Omacetaxine Mepesuccinate

Name: Omacetaxine Mepesuccinate

Uses for Omacetaxine Mepesuccinate

Chronic Myelogenous Leukemia (CML)

Treatment of CML in adults in the chronic or accelerated phase of the disease after failure (secondary to resistance and/or intolerance) of prior therapy with ≥2 tyrosine kinase inhibitors (designated an orphan drug by FDA for treatment of CML4 ).1 2 3 21

Interactions for Omacetaxine Mepesuccinate

No formal drug interaction studies to date.1

Not a substrate of CYP isoenzymes in vitro; does not inhibit major CYP isoenzymes in vitro at clinically relevant concentrations.1

Substrate of P-glycoprotein (P-gp) in vitro, but does not appear to inhibit P-gp at clinically relevant concentrations.1

Drugs Affecting Hemostasis

Potential risk of bleeding.1

Specific Drugs

Drug

Interaction

Comments

Aspirin

Possible bleeding1

Avoid concomitant use if platelet count <50,000/mm31

Anticoagulants

Possible bleeding1

Avoid concomitant use if platelet count <50,000/mm31

NSAIAs

Possible bleeding1

Avoid concomitant use if platelet count <50,000/mm31

Omacetaxine Mepesuccinate Pharmacokinetics

Absorption

Bioavailability

Peak plasma concentrations achieved approximately 30 minutes after sub-Q administration.1 18

Distribution

Extent

Not known whether omacetaxine mepesuccinate is distributed into milk.1

Plasma Protein Binding

≤50%.1

Elimination

Metabolism

Primarily hydrolyzed by plasma esterases to an inactive 4'-desmethyl metabolite; undergoes minimal hepatic microsomal oxidation and/or esterase-mediated metabolism in vitro.1 18

Elimination Route

Major route of elimination not known; following sub-Q administration, approximately 12–15% of a dose is excreted unchanged in urine.1 18

Half-life

Approximately 6–7 hours following sub-Q administration.1 18

Special Populations

Effect of hepatic impairment on pharmacokinetic disposition not formally evaluated;1 results of population pharmacokinetic analysis indicate that mild hepatic impairment (total bilirubin concentration ≤1.5 times the ULN and AST >ULN) does not appear to affect pharmacokinetics.20

Effect of renal impairment on pharmacokinetic disposition not formally evaluated;1 results of population pharmacokinetic analysis indicate that Clcr of 50–80 or <50 mL/minute does not appear to affect pharmacokinetics.20

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