Safety profile
Safety was evaluated across 3 clinical trials
Safety data were drawn from 163 adult patients with TKI-resistant and/or -intolerant chronic phase or accelerated phase CML
Adverse reactions, including those leading to discontinuation
Adverse reactions were reported for 99% of chronic phase patients and 100% of accelerated phase patients
18% of chronic phase patients and 33% of accelerated phase patients had adverse reactions leading to withdrawal. The following are those reported most frequently
- Chronic phase: pancytopenia, thrombocytopenia, and increased alanine aminotransferase (each 2%)
- Accelerated phase: leukocytosis (6%) and thrombocytopenia (4%)
Serious adverse reactions were reported for 51% of chronic phase patients and 60% of accelerated phase patients. The following are those reported for at least 5% of patients
- Chronic phase: bone marrow failure and thrombocytopenia (each 10%), infections (8%), and febrile neutropenia (6%)
- Accelerated phase: febrile neutropenia (18%), infections (11%), thrombocytopenia (9%), anemia (7%), and diarrhea (6%)
Incidence of adverse reactions
*Safety population included trials 202, 203, and 04.2. Adverse reactions occurred in the period between the first dose and 30 days after the last dose.1
†Infection includes bacterial, viral, fungal, and non-specified.
‡Includes infusion related reaction, injection site erythema, injection site hematoma, injection site hemorrhage, injection site hypersensitivity, injection site induration, injection site inflammation, injection site irritation, injection site mass, injection site edema, injection site pruritus, injection site rash, and injection site reaction.
†Infection includes bacterial, viral, fungal, and non-specified.
‡Includes infusion related reaction, injection site erythema, injection site hematoma, injection site hemorrhage, injection site hypersensitivity, injection site induration, injection site inflammation, injection site irritation, injection site mass, injection site edema, injection site pruritus, injection site rash, and injection site reaction.
Incidence of lab abnormalities
Indication
- SYNRIBO® (omacetaxine mepesuccinate) for injection, for subcutaneous use, is indicated for the treatment of adult patients with chronic or accelerated phase chronic myeloid leukemia (CML) with resistance and/or intolerance to two or more tyrosine kinase inhibitors (TKI)
Important Safety Information
Warnings and Precautions
- Myelosuppression: Patients with chronic phase and accelerated phase CML who used SYNRIBO experienced severe and fatal myelosuppression including thrombocytopenia, neutropenia, and anemia. 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. Monitor complete blood counts weekly during induction and initial maintenance cycles and every two weeks during later maintenance cycles, as clinically indicated
- Bleeding: SYNRIBO causes severe thrombocytopenia which increases the risk of hemorrhage. Fatalities from cerebral hemorrhage have occurred. Severe, non-fatal gastrointestinal hemorrhages have also occurred. Monitor platelet counts as part of the complete blood count (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
- Hyperglycemia: SYNRIBO can induce glucose intolerance. Monitor blood glucose levels frequently, especially in patients with diabetes or risk factors for diabetes. Avoid SYNRIBO in patients with poorly controlled diabetes mellitus until good glycemic control has been established
- Embryo-Fetal Toxicity: Based on findings from animal reproduction studies and the drug’s mechanism of action, SYNRIBO can cause fetal harm when administered to a pregnant woman. Conduct pregnancy testing prior to initiating treatment and advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use an effective method of contraception during treatment with SYNRIBO and for 6 months after the final dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with SYNRIBO and for 3 months after the final dose. SYNRIBO may impair male fertility.
- Lactation: Advise patients that breastfeeding is not recommended during treatment with SYNRIBO, and for at least 2 week after the final dose.
Adverse Reactions
- Serious adverse reactions (frequency ≥5%) in chronic phase patients: bone marrow failure, thrombocytopenia, febrile neutropenia, and infections
- Serious adverse reactions (frequency ≥5%) in accelerated phase patients: febrile neutropenia, thrombocytopenia, anemia, diarrhea, and infections
- Most common adverse reactions (frequency ≥20%) in chronic and accelerated phase patients: thrombocytopenia, anemia, neutropenia, diarrhea, nausea, fatigue, asthenia, injection site reaction, pyrexia, infection, and lymphopenia