Methotrexatedosage

Verify pregnancy status in females of reproductive potential before starting Methotrexate Injection.

Neoplastic diseases: Refer to the prescribing information for disease specific dosing recommendations. Follow guidelines for high-dose regimens.

RA: Recommended starting dosage of 7.5 mg once weekly intramuscularly; adjust dose to achieve an optimal response. pJIA: Recommended starting dosage of 10 mg/m 2 once weekly subcutaneously or intramuscularly; adjust dose to achieve an optimal response.

Psoriasis: Recommended dosage of 10 mg to 25 mg once weekly intramuscularly or intravenously; adjust dose to achieve optimal response. Once achieved, reduce to lowest possible dosage.

2.1 Important

Dosage and Safety Information Use only preservative-free Methotrexate Injection for treatment of neonates or low birth weight infants and for intrathecal use. Do not use benzyl alcohol-containing formulations for high-dose regimens unless immediate treatment is required and preservative-free formulations are not available. Verify pregnancy status in females of reproductive potential before starting Methotrexate Injection. For patients switching between a methotrexate product administered orally and Methotrexate Injection, consider potential differences in bioavailability.

2.2 Recommended

Monitoring and Concomitant Therapies for Intermediate- and High-Dose Regimens To decrease the risk of severe adverse reactions: Administer leucovorin rescue in patients receiving Methotrexate Injection doses of 500 mg/m 2 or greater (e.g., high-dose). Consider leucovorin rescue for patients receiving Methotrexate Injection doses between 100 mg/m 2 to less than 500 mg/m 2 (e.g., intermediate-dose). Refer to the leucovorin prescribing information for additional information. For high-dose Methotrexate Injection regimens, follow the supportive care and monitoring instructions below. Also consider for patients receiving intermediate-dose Methotrexate Injection regimens. - Monitor serum creatinine, electrolytes, at baseline and at least daily during therapy - Administer intravenous fluids starting before the first dose and continuing throughout treatment to maintain adequate hydration and urine output - Alkalinize urine starting before the first dose and continuing throughout treatment to maintain a urinary pH of 7 or higher - Monitor methotrexate concentrations at least daily and adjust hydration and leucovorin dosing as needed Administer glucarpidase in patients who have toxic plasma methotrexate concentrations (>1 micromole per liter) and delayed methotrexate clearance due to impaired renal function (refer to the glucarpidase prescribing information for additional information).

2.3 Recommended

Dosage for Acute Lymphoblastic Leukemia Methotrexate Injection is used as part of a multi-drug regimen. The recommended dosage varies from 10 to 5000 mg/m 2 intravenously. For high-dose Methotrexate Injection regimens, use leucovorin rescue in accordance with high-dose methotrexate regimen guidelines. Lower doses (e.g., 20 to 30 mg/m 2 per week) may be used intramuscularly. Individualize the dose and schedule of Methotrexate Injection based on disease state, patient risk category, concurrent drugs used, phase of treatment, and response to treatment.

2.4 Recommended

Dosage for Meningeal Leukemia: Prophylaxis and Treatment Use only preservative-free Methotrexate Injection for intrathecal use. Prior to administration, dilute preservative-free Methotrexate Injection to a concentration of 1 mg/mL in preservative-free 0.9% Sodium Chloride Injection, USP. The recommended intrathecal dose of Methotrexate Injection (preservative-free) is based on age: less than 1 year: 6 mg 1 to less than 2 years: 8 mg 2 to less than 3 years: 10 mg 3 to less than 9 years: 12 mg greater than or equal to 9 years: 12 to 15 mg For treatment of meningeal leukemia, intrathecal methotrexate may be given at intervals of 2 or more days up to twice weekly; however, administration at intervals of less than 1 week may result in increased subacute toxicity. For meningeal leukemia prophylaxis, Methotrexate Injection is administered no more than once weekly. For patients with Down Syndrome, administer leucovorin rescue with intrathecal Methotrexate Injection.

