Dosing and uses of Synribo (omacetaxine)
Adult dosage forms and strengths
lyophilized powder for injection
- 3.5mg/vial (3.5mg/mL following reconstitution)
Chronic Myeloid Leukemia
Indicated for treatment of chronic or accelerated phase chronic myeloid leukemia (CML) with resistance and/or intolerance to ≥2 tyrosine kinase inhibitors
Induction: 1.25 mg/m² SC BID for 14 consecutive days q28 days; repeat q28 days until hematologic response achieved
Maintenance: 1.25 mg/m² SC BID for 7 consecutive days q28 days; continue as long as clinically beneficiaL
Dosing Modifications
Nonhematologic toxicities: Manage symptomatically; may interrupt and/or delay treatment until toxicity resolved
Neutropenia or thrombocytopenia
- Dosage cycles may be delayed and/or the number of days during the cycle reduced for hematologic toxicities (eg, neutropenia, thrombocytopenia)
- Grade 4 neutropenia (AND < 0.5 x 10^9/L) or grade 3 thrombocytopenia (platelets < 50 x 10^9/L): Delay starting next cycle until ANC ≥1 X 10^9/L and platelets ≥50 x 10^9/L
- For next cycle, reduce number of dosing days by 2 days (eg, to 12 or 5 days)
Pediatric dosage forms and strengths
Safety and efficacy not established
Synribo (omacetaxine) adverse (side) effects
>10% (Chronic Phase CML)
Thrombocytopenia (74%)
Anemia (61%)
Neutropenia (50%)
Infections and infestations (46%)
Diarrhea (42%)
Injection site reactions (34%)
Nausea (32%)
Fatigue (26%)
Pyrexia (24%)
Asthenia (23%)
Arthralgia (19%)
Headache (19%)
Lymphopenia (17%)
Cough (16%)
Alopecia (15%)
Constipation (15%)
Epistaxis (15%)
Abdominal pain, upper (14%)
Pain in extremities (13%)
Peripheral edema (13%)
Vomiting (12%)
Back pain (11%)
Hyperglycemia, grade 4 (11%)
Bone marrow failure (10%)
Febrile neutropenia (10%)
Insomnia (10%)
Rash (10%)
>10% (Accelerated Phase CML)
Thrombocytopenia (56%)
Infections and infestations (56%)
Anemia (51%)
Diarrhea (35%)
Fatigue (31%)
Pyrexia (29%)
Nausea (27%)
Asthenia (24%)
Injection site reactions (22%)
Febrile neutropenia (20%)
Neutropenia (20%)
Cough (15%)
Vomiting (15%)
Abdominal pain (13%)
Anorexia (13%)
Chills (13%)
Headache (13%)
Dyspnea (11%)
Epistaxis (11%)
Pain in extremities (11%)
Warnings
Contraindications
None
Cautions
Monitor CBC panel for myelosuppression
Grade 3/4 neutropenia, thrombocytopenia and anemia commonly occur; avoid use of anticoagulants, aspirin, and NSAIDs when platelet count is <50,000/ mm³
Therapy may induce glucose intolerance; monitor glucose levels frequently, especially in patients with diabetes or with risk factors for diabetes; avoid use in patients with poorly controlled diabetes; may initiate after glycemic control established
Avoid pregnancy
Pregnancy and lactation
Pregnancy category: d
May cause serious embryo-fetal toxicity and death; women should avoid becoming pregnant
Lactation: Unknown whether distributed in breast milk
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Synribo (omacetaxine)
Mechanism of action
Inhibition of protein synthesis and is independent of direct Bcr-Abl binding; binds to the A-site cleft in the peptidyl-transferase center of the large ribosomal subunit from a strain of archaeabacteria
Absorption
Peak Plasma Time: 30 minutes
Distribution
Protein Bound: 50%
Vd: 141 ±93.4 L
Metabolism
Hydrolyzed to 4′-DMHHT via plasma esterases; little evidence of hepatic microsomal oxidative and/or esterase-mediated metabolism in vitro
Elimination
Half-life: 6 hr
Excretion: ≤15% unchanged in urine
Administration
Administration
Inject subcutaneously
Follow institutional guidelines for preparing, administering, and disposal of chemotherapy
Preparation
- Reconstitute with 1 mL of 0.9% NaCl
- After addition of the diluent, gently swirl until a clear solution obtained
- Lyophilized powder should be completely dissolved in <1 minute
- Resulting solution concentration is 3.5 mg/mL
- Does not contain antimicrobial preservatives
Home administration
Provide training on proper handling, storage conditions, administration, disposal, and clean-up of accidental spillage of the product
Ensure that patients receive the necessary supplies for home administration. at minimum these should include:
- Reconstituted omacetaxine with patient-specific dose in syringe with a capped needle for SC injection
- Protective eyewear
- Gloves
- An appropriate biohazard container
- Absorbent pad(s) for placement of administration materials and for accidental spillage
- Alcohol swabs
- Gauze pads
- Ice packs or cooler for transportation of reconstituted syringes
Storage
Reconstituted solution: Use within 12 hr when stored at room temperature and within 6 days if refrigerated between 2- 8 °C (36-46°F)
Protect reconstituted solution from light
