nelarabine


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nelarabine

Arranon, Atriance (UK)

Pharmacologic class: Antimetabolite

Therapeutic class: Antineoplastic

Pregnancy risk category D

FDA Box Warning

Administer I.V. only.

Give under supervision of physician experienced in use of cancer chemotherapy.

Drug has caused severe neurologic events, including severe somnolence, seizures, and peripheral neuropathy. Demyelination-associated events also have occurred. Drug discontinuation doesn't always lead to full recovery from these events. Monitor patient closely for neurologic changes; discontinue drug for serious neurologic events.

Action

Inhibits DNA synthesis in leukemic blasts, leading to cell death

Availability

Solution for injection: 250 mg/50 ml

Indications and dosages

T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma in patients whose disease hasn't responded to at least two chemotherapy regimens or who've relapsed after such therapy

Adults: 1,500 mg/m2 I.V. undiluted over 2 hours on days 1, 3, and 5; repeat every 21 days. Continue therapy until disease progresses, unacceptable toxicity occurs, patient becomes eligible for bone marrow transplant, or patient no longer benefits from therapy.

Children: 650 mg/m2 I.V. undiluted over 1 hour daily for 5 consecutive days; repeat every 21 days. Continue therapy until disease progresses, unacceptable toxicity occurs, patient becomes eligible for bone marrow transplant, or patient no longer benefits from therapy.

Dosage adjustment

• Neurologic or hematologic toxicity

Contraindications

• Hypersensitivity to drug or its components

Precautions

Use cautiously in:

• renal or hepatic dysfunction

• patients undergoing concurrent intrathecal chemotherapy

• patients previously treated with intrathecal chemotherapy or craniospinal irradiation

• concurrent administration of live vaccines (immunocompromised patients)

• elderly patients

• pregnant or breastfeeding patients.

Administration

• Administer undiluted.

• Infuse over 2 hours in adults or over 1 hour in children.

• In patients at risk for tumor lysis syndrome, take measures to prevent hyperuricemia (such as hydration, urine alkalization, and allopurinol prophylaxis).

Discontinue drug if serious neurologic adverse reactions occur.

Adverse reactions

CNS: confusional state, insomnia, depression, headache, peripheral neuropathy, somnolence, paresthesia, hypoesthesia, fine motor dysfunction, neurologic disorder, tremor, ataxia, abnormal gait, dizziness, amnesia, balance disorder, sensory loss, demyelination, asthenia, fatigue, rigors, decreased level of consciousness, seizures, cerebral hemorrhage, coma

CV: tachycardia, chest pain, hypotension

EENT: blurred vision, epistaxis, sinusitis

GI: nausea, vomiting, diarrhea, constipation, abdominal pain, abdominal distention, stomatitis, anorexia

Hematologic: anemia, neutropenia, thrombocytopenia, leukopenia

Metabolic: dehydration

Musculoskeletal: myalgia, arthralgia, back pain, muscle weakness, extremity pain

Respiratory: pneumonia, cough, dyspnea, exertional dyspnea, wheezing, pleural effusion

Skin: petechiae

Other: abnormal taste, infection, fever, edema, peripheral edema, pain, non-cardiac chest pain

Interactions

Drug-drug. Pentostatin: decreased nelarabine efficacy

Drug-diagnostic tests. Bilirubin, serum creatinine, transaminases: increased

Blood albumin, CBC, calcium, glucose, magnesium, platelets, potassium: decreased

Patient monitoring

Watch closely for neurologic events, such as somnolence, confusion, seizures, ataxia, motor incoordination, and peripheral neuropathy (which may not subside even after therapy ends). Know that previous craniospinal irradiation or current or previous intrathecal chemotherapy may increase patient's risk of adverse neurologic events.

• Closely monitor patients with hepatic or renal dysfunction for adverse reactions.

• Monitor CBC regularly.

Patient teaching

• Instruct patient or caregiver to read patient information leaflet thoroughly.

Urge patient or caregiver to immediately report neurologic symptoms, such as extreme sleepiness, confusion, seizures, unsteadiness or weakness on walking, difficulty with tasks such as buttoning clothing, and numbness and tingling in fingers, hands, or feet.

Tell patient to immediately report easy bruising, bleeding, fever, or signs or symptoms of infection.

• Inform patient that he'll need to undergo frequent blood tests.

• Instruct patient to avoid live virus vaccines.

