METHOTREXATE SODIUM tablet

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

METHOTREXATE SODIUM (UNII: 3IG1E710ZN) (METHOTREXATE - UNII:YL5FZ2Y5U1)

Available from:

Hikma Pharmaceuticals USA Inc.

INN (International Name):

METHOTREXATE SODIUM

Composition:

METHOTREXATE 2.5 mg

Administration route:

ORAL

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

Methotrexate Tablets are indicated for the: Methotrexate Tablets are indicated for the treatment of adults with rheumatoid arthritis. Methotrexate Tablets are indicated for the treatment of pediatric patients with polyarticular Juvenile Idiopathic Arthritis (pJIA). Methotrexate Tablets are indicated for the treatment of adults with severe psoriasis. Methotrexate Tablets are contraindicated in: Risk Summary Methotrexate Tablets are contraindicated in pregnant women with non-neoplastic diseases [see Contraindications (4)]. Based on published reports and its mechanism of action [see Clinical Pharmacology (12.1)] , methotrexate can cause embryo-fetal toxicity and fetal death when administered to a pregnant woman. There are no animal data that meet current standards for nonclinical developmental toxicity studies. Advise pregnant women with neoplastic diseases 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 Human Data Published data from case reports, literature reviews, and observational studies report that methotrexate exposure during pregnancy is associated with an increased risk of embryo-fetal toxicity and fetal death. Methotrexate exposure during the first trimester of pregnancy is associated with an increased incidence of spontaneous abortions and multiple adverse developmental outcomes, including skull anomalies, facial dysmorphism, central nervous system abnormalities, limb abnormalities, and sometimes cardiac anomalies and intellectual impairment. Adverse outcomes associated with exposure during second and third trimesters of pregnancy include intrauterine growth restriction and functional abnormalities. Because methotrexate is widely distributed and persists in the body for a prolonged period, there is a potential risk to the fetus from preconception methotrexate exposure. A prospective multicenter study evaluated pregnancy outcomes in women taking methotrexate less than or equal to 30 mg/week after conception. The rate of spontaneous abortion and miscarriage in pregnant women exposed to methotrexate was 42% (95% confidence interval [95% CI] 29, 59), which was higher than in unexposed patients with autoimmune disease (22%; 95% CI: 17, 30) and unexposed patients with nonautoimmune disease (17%; 95% CI: 13, 23). Of the live births, the rate of major birth defects in pregnant women exposed to methotrexate after conception was higher than in unexposed patients with autoimmune disease (adjusted odds ratio (OR) 1.8 [95% CI: 0.6, 6]) and unexposed patients with non-autoimmune disease (adjusted OR 3.1 [95% CI: 1, 10]) (2.9%). Major birth defects associated with pregnancies exposed to methotrexate after conception were not always consistent with methotrexate-associated adverse developmental outcomes. Risk Summary Limited published literature report the presence of methotrexate in human milk in low amounts, with the highest breast milk to plasma concentration ratio reported to be 0.08:1. There are no data on the effects of methotrexate or its metabolites on the breastfed child or their effects on milk production. Because of the potential for serious adverse reactions in a breastfed child, instruct women not to breastfeed during treatment with Methotrexate Tablets and for 1 week after the final dose. Methotrexate can cause malformations and fetal death at doses less than or equal to the recommended clinical doses [Use in Specific Populations (8.1)]. Pregnancy Testing Verify the pregnancy status of females of reproductive potential prior to initiating Methotrexate Tablets [see Contraindications (4), Use in Specific Populations (8.1)]. Contraception Females Advise females of reproductive potential to use effective contraception during treatment with Methotrexate Tablets and for 6 months after the final dose. Males Methotrexate can cause chromosomal damage to sperm cells. Advise males with female partners of reproductive potential to use effective contraception during treatment with Methotrexate Tablets and for 3 months after the final dose. Infertility Females Based on published reports of female infertility after methotrexate, advise females of reproductive potential that methotrexate can cause impairment of fertility and menstrual dysfunction during treatment with Methotrexate Tablets and after the final dose. It is not known if the infertility may be reversed in all affected females. Males Based on published reports of male infertility after methotrexate, advise males that methotrexate can cause oligospermia or infertility during treatment with Methotrexate Tablets and after the final dose. It is not known if the infertility may be reversed in all affected males. The safety and effectiveness of Methotrexate Tablets in pediatric patients have been established for the treatment of ALL as part of the combination chemotherapy maintenance regimen and the treatment of pJIA [see Indications and Usage (1), Dosage and Administration (2)] . No new safety signals have been observed in pediatric patients in clinical studies [see Adverse Reactions (6.1)]. The safety and effectiveness of Methotrexate Tablets have not been established in pediatric patients for the other indications [see Indications and Usage (1)]. Clinical studies of methotrexate did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Methotrexate elimination is reduced in patients with renal impairment [see Clinical Pharmacology (12.3)] . Patients with renal impairment are at increased risk for methotrexate adverse reactions. Closely monitor patients with renal impairment [creatinine clearance (CLcr) less than 90 mL/min, Cockcroft-Gault] for adverse reactions. Reduce the dosage or discontinue Methotrexate Tablets as appropriate [see Warnings and Precautions (5.8)]. The pharmacokinetics and safety of methotrexate in patients with hepatic impairment is unknown. Patients with hepatic impairment may be at increased risk for methotrexate adverse reactions based on the elimination characteristics of methotrexate [see Clinical Pharmacology (12.3)]. Closely monitor patients with hepatic impairment for adverse reactions. Reduce the dosage or discontinue Methotrexate Tablets as appropriate [see Warnings and Precautions (5.5)].

