Xatmep (Page 5 of 5)

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

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.

14 CLINICAL STUDIES

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.

15 REFERENCES

1.
“Hazardous Drugs” OSHA. http://www.osha.gov/SLTC/hazardousdrugs/index.html

16 HOW SUPPLIED/STORAGE AND HANDLING

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.

17 PATIENT COUNSELING INFORMATION

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 to contact their healthcare provider for new onset fever, symptoms of infection, easy bruising or persistent bleeding [see Warnings and Precautions (5.1, 5.2)].

Renal Toxicity

Advise patients that methotrexate can cause renal toxicity [see Warnings and Precautions (5.3)].

Gastrointestinal Toxicity

Advise patients to contact their healthcare provider if they develop diarrhea, vomiting, or stomatitis [see Warnings and Precautions (5.4)].

Hepatic Toxicity

Advise patients concerning the risk of hepatic toxicity and avoidance of alcohol during methotrexate treatment [see Warnings and Precautions (5.5)].

Pulmonary Toxicity

Advise patients to contact their healthcare provider for symptoms of cough, fever, and dyspnea [see Warnings and Precautions (5.6)].

Hypersensitivity Reactions

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)].

Secondary Malignancies

Advise patients that there is a risk of secondary malignancies during or following treatment with XATMEP [see Warnings and Precautions (5.8)].

Embryo-Fetal Toxicity

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)].

Infertility

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)].

Lactation

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)].

Manufactured for:

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

PRINCIPAL DISPLAY PANEL — 120 mL Bottle Label

Principal Display Panel -- 120 mL Bottle Label
(click image for full-size original)

120 mL Bottle Label

NDC 52652-2001-1

Xatmep®
(methotrexate)

Oral Solution
2.5 mg/mL

For Oral Use Only

CAUTION: Cytotoxic agent

120 mL

azurity
pharmaceuticals

Rx Only

Each 1 mL contains 2.5 mg
methotrexate (equivalent to
2.74 mg methotrexate sodium).

Usual Dose:
See prescribing information.

KEEP THIS AND ALL MEDICATIONS
OUT OF THE REACH OF CHILDREN

Store refrigerated
2° — 8°C (36° — 46°F)
Patients may store Xatmep
either refrigerated or at
room temperature
(20° — 25°C/68° — 77°F).

If stored at room temperature,
discard after 60 days.

Discard on

_____/_____/_____

Manufactured for:
Azurity Pharmaceuticals, Inc.
Wilmington, MA 01887 USA

Lot:Exp:

XATMEP methotrexate solution
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:52652-2001
Route of Administration ORAL DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
METHOTREXATE (METHOTREXATE) METHOTREXATE 2.5 mg in 1 mL
Inactive Ingredients
Ingredient Name Strength
WATER
SODIUM CITRATE, UNSPECIFIED FORM
CITRIC ACID MONOHYDRATE
METHYLPARABEN SODIUM
PROPYLPARABEN SODIUM
SUCRALOSE
SODIUM HYDROXIDE
HYDROCHLORIC ACID
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:52652-2001-1 120 mL in 1 BOTTLE None
2 NDC:52652-2001-6 60 mL in 1 BOTTLE None
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA NDA208400 05/01/2017
Labeler — Azurity Pharmaceuticals, Inc. (117528301)

Revised: 09/2020 Azurity Pharmaceuticals, Inc.

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