Action and Spectrum

Actions and spectrum: 

Actions: 

• Inhibition of Protein Synthesis: omacetaxine inhibits protein synthesis in cancer cells by binding to the ribosome, the cellular machinery responsible for protein production. This disruption of protein synthesis leads to cell death and a reduction in cancer cell proliferation. 

Spectrum: 

• Chronic Myeloid Leukemia (CML): omacetaxine is approved for the treatment of chronic-phase, accelerated-phase, or blast-phase CML in patients who received previously two or more tyrosine kinase inhibitors (TKIs) and have developed resistance or intolerance to TKI therapy. It is particularly effective against CML with the T315I mutation, which is associated with resistance to other TKIs. 
• Acute Myeloid Leukemia (AML): omacetaxine may also be used in the treatment of certain subtypes of AML, particularly in cases where other therapies have been ineffective or are not suitable. It is often used in older patients who may not be candidates for intensive chemotherapy. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% (CML Accelerated Phase) 

Infestations and infections (56%)

Diarrhea (35%) 

Pyrexia (29%) 

Asthenia (24%) 

Febrile neutropenia (20%) 

Cough (15%) 

Abdominal pain (13%) 

Chills (13%) 

Dyspnea (11%) 

Pain in the extremities (11%) 

Thrombocytopenia (56%) 

Anemia (51%) 

Fatigue (31%) 

Nausea (27%) 

reactions at Injection site (22%) 

Neutropenia (20%) 

Vomiting (15%) 

Anorexia (13%) 

Headache (13%) 

Epistaxis (11%)  

>10% (CML Chronic Phase) 

Anemia (61%) 

Infestations and infections (46%)
reactions at Injection site (34%) 

Fatigue (26%) 

Asthenia (23%) 

Headache (19%) 

Cough (16%) 

Constipation (15%) 

upper Abdominal pain (14%) 

Peripheral edema (13%) 

Back pain (11%) 

Bone marrow injury (10%) 

Insomnia (10%) 

Thrombocytopenia (74%) 

Neutropenia (50%) 

Diarrhea (42%) 

Nausea (32%) 

Pyrexia (24%) 

Arthralgia (19%) 

Lymphopenia (17%) 

Alopecia (15%) 

Epistaxis (15%) 

Pain in the extremities (13%) 

Vomiting (12%) 

grade 4 Hyperglycemia (11%) 

Febrile neutropenia (10%) 

Rash (10%)  

Post marketing Reports 

Bleeding 

Myelosuppression 

Black Box Warning

Black Box Warning: 

omacetaxine does not have a black box warning. 

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

• Hypersensitivity: omacetaxine is contraindicated in patients with known hypersensitivity or allergic reaction to omacetaxine or any of its components. Signs of a hypersensitivity reaction may include rash, itching, swelling, dizziness, or difficulty breathing.  
• Pregnancy and Breastfeeding: omacetaxine may cause harm to the developing fetus, and its use during pregnancy is not recommended. Additionally, it is not known whether omacetaxine is excreted in human breast milk, so breastfeeding should be avoided during treatment with omacetaxine. 
• Severe Hepatic Impairment: omacetaxine should be used with caution in individuals with severe hepatic impairment. Close monitoring of liver function and adjustment of the dosage may be necessary in such cases. 

Caution: 

• Bone Marrow Suppression: omacetaxine can cause bone marrow suppression, leading to low blood cell counts. Close monitoring of blood counts is essential during treatment. If significant decreases in white blood cells, red blood cells, or platelets occur, the dosage may need to be adjusted or treatment may need to be temporarily interrupted. 
• Bleeding: omacetaxine may increase the risk of bleeding. Caution should be exercised in individuals with a history of bleeding disorders or those receiving concurrent anticoagulant therapy. Any signs of bleeding, such as easy bruising, prolonged bleeding from cuts, or blood in the urine or stool, should be promptly reported to a healthcare provider. 
• Infection: omacetaxine can increase the risk of infection. Patients to be monitored for signs and symptoms, such as fever, cough, chills, or sore throat. Prompt medical attention should be sought if any signs of infection occur. 
• Hepatic Impairment: omacetaxine is primarily metabolized in the liver. Patients with pre-existing liver impairment may require close monitoring and dose adjustments. It is important to inform healthcare providers about any existing liver conditions before starting omacetaxine treatment. 
• Renal Impairment: Limited information is available regarding the use of omacetaxine in patients with renal impairment. Close monitoring may be necessary in individuals with severe renal dysfunction, and dose adjustments may be required. 

