A-Z Drug Facts > Nelarabine

Nelarabine

Pronouncation: (neh-LAY-rah-bean)
Class: DNA demethylating agent

Trade Names:
Arranon
- Injection 250 mg (5 mg/mL)

Pharmacology

Feedback for Nelarabine As a treatment for... Avg User Ratings [?] Lymphoma Be the first to rate it 0 comments   Acute Lymphoblastic Leukemia Be the first to rate it 0 comments   Compare with other drugs.

Converted to ara-G, then activated to ara-GTP. Ara-GTP accumulates in leukemic blasts and is incorporated into DNA, leading to inhibition of DNA synthesis and cell death.

Pharmacokinetics

Absorption

C _max of ara-G generally occurs at end of nelarabine infusion.

Distribution

Nelarbine and ara-G are extensively distributed. Protein binding is less than 25%. Nelarabine Vd at steady state is 197 L/m ² (adults) and 213 L/m ² (children). Ara-G Vd at steady state is 50 L/m ² (adults) and 33 L/m ² (children). Intracellular C _max for ara-GTP occurs within 3 to 25 h on day 1. AUC of intracellular ara-GTP is 532 times higher than nelarabine and 14 times higher than ara-G.

Metabolism

Rapid and extensive conversion of nelarabine to ara-G by O-demethylation. Ara-G is hydrolyzed to guanine, which is N-deaminated to xanthine and then oxidized to uric acid.

Elimination

Rapidly eliminated from plasma. Apparent Cl is 10.5 L/h/m ² (adults) and 11.3 L/h/m ² (children). Partially eliminated by kidneys (6.6% nelarabine; 27% ara-g); t _½ is approximately 30 min (nelarabine) and 3 h (ara-G).

Special Populations

Renal Function Impairment

Cl reduced 15% in patients with mild renal function impairment (CrCl 50 to 80 mL/min) and 40% in patients with moderate renal function impairment (CrCl less than 50 mL/min).

Elderly

Reduced renal function in elderly patients may reduce ara-G Cl.

Indications and Usage

Treatment of T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma in patients whose disease has not responded to or has relapsed following treatment with at least 2 chemotherapy regimens.

Contraindications

Standard considerations.

Dosage and Administration

Leukemia/Lymphoma
Adults

IV 1,500 mg/m ² over 2 h on days 1, 3, and 5; repeated every 21 days.

Leukemia/Lymphoma
Children

IV 650 mg/m ² over 1 h daily for 5 consecutive days; repeated every 21 days.

Duration of Therapy
Adults and children

IV Duration of treatment has not been clearly established. Generally, treatment is continued until there is evidence of disease progression, the patient experiences unacceptable toxicity, the patient no longer continues to benefit from treatment, or the patient becomes a candidate for bone marrow transplantation.

General Advice

• For IV infusion only. Not for intradermal, subcutaneous, IM, IV bolus, or intra-arterial administration.
• Follow institutional procedures for handling, administration, and disposal of anticancer drugs. Wear appropriate protective equipment when preparing and administering medication.
• Injection solution does not need to be diluted prior to administration. Transfer prescribed dose of nelarabine into a PVC infusion bag or glass infusion container and administer over appropriate interval.
• Solution should be clear and colorless. Do not use if solution is discolored, cloudy, or contains particulate matter.
• Discard unused portions of vial. Do not save any unused portions for future use.

Storage/Stability

Store unopened vials at controlled room temperature (59° to 86°F). Nelarabine is stable in glass infusion containers and PVC infusion bags for up to 8 h if stored at room temperatures up to 86°F.

Drug Interactions

None well documented.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Chest pain, hypotension, petechiae, sinus tachycardia (at least 5%).

CNS

Abnormal gait, asthenia, confusion, depression, fatigue, insomnia (at least 5%); amnesia, ataxia, balance disorder, convulsions, depressed level of consciousness, dizziness, grand mal convulsions, headache, hypesthesia, motor dysfunction, motor neuropathy, nervous system disorder, paresthesia, peripheral neuropathy, sensory loss, sensory neuropathy, somnolence, status epilepticus, tremor (at least 2%); abnormal coordination, burning sensation, disturbance in attention, dysarthria, hyporeflexia, neuropathic pain, nystagmus, peroneal nerve palsy, sciatica, sensory disturbance, speech disorder (1%); demyelination and ascending peripheral neuropathies similar to Guillain-Barré syndrome.

