nelarabine
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.