Mitotane

Mitotane

Mitotane (2S)-enantiomer

Information about Mitotane

Omacetaxine is a semisynthetic cephataxine that acts as a protein translation inhibitor and is used to treated chronic myeloid leukemia that is resistant to tyrosine kinase receptor antagonists. 

Liver safety of Mitotane

Omacetaxine is associated with a low rate of serum enzyme elevation during therapy, but has not been linked to cases of clinically apparent liver injury with jaundice. 

Mechanism of action of Mitotane

Omacetaxine (oh" ma se tax' een) mepesuccinate is a semisynthetic molecule previously known as homoharringtonine which is derived from the leaves and bark of Cephalotaxus harringionia (plum yew).  Omacetaxine is an inhibitor of protein translation which binds to ribosomes and blocks the initial elongation step in the synthesis of proteins from mRNA.  Therapy with omacetaxine was found to have activity against chronic myeloid leukemia (CML) and was considered a first line agent before the introduction of the tyrosine kinase inhibitor imatinib.  More recently, omacetaxine has found to improve survival in patients with refractory CML and resistance to multiple tyrosine kinase inhibitors and was approved for this use in the United States in 2012. 

Omacetaxine is administered parenterally and is available in single use vials of 3.5 mg of lyophilized powder for reconstitution.  The recommended dose is 1.25 mg/m2 injected subcutaneously twice daily on days 1 to 14 of 28-day cycles, with subsequent modification once remission is achieved to twice daily on days 1 to 7 of 28-day cycles. 

Side effects of Mitotane

Common side effects include myelosuppression which can be severe, injection site reactions, diarrhea, fatigue, weakness, nausea, headache, pyrexia and infections.  Uncommon, but potentially severe adverse events include neutropenic fever and sepsis, cerebral hemorrhage and hyperglycemia.