EENT

Epistaxis, sinusitis (at least 5%); blurred vision (4%); sinus headache (1%).

GI

Abdominal distension and pain, constipation, diarrhea, nausea, stomatitis, vomiting (at least 5%); dysgeusia (at least 2%).

Hematologic-Lymphatic

Anemia, febrile neutropenia, leukopenia, neutropenia, thrombocytopenia (at least 5%).

Lab Tests

Decreased albumin, calcium, glucose, magnesium, or potassium (at least 5%); increased AST, bilirubin, creatinine, or transaminases (at least 5%).

Metabolic-Nutritional

Dehydration, hyperglycemia (at least 5%).

Musculoskeletal

Arthralgia, back pain, muscular weakness, myalgia, pain in extremities, rigors (at least 5%).

Respiratory

Cough, dyspnea, exertional dyspnea, pleural effusion, pneumonia, wheezing (at least 5%).

Miscellaneous

Edema, infection, noncardiac chest pain, pain, peripheral edema, pyrexia (at least 5%).

Precautions

Warnings Severe neurologic events have been reported. Events included altered mental status (eg, somnolence, confusion), CNS effects (eg, ataxia, convulsions), peripheral neuropathy, ranging from numbness and paresthesias to motor weakness and paralysis, and demyelination and ascending peripheral neuropathies similar in appearance to Guillain-Barré syndrome. Patients treated previously or concurrently with intrathecal chemotherapy, or previously with craniospinal irradiation, may be at increased risk. Full recovery from these events has not always occurred with cessation of therapy.

Monitor Closely monitor patients for neurologic events. Monitor CBC and platelet count regularly.

Pregnancy

Category D .

Lactation

Undetermined.

Elderly

May be at increased risk for neurologic adverse reactions.

Renal Function

Risk of reactions may be greater in patients with severe renal function impairment (CrCl less than 30 mL/min); closely monitor these patients for toxicity.

Hepatic Function

Risk of reactions may be greater in patients with severe hepatic function impairment (bilirubin greater than 3 mg/dL); closely monitor these patients for toxicity.

Hazardous Tasks

May cause somnolence.

Discontinuation/Delay of therapy

Discontinue therapy for neurologic events of NCI Common Toxicity Criteria grade 2 or higher. Dosage may be delayed for other toxicities, including hematologic toxicity.

Hematologic toxicity

Anemia, leukopenia, neutropenia, and thrombocytopenia, including febrile neutropenia, have been associated with nelarabine therapy.

Live vaccines

Avoid administering live vaccines to immunocompromised patients.

Tumor lysis syndrome/hyperuricemia

Provide appropriate measures (eg, IV hydration, prophylaxis with allopurinol, urine alkalinization) to prevent hyperuricemia of tumor lysis syndrome.

Overdosage

Symptoms

Myelosuppression, neurotoxicity (possibly including coma, paralysis), potentially death.

Patient Information

• Advise patient, family, or caregiver that medication will be prepared and administered by health care providers in a health care setting.
• Advise patient, family, or caregiver to review the patient information leaflet carefully before starting therapy and to read and check for new information before each treatment.
• Review dosing schedule with patient, family, or caregiver.
• Advise patient to immediately report any of the following to health care provider: bleeding or unusual bruising; chills, fever, or other signs of infection; difficulty breathing or unexplained shortness of breath; difficulty with fine motor coordination tasks (eg, buttoning clothing); hives; increased tripping while walking; pain, redness, or swelling at injection site; paleness; rash; seizures; tingling or numbness in fingers, hands, toes, or feet; unsteadiness while walking; weakness in climbing stairs or arising from a chair.
• Advise patient to report any of the following to health care provider: persistent appetite loss, nausea, or vomiting; persistent or worsening general body weakness.
• Advise women of childbearing potential to use effective contraception to avoid becoming pregnant during therapy.
• Advise lactating women to avoid breastfeeding during therapy.

Link to this page

Printable Version

Email Page

Add to my drug list