Chronic myeloid leukemia (CML), chronic or accelerated phase: SubQ:
Induction: 1.25 mg/m2 twice daily for 14 consecutive days of a 28-day treatment cycle; continue until hematologic response is achieved
Maintenance: 1.25 mg/m2 twice daily for 7 consecutive days of a 28-day treatment cycle; continue until no longer achieving clinical treatment benefit
Missed doses: If a dose is missed, skip that dose and resume with the next regularly scheduled dose. Do not administer 2 doses at the same time to make up for a missed dose.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied). Based on the minimal amount of unchanged drug excreted in the urine, dosage adjustment is not likely necessary (Nemunaitis 2013).
There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).
Refer to adult dosing.
Hematologic toxicity: May delay treatment cycles and/or reduce the number of treatment days during a cycle for hematologic toxicities.
Neutropenia grade 4 (ANC <500/mm3) or thrombocytopenia ≥ grade 3 (platelets <50,000/mm3) during a cycle: Delay the start of the next cycle until ANC ≥1000/mm3 and platelets ≥50,000/mm3 AND reduce the number of treatment days by 2 days (eg, reduce from 14 days to 12 days or reduce from 7 days to 5 days)
Nonhematologic toxicity: Manage symptomatically; interrupt and/or delay treatment until toxicity resolves.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Subcutaneous, as mepesuccinate [preservative free]:
Synribo: 3.5 mg (1 ea)
No
An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/203585s007lbl.pdf#page=16, must be dispensed with this medication.
SubQ: Administer subcutaneously at approximately 12 hour intervals. If home administration is to occur, advise patient on proper handling, storage conditions, administration, disposal, and clean-up of accidental spillage; ensure that the patient or patient’s caregiver is an appropriate candidate for home administration. Avoid skin and eye contact; wear protective eyewear and gloves during handling and administration.
Hazardous agent (NIOSH 2016 [group 1]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).
Chronic myeloid leukemia: Treatment of chronic or accelerated phase chronic myeloid leukemia (CML) in adult patients resistant and/or intolerant to 2 or more tyrosine kinase inhibitors
This medication is in a class the Institute for Safe Medical Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Cardiovascular: Peripheral edema (16%)
Central nervous system: Fatigue (29% to 31%), headache (13% to 20%), chills (13%), insomnia (12%)
Dermatologic: Alopecia (15%), skin rash (11%)
Endocrine & metabolic: Increased uric acid (grades 3/4: 56% to 57%), hyperglycemia (grades 3/4: 10% to 15%; hyperosmolar nonketotic hyperglycemia <1%)
Gastrointestinal: Diarrhea (35% to 41%), nausea (29% to 35%), abdominal pain (16% to 23%), vomiting (12% to 15%), constipation (14%), anorexia (10% to 13%)
Hematologic & oncologic: Thrombocytopenia (58% to 76%; grades 3/4: 49% to 88%), neutropenia (20% to 53%; grades 3/4: 18% to 81%), anemia (51% to 61%; grades 3/4: 36% to 80%), leukocyte disorder (decreased: grades 3/4: 61% to 72%), febrile neutropenia (10% to 20%; grades 3/4: 10% to 16%), lymphocytopenia (17%; grades 3/4: 16%)
Infection: Infection (46% to 56%; grades 3/4: 11% to 20%)
Local: Injection site reaction (22% to 35%; includes edema, erythema, hematoma, hemorrhage, hypersensitivity, induration, inflammation, infusion related reaction, irritation, mass, pruritus, rash)
Neuromuscular & skeletal: Weakness (23% to 24%), arthralgia (19%), limb pain (11% to 13%), back pain (12%), myalgia (11%)
Renal: Increased serum creatinine (grades 3/4: 9% to 16%)
Respiratory: Epistaxis (11% to 17%), cough (≤16%), dyspnea (11%)
Miscellaneous: Fever (25% to 29%)
1% to 10%:
Cardiovascular: Acute coronary syndrome, angina pectoris, bradycardia, cardiac arrhythmia, chest pain, edema, hypertension, hypotension, palpitations, tachycardia, ventricular premature contractions
Central nervous system: Agitation, anxiety, cerebral hemorrhage, confusion, depression, dizziness, hyperthermia, hypoesthesia, lethargy, malaise, mental status changes, mouth pain, myasthenia, pain, paresthesia, sciatica, seizure, voice disorder
Dermatologic: Burning sensation of skin, dermal ulcer, desquamation, erythema, hyperhidrosis, hyperpigmentation, night sweats, pruritus, skin lesion, xeroderma
Endocrine & metabolic: Decreased serum glucose (grades 3/4: 6% to 8%), dehydration, diabetes mellitus, gout, hot flash
Gastrointestinal: Abdominal distention, anal fissure, aphthous stomatitis, decreased appetite, dysgeusia, dyspepsia, dysphagia, gastritis, gastroesophageal reflux disease, gastrointestinal hemorrhage, gingival hemorrhage, gingival pain, gingivitis, hemorrhoids, melena, mucosal inflammation, oral mucosa ulcer, stomatitis, xerostomia
