Xatmep

Methotrexate interferes with the growth of certain cells of the body, especially cells that reproduce quickly, such as cancer cells, bone marrow cells, and skin cells.

Methotrexate is used to treat certain types of cancer of the breast, skin, head and neck, or lung. Methotrexate is also used to treat severe psoriasis and rheumatoid arthritis.

Methotrexate is usually given after other medications have been tried without successful treatment of symptoms.

Methotrexate may also be used for purposes not listed in this medication guide.

Methotrexate is usually not taken every day. You must use the correct dose of methotrexate for your condition. Some people have died after taking methotrexate every day by accident.

Do not use methotrexate if you are pregnant or breast-feeding a baby.

Do not use methotrexate to treat psoriasis or rheumatoid arthritis if you have liver disease (especially if caused by alcoholism), or a blood cell or bone marrow disorder.

Call your doctor if you have unusual bruising or bleeding, or signs of infection (fever, chills, body aches).

Methotrexate can cause serious or life-threatening side effects on your liver, lungs, or kidneys. Tell your doctor if you have upper stomach pain, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes), dry cough, shortness of breath, blood in your urine, or little or no urinating.

You should not use this medicine if you are allergic to methotrexate. Do not use methotrexate to treat psoriasis or rheumatoid arthritis if you have:

• alcoholism, cirrhosis, or other liver disease;

• a blood cell disorder such as anemia (lack of red blood cells) or leukopenia (lack of white blood cells);

• a bone marrow disorder; or

• if you are breast-feeding a baby.

Methotrexate is sometimes used to treat cancer even when patients do have one of the conditions listed above. Your doctor will decide if this treatment is right for you.

To make sure methotrexate is safe for you, tell your doctor if you have:

• kidney disease;

• a folate deficiency;

• pneumonia or lung disease;

• stomach ulcers;

• any type of infection; or

• if you are receiving radiation treatments.

Methotrexate can cause birth defects in an unborn baby. Do not use methotrexate to treat psoriasis or rheumatoid arthritis if you are pregnant. Tell your doctor right away if you become pregnant during treatment.

You may need to have a negative pregnancy test before starting this treatment.

Use birth control to prevent pregnancy while you are using methotrexate, whether you are a man or a woman. Methotrexate use by either parent may cause birth defects.

If you are a man, use a condom to keep from causing a pregnancy while you are using methotrexate. Continue using condoms for at least 3 months after your last dose.

If you are a woman, use an effective form of birth control while you are taking methotrexate, and for 6 months after your last dose.

This medicine may affect fertility (your ability to have children), whether you are a man or a woman.

Methotrexate can pass into breast milk and may harm a nursing baby. You should not breast-feed while using this medicine.

Do not give this medicine to a child without the advice of a doctor.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. An overdose of methotrexate can be fatal.

In the U.S.

• Rheumatrex Dose Pack
• Trexall
• Xatmep

Available Dosage Forms:

• Solution
• Tablet

Therapeutic Class: Antineoplastic Agent

Pharmacologic Class: Antimetabolite

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of methotrexate for the treatment of cancer (including acute lymphoblastic leukemia) and juvenile idiopathic arthritis in children. However, safety and efficacy have not been established in children with psoriasis.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of methotrexate in the elderly. However, elderly patients are more likely to have kidney problems, which may require caution and an adjustment in the dose.

Breast Feeding

Studies in women breastfeeding have demonstrated harmful infant effects. An alternative to this medication should be prescribed or you should stop breastfeeding while using this medicine.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Measles Virus Vaccine, Live
• Mumps Virus Vaccine, Live
• Rotavirus Vaccine, Live
• Rubella Virus Vaccine, Live
• Varicella Virus Vaccine

