protein synthesis inhibitors
Treatment of chronic or accelerated phase chronic myeloid leukemia (CML) that has become resistant or intolerant to at least 2 tyrosine kinase inhibitors.
Inhibits protein synthesis.
Improved hematologic parameters and survival in CML.
Absorption: Absorbed following subcutaneous administration.
Distribution: Widely distributed.
Metabolism and Excretion: Metabolized by enzymes in plasma; not metabolized by the liver; 37% excreted unchanged in urine.
Half-life: 6 hr.
TIME/ACTION PROFILE (response in Chronic Phase CML)
|Subcut||3.5 mo||unknown||12.5 mo|
TIME/ACTION PROFILE (response in Accelerated Phase CML)
|Subcut||2.3 mo||unknown||4.7 mo|
- OB: Pregnancy (may cause fetal harm)
- Lactation: Lactation.
Use Cautiously in:
- Rep: Women of reproductive potential and men with female partners of reproductive potential
- Pedi: Safety and effectiveness not established in children
- Geri: ↑ risk of hematologic toxicity in older adults.
Adverse Reactions/Side Effects
CNS: fatigue, headache, insomnia, anxiety, depression, mental status changes
CV: angina, arrhythmias, peripheral edema
Derm: alopecia, rash, hyperpigmentation, pruritus
EENT: epistaxis, ear pain, tinnitus
GI: diarrhea, anorexia, mucositis, nausea, constipation, stomatitis, ↑ liver function tests, upper abdominal pain, vomiting
GU: ↓ fertility (males)
Hemat: ANEMIA, NEUTROPENIA, THROMBOCYTOPENIA, lymphopenia
Local: injection site reactions
MS: arthralgia, myalgia, musculoskeletal pain
Metabolic: INFECTION, fever
Misc: hypersensitivity reactions, night sweats
* CAPITALS indicate life-threatening.
Underline indicate most frequent.
Subcut (Adults): Induction– 1.25 mg/m2 twice daily for 14 consecutive days of a 28-day cycle; maintenance– 1.25 mg/m2 twice daily for 7 consecutive days of a 28-day cycle. Modifications required for toxicity, treatment should be continued as long as benefit is noted.
Lyophilized powder for injection: 3.5 mg/vial
- 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:
Verify negative pregnancy test before starting therapy.
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, serum creatinine, glucose, and uric acid.
Reconstitution: Reconstitute with 1 mL of 0.9% NaCl prior to use. Swirl gently until solution is clear; usually <1 minute. Concentration: 3.5 mg/mL.Solution is clear and colorless; do not administer solutions that are cloudy, 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 6 days if refrigerated. Discard unused solution.
- Solution should be prepared in a biologic cabinet. Wear gloves, gown, and protective eyewear while handling medication. Discard IV equipment in specially designated containers.
- Subcut Inject twice daily. Avoid areas that are tender, red, bruised, hard, or that have scars or stretch marks.
- 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.
- Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
- Discuss with patient the possibility of hair loss. Explore methods of coping. May also cause darkening of skin and fingernails.
- Rep: May cause fetal harm. Advise females of reproductive potential to use effective contraception during and for 6 months after last dose and to avoid breastfeeding during and for 2 wks after last dose. Advise males with female partners of reproductive potential to use effective contraception during and for 3 months after last dose. May impair male fertility.
- Home Care Issues: If patient is to administer omacetaxine at home, teach patient proper technique for injection, storage, and disposal of equipment. Provide solution prepared by health care professional, protective eye wear, and sharps container. If accidental spillage occurs, continue to use protective eyewear and gloves, wipe spilled liquid with the absorbent pad, and wash the area with water and soap. Then, place the pad and gloves into the biohazard container and wash hands thoroughly. Return the biohazard container to the clinic or pharmacy for final disposal. Advise patient to read Medication Guide before starting therapy and with each Rx refill in case of changes.
Improved hematologic parameters in CML.