OXALIPLATIN injection, solution

Riik: Ameerika Ühendriigid

keel: inglise

Allikas: NLM (National Library of Medicine)

Toimeaine:

oxaliplatin (UNII: 04ZR38536J) (oxaliplatin - UNII:04ZR38536J)

Saadav alates:

Meitheal Pharmaceuticals Inc.

INN (Rahvusvaheline Nimetus):

oxaliplatin

Koostis:

oxaliplatin 5 mg in 1 mL

Manustamisviis:

INTRAVENOUS

Retsepti tüüp:

PRESCRIPTION DRUG

Näidustused:

Oxaliplatin Injection, in combination with infusional fluorouracil and leucovorin, is indicated for: - adjuvant treatment of stage III colon cancer in patients who have undergone complete resection of the primary tumor. - treatment of advanced colorectal cancer. Oxaliplatin is contraindicated in patients with a history of a hypersensitivity reaction to oxaliplatin or other platinum-based drugs. Reactions have included anaphylaxis [see Warnings and Precautions (5.1)] . Risk Summary Based on its direct interaction with DNA, oxaliplatin can cause fetal harm when administered to a pregnant woman. The available human data do not establish the presence or absence of major birth defects or miscarriage related to the use of oxaliplatin. Reproductive toxicity studies demonstrated adverse effects on embryo-fetal development in rats at maternal doses that were below the recommended human dose based on body surface area (see Data) . Advise a pregnant woman of the potential risk to a fetus. 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 Animal data Pregnant rats were administered oxaliplatin at less than one-tenth the recommended human dose based on body surface area during gestation days (GD) 1 to 5 (preimplantation), GD 6 to 10, or GD 11 to 16 (during organogenesis). Oxaliplatin caused developmental mortality (increased early resorptions) when administered on days GD 6 to 10 and GD 11 to 16 and adversely affected fetal growth (decreased fetal weight, delayed ossification) when administered on days GD 6 to 10. Risk Summary There are no data on the presence of oxaliplatin or its metabolites in human or animal milk or its effects on the breastfed infant or on milk production. Because of the potential for serious adverse reactions in breastfed infants, advise women not to breastfeed during treatment with oxaliplatin and for 3 months after the final dose. Pregnancy Testing Verify pregnancy status in females of reproductive potential prior to initiating oxaliplatin [see Use in Specific Populations (8.1)] . Contraception Oxaliplatin can cause embryo-fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)] . Females Advise female patients of reproductive potential to use effective contraception while receiving oxaliplatin and for 9 months after the final dose. Males Based on its mechanism action as a genotoxic drug, advise males with female partners of reproductive potential to use effective contraception while receiving oxaliplatin and for 6 months after the final dose [see Nonclinical Toxicology (13.1)] . Infertility Based on animal studies, oxaliplatin may impair fertility in males and females [see Nonclinical Toxicology (13.1)] . The safety and effectiveness of oxaliplatin in pediatrics have not been established. Safety and effectiveness were assessed across 4 open-label studies in 235 patients aged 7 months to 22 years with solid tumors. In a multicenter, open-label, non-comparative, non-randomized study (ARD5531), oxaliplatin was administered to 43 patients with refractory or relapsed malignant solid tumors, mainly neuroblastoma and osteosarcoma. The dose limiting toxicity (DLT) was sensory neuropathy at a dose of 110 mg/m2 . The main adverse reactions were: paresthesia (60%, grade 3 to 4: 7%), fever (40%, grade 3 to 4: 7%), and thrombocytopenia (40%, grade 3 to 4: 27%). No responses were observed. In an open-label non-randomized study (DFI7434), oxaliplatin was administered to 26 pediatric patients with metastatic or unresectable solid tumors, mainly neuroblastoma and ganglioneuroblastoma. The DLT was sensory neuropathy at a dose of 160 mg/m2 . No responses were observed. In an open-label, single-agent study (ARD5021), oxaliplatin was administered to 43 pediatric patients with recurrent or refractory embryonal CNS tumors. The most common adverse reactions reported were: leukopenia (67%, grade 3 to 4: 12%), anemia (65%, grade 3 to 4: 5%), thrombocytopenia (65%, grade 3 to 4: 26%), vomiting (65%, grade 3 to 4: 7%), neutropenia (58%, grade 3 to 4: 16%), and sensory neuropathy (40%, grade 3 to 4: 5%). In an open-label single-agent study (ARD5530), oxaliplatin was administered to 123 pediatric patients with recurrent solid tumors, including neuroblastoma, osteosarcoma, Ewing sarcoma or peripheral PNET, ependymoma, rhabdomyosarcoma, hepatoblastoma, high grade astrocytoma, brain stem glioma, low grade astrocytoma, malignant germ cell tumor and other tumors. The most common adverse reactions reported were: sensory neuropathy (52%, grade 3 to 4: 12%), thrombocytopenia (37%, grade 3 to 4: 17%), anemia (37%, grade 3 to 4: 9%), vomiting (26%, grade 3 to 4: 4%), increased ALT (24%, grade 3 to 4: 6%), increased AST (24%, grade 3 to 4: 2%), and nausea (23%, grade 3 to 4: 3%). The pharmacokinetic parameters of ultrafiltrable platinum were evaluated in 105 pediatric patients during the first cycle. The mean clearance in pediatric patients estimated by the population pharmacokinetic analysis was 4.7 L/h (%CV, 41%). Mean platinum pharmacokinetic parameters in ultrafiltrate were Cmax of 0.75 ± 0.24 mcg/mL, AUC0-48h of 7.52 ± 5.07 mcg∙h/mL and AUCinf of 8.83 ± 1.57 mcg.h/mL at 85 mg/m2 of oxaliplatin and Cmax of 1.10 ± 0.43 mcg/mL, AUC0-48h of 9.74 ± 2.52 mcg.h/mL and AUCinf of 17.3 ± 5.34 mcg.h/mL at 130 mg/m2 of oxaliplatin. In the adjuvant treatment trial [see Clinical Studies (14.1)] , 400 patients who received oxaliplatin with fluorouracil/leucovorin were greater than or equal to 65 years. The effect of oxaliplatin in patients greater than or equal to 65 years was not conclusive. Patients greater than or equal to 65 years receiving oxaliplatin experienced more diarrhea and grade 3 to 4 neutropenia (45% vs 39%) compared to patients less than 65 years. In the previously untreated advanced colorectal cancer trial [see Clinical Studies (14.2)] , 99 patients who received oxaliplatin with fluorouracil and leucovorin were greater than or equal to 65 years. The same efficacy improvements in response rate, time to tumor progression, and overall survival were observed in the greater than or equal to 65 years patients as in the overall study population. Adverse reactions were similar in patients less than 65 and greater than or equal to 65 years, but older patients may have been more susceptible to diarrhea, dehydration, hypokalemia, leukopenia, fatigue, and syncope. In the previously treated advanced colorectal cancer trial [see Clinical Studies (14.3)] , 55 patients who received oxaliplatin with fluorouracil and leucovorin were greater than or equal to 65 years. No overall differences in effectiveness were observed between these patients and younger adults. Adverse reactions were similar in patients less than 65 and greater than or equal to 65 years, but older patients may have been more susceptible to diarrhea, dehydration, hypokalemia, and fatigue. No significant effect of age on the clearance of ultrafiltrable platinum has been observed [see Clinical Pharmacology (12.3)] . The AUC of unbound platinum in plasma ultrafiltrate was increased in patients with renal impairment [see Clinical Pharmacology (12.3)] . No dose reduction is recommended for patients with mild (creatinine clearance 50 to 79 mL/min) or moderate (creatinine clearance 30 to 49 mL/min) renal impairment, calculated by Cockcroft-Gault equation. Reduce the dose of oxaliplatin in patients with severe renal impairment (creatinine clearance less than 30 mL/min) [see Dosage and Administration (2.3)] .

