vincristine liposome

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vincristine liposome

(vin-kriss-teen) ,

Marqibo

(trade name)

Classification

Therapeutic: antineoplastics
Pharmacologic: vinca alkaloids
Pregnancy Category: D

Indications

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.

Action

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.

Therapeutic effects

Death of rapidly replicating cells, particularly malignant ones. Has immunosuppressive properties.

Pharmacokinetics

Absorption: Liposome encapsulation causes delayed release into circulation.
Distribution: Unknown.
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)

ROUTEONSETPEAKDURATION
unknownunknownunknown28–56 days

Contraindications/Precautions

Contraindicated in: Hypersensitivity; Demyelinating conditions including Charcot-Marie-Tooth syndrome; Intrathecal administration (can be fatal); Concurrent use of strong inhibitors/inducers of the CYP3A4 enzyme system; Obstetric: 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); Geriatric: Consider age-related decreases hepatic, renal, or cardiac function, concomitant disease or other drug therapies which may ↑ risk of adverse reactions; Pediatric: Safe and effective use in children <18 yr has not been established.

Adverse Reactions/Side Effects

Central nervous system

  • fatigue (most frequent)
  • insomnia (most frequent)
  • mental starus changes
  • weakness

Respiratory

  • respiratory distress/failure

Cardiovascular

  • cardiac arrest (life-threatening)
  • hypotension

Gastrointestinal

  • bowel obstruction/paralytic ileus (life-threatening)
  • ↓ appetite (most frequent)
  • diarrhea (most frequent)
  • nausea (most frequent)
  • abdominal pain
  • constipation
  • hepatotoxicity

Hematologic

  • bone marrow depressions

Local

  • tissue damage following extravasation

Musculoskeletal

  • muscular weakness

Neurologic

  • peripheral neuropathy (most frequent)

Miscellaneous

  • tumor lysis syndrome (life-threatening)
  • fever (most frequent)

Interactions

Drug-Drug interaction

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, telithromycin, 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.

Route/Dosage

Intravenous (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.

Availability

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)

Nursing implications

Nursing assessment

  • 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.

Potential Nursing Diagnoses

Risk for constipation (Adverse Reactions)
Risk for infection (Adverse Reactions)
Risk for injury (Adverse Reactions)

Implementation

  • 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 (see ).
  • Intravenous Administration
  • 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.

Patient/Family Teaching

  • 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.

Evaluation/Desired Outcomes

  • Regression of malignancy without the appearance of detrimental side effects.
References in periodicals archive ?
Among other things, there can be no assurances that any of Hana's development efforts relating to Marqibo or its other product candidates will be successful.
2007 goals include commercially launching Zensana[TM], initiating pivotal trial for Marqibo in ALL, and Talotrexin Phase II in NSCLC and ALL
CASI's product pipeline includes exclusive rights to ZEVALIN (ibritumomab tiuxetan), MARQIBO (vinCRIStine sulfate LIPOSOME injection) and Captisol-Enabled[sup.
The company will also provide a summary of its October 31, 2006 discussion with the FDA on Marqibo.
AG-858, Aldesleukin , Alemtuzumab, AP23573, Apolizumab, Arsenic trioxide, Atra, Avastin, BAY 43-9006, Bevacizumab, BiovaxID , Bortezomib , CEP-701, Ceplene, Clofarabine, Cloretazine, CMC-544 , Decitabine, Enzastaurin , Epratuzumab, FavId , FK228, Flavopiridol, Gemtuzumab, Genasense, Gvax, IDEC-114 , Imatinib, Marqibo, MyVax, Nelarabine , OSI-461, Pixantrone , PKC412, PTK787, Rituximab, SGN-30, SGN-40 , SU5416, Temsirolimus , Troxacitabine, Valspodar, VELCADE, Xcytrin, Zanolimumab, Zarnestra etc.
File Import drug registration for MARQIBO in China, Hong Kong, and Taiwan.
We are pleased to make Marqibo also available to leukemia patients outside of the United States, in countries where the treatment did not yet receive market approval," said Dr.
In addition, three drugs, namely, Graspa (ERYtech Pharma), Marqibo (Talon Therapeutics), and Inotuzumab Ozogamicin (Pfizer, Inc.
Talon submitted a new drug application (NDA) to the FDA in July 2011 seeking accelerated approval of Marqibo in adult Ph- ALL, in second or greater relapse or that has progressed following two or more prior lines of anti-leukemia therapy.
Hana said it expects that the financing will provide the funds needed to develop Marqibo to approval and commercialisation for relapsed/refractory adult ALL patients; to study Marqibo in front-line adult ALL and lymphoma patients; and to unlock the full potential of menadione topical lotion, a first-in-class therapeutic targeted at the dose-limiting skin toxicities in cancer patients taking EGFR inhibitors.
The committee will also review Ilex/Enzon's liposomal vincristine formulation Marqibo NDA (21-600) for relapsed aggressive non-Hodgkin's lymphoma and Ilex' Clolar (clofarabine) NDA (21-673) for pediatric patients (1-21 years) with refractory or relapsed acute leukemias on Dec 1.