ARSENIC TRIOXIDE injection, solution

Šalis: Jungtinės Valstijos

kalba: anglų

Šaltinis: NLM (National Library of Medicine)

Veiklioji medžiaga:

ARSENIC TRIOXIDE (UNII: S7V92P67HO) (ARSENIC CATION (3+) - UNII:C96613F5AV)

Prieinama:

Sintetica US LLC

Vartojimo būdas:

INTRAVENOUS

Recepto tipas:

PRESCRIPTION DRUG

Terapinės indikacijos:

Arsenic trioxide injection is indicated for induction of remission and consolidation in patients with APL who are refractory to, or have relapsed from, retinoid and anthracycline chemotherapy, and whose APL is characterized by the presence of the t(15;17) translocation or PML/RAR-alpha gene expression. Arsenic trioxide injection is contraindicated in patients with hypersensitivity to arsenic. Risk Summary Based on the mechanism of action [see Clinical Pharmacology (12.1)] and findings in animal studies, arsenic trioxide can cause fetal harm when administered to a pregnant woman. Arsenic trioxide was embryolethal and teratogenic in rats when administered on gestation day 9 at a dose approximately 10 times the recommended human daily dose on a mg/m2 basis (see Data ). A related trivalent arsenic, sodium arsenite, produced teratogenicity when administered during gestation in mice at a dose approximately 5 times the projected human dose on a mg/m2 basis and in hamsters at an intravenous dose approximately equivalent to the projected human daily dose on a mg/m2 basis. There are no studies with the use of arsenic trioxide in pregnant women, and limited published data on arsenic trioxide use during pregnancy are insufficient to inform a drug-associated risk of major birth defects and miscarriage. Advise pregnant women of the potential risk to a 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 is 2% to 4% and 15% to 20%, respectively. Data Human Data One patient was reported to deliver a live infant with no reported congenital anomalies after receiving arsenic trioxide during the first five months of pregnancy. A second patient became pregnant three months after discontinuing arsenic trioxide and was reported to have a normal pregnancy outcome. A third patient was a pregnant healthcare provider who experienced dermal contact with liquid arsenic trioxide and had a normal pregnancy outcome after treatment and monitoring. A fourth patient who became pregnant while receiving arsenic trioxide had a miscarriage. Animal Data Studies in pregnant mice, rats, hamsters, and primates have shown that inorganic arsenicals cross the placental barrier when given orally or by injection. An increase in resorptions, neural-tube defects, anophthalmia and microphthalmia were observed in rats administered 10 mg/kg of arsenic trioxide on gestation day 9 (approximately 10 times the recommended human daily dose on a mg/m  basis). Similar findings occurred in mice administered a 10 mg/kg dose of a related trivalent arsenic, sodium arsenite (approximately 5 times the projected human dose on a mg/m2 basis), on gestation days 6, 7, 8, or 9. Intravenous injection of 2 mg/kg sodium arsenite (approximately equivalent to the projected human daily dose on a mg/m2 basis) on gestation day 7 (the lowest dose tested) resulted in neural-tube defects in hamsters. Risk Summary Arsenic trioxide is excreted in human milk. There are no data on the effects of arsenic trioxide on the breastfed child or on milk production. Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with arsenic trioxide and for 2 weeks after the final dose. Arsenic trioxide can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)] . Pregnancy Testing Conduct pregnancy testing in females of reproductive potential prior to initiation of arsenic trioxide. Contraception Females Advise females of reproductive potential to use effective contraception during treatment with arsenic trioxide and for 6 months after the final dose. Males Advise males with female partners of reproductive potential to use effective contraception during treatment with arsenic trioxide and for 3 months after the final dose. Infertility Males Based on testicular toxicities including decreased testicular weight and impaired spermatogenesis observed in animal studies, arsenic trioxide may impair fertility in males of reproductive potential [see Nonclinical Toxicology (13.1)] . The safety and efficacy of arsenic trioxide as a single agent for treatment of pediatric patients with relapsed or refractory APL is supported by the pivotal phase 2 study in 40 patients with relapsed or refractory APL. Five patients below the age of 18 years (age range: 5 to 16 years) were treated with arsenic trioxide at the recommended dose of 0.15 mg/kg/day. A literature review included an additional 17 patients treated with arsenic trioxide for relapsed or refractory APL, with ages ranging from 4 to 21 years. No differences in efficacy and safety were observed by age. Use of arsenic trioxide as monotherapy in patients with relapsed or refractory APL is supported by the open-label, single-arm trial that included 6 patients aged 65 and older (range: 65 to 73 years). A literature review included an additional 4 patients aged 69 to 72 years who were treated with arsenic trioxide for relapsed or refractory APL. No overall differences in safety or effectiveness were observed between these patients and younger patients. Exposure of arsenic trioxide may be higher in patients with severe renal impairment [see Clinical Pharmacology (12.3)] . Monitor patients with severe renal impairment (creatinine clearance [CLcr] less than 30 mL/min) frequently for toxicity; a dose reduction may be warranted. The use of arsenic trioxide in patients on dialysis has not been studied. Since limited data are available across all hepatic impairment groups, caution is advised in the use of arsenic trioxide in patients with hepatic impairment [see Clinical Pharmacology (12.3)] . Monitor patients with severe hepatic impairment (Child-Pugh Class C) frequently for toxicity.

