Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0000737 (abdominal pain)
 31,184 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Anagrelide, a selective thrombocytopenic agent. 978 84

Anagrelide hydrochloride (Agrylin, Roberts Pharmaceutical Corp.) is an oral imidazoquinazoline agent that has been shown to reduce elevated platelet counts and the risk of thrombosis in patients with thrombocythaemia in various myeloproliferative disorders (MPD). It is currently approved by the FDA as oral treatment for essential thrombocythaemia (ET) and thrombocythaemia associated with polycythaemia vera (PV). Anagrelide selectively suppresses bone marrow megakaryocytes by interfering with the maturation process and decreasing platelet production without affecting the erythroid and myeloid progenitor cells. Other medications indicated for the treatment of thrombocythaemia, including interferon alpha (IFN-alpha), alkylating agents and hydroxyurea, suppress all cell lines. Anagrelide is known to inhibit platelet cyclic adenosine monophosphate (cAMP) phosphodiesterase at concentrations that exceed those achieved at doses used to treat ET. Anagrelide is extensively metabolised in the liver and its metabolites are primarily excreted in the urine. Adverse effects associated with the use of anagrelide are primarily caused by the drugs' direct vasodilating and positive inotropic effects. These include headache, hypotension and diarrhoea. It has also been known to cause fluid retention, tachycardia, nausea, abdominal pain and arrhythmias. The starting dose of anagrelide ranges from 0.5 mg q.i.d. to 1 mg b.i.d. with a maximum dose of 2.5 mg q.i.d. Adequate responses have been maintained with a median dose of 2-2.5 mg/day. Platelet counts begin to decrease in 7-10 days, however, they return to pre-treatment levels within 4-8 days if therapy is stopped. Anagrelide 2 mg/day for one year costs approximately US$6439, and treatment must continue indefinitely [1].
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PMID:Anagrelide: a novel agent for the treatment of myeloproliferative disorders. 1124 36

(1) For patients aged over 60 years who have essential thrombocythaemia, and are considered to be at increased risk of thromboembolism, the standard cytotoxic agent is hydroxycarbamide (hydroxyurea), which reduces the risk of thrombocytosis but adversely affects other blood cell lines. It may also increase the risk of progression to cancer. (2) Anagrelide, initially studied as an antiplatelet drug, was approved in Europe for the treatment of essential thrombocythaemia in high-risk patients when other treatments fail or are poorly tolerated. (3) Evaluation data includes a trial versus hydroxycarbamide that was prematurely halted because of an excess of cardiovascular events among patients on anagrelide. Among 809 patients who were also receiving aspirin as an antithrombotic (and who may not have met strict criteria for essential thrombocythaemia), arterial or venous thrombosis and haemorrhage were significantly more frequent with anagrelide, during a median follow-up of 39 months (55 versus 36 patients). (4) According to the results of 3 non comparative trials involving about 500 patients, and the European Medicines Agency report analysing these and other study populations, anagrelide reduces the platelet count to below 600 times 10 to the 9th power/litre in two-thirds of patients. No data are available on the clinical implications of this reduction in platelets. (5) Between 10% and 20% of patients treated with anagrelide experience cardiovascular adverse effects (palpitations, myocardial infarction, heart failure) or neurological adverse effects (headache, stroke, transient ischaemic attack). Gastrointestinal disturbances are also frequent (diarrhoea, nausea, abdominal pain, pancreatitis). Some of these adverse effects can be fatal. (6) Follow-up is too short to show whether anagrelide affects the risk of progression to cancer. (7) In practice, anagrelide has a less favourable risk-benefit balance than hydroxycarbamide, which remains the first-line cytotoxic agent in this setting. Anagrelide therapy can be considered if hydroxycarbamide fails or is poorly tolerated, provided patients are included in a long-term clinical trial.
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PMID:Anagrelide: new drug. Essential thrombocythaemia: further evaluation needed for this last-resort treatment. 1676 90