Treatment of adults with Philadelphia chromosome-negative (Ph-) acute lymphoblastic leukemia (ALL) in second or greater relapse or whose disease has progressed following 2 or more other therapies.
- Vincristine binds to tubulin, altering microtubule structure and function; also stabilizes spindle apparatus, triggering metaphase arrest and inhibition of mitosis.
- Liposome encapsulation delays and prolongs release of active drug.
Death of rapidly replicating cells, particularly malignant ones. Has immunosuppressive properties.
Absorption: Liposome encapsulation causes delayed release into circulation.
Metabolism and Excretion: Metabolized by the liver and eliminated in the feces via biliary excretion (69%), <8% eliminated in urine.
Half-life: Non-liposomal –10.5–37.5 hr.
TIME/ACTION PROFILE (median duration of remission)
- Demyelinating conditions including Charcot-Marie-Tooth syndrome
- Intrathecal administration (can be fatal)
- Concurrent use of strong inhibitors/inducers of the CYP3A4 enzyme system
- OB: Pregnancy (can cause fetal harm)
- Lactation: Should not be used in nursing mothers.
Use Cautiously in:
- Pre-existing severe neuropathy
- Female patients with child-bearing potential (contraception is necessary)
- Geri: Consider age-related decreases hepatic, renal, or cardiac function, concomitant disease or other drug therapies which may ↑ risk of adverse reactions
- Pedi: Safe and effective use in children <18 yr has not been established.
Adverse Reactions/Side Effects
CNS: fatigue, insomnia, mental starus changes, weakness
Resp: respiratory distress/failure
CV: CARDIAC ARREST, hypotension
GI: BOWEL OBSTRUCTION/PARALYTIC ILEUS, ↓ appetite, diarrhea, nausea, abdominal pain, constipation, hepatotoxicity
Hemat: BONE MARROW DEPRESSIONS
Local: tissue damage following extravasation
MS: muscular weakness
Neuro: peripheral neuropathy
Misc: TUMOR LYSIS SYNDROME, fever
* CAPITALS indicate life-threatening.
Underline indicate most frequent.
- May ↓ blood levels and effectiveness of phenytoin.
- Blood levels and the risk of toxicity may be ↑ by concurrent use of strong CYP3A4 inhibitors including atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, and voriconazole and should be avoided.
- Blood levels and effectiveness may be ↓ by concurrent use of strong CYP3A inducers including carbamazepine, dexamethasone, phenytoin, rifabutin, rifampin, rifapentine, and phenobarbital, and should be avoided.
- Blood levels and effects may be altered by concurrent use of potent P-gp inhibitors or inducers should be avoided.
Blood levels and effectiveness may be ↓ by St. John's wort, concurrent use should be avoided.
IV (Adults and Children) >18 yr) 2.25 mg/m2 intravenously every 7 days. Modifications required for peripheral neuropathy, hepatotoxicity, bone marrow depression or extreme fatigue.
Suspension for intravenous infusion only (prepared by pharmacy): 5 mg/31 mL (0.16 mg/mL) single-dose vial (included in kit are Sphingomyelin/Cholesterol Liposome Injection (103 mg/mL) and sodium Phosphate Injection (355 mg/25 mL)
- Monitor neurologic status before and during treatment. Assess for paresthesia (numbness, tingling, pain, burning sensation), loss of deep tendon reflexes (Achilles reflex is usually first involved), weakness (wrist drop or footdrop, gait disturbances), cranial nerve palsies (jaw pain, hoarseness, ptosis, visual changes), arthralgia, myalgia, muscle spasm, autonomic dysfunction (ileus, difficulty voiding, orthostatic hypotension, impaired sweating), and CNS dysfunction (decreased level of consciousness, agitation, hallucinations). Patients with pre-existing neuromuscular disorders may be at increased risk. May require dose modifications.
- Assess infusion site frequently for redness, irritation, or inflammation. If extravasation occurs, infusion must be stopped and restarted elsewhere to avoid damage to subcut tissue. Consider local treatment measures.
- Monitor for tumor lysis syndrome (abnormal heart beat, renal failure potentially requiring dialysis). Maintain adequate hydration. Treat symptomatically.
