nelarabine

nelarabine,

an antineoplastic.

indications This drug is used to treat T-cell lymphoblastic leukemia and T-cell lymphoblastic lymphoma after relapse or treatment failure with at least two chemotherapeutic agents.

contraindications Pregnancy, severe neurotoxicity, and known hypersensitivity to this drug prohibit its use.

adverse effects Adverse effects of this drug include dizziness; insomnia; rigors; peripheral neuropathy; confusion; headache; edema; leukopenia; anemia; decreased potassium, calcium magnesium, glucose, albumin, bilirubin, aspartate aminotransferase, and alanine aminotransferase; hyperuricemia; increased glucose; myalgia; arthralgia; back pain; weakness; cough; dyspnea; wheezing; and epistaxis. Life-threatening side effects include seizures, paralysis, neutropenia, thrombocytopenia, and pleural effusion. Common side effects include fatigue, nausea, vomiting, anorexia, diarrhea, stomatitis, and constipation.

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nelarabine Warning - High-alert drug!

Arranon

Pharmacologic class: Antimetabolite

Therapeutic class: Antineoplastic

Pregnancy risk category D

FDA Boxed 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.

Route	Onset	Peak	Duration
I.V.	Unknown	End of infusion	Unknown

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, noncardiac 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.