Comorbidities: 

• Cardiovascular Disease: CML patients may have an increased risk of stroke, heart attack, or peripheral vascular disease.  
• Diabetes Mellitus: CML patients may have an increased prevalence of diabetes mellitus.  
• Other Hematological Disorders: Patients with CML may have additional hematological disorders, such as thrombocytopenia or anemia, which may influence treatment decisions and management. 

Pregnancy / Lactation

Pregnancy consideration: FDA pregnancy category: D 

Lactation: N/A  

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 
• <b>Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 
• Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.   
• Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits. 
• Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women. 
• Category N: There is no data available for the drug under this category. 

Pharmacology

Pharmacology: 

omacetaxine is a protein synthesis inhibitor with antineoplastic activity. It belongs to protein synthesis inhibitors and is derived from the cephalotaxus tree. omacetaxine exerts its pharmacological effects through multiple mechanisms.

It inhibits protein synthesis by binding on the A-site cleft of the ribosome, thereby disrupting the elongation phase of protein synthesis. It specifically targets the synthesis of short-lived oncoproteins which are overexpressed in certain types of cancer cells, including chronic myeloid leukemia (CML).  

Pharmacodynamics: 

• Protein Synthesis Inhibition: Omacetaxine inhibits protein synthesis by binding to the A-site cleft of the ribosome, disrupting the elongation phase of protein synthesis. This inhibition selectively affects the synthesis of short-lived oncoproteins that are overexpressed in cancer cells. 
• Apoptosis Induction: omacetaxine promotes apoptosis, or programmed cell death, in cancer cells. It activates pro-apoptotic pathways and inhibits anti-apoptotic signalling, leading to the death of cancer cells. 
• Inhibition of Oncogenic Signalling: omacetaxine interferes with signalling pathways that promote cell growth and survival in cancer cells. It can inhibit the activity of certain tyrosine kinases and downstream signalling molecules, disrupting the signalling cascades that contribute to cancer cell proliferation. 
• Cytotoxic Effects: omacetaxine exhibits direct cytotoxic effects on cancer cells. It can destroy the integrity of the cell membrane, induce DNA damage, and interfere with cellular processes essential for cancer cell survival and proliferation. 
• Anti-angiogenic Activity: omacetaxine has been shown to possess anti-angiogenic properties, inhibiting the formation of new blood vessels that are necessary for tumor growth and metastasis.

Pharmacokinetics: 

Absorption 

omacetaxine is administered through subcutaneous injection. After injection, it is rapidly absorbed into the bloodstream. 

Distribution 

omacetaxine has a large volume of distribution, indicating that it distributes extensively into tissues. It has been found to distribute primarily in the plasma and extracellular fluid compartments. 

Metabolism 

omacetaxine undergoes hepatic metabolism primarily by the enzyme CYP3A4. It is metabolized into several active and inactive metabolites. 

Elimination and excretion 

omacetaxine and its metabolites are eliminated primarily through the feces. Renal excretion plays a minor role in the elimination of omacetaxine. 

Adminstartion

Administration: 

• Injection Site: omacetaxine is typically injected into the subcutaneous tissue. Common injection sites include the upper arm, thigh, or abdomen. 
• Injection Technique: The injection should be given using a sterile technique. The injection site skin should be cleansed with an alcohol swab before the injection. A suitable needle and syringe should be used for the injection. 
• Dosage and Schedule: The specific dosage and schedule of omacetaxine may vary depending on the individual patient’s condition and response to treatment.  
• Rotation of Injection Sites: To minimize discomfort and reduce the risk of injection site reactions, it is recommended to rotate the injection sites with each dose. This helps to prevent tissue irritation or damage at a single site. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: omacetaxine 

Pronounced: (oh-muh-SEH-tuh-zeen)  

Why do we use omacetaxine? 

• Chronic Myeloid Leukemia (CML): omacetaxine is indicated for the treatment of adult patients with CML who are not respond to, or are intolerant of, at least two tyrosine kinase inhibitors (TKIs). It is specifically used in patients with CML in the chronic phase, accelerated phase, or myeloid blast phase. 
• CML with T315I Mutation: omacetaxine is particularly effective in treating CML patients with a specific genetic mutation known as the T315I mutation. This mutation is associated with resistance to other TKIs, and omacetaxine can be used as an alternative therapy in these cases.