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Cytarabine (Liposomal)

Medically reviewed by Drugs.com. Last updated on Mar 18, 2020.

Pronunciation

(sye TARE a been lye po SO mal)

Index Terms

  • Cytarabine Lipid Complex
  • Cytarabine Liposome
  • Cytarabine Liposome Injection
  • DepoFoam-Encapsulated Cytarabine
  • DTC 101
  • Liposomal Cytarabine

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Suspension, Intrathecal [preservative free]:

DepoCyt: 50 mg/5 mL (5 mL [DSC]) [contains cholesterol, dioleoylphosphatidylcholine (dopc), dipalmitoylphosphatidylglycerol (dppg), triolein]

Brand Names: U.S.

  • DepoCyt [DSC]

Pharmacologic Category

  • Antineoplastic Agent, Antimetabolite
  • Antineoplastic Agent, Antimetabolite (Pyrimidine Analog)

Pharmacology

Cytarabine liposomal is a sustained-release formulation of the active ingredient cytarabine, an antimetabolite which acts through inhibition of DNA synthesis and is cell cycle-specific for the S phase of cell division. Cytarabine is converted intracellularly to its active metabolite cytarabine-5’-triphosphate (ara-CTP). Ara-CTP also appears to be incorporated into DNA and RNA; however, the primary action is inhibition of DNA polymerase, resulting in decreased DNA synthesis and repair. The liposomal formulation allows for gradual release, resulting in prolonged exposure.

Absorption

Systemic exposure following intrathecal administration is negligible since transfer rate from CSF to plasma is slow

Time to Peak

Cerebrospinal fluid: Intrathecal: Within 1 hour.

Half-Life Elimination

Cerebrospinal fluid: ~6 to 82 hours.

Use: Labeled Indications

Lymphomatous meningitis: Intrathecal treatment of lymphomatous meningitis

Contraindications

Hypersensitivity to cytarabine or any component of the formulation; active meningeal infection

Dosing: Adult

Note: DepoCyt is no longer available in the US.

Note: Initiate dexamethasone 4 mg twice daily (oral or IV) for 5 days, beginning on the day of cytarabine liposomal administration.

Lymphomatous meningitis: Intrathecal:

Induction: 50 mg every 14 days for a total of 2 doses (weeks 1 and 3)

Consolidation: 50 mg every 14 days for 3 doses (weeks 5, 7, and 9), followed by an additional dose at week 13

Maintenance: 50 mg every 28 days for 4 doses (weeks 17, 21, 25, and 29)

Dosing: Geriatric

Refer to adult dosing.

Dosing: Adjustment for Toxicity

Neurotoxicity: If drug-related neurotoxicity develops, reduce dose to 25 mg. If toxicity persists, discontinue treatment.

Reconstitution

Allow vial to warm to room temperature. Particles may settle in diluent over time, and may be resuspended with gentle agitation or inversion immediately prior to withdrawing from the vial. Do not agitate aggressively. Withdraw from the vial immediately prior to administration. No further reconstitution or dilution is required. Do not mix with any other medications. Intrathecal medications should not be prepared during the preparation of any other agents (Jacobson 2009).

Administration

Intrathecal: For intrathecal use (intraventricular or lumbar puncture) only. Dose should be removed from vial immediately before administration (must be administered within 4 hours of removal from the vial). An in-line filter should NOT be used. Administer directly into the cerebrospinal fluid via an intraventricular reservoir or by direct injection into the lumbar sac. Injection should be made slowly (over 1 to 5 minutes). Patients should lie flat for 1 hour after lumbar puncture. After administration, observe for immediate toxic reactions.

Storage

Store intact vial at 2°C to 8°C (36°F to 46°F); protect from freezing. Avoid aggressive agitation. Withdraw from the vial immediately prior to administration; solutions should be used within 4 hours of withdrawal from the vial.

After preparation, store intrathecal medications in an isolated location or container clearly marked with a label identifying as "intrathecal" use only (Jacobson 2009).

Drug Interactions

Cedazuridine: May increase the serum concentration of Cytidine Deaminase Substrates. Avoid combination

Cladribine: Agents that Undergo Intracellular Phosphorylation may diminish the therapeutic effect of Cladribine. Avoid combination

Solriamfetol: May enhance the hypertensive effect of Hypertension-Associated Agents. Monitor therapy

Adverse Reactions

>10%:

Cardiovascular: Peripheral edema (11%)

Central nervous system: Chemical arachnoiditis (without dexamethasone premedication: 100%; with dexamethasone premedication: 33% to 42%; grade 4: 19% to 30%; onset: ≤5 days), headache (56%), confusion (33%), fatigue (25%), abnormal gait (23%), seizure (20% to 22%), dizziness (18%), lethargy (16%), insomnia (14%), memory impairment (14%), pain (14%)

Endocrine & metabolic: Dehydration (13%)

Gastrointestinal: Nausea (46%), vomiting (44%), constipation (25%), diarrhea (12%), decreased appetite (11%)

Genitourinary: Urinary tract infection (14%)

Hematologic & oncologic: Anemia (12%), thrombocytopenia (3% to 11%)

Neuromuscular & skeletal: Weakness (40%), back pain (24%), limb pain (15%), neck pain (14%), arthralgia (11%), neck stiffness (11%)

Ophthalmic: Blurred vision (11%)

Miscellaneous: Fever (32%)

1% to 10%:

Cardiovascular: Tachycardia (9%), hypotension (8%), hypertension (6%), syncope (3%), edema (2%)

