omacetaxine

omacetaxine

(oh-ma-sat-axeen) ,

Synribo

(trade name)

Classification

Therapeutic: antineoplastics
Pharmacologic: protein synthesis inhibitors
Pregnancy Category: D

Indications

Treatment of chronic or accelerated phase chronic myeloid leukemia (CML) that has become resistant or intolerant to at least 2 tyrosine kinase inhibitors.

Action

Inhibits protein synthesis.

Therapeutic effects

Improved hematologic parameters and survival in CML.

Pharmacokinetics

Absorption: Absorbed following subcutaneous administration.
Distribution: Unknown.
Metabolism and Excretion: Metabolized by enzymes in plasma; not metabolized by the liver; <15 % excreted unchanged in urine.
Half-life: 6 hr.

Time/action profile (response in Chronic Phase CML)

ROUTEONSETPEAKDURATION
Subcut 3.5 mounknown12.5 mo

Time/action profile (response in Accelerated Phase CML)

ROUTEONSETPEAKDURATION
Subcut 2.3 mounknown 4.7 mo

Contraindications/Precautions

Contraindicated in: Obstetric / Lactation: Pregnancy or lactation.
Use Cautiously in: Geriatric: ↑ risk of hematologic toxicity in patients >65 yr; Pediatric: Safe and effective use in children has not been established.

Adverse Reactions/Side Effects

Central nervous system

  • fatigue (most frequent)
  • headache (most frequent)
  • insomnia (most frequent)
  • anxiety
  • depression
  • mental status changes

Ear, Eye, Nose, Throat

  • epistaxis (most frequent)
  • ear pain
  • tinnitus

Respiratory

  • cough (most frequent)

Cardiovascular

  • angina
  • arrhythmias
  • peripheral edema

Gastrointestinal

  • diarrhea (most frequent)
  • anorexia
  • mucusitis
  • nausea
  • constipation
  • stomatitis
  • ↑ transaminases
  • upper abdominal pain
  • vomiting

Dermatologic

  • alopecia (most frequent)
  • rash (most frequent)
  • hyperpigmentation
  • pruritus

Endocrinologic

  • hyperglycemia

Hematologic

  • anemia
  • Neutropenia
  • thrombocytopenia
  • lymphopenia (most frequent)

Local

  • injection site reactions (most frequent)

Musculoskeletal

  • athralgia
  • myalgia
  • musculoskeletal pain

Metabolic

  • infection (life-threatening)
  • fever (most frequent)

Miscellaneous

  • hypersensitivity reactions
  • night sweats

Interactions

Drug-Drug interaction

None noted.

Route/Dosage

Subcutaneous (Adults) Induction—1.25 mg/m2twice daily for 14 consecutive days of a 28-day cycle; maintenance—1.25 mg/m2twice daily for 7 consecutive days of a 28-day cycle. Modifications required for toxicity, treatment should be continued as long as benefit is noted.

Availability

Lyophilized powder for subcutaneous injection (requires reconstitution): 3.5 mg/single-use vial

Nursing implications

Nursing assessment

  • Monitor for bone marrow depression. Assess for bleeding (bleeding gums; bruising; petechiae; blood in stools, urine, and emesis; confusion, slurred speech, altered vision) and avoid IM injections and taking rectal temperatures if platelet count is low. Apply pressure to venipuncture sites for 10 min. Assess for signs of infection during neutropenia. Anemia may occur. Monitor for increased fatigue, dyspnea, and orthostatic hypotension.
  • Assess for non-hematologic toxicities. Manage symptomatically and interrupt or delay therapy until toxicity is resolved.
  • Lab Test Considerations: Monitor CBC and platelet count weekly during induction and maintenance cycles. After initial maintenance cycles, monitor CBC and platelet count every 2 wks or as clinically indicated. If Grade 4 neutropenia occurs (ANC <0.5 × 109/L) or Grade 3 thrombocytopenia (platelet count <50 × 109/L) during a cycle, delay starting next cycle until ANC is ≥1.0 × 109/L and platelet count is ≥50 × 109/L. For next cycle, also reduce number of days by 2 days (e.g. to 12 or 5 days).
    • Monitor blood glucose levels frequently, especially in patients with diabetes or risk factors for diabetes. Avoid use in patients with poorly controlled diabetes mellitus until glycemic control is established.
    • May cause ↓ hemoglobin, leukocytes, neutrophils, and platelets. May cause ↑ ALT, bilirubin, creatinine, glucose, and uric acid.

