Omacetaxine (Synribo) belongs to the drug class of plant alkaloids that has BCR-ABL1 kinase-binding activity & is active against tyrosine kinase inhibitor-resistant BCR-ABL mutations.

Omacetaxine (Synribo) Uses:

• Chronic myeloid leukemia:

  •  In adult patients resistant, treatment of chronic or accelerated phase chronic myeloid leukemia (CML) & intolerant to two or more tyrosine kinase inhibitors

Omacetaxine (Synribo) dose in Adults

Omacetaxine (Synribo) dose in the treatment of Chronic myeloid leukemia (CML), chronic or accelerated phase: SubQ:

• Induction:

  • 1.25 mg/m twice a day for 14 consecutive days of a 28-day treatment cycle.
  • Continue until a hematologic response is achieved

• Maintenance:

  • 1.25 mg/m² twice a day 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.
  • To make up for a missed dose, do not administer 2 doses at the same time.

Use in Children:

Not indicated.

Pregnancy Risk Factor D

• If administered during pregnancy, Omacetaxine can cause harm to fetuses based on its mechanism of action as well as data from animal reproduction studies.
• Women with reproductive potential should not have children during therapy.

Omacetaxine use during breastfeeding:

• It is unknown if breast milk contains omacetaxine or not.
• Consider the impact of breastfeeding on the decision to stop omacetaxine treatment or discontinue it altogether. There are potential adverse reactions that could occur in breastfed infants.

Omacetaxine (Synribo) Dose in Kidney Disease:

• In the manufacturer’s labeling, there are no dosage adjustments provided  (has not been studied).
• Dosage adjustment is not likely necessary, based on the minimal amount of unchanged drug excreted in the urine.

Omacetaxine (Synribo) Dose in Liver Disease:

• Provided in the manufacturer’s labeling, there are no dosage adjustments  (has not been studied).

Common Side Effects of Omacetaxine (Synribo):

• Cardiovascular:

  • Peripheral Edema

• Central Nervous System:

  • Fatigue
  • Headache
  • Chills
  • Insomnia

• Dermatologic:

  • Alopecia
  • Skin Rash

• Endocrine & Metabolic:

  • Increased Uric Acid
  • Hyperglycemia

• Gastrointestinal:

  • Diarrhea
  • Nausea
  • Abdominal Pain
  • Vomiting
  • Constipation
  • Anorexia

• Hematologic & Oncologic:

  • Thrombocytopenia
  • Neutropenia
  • Anemia
  • Leukocyte Disorder
  • Febrile Neutropenia
  • Lymphocytopenia

• Infection:

  • Infection

• Local:

  • Injection Site Reaction Includes
    • Edema
    • Erythema
    • Hematoma
    • Hemorrhage
    • Hypersensitivity
    • Induration
    • Inflammation
    • Infusion Related Reaction
    • Irritation
    • Mass
    • Pruritus
    • Rash

• Neuromuscular & Skeletal:

  • Weakness
  • Arthralgia
  • Limb Pain
  • Back Pain
  • Myalgia

• Renal:

  • Increased Serum Creatinine

• Respiratory:

  • Epistaxis
  • Cough
  • Dyspnea

• Miscellaneous:

  • Fever

Less Common Side Effects Of Omacetaxine (Synribo):

• 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
  • 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
  • Bruise
  • Hematoma
  • Hemorrhage
  • Oral Hemorrhage
  • Petechia
  • Purpura

• Hepatic:

  • Increased Serum Bilirubin
  • Increased Serum ALT

• Hypersensitivity:

  • Hypersensitivity Reaction
  • Transfusion Reaction

• Neuromuscular & Skeletal:

  • Muscle Spasm
  • Musculoskeletal Chest Pain
  • Musculoskeletal Pain
  • 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

Contraindications to Omacetaxine (Synribo):

• There are no contraindications in the manufacturer's labeling.

Warnings and precautions

• Suppression of bone marrow

  • Anemia, grade 3/4 thrombocytopenia, and neutropenia are common.
  • Although generally reversible it may be necessary to delay treatment and decrease the number of days required for future cycles.
  • Rarely, myelosuppression can be fatal.
  • Induction and maintenance cycles, blood counts should be examined.
  • The risk of infection may be increased by neutropenia.
  • The risk of bleeding may be increased by thrombocytopenia.
  • Some fatalities have been reported from cerebrovascular hemorhages.
  • There have been cases of gastrointestinal hemorhages.
  • Anticoagulants, aspirin and NSAIDs should be avoided if the platelet count is 50,000/mm3. This increases the risk of bleeding.

• Glucose intolerance:

  • Omacetaxine may cause glucose intolerance.
  • It has been reported that hyperglycemia was a problem (including events of grade 3 and 4).
  • A case report has been filed about hyperosmolar, nonketotic hyperglycemia.
  • Patients with diabetes and those at risk for developing it should be examined frequently to determine their blood glucose levels.
  • Patients with diabetes that is not well controlled should be advised to stop using this product.
  • May begin after glycemic control is established.

Omacetaxine: Drug Interaction

Monitoring Parameters:

• 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).
• Signs/symptoms of infection.
• Signs of bleeding.

How to administer Omacetaxine (Synribo)?

SubQ:

• At approximately 12 hour intervals, administer subcutaneously.
• Advise patient on proper handling, storage conditions, administration, disposal, and clean-up of accidental spillage, if home administration is to occur.
• Make sure that the patient or patient’s caregiver is an appropriate candidate for home administration.
• Avoid skin and eye contact.
• During handling and administration, wear protective eyewear and gloves.

Mechanism of action of Omacetaxine (Synribo):

• Omacetaxine, a reversible inhibitor of protein synthesis, binds to A-site cleft in the ribosomal ribosomal to inhibit chain elongation and protein synthesis.
• It is independent of BCR–ABL1 kinase binding activity and has shown activity against tyrosine-kinase inhibitor resistant BCR–ABL mutations.

The onset of action:

• 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

Protein binding:

• ≤50 percent

Metabolism:

• Hydrolyzed by plasma esterases to 4’-DMHHT.
• Minimal hepatic metabolism.

Half-life elimination:

• 14.6 hours

Time to peak:

• SubQ: ~30 mins

Excretion:

• Urine (~37).
• Feces (~44 percent)

International Brands of Omacetaxine:

• Synribo
• Chuan Shan Ning
• Fu Er
• Gao Rui Te
• Hua Pu Le
• Jin Nuo Xing

Omacetaxine Brand Names in Pakistan:

No Brands Available in Pakistan.