NELARABINE Drug Interactions: What You Need to Know

INTERACTIONS Administration of Nelarabine Injection in combination with adenosine deaminase (ADA) inhibitors, such as pentostatin, is not recommended [ see Clinical Pharmacology ( 12.3 ) ] . Administration in combination with adenosine deaminase (ADA) inhibitors, such as pentostatin, is not recommended. ( 7 , 12.3 )

None. None. ( 4 )

AND PRECAUTIONS Neurologic Adverse Reactions : Severe neurologic reactions have been reported. Monitor for signs and symptoms of neurologic toxicity. ( 5.1 )

Hematologic

Reactions : Complete blood counts including platelets should be monitored regularly. ( 5.2 ) Embryo-Fetal Toxicity : Can cause fetal harm. Advise females of reproductive potential of the potential risk to the fetus and to use effective contraception; and advise males to use condoms. ( 5.3 , 8.1 , 8.3 ) Effects on Ability to Drive and Use Machines : Somnolence may occur. Advise patients to refrain from these activities until somnolence has resolved. ( 5.6 )

5.1 Neurologic Adverse Reactions 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 Injection therapy [ see Adverse Reactions ( 6.1 ) ] . Based on patients with complete data, the median time to onset of first event is 5 days from start of first infusion (range: 1-166), and the median duration is 6 days (range: 1-393 days). 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 Injection therapy [ see Adverse Reactions ( 6.1 ) ] . Based on patients with complete data, the median time to onset of first event is 8 days from start of first infusion (range: 1-269), and the median duration is 2 days (range: 1-82 days). Common signs and symptoms of Nelarabine Injection-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-Barré syndrome. Full recovery from these adverse reactions has not always occurred with cessation of therapy with Nelarabine Injection. 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 Injection.

Discontinue Nelarabine

Injection for neurologic adverse reactions of NCI CTCAE Grade 2 or greater and provide supportive care [ see Dosage and Administration ( 2.2 ), Adverse Reactions ( 6.1 ) ] .

5.2 Hematologic Adverse Reactions Leukopenia, thrombocytopenia, anemia, and neutropenia, including febrile neutropenia, have been associated with Nelarabine Injection therapy. Complete blood counts including platelets should be monitored regularly [ see Dosage and Administration ( 2.2 ), Adverse Reactions ( 6.1 ) ] .

5.3 Embryo-Fetal Toxicity Based on its mechanism of action and findings in animal studies, Nelarabine Injection can cause fetal harm when administered to a pregnant woman [ see Clinical Pharmacology ( 12.1 ) ] . In animal reproduction studies, intravenous administration of nelarabine to pregnant rabbits during the period of organogenesis resulted in teratogenicity at maternal doses below the recommended human adult dose of 1,500 mg/m 2 /day ( see Data ). Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with Nelarabine Injection. Advise males with female partners of reproductive potential to use condoms during treatment with Nelarabine Injection and for 3 months after the last dose [ see Use in Specific Populations ( 8.1 , 8.3 ), Nonclinical Toxicology ( 13.1 ) ] .

5.4 Tumor Lysis Syndrome Patients receiving Nelarabine Injection should receive intravenous hydration according to standard medical practice for the management of hyperuricemia in patients at risk for tumor lysis syndrome. Consideration should be given to the use of allopurinol in patients at risk of hyperuricemia [ see Dosage and Administration ( 2.4 ) ] .

5.5 Vaccinations Avoid administration of live vaccines to immunocompromised patients.

5.6 Effects on Ability to Drive and Use Machines Patients treated with Nelarabine Injection may experience somnolence during and for several days after treatment [ see Adverse Reactions ( 6.1 ) ] . Advise patients to refrain from driving or engaging in hazardous occupations or activities until somnolence has resolved.