• Caution patient to avoid driving and other hazardous activities until drug effects are known.

• Urge female with childbearing potential to avoid pregnancy and breastfeeding during therapy.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.

nelarabine

(ne-lar-a-been) ,

Arranon

(trade name)

Classification

Therapeutic: antineoplastics
Pharmacologic: antimetabolites
Pregnancy Category: D

Indications

T-cell acute lymphoblastic leukemia or T-cell lymphoblastic lymphoma unresponsive to at least 2 other previous chemotherapy regimens.

Action

Converted intracellularly to ara-G and then to ara-GTP. In leukemic cells, it is incorporated into DNA, leading to inhibition of DNA synthesis and cell death.

Therapeutic effects

Decreased proliferation of leukemic cells.

Pharmacokinetics

Absorption: IV administration results in complete bioavailability. Intracellular conversion is required for activation of prodrug.
Distribution: Extensively distributed.
Metabolism and Excretion: Mostly metabolized intracellulary. Partially eliminated by the kidneys as nelarabine and ara-G.
Half-life: Unknown.

Time/action profile

ROUTEONSETPEAKDURATION
IVunknownend of infusionunknown

Contraindications/Precautions

Contraindicated in: Hypersensitivity; CCr <50 ml/min; Obstetric: Pregnancy, lactation.
Use Cautiously in: Obstetric: Patients with child-bearing potential; Geriatric: Risk of neurologic events may be ↑; Severe hepatic impairment (bilirubin >3.0 mg/dL).

Adverse Reactions/Side Effects

Hematologic

  • anemia
  • leukopenia
  • neutropenia
  • thrombocytopenia

Neurologic

  • severe neurologic events (life-threatening)

Interactions

Drug-Drug interaction

Decreases antibody response to and increases risk of adverse reactions from live-virus vaccines.

Route/Dosage

Intravenous (Adults) 1500 mg/m² on days 1, 3 and 5 of every 21 day cycle.
Intravenous (Children) 650 mg/m²/day for first 5 days of every 21 day cycle.

Availability

Solution for IV injection: 5 mg/ml

Nursing implications

Nursing assessment

  • Assess neurologic status frequently. May cause altered mental states (severe somnolence, confusion, coma), CNS effects (convulsions, status epilepticus) and peripheral neuropathy (numbness, parathesias, motor weakness, ataxia, hypoesthesia, craniospinal demyelination, ascending neuropathy, paralysis). Risk is increased in patients treated previously or concurrently with intrathecal chemotherapy or previously with craniospinal irradiation. May be irreversible. Discontinue nelarabine if neurologic toxicity is severe (NCI Grade 2 or greater).
  • Lab Test Considerations: Monitor CBC regularly. May cause leukopenia, thrombocytopenia, anemia, neutropenia, including febrile neutropenia.
    • May cause hyperuricemia.
    • May cause ↑ transaminase, serum bilirubin, and creatinine levels, and ↓ serum potassium, calcium, magnesium, glucose, and albumin levels.

Potential Nursing Diagnoses

Risk for infection (Adverse Reactions)

Implementation

  • Nelarabine should be administered under the supervision of a physician experienced in antineoplastic therapy.
    • Administer IV hydration to prevent hyperuricemia. Consider allopurinol administration.
    • .
  • Intravenous Administration
  • Intermittent Infusion: Diluent: Do not dilute prior to administration. Transfer the dose into PVC infusion bags or glass containers. Do not administer solution that is discolored or contains particulate matter.
  • Rate: Administer over 2 hr for adults and over 1 hr in children.

Patient/Family Teaching

  • Instruct patient to read the Patient Information Leaflet before starting treatment and with each treatment.
  • May cause somnolence. Caution patient to avoid driving and other activities requiring alertness until response to medication is known.
  • Advise patient to notify health care professional promptly if new or worsening symptoms of peripheral neuropathy (tingling or numbness in fingers, hands, toes, or feet; difficulty with fine motor coordination tasks such as buttoning clothing; unsteadiness while walking; weakness arising from a low chair or climbing stairs, increased tripping while walking over uneven surfaces occur or if seizures or fever or signs of infection occur.
  • Advise 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.
  • Caution patient not to receive vaccines made with live viruses during therapy.
  • Advise patient to use effective contraception and to avoid breast feeding during therapy.

Evaluation/Desired Outcomes

  • Decrease in production of cancer cells.
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