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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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