF) and acute leukemia (AL). For ET patients who are at a high risk of developing thrombosis, the administration of antiplatelet and cytoreductive treatments is recommended. Anagrelide, a drug used in cytoreductive therapy, was approved in the United States in 1997 for treating thrombocytosis associated with myeloproliferative neoplasms. Although anagrelide is positioned as a second‐line drug in Europe, it has been approved as a first‐line drug in Japan and several other countries. Currently, the United States and Europe have different views regarding the use of anagrelide, and debates about its efficacy and safety are ongoing.Aims:This study aimed to retrospectively assess the efficacy and safety of anagrelide in cytoreductive treatment‐naïve ET patients in a real world setting.Methods:Data of 53 ET patients administered anagrelide as a first‐line treatment were reviewed with respect to patient characteristics, status of antiplatelet and cytoreductive treatments, therapeutic effects, adverse events, development of THEs after treatment, progression to MF or AL after treatment, and cause of death.Results:The median duration of anagrelide administration was 642 days, and the median daily dosage was 1.44 mg/day. The rate of achieving a platelet count &lt;600 × 109/L was 83.0%, and the median duration of time required for the achievement was 53 days. Treatment‐related adverse events occurred in 32 of 53 patients (60.4%). The reported adverse events tended to be slightly more severe in patients with heart failure but were mostly tolerable. The median observation period was 4.1 years, and 12 patients (22.6%) developed THEs during the follow‐up, i.e., thrombotic events in 8 patients (15.1%) and bleeding events in 4 (7.5%). Transformation occurred in 3 patients, all of which were MF. Comparisons between patients who were positive for the JAK2V617F mutation (JAK2‐ET group: 34 patients) and those positive for the CALR mutation (CALR‐ET group: 11 patients) revealed that anagrelide demonstrated equivalent therapeutic effects between the two groups and showed no significant differences in white blood cell counts, hemoglobin counts, and rates of decrease in platelet counts. The incidence of anemia as an adverse event was significantly higher in the CALR‐ET group than in the JAK2‐ET group. Favorable platelet counts were also achieved in cases wherein hydroxyurea was introduced as a replacement of anagrelide (8 patients) or in addition to anagrelide (9 patients) owing to unresponsiveness or intolerance to treatment.Summary/Conclusion:In Japanese ET patients who are cytoreductive treatment naïve, the administration of anagrelide as a first‐line drug demonstrated favorable effects in reducing platelet counts, along with safety profiles generally consistent with those reported previously. Although the therapeutic effects of anagrelide are the same regardless of the genetic mutation profiles, ET patients who are positive for the CALR mutation should be closely monitored for the development of anemia as an adverse event. To alleviate the adverse events of anagrelide, the drug can be administered in combination with hydroxyurea, for instance, and the treatment plan should be formulated in such a way that it can maximize the benefits of the two drugs.

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

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-hydroxyanagrelide.ObjectivesThe objectives of this study were to determine the effect of food and caffeine on the pharmacokinetics of anagrelide and its active metabolite, 3-hydroxyanagrelide, to monitor electrocardiogram (ECG) parameters following drug administration, and to document the relationship between palpitations, ECG changes and caffeine intakeMethodsThirty-five healthy subjects who received 1 mg of anagrelide following either a 10-h fast or within 30 min of a standardized breakfast, including two cups of coffee, were studied.ResultsTime to maximum (peak) plasma concentration (Cmax) of anagrelide was 4.0 h in the fed and 1.5 h in the fasted group (p < 0.05); similar results were observed for 3-hydroxyanagrelide. The mean Cmax of anagrelide was 4.45 ± 2.32 ng/mL and 5.08 ± 2.99 ng/mL in the fed/caffeine and fasted groups, respectively; peak concentrations were higher for 3-hydroxyanagrelide in both the fed/caffeine and fasted groups. The most frequent adverse events (AEs) were headache (60 %) and palpitations (40 %). There were no serious AEs and all ECGs were normal, although significant reductions in PR interval, QRS length and QT interval were observed in both groups. Heart rate increased after anagrelide administration in both fed/caffeine and fasted states (p < 0.01); however, increased heart rate was significantly more frequent in the fed/caffeine state than in the fasted state (p < 0.001 for heart rate increase in the first hour after drug administration). There was a trend towards a greater heart rate increase in subjects reporting palpitations than in those without (mean heart rate ± SD at 1 h: 10.1 ± 6.4 vs. 8.0 ± 8.4 beats/min [p = 0.35]; at 4 h: 12.7 ± 7.5 vs. 9.1 ± 8.8 beats/min [p = 0.10], respectively).ConclusionWe conclude that food/caffeine delayed absorption of anagrelide. Anagrelide was generally well tolerated and had small effects on ECG parameters and heart rate. Caffeine may be implicated in a higher increase in heart rate and increased frequency of palpitations observed following administration of anagrelide with food/caffeine versus fasting.

Auftreten von Ulcera crurum in Zusammenhang mit der Einnahme von Anagrelid

Anamnese und klinischer Befund: Wir berichten über einen 38-jährigen Patienten mit äußerst schmerzhaften Ulcera crurum an beiden Außenknöcheln, die 6 Wochen nach Beginn einer Therapie mit Anagrelid bei Thrombozythämie erstmalig auftraten.

Anagrelide, a selective thrombocytopenic agent.

The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage and administration of anagrelide are reviewed. Anagrelide is a selective thrombocytopenic agent with FDA-approved labeling for the treatment of essential thrombocythemia. Clinical trials have shown that the drug may have a role in the treatment of other chronic myeloproliferative disorders, including polycythemia vera, chronic myeloid leukemia, and agnogenic myeloid metaplasia. The mechanism by which anagrelide reduces platelet count is not yet clear. The current hypothesis is that anagrelide affects the late (postmitotic) phases of megakaryocyte development. Anagrelide has a large volume of distribution and is extensively metabolized; less than 1% is recovered unchanged in the urine. Plasma half-life after a 0.5-mg dose is 1.3 hours. Anagrelide's efficacy and safety have been evaluated in open-label, noncomparative trials, in which the response rate was 60-93%. Adverse effects include headache, diarrhea, edema, palpitations, and abdominal pain. Patients with renal or hepatic dysfunction need to be closely monitored for signs of toxicity. The recommended starting dosage is 0.5 mg four times a day or 1 mg twice a day, with dosage adjustment to the lowest effective amount required to reduce and maintain platelet count below 600 x 10(9)/L. The wholesale acquisition price for 0.5-mg capsules is $350 per 100. Whether anagrelide will replace hydroxyurea as first-line therapy in some or all patients remains to be determined. Anagrelide is effective in the treatment of essential thrombocythemia and may have a role in the treatment of other myeloproliferative disorders.