METHOTREXATE

2 DOSAGE AND ADMINISTRATION • Instruct patients and caregivers to take the recommended dosage as directed, because medication errors have led to deaths. 9) • Verify pregnancy status in females of reproductive potential before starting methotrexate tablets.

1) • ALL: The recommended dosage is 20 mg/m 2 orally once weekly as a part of a combination chemotherapy maintenance regimen. 2) • Mycosis fungoides: The recommended dosage is 25 to 75 mg orally once weekly as monotherapy; 10 mg/m 2 orally twice weekly as part of combination chemotherapy.

5 mg orally two to four times per week as part of metronomic combination chemotherapy. 5 mg orally once weekly; adjust dose to achieve an optimal response. 3) • pJIA: The recommended starting dosage is 10 mg/m 2 orally once weekly; adjust dose to achieve an optimal response.

4) • Psoriasis: The recommended dosage is 10 to 25 mg orally once weekly until adequate response is achieved. 1)]. 9)]. When switching the dosing regimen from oral administration to intravenous, intramuscular, or subcutaneous administration, an alternative dosing regimen may be necessary.

Do not administer to patients who are unable to swallow a tablet. Methotrexate tablets are a cytotoxic drug. Follow applicable special handling and disposal procedures. 2 Recommended Dosage for Neoplastic Diseases Acute Lymphoblastic Leukemia The recommended starting dosage of methotrexate tablets is 20 mg/m 2 orally once weekly, as part of a combination chemotherapy maintenance regimen.

After initiating methotrexate tablets, periodically monitor absolute neutrophil count (ANC) and platelet count and adjust the dose to maintain ANC at a desirable level and for excessive myelosuppression. Mycosis Fungoides The recommended dosage of methotrexate tablets is 25 to 75 mg orally once weekly when administered as a single agent or 10 mg/m 2 orally twice weekly as part of a combination chemotherapy regimen.

5 mg orally 2 to 4 times per week (maximum 10 mg per week) as part of a metronomic combination chemotherapy regimen. 5 mg orally once weekly with escalation to achieve optimal response. Dosages of more than 20 mg once weekly result in an increased risk of serious adverse reactions, including myelosuppression.

When responses are observed, the majority occurred between 3 and 6 weeks from initiation of treatment; however, responses have occurred up to 12 weeks after treatment initiation. 10)]. 4 Recommended Dosage for Polyarticular Juvenile Idiopathic Arthritis The recommended starting dosage of methotrexate tablets is 10 mg/m 2 orally once weekly with escalation to achieve optimal response.

17)] Common adverse reactions include ulcerative stomatitis, leukopenia, nausea, abdominal distress. gov/medwatch. 1 Clinical Trials Experience Because clinical trials and other studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Common adverse reactions were: ulcerative stomatitis, leukopenia, nausea, and abdominal distress. Other clinically relevant adverse reactions were infection, malaise, fatigue, chills, fever, and dizziness. Rheumatoid Arthritis The most common adverse reactions of methotrexate that exceeded the rate of placebo in 12- to 18-week double-blind studies in patients (n=128) with rheumatoid arthritis are listed below.

5 to 15 mg orally once weekly. Most patients received concomitant nonsteroidal anti-inflammatory drugs (NSAIDs) and some also received corticosteroids. Hepatic histology was not examined in these short-term studies. 5 mg to 15 mg orally once weekly showed the following serious adverse reaction: Incidence 1%: Interstitial pneumonitis Other less common adverse reactions were: anemia, headache, upper respiratory infection, anorexia, arthralgias, chest pain, coughing, dysuria, eye discomfort, epistaxis, fever, infection, sweating, tinnitus, vaginal discharge.

2%. Most patients received concomitant NSAIDs and some also received corticosteroids. Psoriasis In two published series of adults with psoriasis (n=204, 248) who received methotrexate up to 25 mg per week for up to 4 years, adverse reaction rates were similar to those in patients with rheumatoid arthritis, except for alopecia, photosensitivity, and “burning of skin lesions” (3% to 10% each).

Painful plaque erosions have been reported. 2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of methotrexate. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

5 WARNINGS AND PRECAUTIONS • Serious Infections : Monitor patients for infection during and after treatment with methotrexate. Withhold or discontinue methotrexate for serious infections as appropriate. 11) • Neurotoxicity : Monitor patients for neurotoxicity and withhold or discontinue methotrexate as appropriate.

12) • Secondary Malignancies : Can occur with methotrexate. 14) • Immunizations and Risk Live Vaccines : Immunizations with live vaccines is not recommended. Follow current vaccination practice guidelines. 15) • Infertility : Can cause impairment of fertility, oligospermia, and menstrual dysfunction.

1 Embryo-Fetal Toxicity Based on published reports and its mechanism of action, methotrexate can cause fetal harm, including fetal death, when administered to a pregnant woman. Methotrexate is contraindicated for use in pregnant women receiving methotrexate for the treatment of non-malignant diseases.

Advise pregnant women with neoplastic diseases of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with methotrexate and for 6 months after the final dose. 3)]. 1)].

6)]. 1)]. Obtain blood counts at baseline, periodically during treatment, and as clinically indicated. Monitor patients for clinical complications of myelosuppression. 6)]. 4 Gastrointestinal Toxicity Diarrhea, vomiting, nausea, and stomatitis occurred in up to 10% of patients receiving methotrexate for treatment of non-neoplastic diseases.

2)]. 1)]. 6)]. 1)]. The safety of methotrexate in patients with hepatic disease is unknown. The risk of hepatotoxicity is increased with heavy alcohol consumption. 5 g or more. Monitor liver tests at baseline, periodically during treatment and as clinically indicated.

6)]. 2)]. 6)]. 2)]. Exposure to ultraviolet radiation while taking methotrexate may aggravate psoriasis. Methotrexate can cause radiation recall dermatitis and photodermatitis (sunburn) reactivation. 6)]. Advise patients to avoid excessive sun exposure and use sun protection measures.

3)]. • Patients with a history of severe hypersensitivity reactions, including anaphylaxis, to methotrexate. 2)]. • In pregnancy for non-neoplastic diseases (4) • History of severe hypersensitivity to methotrexate (4)