Produkto santrauka:

How Supplied Arsenic trioxide injection is supplied as a sterile, clear, colorless solution in glass, single-dose vials. It is available as follows: 10 mg/10 mL (1 mg/mL) NDC number 83090-009-05 10 mL Single-dose vial (10 mL fill) 12 mg/6 mL (2 mg/mL) NDC number 83090-010-05 10 mL Single-dose vial (6 mL fill) Storage and Handling Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Do not freeze. Arsenic trioxide injection is a hazardous drug. Follow applicable special handling and disposal procedures.1

Autorizacija statusas:

Abbreviated New Drug Application

Prekės savybės

ARSENIC TRIOXIDE- ARSENIC TRIOXIDE INJECTION, SOLUTION
SINTETICA US LLC
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
ARSENIC TRIOXIDE
INJECTION SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR
ARSENIC TRIOXIDE
INJECTION.
ARSENIC TRIOXIDE INJECTION, FOR INTRAVENOUS USE
INITIAL U.S. APPROVAL: 2000
WARNING: DIFFERENTIATION SYNDROME,
CARDIAC CONDUCTION ABNORMALITIES, AND ENCEPHALOPATHY INCLUDING
WERNICKE'S
_SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING._
PATIENTS WITH ACUTE PROMYELOCYTIC LEUKEMIA (APL) TREATED WITH ARSENIC
TRIOXIDE HAVE
EXPERIENCED SYMPTOMS OF DIFFERENTIATION SYNDROME, WHICH MAY BE
LIFE-THREATENING
OR FATAL. IF DIFFERENTIATION SYNDROME IS SUSPECTED, IMMEDIATELY
INITIATE HIGH-DOSE
CORTICOSTEROIDS AND HEMODYNAMIC MONITORING UNTIL RESOLUTION.
TEMPORARILY WITHHOLD
ARSENIC TRIOXIDE. (2.3, 5.1)
ARSENIC TRIOXIDE CAN CAUSE QTC INTERVAL PROLONGATION, COMPLETE
ATRIOVENTRICULAR BLOCK
AND TORSADE DE POINTES, WHICH CAN BE FATAL. BEFORE ADMINISTERING
ARSENIC TRIOXIDE,
ASSESS THE QTC INTERVAL, CORRECT ELECTROLYTE ABNORMALITIES, AND
CONSIDER
DISCONTINUING DRUGS KNOWN TO PROLONG QTC INTERVAL. DO NOT ADMINISTER
ARSENIC
TRIOXIDE TO PATIENTS WITH VENTRICULAR ARRHYTHMIA OR PROLONGED QTC
INTERVAL. WITHHOLD
ARSENIC TRIOXIDE UNTIL RESOLUTION AND RESUME AT REDUCED DOSE FOR QTC
PROLONGATION.
(2.3, 5.2)
SERIOUS ENCEPHALOPATHY, INCLUDING WERNICKE'S, HAS OCCURRED WITH
ARSENIC TRIOXIDE. IF
WERNICKE'S ENCEPHALOPATHY IS SUSPECTED, IMMEDIATELY INTERRUPT ARSENIC
TRIOXIDE AND
INITIATE PARENTERAL THIAMINE. MONITOR UNTIL SYMPTOMS RESOLVE OR
IMPROVE AND
THIAMINE LEVELS NORMALIZE. (5.3)
INDICATIONS AND USAGE
Arsenic trioxide injection is an arsenical indicated:
For induction of remission and consolidation in patients with APL who
are refractory to, or have relapsed
from, retinoid and anthracycline chemotherapy, and whose APL is
characterized by the presence of the
t(15;17) translocation or PML/RAR-alpha gene expression. (1.2)
DOSAGE AND ADMINIS