Genitourinary: Dysuria
Hematologic & oncologic: Bone marrow failure (10%; grades 3/4: 10%), bruise, hematoma, hemorrhage (ear), oral hemorrhage, petechia, purpura
Hepatic: Increased serum bilirubin (grades 3/4: 6% to 9%), increased serum ALT (grades 3/4: 2% to 6%)
Hypersensitivity: Hypersensitivity reaction, transfusion reaction
Neuromuscular & skeletal: Muscle spasm, musculoskeletal chest pain, musculoskeletal pain (or discomfort), ostealgia, stiffness, tremor
Ophthalmic: Blurred vision, cataract, conjunctival hemorrhage, conjunctivitis, diplopia, eyelid edema, eye pain, increased lacrimation, xerophthalmia
Otic: Otalgia, tinnitus
Respiratory: Flu-like symptoms, hemoptysis, nasal congestion, pharyngolaryngeal pain, rales, rhinorrhea, sinus congestion
There are no contraindications listed in the manufacturer’s labeling.
Concerns related to adverse effects:
• Bone marrow suppression: Grade 3/4 neutropenia, thrombocytopenia and anemia commonly occur; generally reversible, although may require treatment delay and/or a reduction in the number of treatment days with future cycles. Myelosuppression may rarely be fatal. Monitor blood counts (in induction and maintenance cycles). Neutropenia may increase the risk for infection. Thrombocytopenia may increase the risk of bleeding; cerebrovascular hemorrhages have been reported (some fatal); gastrointestinal hemorrhages have occurred. Due to the increased risk of bleeding, avoid the use of anticoagulants, aspirin, and NSAIDs when the platelet count is <50,000/mm3.
• Glucose intolerance: Omacetaxine may induce glucose intolerance. Hyperglycemia (including grade 3 and 4 events) has been observed; hyperosmolar nonketotic hyperglycemia has been reported (case report). Monitor blood glucose 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 has been established.
Special populations:
• Elderly: Patients ≥65 years of age are more likely to experience toxicity, especially hematologic toxicity.
Substrate of P-glycoprotein/ABCB1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Anticoagulants: May enhance the adverse/toxic effect of Omacetaxine. Specifically, the risk for bleeding-related events may be increased. Management: Avoid concurrent use of anticoagulants with omacetaxine in patients with a platelet count of less than 50,000/uL. Risk X: Avoid combination
Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Aspirin: May enhance the adverse/toxic effect of Omacetaxine. Specifically, the risk for bleeding-related events may be increased. Management: Avoid concurrent use of aspirin with omacetaxine in patients with a platelet count of less than 50,000/uL. Risk X: Avoid combination
Baricitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination
BCG Products: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination
Brincidofovir: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy
Cladribine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination
Coccidioides immitis Skin Test: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing these oncologic agents several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider therapy modification
COVID-19 Vaccine (Adenovirus Vector): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: In the US, after receipt of the single dose COVID-19 adenovirus vector vaccine (Janssen), administer an additional 2nd dose using an mRNA COVID-19 vaccine, at least 28 days after the primary vaccine dose, in patients taking immunosuppressive therapies. Risk D: Consider therapy modification
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy
COVID-19 Vaccine (mRNA): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: Consider administration of a 3rd dose of COVID-19 vaccine, at least 28 days after completion of the primary 2-dose series, in patients 5 years of age and older taking immunosuppressive therapies. Risk D: Consider therapy modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination
Denosumab: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and immunosuppressants. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider therapy modification
Echinacea: May diminish the therapeutic effect of Immunosuppressants (Miscellaneous Oncologic Agents). Management: Consider avoiding echinacea in patients receiving therapeutic immunosuppressants, such as the oncology agents listed in this monograph. If coadministered, monitor for reduced efficacy of the immunosuppressant during concomitant use. Risk D: Consider therapy modification
Inebilizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy
Influenza Virus Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating immunosuppressants if possible. If vaccination occurs less than 2 weeks prior to or during therapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider therapy modification
