NELARABINE injection

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

NELARABINE (UNII: 60158CV180) (NELARABINE - UNII:60158CV180)

Available from:

Gland Pharma Limited

Administration route:

INTRAVENOUS

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

Nelarabine 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 two chemotherapy regimens. None.  Risk Summary Based on its mechanism of action and findings in animal studies, nelarabine can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1)] . Limited available data with nelarabine use in pregnant women are insufficient to determine a drug-associated risk for major birth defects, miscarriage or adverse maternal or fetal outcomes. There are risks to the pregnant woman associated with untreated leukemia or lymphoma (see Clinical Considerations) . 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 1500 mg/m2 /day (see Data) . Advise pregnant women of the potential risk to the fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies are 2% to 4% and 15% to 20%, respectively. Clinical Considerations   Disease-Associated Maternal and/or Embryo-fetal Risk There are risks to the mother from untreated leukemia or lymphoma, including anemia, thrombocytopenia, and death. Data   Animal Data   In an embryo-fetal development study in which pregnant rabbits were administered daily doses of nelarabine during organogenesis, increased incidences of fetal malformations, anomalies, and variations were observed at doses greater than or equal to 360 mg/m2 /day (8-hour IV infusion; approximately 25% of the recommended human adult dose compared on a mg/m2 basis), which was the lowest dose tested. Cleft palate was seen in rabbits given 3,600 mg/m2 /day (approximately 2-fold the adult dose), absent pollices (digits) in rabbits given greater than or equal to 1,200 mg/m2 /day (approximately 75% of the recommended adult dose), while absent gall bladder, absent accessory lung lobes, fused or extra sternebrae, and delayed ossification was seen at all doses. Maternal body weight gain and fetal body weights were reduced in rabbits given 3,600 mg/m2 /day (approximately 2-fold the adult dose), but could not account for the increased incidence of malformations seen at this or lower administered doses.   Risk 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. Pregnancy Testing Nelarabine can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)] . Verify the pregnancy status of females of reproductive potential prior to starting treatment with nelarabine. Contraception Females Nelarabine can cause fetal harm when administered to a pregnant woman [see Warnings and Precautions (5.3), Use in Specific Populations (8.1)]. Because of the potential for genotoxicity, advise females of reproductive potential to use effective contraception during treatment with nelarabine. Males Because of the potential for genotoxicity, advise males (including those who have had vasectomies) with female partners of reproductive potential to use condoms during treatment with nelarabine and for 3 months after the last dose [see Nonclinical Toxicology (13.1)]. The safety and effectiveness of nelarabine for relapsed or refractory T-ALL and T-LBL has been established in pediatric patients age 1 year and older. The effectiveness of nelarabine in pediatric patients is supported by one single-arm clinical trial, and safety has been assessed in 165 pediatric patients age 1 year and older across multiple Phase I and Phase II trials. The trial establishing efficacy included 84 patients aged 21 years and younger, who had relapsed or refractory T-ALL or T-LBL. The most frequent adverse reactions of any grade occurring on treatment in this study were hematologic laboratory abnormalities. Hematologic toxicity observed in the pediatric population was higher than that seen in the adult population. [see Dosage and Administration (2.1), Adverse Reactions (6.1), Clinical  Studies (14.2)] .  Nervous system adverse reactions have been reported for 42% of pediatric patients across the Phase I and Phase II trials. The incidence of nervous system adverse reactions was less in the pediatric population than that seen in adult patients with relapsed/refractory TALL/T-LBL [see Adverse Reactions (6.1)] .  In a phase III study of nelarabine in combination with multi-agent chemotherapy as first-line therapy, there were 411 patients with T-ALL or T-LBL treated with nelarabine. The safety profile in the 357 patients age 1 to 16 years was consistent with that seen in older patients in the study. [see Adverse Reactions (6.1)].  Due to lack of long-term follow up data, a determination of the impact of nelarabine on the growth and pubertal development of pediatric patients cannot be made. Clinical studies of nelarabine did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients. In an exploratory analysis, increasing age, especially age 65 years and older, appeared to be associated with increased rates of neurologic adverse reactions. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, [see Use in Specific Populations (8.6)] . Ara-G clearance decreased as renal function decreased [see Clinical Pharmacology (12.3)]. 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 (2.3)]. 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.

Product summary:

Nelarabine Injection is supplied as a clear, colorless, sterile solution in Type I, clear glass single-dose vials with a gray bromobutyl rubber stopper (not made with natural rubber latex) and an aluminum seal with a red snap-off cap. Each vial contains 250 mg of nelarabine (5 mg nelarabine per mL) and the inactive ingredient sodium chloride (4.5 mg per mL) in 50 mL Water for Injection, USP.  Single-dose Vials are available in the following carton sizes:  NDC 68083-233-01 (single-dose vial)  NDC 68083-233-06 (package of 6) Store at 20° to 25°C (68°-77°F) [see USP Controlled Room Temperature].

Authorization status:

Abbreviated New Drug Application

Summary of Product characteristics

NELARABINE - NELARABINE INJECTION
GLAND PHARMA LIMITED
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
NELARABINE INJECTION
SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR
NELARABINE INJECTION.
NELARABINE INJECTION, FOR INTRAVENOUS USE
INITIAL U.S. APPROVAL: 2005
WARNING: NEUROLOGIC ADVERSE REACTIONS
_SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING._
SEVERE NEUROLOGIC ADVERSE REACTIONS HAVE BEEN REPORTED WITH THE USE OF
NELARABINE.
THESE ADVERSE REACTIONS HAVE INCLUDED ALTERED MENTAL STATES INCLUDING
SEVERE
SOMNOLENCE, CENTRAL NERVOUS SYSTEM EFFECTS INCLUDING CONVULSIONS, AND
PERIPHERAL
NEUROPATHY RANGING FROM NUMBNESS AND PARESTHESIAS TO MOTOR WEAKNESS
AND
PARALYSIS. THERE HAVE ALSO BEEN REPORTS OF ADVERSE REACTIONS
ASSOCIATED WITH
DEMYELINATION, AND ASCENDING PERIPHERAL NEUROPATHIES SIMILAR IN
APPEARANCE TO
GUILLAIN-BARRÉ SYNDROME. (5.1)
FULL RECOVERY FROM THESE ADVERSE REACTIONS HAS NOT ALWAYS OCCURRED
WITH CESSATION OF
THERAPY WITH NELARABINE. MONITOR FREQUENTLY FOR SIGNS AND SYMPTOMS OF
NEUROLOGIC
TOXICITY. DISCONTINUE NELARABINE FOR NEUROLOGIC ADVERSE REACTIONS OF
NCI COMMON
TOXICITY CRITERIA FOR ADVERSE EVENTS (CTCAE) GRADE 2 OR GREATER. (5.1)
INDICATIONS AND USAGE
Nelarabine is a nucleoside metabolic inhibitor indicated for the
treatment of patients with T-cell acute
lymphoblastic leukemia and T-cell lymphoblastic lymphoma in adult and
pediatric patients age 1 year and
older whose disease has not responded to or has relapsed following
treatment with at least two
chemotherapy regimens. (1)
DOSAGE AND ADMINISTRATION
• Adult Dose: 1,500 mg/m² administered intravenously over 2 hours
on Days 1, 3, and 5 repeated every
21 days. (2.1)
• Pediatric Dose: 650 mg/m² administered intravenously over 1 hour
daily for 5 consecutive days repeated
every 21 days. (2.1)
• Discontinue treatment for neurologic reactions greater than or
equal to Grade 2. (2.2)
• Dosage may be delayed for hematologic reactions (2.2)
• Take m