Potential Nursing Diagnoses

Risk for infection (Adverse Reactions)

Implementation

  • Reconstitute wiith 1 mL of 0.9% NaCl prior to use. Swirl gently until solution is clear; usually <1 minute. Do not administer solutions that are discolored or contain particulate matter. Avoid contact with skin; immediately wash affected area with soap and water. Protect from light. Use solution within 12 hr at room temperature or 24 hr if refrigerated. Discard unused solution.
  • Subcutaneous: Inject twice daily.

Patient/Family Teaching

  • Instruct patient to notify health care professional promptly if fever; chills; cough; hoarseness; sore throat; signs of infection; lower back or side pain; painful or difficult urination; bleeding gums; bruising; petechiae; blood in stools, urine, or emesis; increased fatigue; dyspnea occurs. Caution patient to avoid crowds and persons with known infections. Instruct patient to use soft toothbrush and electric razor and to avoid falls. Caution patient not to drink alcoholic beverages or take medication containing aspirin or NSAIDs; may precipitate gastric bleeding.
  • May cause fatigue; caution patient to avoid driving and other activities requiring alertness until response to medication is known.
  • Advise patients with diabetes to monitor blood glucose levels closely; may cause hyperglycemia.
  • May cause rash, nausea, diarrhea, abdominal pain, constipation, and vomiting. Advise patient to notify health care professional if symptoms persist or if rash is severe.
  • Discuss with patient the possibility of hair loss. Explore methods of coping. May also cause darkening of skin and fingernails.
  • Advise female patient to that omacetaxine is teratogenic. Avoid pregnancy and breastfeeding during therapy.

Evaluation/Desired Outcomes

  • Improved hematologic parameters in CML.
Mentioned in ?
References in periodicals archive ?
Association of differential gene expression with imatinib mesylate and omacetaxine mepesuccinate toxicity in lymphoblastoid cell lines.
A cautionary tale is exemplified with the pharmaceutical company ChemGeneX and its drug omacetaxine for T315I mutant chronic myelogenous leukemia.
Generic Name Annual Cost Ponatinib $138,000 Bosutinib $118,000 Omacetaxine Over $100,000
Other new antineoplastics are the antiandrogen enzalutamide (Xtandi; prostate cancer but could be used for other cancers), the proteasome inhibitor carfilzomib (Kyprolis; multiple myeloma), and the protein synthesis inhibitor omacetaxine (Synribo; leukemia).
The Oncologic Drugs Advisory Committee agreed with the agency that a validated test for the Bcr-Abl T3151 mutation is required before omacetaxine mepesuccinate (Omapro)--a drug targeting that mutation--can be considered for approval.
In many patients with a mutation that makes the leukemia cells resistant to other drugs, omacetaxine stopped the cancer, Jorge Cortes of the University of Texas M.
New Clinical Data Presented at EHA Suggests That Omacetaxine May Provide a Useful Treatment Option for CML Patients Resistant to Multiple TKI Therapies
On the other hand, the FDA's refusal to clear omacetaxine for targeted T315I mutation-positive chronic myelogenous leukemia was based on a failure to show interlaboratory concordance, which can lead to misclassification of patients and potential risk.
In terms of therapies in development for CML, Ariad's ponatinib and Teva Pharmaceutical's (formally Cephalon) omacetaxine are perceived as having efficacy in T315I mutations.
Subcutaneous Omacetaxine (OM) Treatment of Chronic Phase (CP) Chronic Myeloid Leukemia (CML) Patients Following Multiple Tyrosine Kinase Inhibitor (TKI) Failure".
Food and Drug Administration in H2 2011 for omacetaxine in CML patients who have failed two or more currently approved tyrosine kinase inhibitors.
Omacetaxine has been granted Orphan Drug designations by the U.