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Aceclofenac
• Acemetacin
• Adenovirus Vaccine
• Amoxicillin
• Amtolmetin Guacil
• Asparaginase
• Aspirin
• Bacillus of Calmette and Guerin Vaccine, Live
• Bentiromide
• Bromfenac
• Bufexamac
• Capecitabine
• Celecoxib
• Chloral Hydrate
• Cholera Vaccine, Live
• Choline Salicylate
• Clonixin
• Dantrolene
• Dasabuvir
• Dexibuprofen
• Dexketoprofen
• Dexlansoprazole
• Diclofenac
• Dicloxacillin
• Diflunisal
• Dipyrone
• Doxifluridine
• Doxycycline
• Droxicam
• Esomeprazole
• Etodolac
• Etofenamate
• Felbinac
• Fenbufen
• Fenoprofen
• Fepradinol
• Feprazone
• Floctafenine
• Floxacillin
• Flufenamic Acid
• Fluorouracil
• Flurbiprofen
• Foscarnet
• Fosphenytoin
• Hydrochlorothiazide
• Ibuprofen
• Ibuprofen Lysine
• Indomethacin
• Influenza Virus Vaccine, Live
• Ketoprofen
• Ketorolac
• Leflunomide
• Levetiracetam
• Lornoxicam
• Loxoprofen
• Lumiracoxib
• Meclofenamate
• Mefenamic Acid
• Meloxicam
• Mezlocillin
• Morniflumate
• Nabumetone
• Naproxen
• Nepafenac
• Niflumic Acid
• Nimesulide
• Nimesulide Beta Cyclodextrin
• Omeprazole
• Oxaprozin
• Oxyphenbutazone
• Pantoprazole
• Parecoxib
• Penicillin G
• Penicillin V
• Phenylbutazone
• Phenytoin
• Piketoprofen
• Piperacillin
• Piroxicam
• Pirprofen
• Poliovirus Vaccine, Live
• Pristinamycin
• Probenecid
• Proglumetacin
• Propionic Acid
• Propyphenazone
• Proquazone
• Pyrimethamine
• Rabeprazole
• Salicylic Acid
• Salsalate
• Simeprevir
• Smallpox Vaccine
• Sodium Salicylate
• Sulfamethizole
• Sulfamethoxazole
• Sulfapyridine
• Sulfisoxazole
• Sulindac
• Tamoxifen
• Tegafur
• Tenoxicam
• Teriflunomide
• Tiaprofenic Acid
• Ticarcillin
• Tolfenamic Acid
• Tolmetin
• Triamterene
• Trimethoprim
• Typhoid Vaccine
• Valdecoxib
• Warfarin
• Yellow Fever Vaccine

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Amiodarone
• Cyclosporine
• Eltrombopag
• Etoricoxib
• Mercaptopurine
• Procarbazine
• Rofecoxib
• Theophylline

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following is usually not recommended, but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.

• Cola

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Alcohol abuse, or history of or
• Anemia or
• Leukopenia (low white blood cells) or
• Liver disease, severe or
• Thrombocytopenia (low platelet blood level) or
• Weak immune system—Methotrexate tablets should not be used in patients with these conditions.

• Ascites (extra fluid in the stomach area) or
• Kidney disease or
• Pleural effusion (extra fluid in the lung)—Use with caution. The effects may be increased because of slower removal of the medicine from the body.

• Diabetes or
• Liver disease or
• Obesity or
• Peptic ulcers or
• Ulcerative colitis (inflammation of the colon)—Use with caution. May cause side effects to become worse.

• Infection (bacteria, fungus, virus)—Use with caution. May decrease your ability to fight an infection.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of infection like fever, chills, very bad sore throat, ear or sinus pain, cough, more sputum or change in color of sputum, pain with passing urine, mouth sores, or wound that will not heal.
• Signs of bleeding like throwing up blood or throw up that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; vaginal bleeding that is not normal; bruises without a reason or that get bigger; or any bleeding that is very bad or that you cannot stop.
• Signs of a pancreas problem (pancreatitis) like very bad stomach pain, very bad back pain, or very bad upset stomach or throwing up.
• Signs of kidney problems like unable to pass urine, change in how much urine is passed, blood in the urine, or a big weight gain.
• Signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.
• Signs of lung or breathing problems like shortness of breath or other trouble breathing, cough, or fever.
• Pinpoint red spots on the skin.
• Very bad dizziness or passing out.
• Seizures.
• Feeling confused.
• Change in eyesight.
• Bone pain.
• Swelling, warmth, numbness, change of color, or pain in a leg or arm.
• Weakness on 1 side of the body, trouble speaking or thinking, change in balance, drooping on one side of the face, or blurred eyesight.
• Headache.
• Neck stiffness.
• Not able to move.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about this medicine, please talk with your doctor, nurse, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take Xatmep (methotrexate oral solution) or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to Xatmep. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Review Date: October 4, 2017

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.

Importance of Proper Dosing and Administration

Advise patient 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 (5.5)].

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 patient 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) for up to 60 days; excursions permitted to 15°C to 30°C (59°F to 86°F). Inform patients and caregivers of the need for proper storage and disposal of dispensing bottles and dosing devices [see References (15)].

Manufactured For:

Silvergate Pharmaceuticals, Inc.
6251 Greenwood Plaza Blvd, Ste 101
Greenwood Village, CO 80111

MTX-1704b