omacetaxine- cml
TRANSCRIPT
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OMACETAXINEMEPOSUCCINATE
DR. AMEENA KHATOONKORALLI
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INTRODUCTION
Omacetaxine mepesuccinate(or homoharringtonine)
It is an alkaloid from Cephalotaxus harringtonia.
Approval status: October 2012
Treatment area:
Adult patients of CML who show resistance &/or
intolerance to 2 or more tyrosine kinaseinhibitors
It can be used in both the chronic phase and theaccelerated phase of CML
http://en.wikipedia.org/wiki/Alkaloidhttp://en.wikipedia.org/wiki/Cephalotaxus_harringtoniahttp://en.wikipedia.org/wiki/Cephalotaxus_harringtoniahttp://en.wikipedia.org/wiki/Cephalotaxus_harringtoniahttp://en.wikipedia.org/wiki/Cephalotaxus_harringtoniahttp://en.wikipedia.org/wiki/Alkaloid -
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INTRODUCTION
Omacetaxine is a protein translation inhibitor
Chemical Formula - C29H39NO9
Mol. Mass - 545.62 g/mol
Stuctural formula-
http://en.wikipedia.org/wiki/Translationhttp://en.wikipedia.org/wiki/Chemical_formulahttp://en.wikipedia.org/wiki/Carbonhttp://en.wikipedia.org/wiki/Hydrogenhttp://en.wikipedia.org/wiki/Nitrogenhttp://en.wikipedia.org/wiki/Oxygenhttp://en.wikipedia.org/wiki/Molecular_masshttp://en.wikipedia.org/wiki/Molecular_masshttp://en.wikipedia.org/wiki/Oxygenhttp://en.wikipedia.org/wiki/Nitrogenhttp://en.wikipedia.org/wiki/Hydrogenhttp://en.wikipedia.org/wiki/Carbonhttp://en.wikipedia.org/wiki/Chemical_formulahttp://en.wikipedia.org/wiki/Translation -
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In addition to the APE sites, there is an mRNA bindinggroove that holds onto the message being translated
Mechanism of action
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Mechanism of action
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Clinical pharmacology
Mechanism of action Omacetaxine is a protein translation inhibitor.
It inhibits protein translation by preventing the
initial elongation step of protein synthesis. It interacts with the ribosomal A-site and
prevents the correct positioning of amino acid
side chains of incoming aminoacyl-tRNAs.
http://en.wikipedia.org/wiki/Translationhttp://en.wikipedia.org/wiki/Translation -
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Clinical pharmacology
Pharmacokinetics:Absorption
It is absorbed following subcutaneousadministration.
Max. conc are achieved after approx.30 minDistribution
Vol. of distribution ranges from 234.4 to 47.6 L
Plasma protein binding is 50%
Metabolism
It is hydrolysed to 4-DMHHT via plasma esterasewith little hepatic microsomal oxidation
Mean t1/2 6hrs.
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Dosage and administration Induction schedule
Starting dose-1.25mg/m2 administered S.C, twicedaily for 14 consecutive days every 28 days, over a28 day cycle
Maintenance dosing
Recommended dose 1.25mg/m2 administered S.C,
twice daily for 7 consecutive days every 28 days,over a 28 day cycle.
Contraindication
none
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Adverse drug reactions
Blood disordersAnaemia Thrombocytopenia
Neutropenia Lymphopenia
Bone marrow failure Febrile neutropenia
Gastrointestinal disordersDiarrhoea Nausea
Constipation Abdominal pain
Vomiting
General disorders
Fatigue Pyrexia
Asthenia Peripheral edema
Headache InsomniaInfusions and in ection site related reactions
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Adverse drug reactions
Infections and infestations Musculoskeletal and connective tissue disorders
Arthralgia Pain in extremity
Back pain
Respiratory disordersCough Dyspnea
Epistaxis
Skin and subcutaneous tissue disorders
Alopecia Rash
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Use in specific populations
Pregnancy- it is category D it can cause fetal harm when administered to a
pregnant female based on its mechanism of action.
Embryonic death.
Reduced bone ossification, decreased fetal weight
Nursing mothers
It is not known whether drug is excreted in human
breast milk.
Pediatric use
Safety and efficacy is not yet established
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Use in specific population
Hepatic impairment The safety and effectiveness of omacetaxine
have not been established in patients with
hepatic impairment.Renal impairment
The safety and effectiveness of omacetaxinehave not been established in patients with renal
impairment
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