- May cause constipation leading to ileus and bowel obstruction. Institute prophylactic bowel regimen to minimize risk. Consider adequate dietary fiber intake, hydration, and routine use of stool softners. May add laxatives such as senna, bisacodyl, milk of magnesia, magnesium citrate and lactulose.
- Assess for fatigue; may require dose delay, reduction, or discontinuation of therapy.
Lab Test Considerations:
Monitor CBC prior to each dose of vincristine liposome. If Grade 3 or 4 neutropenia, thrombocytopenia, or anemia develop, consider dose modification or reduction along with supportive measures.
- Monitor hepatic function tests periodically during therapy. May cause ↑ AST and ALT. Mau require dose reduction or interruption.
- High Alert: Fatalities have occurred with chemotherapeutic agents. Before administering, clarify all ambiguous orders; double check single, daily, and course-of-therapy dose limits; have second practitioner independently double check original order, dose calculations, and infusion pump settings. Do not administer subcut, IM, or intrathecally (IT). IT administration is fatal.
- High Alert: Do not confuse vincristine liposome with vincristine.
- Solution should be prepared in a biologic cabinet. Wear gloves, gown, and mask while handling medication. Discard IV equipment in specially designated containers.
- Administer IV only; may be fatal if given by other routes.
- Dose modifications for patients experiencing peripheral neuropathy:
- If patient develops Grade 3 (severe symptoms; limiting self-care activities of daily living (ADL) or persistent Grade 2 (moderate symptoms; limiting instrumental ADL) peripheral neuropathy: Interrupt vincristine liposome. If peripheral neuropathy remains at Grade 3 or 4, discontinue vincristine liposome. If peripheral neuropathy recovers to Grade 1 or 2, reduce dose to 2 mg/m2.
- If patient has persistent Grade 2 peripheral neuropathy after first dose reduction to 2 mg/m2: Interrupt vincristine liposome for up to 7 days. If peripheral neuropathy ↑ to Grade 3 or 4, discontinue therapy. If peripheral neuropathy recovers to Grade 1, reduce dose to 1.825 mg/m2.
- If patient has persistent Grade 2 peripheral neuropathy after second dose reduction to 1.825 mg/m2: Interrupt vincristine liposome for up to 7 days. If peripheral neuropathy ↑ to Grade 3 or 4, discontinue therapy. If peripheral neuropathy recovers to Grade 1, reduce dose to 1.5 mg/m2.
- Intermittent Infusion: Each single dose vial contains 5 mg/31 mL vincristine sulfate. When diluted, final volume is 100 mL. Do not administer solutions that are discolored or contain precipitate. Do not use with in-line filters. Store kit in refrigerator; do not freeze.
- Rate:Infuse over 1 hr. Solution must be administered within 12 hr of initiation of preparation.
- Y-Site Incompatibility:
- Do not mix with other drugs.
- Instruct patient to read the Patient Information sheet prior to starting vincristine liposome and before each infusion in case of changes.
- Instruct patient to notify health care professional immediately if redness, swelling, burning, or pain at injection site occurs.
- May cause fatigue and mental impairment. Caution patient to avoid driving and other activities requiring alertness until response to medication is known.
- Instruct patient to report symptoms of neurotoxicity (paresthesia, pain, difficulty walking, persistent constipation). Inform patient that increased fluid intake, dietary fiber, and exercise may minimize constipation. Stool softeners or laxatives may be used. Patient should inform health care professional if severe constipation, abdominal pain, bloating, diarrhea, nausea, or vomiting occurs, as this may be a sign of neuropathy.
- Advise patient to notify health care professional if fever; chills; sore throat; signs of infection; bleeding gums; bruising; petechiae; blood in urine, stool, or emesis; or mouth sores occur. Caution patient to avoid crowds and persons with known infections.
- Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications, especially St. John's Wort.
- Discuss with patient the possibility of hair loss. Explore coping strategies.
- Instruct patient not to receive any vaccinations without advice of health care professional.
- Advise patient that this medication may have teratogenic effects. Contraception should be used during and for at least 2 mo after therapy is concluded.
- Emphasize need for periodic lab tests to monitor for side effects.
Regression of malignancy without the appearance of detrimental side effects.
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