Leflunomide: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents. Risk D: Consider therapy modification
Natalizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination
Nonsteroidal Anti-Inflammatory Agents: May enhance the adverse/toxic effect of Omacetaxine. Specifically, the risk for bleeding-related events may be increased. Risk C: Monitor therapy
Ocrelizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy
Ofatumumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy
Pidotimod: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy
Pimecrolimus: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Pneumococcal Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination
Polymethylmethacrylate: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the potential for allergic or hypersensitivity reactions to Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modification
Rabies Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If post-exposure rabies vaccination is required during immunosuppressant therapy, administer a 5th dose of vaccine and check for rabies antibodies. Risk D: Consider therapy modification
Rubella- or Varicella-Containing Live Vaccines: May enhance the adverse/toxic effect of Immunosuppressants (Miscellaneous Oncologic Agents). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination
Ruxolitinib (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination
Sipuleucel-T: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification
Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk C: Monitor therapy
Tacrolimus (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination
Talimogene Laherparepvec: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination
Tertomotide: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination
Tofacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tofacitinib. Risk X: Avoid combination
Typhoid Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination
Upadacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination
Vaccines (Inactivated): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Vaccines (Inactivated). Management: Give inactivated vaccines at least 2 weeks prior to initiation of immunosuppressants when possible. Patients vaccinated less than 14 days before initiating or during therapy should be revaccinated at least 3 after therapy is complete. Risk D: Consider therapy modification
Vaccines (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination
Yellow Fever Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination
Evaluate pregnancy status prior to use in females of reproductive potential. Females of reproductive potential should use effective contraception during therapy and for 6 months after the last omacetaxine dose. Males with female partners of reproductive potential should use effective contraception during therapy and for 3 months after the last dose of omacetaxine.
Based on the mechanism of action and data from animal reproduction studies, omacetaxine may cause fetal harm if administered during pregnancy.
It is not known if omacetaxine is present in breast milk.
Due to the potential for serious adverse reactions in the breastfed infant, the manufacturer does not recommend breastfeeding during therapy and for 2 weeks after the last dose of omacetaxine.
CBC with differential and platelets (weekly during induction and initial maintenance cycles, then every 2 weeks or as clinically indicated after initial maintenance cycles); blood glucose (frequently). Evaluate pregnancy status prior to use in females of reproductive potential. Monitor for signs/symptoms of infection and signs of bleeding.
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Omacetaxine is a reversible protein synthesis inhibitor which binds to the A-site cleft of the ribosomal subunit to interfere with chain elongation and inhibit protein synthesis. It acts independently of BCR-ABL1 kinase-binding activity, and has demonstrated activity against tyrosine kinase inhibitor-resistant BCR-ABL mutations.
Onset:
Chronic phase CML: Mean time to major cytogenetic response: 3.5 months
Accelerated phase CML: Mean time to response: 2.3 months
Duration:
Chronic phase CML: Median duration of major cytogenetic response: 12.5 months
Accelerated phase CML: Median duration of major hematologic response: 4.7 months
Absorption: SubQ: Rapid (Nemunaitis 2013)
Distribution: Vdss: 141 ± 93.4 L
Protein binding: ≤50%
Metabolism: Hydrolyzed by plasma esterases to 4’-DMHHT; minimal hepatic metabolism
Half-life elimination: 14.6 hours
Time to peak: SubQ: ~30 minutes
Excretion: Urine (~37); feces (~44%)
Solution (reconstituted) (Synribo Subcutaneous)
3.5 mg (per each): $1,459.80
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