2.5 Recommended

Dosage for Non-Hodgkin Lymphoma The recommended dosage of Methotrexate Injection varies. When used in combination, recommended dosages range from 10 mg/m 2 to 8,000 mg/m 2 intravenously. When used as a single agent, recommended dosages include 8,000 mg/m 2 intravenously for central nervous system-directed therapy or 5 to 75 mg intravenously for cutaneous forms of non-Hodgkin lymphoma. As part of a combination chemotherapy regimen, a recommended dosage of Methotrexate Injection is 1,000 mg/m 2 or 3,000 mg/m 2 as an intravenous infusion over 24 hours followed by leucovorin rescue in accordance with high-dose methotrexate regimen guidelines. For central nervous system-directed therapy, a recommended dosage of Methotrexate Injection is 8,000 mg/m 2 as an intravenous infusion over 4 hours as a single agent or in combination with immunochemotherapy at doses ranging from 3,000 mg/m 2 to 8,000 mg/m 2 followed by leucovorin rescue in accordance with high-dose methotrexate regimen guidelines. For intrathecal Methotrexate Injection (preservative-free), the recommended dose is based on age. The frequency of administration varies based on whether it is being used for treatment or prophylaxis, and other factors.

2.6 Recommended

Dosage for Osteosarcoma The recommended dosage of Methotrexate Injection is typically 12 g/m 2 (maximum 20 g/dose) as an intravenous infusion over 4 hours administered as a component of a combination chemotherapy regimen. Administer leucovorin rescue in accordance with high-dose methotrexate regimen guidelines. Subsequent doses may need to be adjusted based on observed peak serum methotrexate concentrations. Dosage and schedule may vary based upon factors such as patient comorbidities, disease state, and prior treatments.

2.7 Recommended

Dosage for Breast Cancer A recommended dosage of Methotrexate Injection is 40 mg/m 2 intravenously as a component of a cyclophosphamide- and fluorouracil-based multi-drug regimen.

2.8 Recommended

Dosage for Squamous Cell Carcinoma of Head and Neck The recommended dosage of Methotrexate Injection ranges from 40 to 60 mg/m 2 intravenously once weekly.

2.9 Recommended

Dosage for Gestational Trophoblastic Neoplasia For patients with low-risk gestational trophoblastic neoplasia (GTN) a recommended dosage for Methotrexate Injection is 30 mg/m 2 to 200 mg/m 2 or 0.4 mg/kg to 1 mg/kg intravenously or intramuscularly. For patients with high-risk GTN, a recommended dosage for Methotrexate Injection is 300 mg/m 2 over 12 hours as an intravenous infusion as a component of a multi-drug regimen.

2.10 Recommended

Dosage for Rheumatoid Arthritis The recommended starting dosage of Methotrexate Injection is 7.5 mg once weekly, administered intramuscularly 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. Administer folic acid or folinic acid to reduce the risk of methotrexate adverse reactions.

2.11 Recommended

Dosage for Polyarticular Juvenile Idiopathic Arthritis The recommended starting dosage of Methotrexate Injection is 10 mg/m 2 once weekly administered subcutaneously or intramuscularly, with escalation to achieve optimal response. Dosages over 30 mg/m 2 per week may 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. Administer folic acid or folinic acid to reduce the risk of methotrexate adverse reactions.

2.12 Recommended

Dosage for Psoriasis The recommended dosage of Methotrexate Injection is 10 mg to 25 mg intramuscularly or intravenously once weekly until adequate response is achieved. Adjust the dose gradually to achieve optimal clinical response; do not exceed 25 mg per week. Once optimal clinical response has been achieved, reduce the dosage to the lowest possible dosing regimen. Administer folic acid or folinic acid to reduce the risk of methotrexate adverse reactions.

2.13 Dosage Modifications for

Adverse Reactions Discontinue Methotrexate Injection for: Anaphylaxis or other severe hypersensitivity reactions Lymphoproliferative disease Withhold, dose reduce or discontinue Methotrexate Injection as appropriate for: Myelosuppression Withhold or discontinue Methotrexate Injection as appropriate for: Serious infections Renal toxicity Hepatotoxicity Neurotoxicity Gastrointestinal toxicity Pulmonary toxicity Dermatologic reactions

2.14 Administration and

Handling Information Methotrexate Injection is a hazardous drug. Follow applicable special handling and disposable procedures. 1 Preservative-Free (Single-Dose Vial) Methotrexate Injection preservative-free may be administered by intramuscular, intravenous, subcutaneous, or intrathecal injection. Use only preservative-free Methotrexate Injection for treatment of neonates or low-birth weight infants and for intrathecal use. Use preservative-free Methotrexate Injection for high-dose regimens unless immediate treatment is required, and preservative-free formulations are not available. Preservative-free Methotrexate Injection may be further diluted before use with preservative-free 0.9% Sodium Chloride Injection, USP. Diluted product should be used within 4 hours when stored at room temperature (20°C to 25°C) or 24 hours when stored under refrigeration (2°C to 8°C). Visually inspect for particulate matter and discoloration prior to administration. Discard if particulate matter or discoloration is observed.