Methotrexate has been evaluated in a number of animal studies for carcinogenic potential with inconclusive results. Although there is evidence that methotrexate causes chromosomal damage to animal somatic cells and human bone marrow cells, the clinical significance remains uncertain.
Polyarticular Juvenile Idiopathic Arthritis
Clinical trials in patients with polyarticular juvenile idiopathic arthritis were performed using other formulations of methotrexate.
In a 6-month, double-blind, placebo-controlled trial of 127 pediatric patients with juvenile idiopathic arthritis (JIA) (mean age, 10.1 years; age range 2.5 to 18 years, mean duration of disease, 5.1 years) on background non-steroidal anti-inflammatory drugs (NSAIDs) and/or prednisone, methotrexate given one time weekly at an oral dose of 10 mg/m2 provided significant clinical improvement compared to placebo as measured by either the physician’s global assessment, or by a patient composite (25% reduction in the articular-severity score plus improvement in parent and physician global assessments of disease activity). Over two-thirds of the patients in this trial had polyarticular-course JIA, and the numerically greatest response was seen in this subgroup treated with 10 mg/m2 /week methotrexate. The overwhelming majority of the remaining patients had systemic-course JIA. All patients were unresponsive to NSAIDs; approximately one-third were using low dose corticosteroids. Weekly methotrexate at a dose of 5 mg/m2 was not significantly more effective than placebo in this trial.
- “Hazardous Drugs” OSHA. http://www.osha.gov/SLTC/hazardousdrugs/index.html
XATMEP is a clear yellow to orange oral solution that contains 2.5 mg of methotrexate per milliliter (equivalent to 2.74 mg of methotrexate sodium/mL). It is packaged in a high-density polyethylene (HDPE) bottle with a child-resistant cap and tamper-evident seal.
XATMEP is available in bottles of 60 mL (NDC 52652-2001-6) and 120 mL (NDC 52652-2001-1).
Store XATMEP refrigerated (2°C to 8°C/36°F to 46°F) tightly closed in the original container prior to dispensing.
Once dispensed, patients may store XATMEP either refrigerated (2°C to 8°C/36°F to 46°F) or at room temperature (20°C to 25°C/68°F to 77°F) with excursions permitted to 15°C to 30°C/59°F to 86°F [see USP Controlled Room Temperature]. If stored at room temperature, discard after 60 days. Avoid freezing and excessive heat.
Importance of Proper Dosing and Administration
Advise patients that the recommended dose should be taken one time weekly, as directed, and that mistaken daily use of the recommended dose has led to fatal toxicity [see Dosage and Administration (2.1), Warnings and Precautions ( 5.15)].
Advise patients and caregivers to measure XATMEP with an accurate milliliter measuring device. A household teaspoon is not an accurate measuring device. Advise patients and caregivers to ask their pharmacist to recommend an appropriate measuring device and for instructions for measuring the correct dose.
Bone Marrow Suppression and Serious Infections
Advise patients that methotrexate can cause renal toxicity [see Warnings and Precautions (5.3)].
Advise patients to contact their healthcare provider if they develop diarrhea, vomiting, or stomatitis [see Warnings and Precautions (5.4)].
Advise patients concerning the risk of hepatic toxicity and avoidance of alcohol during methotrexate treatment [see Warnings and Precautions (5.5)].
Advise patients to contact their healthcare provider for symptoms of cough, fever, and dyspnea [see Warnings and Precautions (5.6)].
Advise patients concerning the risk for severe hypersensitivity reactions due to XATMEP treatment. These can be fatal and may include severe dermatologic reactions such as toxic epidermal necrolysis, Stevens-Johnson syndrome, exfoliative dermatitis, and erythema multiforme. Advise patients to contact their healthcare provider for signs of a new or worsening rash [see Warnings and Precautions (5.7)].
Advise patients that there is a risk of secondary malignancies during or following treatment with XATMEP [see Warnings and Precautions (5.8)].
Advise females of reproductive potential of the potential risk to a fetus and to inform their healthcare provider of a known or suspected pregnancy [see Boxed Warning, Contraindications (4), Warnings and Precautions (5.9), Use in Specific Populations (8.1)].
Advise females of reproductive potential to use effective contraception during XATMEP therapy and for 6 months after the final dose [see Use in Specific Populations (8.3)].
Advise males of reproductive potential to use effective contraception during XATMEP therapy and for 3 months after the final dose [see Use in Specific Populations (8.3)].
Ineffective Immunization and Risks Associated with Live Vaccines
Advise patients to avoid receiving vaccines during treatment with XATMEP because they may not be effective and live virus vaccines may cause infection [see Warnings and Precautions (5.10)].
Advise patients of reproductive potential that XATMEP may cause impairment of fertility, oligospermia, and menstrual dysfunction [see Warnings and Precautions (5.11), Use in Specific Populations (8.3)].
Advise females not to breastfeed during therapy with XATMEP [see Use in Specific Populations (8.2)].
Proper Storage and Disposal
Advise patients to store XATMEP either refrigerated (2°C to 8°C/36°F to 46°F) or at room temperature (20°C to 25°C/68°F to 77°F) with excursions permitted to 15°C to 30°C/59°F to 86°F. If stored at room temperature, discard after 60 days. Inform patients and caregivers of the need for proper storage and disposal of dispensing bottles and dosing devices [see References (15)].
Azurity Pharmaceuticals, Inc.Wilmington, MA 01887 USA
U.S. Patent: 9,259,427; 9,855,215
This product’s label may have been updated. For current full prescribing information, please visit www.xatmep.com
PI100072.03 Rev. 9/2020
120 mL Bottle Label
For Oral Use Only
CAUTION: Cytotoxic agent
Each 1 mL contains 2.5 mg
methotrexate (equivalent to
2.74 mg methotrexate sodium).
See prescribing information.
KEEP THIS AND ALL MEDICATIONS
OUT OF THE REACH OF CHILDREN
2° — 8°C (36° — 46°F)
Patients may store Xatmep
either refrigerated or at
(20° — 25°C/68° — 77°F).
If stored at room temperature,
discard after 60 days.
Azurity Pharmaceuticals, Inc.
Wilmington, MA 01887 USA
|XATMEP methotrexate solution|
|Labeler — Azurity Pharmaceuticals, Inc. (117528301)|
Revised: 09/2020 Azurity Pharmaceuticals, Inc.
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