Product summary:

Methotrexate Tablets USP, 2.5 mg (contain an amount of methotrexate sodium equivalent to 2.5 mg of methotrexate, USP) 2.5 mg tablets are supplied as a yellow, round slightly biconvex tablet, scored on one side and product identification “54 323” debossed on the other side. NDC 0054-8550-25: 10x10 Unit-Dose NDC 0054-4550-15: Bottle of 36 Tablets NDC 0054-4550-25: Bottle of 100 Tablets Dispense with a child-resistant closure in a well closed container, as defined in the USP/NF. Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). [See USP Controlled Room Temperature.] Methotrexate Tablets are a cytotoxic drug. Follow applicable special handling and disposal procedures.1

Authorization status:

Abbreviated New Drug Application

Summary of Product characteristics

METHOTREXATE SODIUM- METHOTREXATE SODIUM TABLET
HIKMA PHARMACEUTICALS USA INC.
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
METHOTREXATE TABLETS
SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR
METHOTREXATE TABLETS.
METHOTREXATE TABLETS, FOR ORAL USE
INITIAL U.S. APPROVAL: 1953
WARNING: EMBRYO-FETAL TOXICITY, HYPERSENSITIVITY REACTIONS, AND SEVERE
ADVERSE REACTIONS
_SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING._
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INDICATIONS AND USAGE
Methotrexate Tablets are a dihydrofolate reductase inhibitor indicated
for the:
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DOSAGE AND ADMINISTRATION
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DOSAGE FORMS AND STRENGTHS
Tablets: 2.5 mg (3)
CONTRAINDICATIONS
METHOTREXATE TABLETS CAN CAUSE EMBRYO-FETAL TOXICITY, INCLUDING FETAL
DEATH. FOR
NON-NEOPLASTIC DISEASES, METHOTREXATE TABLETS ARE CONTRAINDICATED IN
PREGNANCY.
FOR NEOPLASTIC DISEASES, ADVISE PATIENTS OF REPRODUCTIVE POTENTIAL OF
THE POTENTIAL
RISK TO A FETUS AND TO USE EFFECTIVE CONTRACEPTION. (4, 5.1, 8.1, 8.3)
METHOTREXATE TABLETS ARE CONTRAINDICATED IN PATIENTS WITH A HISTORY OF
SEVERE
HYPERSENSITIVITY REACTIONS TO METHOTREXATE, INCLUDING ANAPHYLAXIS. (4,
5.2)
SERIOUS ADVERSE REACTIONS, INCLUDING DEATH, HAVE BEEN REPORTED WITH
METHOTREXATE.
CLOSELY MONITOR FOR ADVERSE REACTIONS OF THE BONE MARROW,
GASTROINTESTINAL TRACT,
LIVER, LUNGS, SKIN, AND KIDNEYS. WITHHOLD OR DISCONTINUE METHOTREXATE
TABLETS AS
APPROPRIATE. (5.3, 5.4, 5.5, 5.6, 5.7, 5.8)
Treatment of adults and pediatric patients with acute lymphoblastic
leukemia (ALL) as part of a
combination chemotherapy maintenance regimen (1.1)
Treatment of adults with mycosis fungoides (1.1)
Treatment of adults with relapsed or refractory non-Hodgkin lymphoma
as part of a metronomic
combination regimen (1.1)
Treatment of adults with rheumatoid arthritis (1.2)
Treatment of pediatric patients with polyarticular juvenile idiopathic
arthritis (pJIA) (1.3)
Treatment of adults with severe psoriasis (1.4)
Instru