Central nervous system: Agitation (10%), hypoesthesia (10%), myasthenia (10%), depression (8%), anxiety (7%), peripheral neuropathy (3% to 4%), abnormal reflexes (3%), sensorimotor neuropathy (3%)

Dermatologic: Diaphoresis (2%), pruritus (2%)

Endocrine & metabolic: Hypokalemia (7%), hyponatremia (7%), hyperglycemia (6%)

Gastrointestinal: Abdominal pain (9%), dysphagia (8%), anorexia (5%), hemorrhoids (3%), mucosal inflammation (3%)

Genitourinary: Urinary incontinence (7%), urinary retention (5%)

Hematologic & oncologic: Neutropenia (10%), bruise (2%)

Neuromuscular & skeletal: Tremor (9%)

Otic: Hypoacusis (6%)

Respiratory: Dyspnea (10%), cough (7%), pneumonia (6%)

<1%, postmarketing, and/or case reports: Anaphylaxis, bladder disease (bladder control impaired), blindness, brain disease, cauda equina syndrome, cranial nerve palsy, deafness, drowsiness, fecal incontinence, hemiplegia, hydrocephalus, increased intracranial pressure, leukocytosis (in CSF), meningitis (infectious), myelopathy, nervous system disease (neurologic deficit), numbness, papilledema, visual disturbance

ALERT: U.S. Boxed Warning

Chemical arachnoiditis:

Chemical arachnoiditis, a syndrome manifested primarily by nausea, vomiting, headache, and fever, was a common adverse event in all clinical studies. If left untreated, chemical arachnoiditis may be fatal. Patients receiving intrathecal cytarabine liposomal should be treated concurrently with dexamethasone to mitigate the symptoms of chemical arachnoiditis.

Warnings/Precautions

Concerns related to adverse effects:

• Chemical arachnoiditis: [US Boxed Warning]: Chemical arachnoiditis (nausea, vomiting, headache, fever) occurs commonly; may be fatal if untreated. Dexamethasone should be administered concomitantly with cytarabine (liposomal) to diminish chemical arachnoid symptoms; the incidence and severity of chemical arachnoiditis is reduced with dexamethasone. If chemical arachnoiditis is suspected, exclude other possible inflammatory, infectious, or neoplastic conditions. Toxic effects may be related to a single dose or to cumulative administration and usually occur within 5 days, although may occur at any time during treatment. Monitor continuously for development of neurotoxicity; dose reduction or discontinuation may be necessary. Hydrocephalus has been reported and may be precipitated by chemical arachnoiditis.

• CSF component elevations: Transient elevations in CSF protein and CSF white blood cell counts have been observed following administration.

• Neurotoxicity: May cause neurotoxicity (including myelopathy), which may lead to permanent neurologic deficit (rare). The risk for neurotoxicity is increased when administered with other antineoplastic agents or with cranial/spinal irradiation. CSF flow blockage may lead to increased free cytarabine concentrations in the CSF and increases the risk for neurotoxicity; consider assessing CSF flow prior to administration. Persistent (extreme) somnolence, hemiplegia, visual disturbances (including blindness; may be total and permanent), deafness, cranial nerve palsies have been reported. Signs/symptoms of peripheral neuropathy (eg, pain, numbness, paresthesia, weakness, impaired bowel/bladder control) have also been reported. Combined neurologic features (cauda equina syndrome) have been reported in some cases. If neurotoxicity develops, reduce subsequent doses or discontinue treatment. Headache, nausea, and fever are early signs of neurotoxicity.

Other warnings/precautions:

• Intrathecal safety: Intrathecal medications should not be prepared during the preparation of any other agents. After preparation, store intrathecal medications in an isolated location or container clearly marked with a label identifying as "intrathecal" use only. Delivery of intrathecal medications to the patient should only be with other medications also intended for administration into the central nervous system (Jacobson 2009).

Monitoring Parameters

Monitor closely for signs/symptoms of an immediate reaction,chemical arachnoiditis, or neurotoxicity

Reproductive Considerations

Systemic exposure following intrathecal administration of cytarabine liposomal is negligible; however, women of childbearing potential should avoid becoming pregnant during treatment.

Pregnancy Considerations

Adverse effects were observed in animal reproductive studies with conventional cytarabine. Conventional cytarabine has been associated with fetal malformations when given as a component of systemic combination chemotherapy during the first trimester. Systemic exposure following intrathecal administration of cytarabine liposomal is negligible.

Patient Education

What is this drug used for?

• It is used to treat a type of cancer in the brain fluid.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Constipation

• Diarrhea

• Abdominal pain

• Back pain

• Trouble sleeping

• Lack of appetite

• Joint pain

• Tremors

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Chemical arachnoiditis like fever, headache, nausea, vomiting, back pain, neck stiffness, or neck pain

• Infection

• Confusion

• Change in balance

• Seizures

• Severe headache

• Severe nausea

• Vomiting

• Severe loss of strength and energy

• Severe dizziness

• Passing out

• Trouble with memory

• Bruising

• Bleeding

• Fluid and electrolyte problems like mood changes, confusion, muscle pain or weakness, abnormal heartbeat, severe dizziness, passing out, fast heartbeat, increased thirst, seizures, loss of strength and energy, lack of appetite, unable to pass urine or change in amount of urine passed, dry mouth, dry eyes, or nausea or vomiting

• High blood sugar like confusion, fatigue, increased thirst, increased hunger, passing a lot of urine, flushing, fast breathing, or breath that smells like fruit

• Swelling of arms or legs

• Severe fatigue

• Abnormal movements

• Shortness of breath

• Severe neuropathy like vision changes, trouble hearing, burning or numbness feeling in hands or feet, or muscle weakness

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.