Mechanism of effect
The mechanism of action of omacetaxine mepesuccinate has not been fully elucidated but includes inhibition of protein synthesis and is independent of direct Bcr-Abl binding. Omacetaxine mepesuccinate binds to the A-site cleft in the peptidyl-transferase center of the large ribosomal subunit from a strain of archaeabacteria. In vitro, omacetaxine mepesuccinate reduced protein levels of the Bcr-Abl oncoprotein and Mcl-1, an anti-apoptotic Bcl-2 family member. Omacetaxine mepesuccinate showed activity in mouse models of wild-type and T315I mutated Bcr-Abl CML
Pharmacokinetics
Bioavailability
Peak plasma concentrations achieved approximately 30 minutes after sub-Q administration.
Distribution
Extent
Not known whether omacetaxine mepesuccinate is distributed into milk.
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.
Elimination Route
Major route of elimination not known; following sub-Q administration, approximately 12–15% of a dose is excreted unchanged in urine.
Half-life
Approximately 6–7 hours following sub-Q administration
Drug indications
Omastaxin is used as a treatment for patients with chronic myeloid leukemia who are resistant to or intolerant to tyrosine kinase inhibitors.
Dosage
Initial induction dose: 1.25 mg / m2 twice daily for 14 consecutive days of a 28-day treatment cycle. 1 Repeat the cycle until a hematologic response is obtained.
Maintenance treatment: 1.25 mg / m2 twice daily for 7 consecutive days of a 28-day treatment cycle.
Drug contraindications
hemorrhage
This drug suppresses bone marrow. Grade 3 or 4 thrombocytopenia (88-88% of patients), neutropenia (81-81% of patients) and anemia (80-62 patients)
In 3% of patients, lethal clinical trials were reported.
Risk of bleeding, including potential CNS or GI bleeding, is usually associated with severe thrombocytopenia.
Risk of glucose intolerance and hyperglycemia.
Grade 3 or 4 hyperglycemia has been reported in clinical trials.
Side effects
Diarrhea
,
edema
,
nausea
,
abdominal pain
,
Bradycardia
,
cardiac arrhythmias
,
rectal hemorrhage
,
GI bleeding
,
tiredness
,
Angina pectoris
,
Neutropenia Associated with Chemotherapy
The most common side effects (with a recurrence greater than 20%) include thrombocytopenia, anemia, neutropenia, diarrhea, nausea, fatigue, asthenia, injection site reaction, pyrexia, infection, and lymphopenia. Serious side effects of at least 5% There are patients including fever neutropenia (18%), thrombocytopenia (9%), anemia (7%), diarrhea (6%) and seizures (6%). The most common side effects were drug withdrawal Leukocytosis (6%) and thrombocytopenia (4%).
Alerts
Bone marrow suppression:
Bone marrow suppression is generally reversible and decreases with a decrease in number or delay in drug administration days. Monitor CBC regularly (weekly during initial drug administration to achieve maintenance dose and then every two weeks).
Dosage adjustment may be necessary in case of severe blood toxicity.
Bleeding:
Risk of bleeding, including potentially fatal CNS or GI bleeding, usually associated with severe thrombocytopenia. Platelet counts are recommended as part of a routine CBC monitoring program.
Hyperglycemia:
There is a risk of intolerance to glucose and blood sugar. A grade 3 or 4 increase in blood sugar has been reported in clinical trials. Monitor blood glucose levels frequently, especially in patients with diabetes mellitus. Consume in patients with uncontrolled diabetes. Avoid until your blood sugar is well controlled.
Complications and fetal / infant mortality
May cause fatal fetal harm. Fetal toxicity has been shown in animals.
If used during pregnancy or if the patient becomes pregnant, estimate the potential risk to the fetus.
Points of recommendation
Tell your doctor if you have any of the following problems:
Diabetes; Bleeding or blood clotting disorder. Or if you are pregnant or you may become pregnant.
Do not use amatoxin if you are pregnant. This can harm the unborn baby. Use an effective method of contraception to prevent pregnancy during treatment with omastaxine. Follow your doctor's instructions for how long to prevent pregnancy after your treatment
Pregnancy level
May cause fetal harm. Fetal toxicity has been shown in animals.
Breast feeding warning
It is not known if this medicine is distributed in milk. Stop breast-feeding or taking the medicine.
Related drugs
Paclitaxel
,
Vinblastin
,
Vincristin
,
Etoposide
Amastoxy is one of the plant-derived agents that has significant cytostatic or antiplasmic activity. Amastaxine-like drugs include vincristine, vinblastine, paclitaxel, and autoposide.
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