ANC) less than 0.5 x 109/L) or Grade 3 thrombocytopenia (platelet counts less than 50 x 109/L) during a cycle, delay starting the next cycle until ANC is greater than or equal to 1.0 x 109/L and platelet count is greater than or equal to 50 x 109/L. Also, for the next cycle, reduce the number of dosing days by 2 days (e.g. to 12 or 5 days).
Non-hematologic Toxicity:
Manage other clinically significant non-hematologic toxicity symptomatically. Interrupt and/or delay SYNRIBO until toxicity is resolved.
2.4 Preparation and Administration Precautions
SYNRIBO should be prepared in a healthcare facility and administered by a healthcare professional. Omacetaxine mepesuccinate is an antineoplastic product. Follow special handling and disposal procedures.
Reconstitute SYNRIBO with one mL of 0.9% Sodium Chloride Injection, USP, prior to subcutaneous injection. After addition of the diluent, gently swirl until a clear solution is obtained. The lyophilized powder should be completely dissolved in less than one minute. The resulting solution will contain 3.5 mg/mL SYNRIBO.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.
Avoid contact with the skin. If SYNRIBO comes into contact with skin, immediately and thoroughly wash affected area with soap and water.
Use SYNRIBO within 12 hours of reconstitution when stored at room temperature and within 24 hours of reconstitution if stored at 2°C to 8 °C (36oF to 46oF). Protect reconstituted solution from light. After administration, any unused solution should be discarded properly1.
3 DOSAGE FORMS AND STRENGTHS
SYNRIBO for Injection contains 3.5 mg omacetaxine mepesuccinate; as a sterile, preservative-free, white to off-white lyophilized powder in a single-use vial.
4 CONTRAINDICATIONS
None.
5 WARNINGS AND PRECAUTIONS
5.1 Myelosuppression
In uncontrolled trials with SYNRIBO, patients with chronic phase and accelerated phase CML experienced NCI CTC (version 3.0) Grade 3 or 4 thrombocytopenia (85%, 88%), neutropenia (81%, 71%), and anemia (62%, 80%), respectively. Fatalities related to myelosuppression occurred in 3% of patients in the safety population (N=163). 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. In clinical trials myelosuppression was generally reversible and usually managed by delaying next cycle and/or reducing days of treatment with SYNRIBO. [see Dosage and Administration (2.3) andAdverse Reactions (6.1)]
5.2 Bleeding
SYNRIBO causes severe thrombocytopenia which increases the risk of hemorrhage. In clinical trials with CP and AP CML patients, a high incidence of Grade 3 and 4 thrombocytopenia (85% and 88%, respectively) was observed. Fatalities from cerebral hemorrhage occurred in 2% of patients treated with SYNRIBO in the safety population. Severe, non-fatal, gastrointestinal hemorrhages occurred in 2% of patients in the same population. Most bleeding events were associated with severe thrombocytopenia.
Monitor platelet counts as part
