omacetaxine [SC]

Adult Dosing

Chronic or accelerated phase myeloid leukemia (CML) with resistance and/or intolerance to two or more tyrosine kinase inhibitors (TKI)

Induction: 1.25 mg/m ² SC bid x 14 consecutive days q28 days; repeat q28 days, until a hematologic response is achieved
Maintenance: 1.25 mg/m ² SC bid x 7 consecutive days q28 days, as long as a clinical benefit is maintained

Pediatric Dosing

Safety and effectiveness in pediatric patients have not been established

[Outline]

Adult Dosing
Pediatric Dosing

Indications ⬆ ⬇

Chronic or accelerated phase myeloid leukemia (CML) with resistance and/or intolerance to two or more tyrosine kinase inhibitors (TKI)

Contraindications ⬆ ⬇

Hypersensitivity to any of the ingredient of the product

Black Box Warnings ⬆ ⬇

Dosing Adjustment ⬆ ⬇

Renal Dose Adjustment

Renal impairment: Dose adjustments not defined

Hepatic Dose Adjustment

Hepatic impairment: Dose adjustments not defined

Neutropenia Grade 4

Delay next cycle and reduce number of dosing days for following cycle by 2 days until neutrophile count is 1 x 10 ⁹ or greater.

Thrombocytopenia Grade 3

Delay next cycle and reduce number of dosing days for following cycle by 2 days until platelet count is 50 x 10 ⁹ or greater.

Warnings/Precautions ⬆ ⬇

Therapy may lead to thrombocytopenia, neutropenia, anemia and fatalities related to myelosuppression. Monitor complete blood counts weekly during induction and initial maintenance cycles and every two weeks during later maintenance cycles, as clinically indicated
Increased risk for hematologic toxicity by elderly
Patients with neutropenia are at increased risk for infections, and should be monitored frequently and advised to contact a physician if they have symptoms of infection or fever
Therapy causes severe thrombocytopenia which increases the risk of hemorrhage. Fatalities from cerebral, severe, non-fatal, gastrointestinal hemorrhages may be associated with severe thrombocytopenia. Monitor platelet counts as part of the CBC monitoring as recommended
Avoid anticoagulants, aspirin, and non-steroidal anti-inflammatory drugs (NSAIDs) when the platelet count is < 50,000/µL as they may increase the risk of bleeding
Omacetaxine can induce glucose intolerance which may lead to hyperglycemia, including hyperosmolar non-ketotic hyperglycemia. Closely monitor blood glucose levels frequently, especially in patients with diabetes or risk factors for diabetes
Avoid use in patients with poorly controlled diabetes mellitus until good glycemic control has been established
Omacetaxine can cause fetal harm when administered to a pregnant woman. Females of reproductive potential should avoid becoming pregnant while being treated. If this drug is used during pregnancy, or if the patient becomes pregnant while receiving this drug, the patient should be apprised of the potential hazard to the fetus

Pregnancy/Breast Feeding ⬆ ⬇

Pregnancy Category:D

Breastfeeding: It is not known whether omacetaxine is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reaction in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Adverse Reactions ⬆ ⬇

HEMA : Anemia, neutropenia, lymphopenia, bone marrow failure, febrile neutropenia, thrombocytopenia, increased uric acid levels
CARDIO: Acute coronary syndrome, dysrhythmia
GI: Diarrhea, nausea, constipation, abdominal pain upper, vomiting
CNS: Fatigue, headache, insomnia, pyrexia, asthenia, seizure
MISC: Edema peripheral infusion and injection site related reactions
MUSC: Arthralgia, pain in extremity, back pain, infectious disease, cerebral and GI hemorrhage
RESP: Cough, epistaxis
DERM: Alopecia, rash

Clinical Pharmacology ⬆ ⬇

Protein synthesis inhibitor; binds to the A-site cleft in the peptidyl-transferase center of the large ribosomal subunit from a strain of archaeabacteria
Metabolism: Primarily hydrolyzed to 4'-DMHHT via plasma esterases with little hepatic microsomal oxidative and/or esterase-mediated metabolism in vitro
Excretion: 15% unchanged in urine
Half-life: 6 hours