Toote kokkuvõte:

Oxaliplatin Injection, USP is supplied in clear, glass, single-dose, moulded vials with dark gray colored bromobutyl omni flex plus coated rubber stoppers and aluminum flip-off seals containing 50 mg or 100 mg of oxaliplatin as a clear, colorless, sterile, preservative-free, aqueous solution at a concentration of 5 mg per mL. Sterile Aqueous Solution, Nonpyrogenic, Preservative-free. The container closure is not made with natural rubber latex. Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° and 30°C (59° and 86°F). [See USP Controlled Room Temperature.] Do not freeze . Protect from light. Keep in outer carton. Discard unused portion. Oxaliplatin is a cytotoxic drug. Follow applicable special handling and disposal procedures.1 The use of gloves is recommended. If a solution of Oxaliplatin Injection, USP contacts the skin, wash the skin immediately and thoroughly with soap and water. If Oxaliplatin Injection, USP contacts the mucous membranes, flush thoroughly with water.

Volitamisolek:

Abbreviated New Drug Application

Toote omadused

OXALIPLATIN- OXALIPLATIN INJECTION, SOLUTION
MEITHEAL PHARMACEUTICALS INC.
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
OXALIPLATIN INJECTION
SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR
OXALIPLATIN INJECTION.
OXALIPLATIN INJECTION, FOR INTRAVENOUS USE
INITIAL U.S. APPROVAL: 2002
WARNING: HYPERSENSITIVITY REACTIONS, INCLUDING ANAPHYLAXIS
_SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING._
SERIOUS AND FATAL HYPERSENSITIVITY ADVERSE REACTIONS, INCLUDING
ANAPHYLAXIS, CAN OCCUR
WITH OXALIPLATIN WITHIN MINUTES OF ADMINISTRATION AND DURING ANY
CYCLE. OXALIPLATIN IS
CONTRAINDICATED IN PATIENTS WITH HYPERSENSITIVITY REACTIONS TO
OXALIPLATIN AND OTHER
PLATINUM-BASED DRUGS. IMMEDIATELY AND PERMANENTLY DISCONTINUE
OXALIPLATIN FOR
HYPERSENSITIVITY REACTIONS AND ADMINISTER APPROPRIATE TREATMENT. (4,
5.1)
INDICATIONS AND USAGE
Oxaliplatin Injection is a platinum-based drug used in combination
with infusional fluorouracil and
leucovorin, which is indicated for:
adjuvant treatment of stage III colon cancer in patients who have
undergone complete resection of the
primary tumor. (1)
treatment of advanced colorectal cancer. (1)
DOSAGE AND ADMINISTRATION
Administer oxaliplatin injection 85 mg/m as an intravenous infusion
over 120 minutes concurrently with
leucovorin over 120 minutes in separate bags, followed by fluorouracil
on Day 1 of each 14-day cycle.
Administer fluorouracil and leucovorin on Day 2 as recommended. (2.1)
Adjuvant Treatment: Continue treatment for up to 12 cycles or
unacceptable toxicity. (2.1)
Advanced Colorectal Cancer: Continue treatment until disease
progression or unacceptable toxicity.
(2.1)
DOSAGE FORMS AND STRENGTHS
Injection: 50 mg (5 mg per mL) or 100 mg (5 mg per mL) in a
single-dose vial (3)
CONTRAINDICATIONS
History of hypersensitivity reaction to oxaliplatin or other
platinum-based drugs. (4, 5.1)
WARNINGS AND PRECAUTIONS
Peripheral Sensory Neuropathy: Acute and delayed neuropathy can occur.
Avoid topical