Nelarabine - Nelarabine injection Prescribing Information
Nervous system adverse reactions of any grade were reported for 223 (76%) adult patients across the Phase I and Phase II trials, and Grade 3 or higher (severe, life-threatening, or fatal) adverse reactions were reported for 55 (19%) patients following initiation of nelarabine therapy
Nervous system adverse reactions of any grade were reported for 69 (42%) pediatric patients across the Phase I and Phase II trials, and Grade 3 or higher (severe, life-threatening, or fatal) adverse reactions were reported for 25 (15%) patients following initiation of nelarabine therapy
Common signs and symptoms of nelarabine-related neurotoxicity include somnolence, headache, paresthesia and dysesthesia, dizziness, neuropathy (sensory and motor), cerebellar disturbances and tremor. Severe neurologic toxicity can manifest as coma, status epilepticus, craniospinal demyelination, or ascending neuropathy similar in presentation to Guillain-Barr¡SR syndrome.
Full recovery from these adverse reactions has not always occurred with cessation of therapy with nelarabine. Patients treated previously or concurrently with intrathecal chemotherapy or previously with craniospinal irradiation may be at increased risk for neurologic adverse events.
Monitor patients frequently for signs and symptoms of neurologic toxicity during and for at least 24 hours after completion of treatment with nelarabine. Discontinue nelarabine for neurologic adverse reactions of NCI CTCAE Grade 2 or greater and provide supportive care
Nervous system adverse reactions of any grade were reported for 223 (76%) adult patients across the Phase I and Phase II trials, and Grade 3 or higher (severe, life-threatening, or fatal) adverse reactions were reported for 55 (19%) patients following initiation of nelarabine therapy
Nervous system adverse reactions of any grade were reported for 69 (42%) pediatric patients across the Phase I and Phase II trials, and Grade 3 or higher (severe, life-threatening, or fatal) adverse reactions were reported for 25 (15%) patients following initiation of nelarabine therapy
Common signs and symptoms of nelarabine-related neurotoxicity include somnolence, headache, paresthesia and dysesthesia, dizziness, neuropathy (sensory and motor), cerebellar disturbances and tremor. Severe neurologic toxicity can manifest as coma, status epilepticus, craniospinal demyelination, or ascending neuropathy similar in presentation to Guillain-Barr¡SR syndrome.
Full recovery from these adverse reactions has not always occurred with cessation of therapy with nelarabine. Patients treated previously or concurrently with intrathecal chemotherapy or previously with craniospinal irradiation may be at increased risk for neurologic adverse events.
Monitor patients frequently for signs and symptoms of neurologic toxicity during and for at least 24 hours after completion of treatment with nelarabine. Discontinue nelarabine for neurologic adverse reactions of NCI CTCAE Grade 2 or greater and provide supportive care
Nelarabine Injection is indicated for the treatment of T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL) in adult and pediatric patients age 1 year and older whose disease has not responded to or has relapsed following treatment with at least 2 chemotherapy regimens.
- Adult Dose: 1,500 mg/m2administered by intravenous infusion over 2 hours on Days 1, 3, and 5 repeated every 21 days. ()2.1 Recommended Dosage
This product is for intravenous use only.
Adult Dosage:The recommended adult dose of nelarabine injection is 1,500 mg/m2administered by intravenous infusion over 2 hours on Days 1, 3, and 5 repeated every 21 days. Administer nelarabine injection undiluted.Pediatric Dosage: The recommended pediatric dose of nelarabine injection is 650 mg/m2administered by intravenous infusion over 1 hour daily for 5 consecutive days repeated every 21 days. Administer nelarabine injection undiluted.The recommended duration of treatment for adult and pediatric patients has not been clearly established. In clinical trials, treatment was generally continued until there was evidence of disease progression, the patient experienced unacceptable toxicity, the patient became a candidate for hematopoietic stem cell transplantation (HSCT), or the patient no longer continued to benefit from treatment.
- Pediatric Dose: 650 mg/m2administered by intravenous infusion over 1 hour daily for 5 consecutive days repeated every 21 days. ()2.1 Recommended Dosage
This product is for intravenous use only.
Adult Dosage:The recommended adult dose of nelarabine injection is 1,500 mg/m2administered by intravenous infusion over 2 hours on Days 1, 3, and 5 repeated every 21 days. Administer nelarabine injection undiluted.Pediatric Dosage: The recommended pediatric dose of nelarabine injection is 650 mg/m2administered by intravenous infusion over 1 hour daily for 5 consecutive days repeated every 21 days. Administer nelarabine injection undiluted.The recommended duration of treatment for adult and pediatric patients has not been clearly established. In clinical trials, treatment was generally continued until there was evidence of disease progression, the patient experienced unacceptable toxicity, the patient became a candidate for hematopoietic stem cell transplantation (HSCT), or the patient no longer continued to benefit from treatment.
- Discontinue treatment for neurologic reactions greater than or equal to Grade 2. ()2.2 Dosage Modification
Discontinue nelarabine injection if the patient develops a neurologic adverse reaction of NCI CTCAE Grade 2 or greater. Dosage may be delayed for other toxicity, including hematologic toxicity
[see Boxed Warning, Warnings and Precautions ]. - Dosage may be delayed for hematologic reactions. ()2.2 Dosage Modification
Discontinue nelarabine injection if the patient develops a neurologic adverse reaction of NCI CTCAE Grade 2 or greater. Dosage may be delayed for other toxicity, including hematologic toxicity
[see Boxed Warning, Warnings and Precautions ]. - Take measures to prevent hyperuricemia. ()2.4 Prevention of Hyperuricemia
Take precautions against hyperuricemia (e.g., hydration, urine alkalinization, and prophylaxis with allopurinol)
[see Warnings and Precautions ].
Nelarabine Injection: 250 mg/50 mL (5 mg/mL) is supplied as a clear, colorless, sterile solution in Type I, clear glass single-dose vials with a grey bromobutyl rubber stopper (not made with natural rubber latex) and an aluminum seal with a red color flip-off cap.
- Lactation: Advise not to breastfeed. ()8.2 LactationRisk Summary
There are no data on the presence of nelarabine or ara-G in human or animal milk, the effect on the breastfed child, or the effect on milk production. Because of the potential for serious adverse reactions in the breastfed child from nelarabine, such as severe neurological reactions, advise women not to breastfeed during treatment with nelarabine.
- Renal Impairment: Closely monitor patients with moderate or severe renal impairment for toxicities. ()8.6 Renal Impairment
Ara-G clearance decreased as renal function decreased
[see Clinical Pharmacology ]. Because the risk of adverse reactions to this drug may be greater in patients with moderate (CLCr 30 to 50 mL/min) or severe (CLCr less than 30 mL/min) renal impairment, these patients should be closely monitored for toxicities when treated with nelarabine[see Dosage and Administration ]. - Hepatic Impairment: Closely monitor patients with severe hepatic impairment for toxicities. ()8.7 Hepatic Impairment
The influence of hepatic impairment on the pharmacokinetics of nelarabine has not been evaluated. Because the risk of adverse reactions to this drug may be greater in patients with severe hepatic impairment (total bilirubin greater than 3 times upper limit of normal), these patients should be closely monitored for toxicities when treated with nelarabine.
None.