vincristine liposome

General

Genetic Implications:

**Off Market Drug**
This medication is no longer available in the United States. Information provided here is for reference purposes only.

Pronunciation:
vin-kriss-teen

Trade Name(s)

• Marqibo

Ther. Class.

antineoplastics

Pharm. Class.

vinca alkaloids

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 Effect(s):

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)

Contraindication/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
• OB:  Pregnancy (may cause fetal harm)
• Lactation: Lactation.

Use Cautiously in:

• Pre-existing severe neuropathy
• Rep:   Women of reproductive potential and men with female partners of reproductive potential
• Pedi:  Safety and effectiveness not established in children
• Geri:  Consider age-related decreases hepatic, renal, or cardiac function, concomitant disease or other drug therapies which may ↑ risk of adverse reactions

Adverse Reactions/Side Effects

CV: CARDIAC ARREST, hypotension

GI: BOWEL OBSTRUCTION/PARALYTIC ILEUS, ↓ appetite, diarrhea, nausea, abdominal pain, constipation, hepatotoxicity

GU: ↓ fertility

Hemat: BONE MARROW DEPRESSIONS

Local: tissue damage following extravasation

MS: muscular weakness

Neuro: peripheral neuropathy, fatigue, insomnia, mental starus changes, weakness

Resp: respiratory distress/failure

Misc: TUMOR LYSIS SYNDROME, fever

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

• 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.

Drug-Natural Products:

Blood levels and effectiveness may be ↓ by  St. John's wort , concurrent use should be avoided.

Route/Dosage

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.

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)

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 SUBQ 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 Diagnoses

• Risk for constipation (Adverse Reaction) 
• Risk for infection (Adverse Reaction) 
• Risk for injury (Adverse Reaction) 

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 SUBQ, 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.

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.