AdultPediatricGeriatricDosage Forms & Strengths injectable solution 25mg/mL powder for injection 1g/vial (25mg/mL when reconstituted) SC autoinjector (Otrexup) 7.5 mg/0.4mL 10mg/0.4mL 12.5mg/0.4mL 15mg/0.4mL 17.5mg/0.4mL 20mg/0.4mL 22.5mg/0.4mL 25mg/0.4mL SC autoinjector (Rasuvo) 2.5mg/0.05mL (delivers doses between 7.5 mg and 30 mg in 2.5 mg increments) SC prefilled syringe (RediTrex) 7.5mg/0.3mL 10mg/0.4mL 12.5mg/0.5mL 15mg/0.6mL 17.5mg/0.7mL 20mg/0.8mL 22.5mg/0.9mL 25mg/mL tablet 2.5mg 5mg 7.5mg 10mg 15mg oral solution (Jylamvo) 2mg/mL Acute Lymphoblastic Leukemia Indicated for adult and pediatric patients with acute lymphoblastic leukemia (ALL) as part of a combination chemotherapy regimen IV: Varies from 10-5,000 mg/m2; dose varies and depends disease state, patient risk category, concurrent drugs used, phase of treatment and response to treatment Use leucovorin rescue in accordance with high-dose methotrexate IV regimen guidelines Meningeal Leukemia Indicated for prophylaxis and treatment of meningeal leukemia in adult and pediatric patients Use preservative-free methotrexate for intrathecal (IT) injection Treatment: 12 mg IT; not to exceed 15 mg/dose every 2-7 days; administer 1 additional dose after cell count on CSF returns to normal Prophylaxis: 12-15 mg IT no more than once weekly Patients with Down syndrome: Administer leucovorin rescue with methotrexate IT Non-Hodgkin Lymphoma Indicated for treatment of adults and pediatric patients with Non-Hodgkin lymphoma (NHL) Recommended dosage varies; refer to specific institutional protocol See leucovorin rescue protocols for intermediate- and high-dose methotrexate regimens Combination with other antineoplastics Range 10-8,000 mg/m2 IV Part of combination chemotherapy regimen: 1,000-3,000 mg/m2 IV infusion over 24 hr followed by leucovorin rescue in accordance with high-dose methotrexate regimen guidelines Single agent Cutaneous forms of NHL: 5-75 mg IV CNS-directed therapy Single agent: 8,000 mg/m2 IV infusion over 4 hr Combination with immunochemotherapy: 3,000-8,000 mg/m2 IV infusion followed by leucovorin rescue in accordance with high-dose methotrexate regimen guidelines Osteosarcoma Indicated for the treatment of adults and pediatric patients with osteosarcoma as part of a combination chemotherapy regimen 12 g/m2 IV over 4 hr on weeks 4, 5, 6, 7, 11, 12, 15, 16, 29, 30, 44, and 45 after surgery in combination with other chemotherapy If peak serum methotrexate <454 mcg/mL at end of initial infusion, dose may be increased to 15 g/m2 in subsequent treatments Not to exceed 20 g/dose Administer leucovorin rescue in accordance with high-dose methotrexate regimen guidelines Breast Cancer Indicated for breast cancer as part of a combination chemotherapy regimen 40 mg/m2 IV as a component of a cyclophosphamide- and fluorouracil-based multidrug regimen Squamous Cell Carcinoma of the Head and Neck Indicated for squamous cell carcinoma of the head and neck as a single-agent 40-60 mg/m2 IV qWeek Gestational Trophoblastic Neoplasia Indicated for adults with gestational trophoblastic neoplasia (GTN) as part of a combination chemotherapy regimen 30-200 mg/m2 or 0.4-1 mg/kg IV or IM High-risk GTN: 300 mg/m2 IV infused over 12 hr as a component of a multidrug regimen Rheumatoid Arthritis Indicated for management of severe, active rheumatoid arthritis (RA) in adults who have had an insufficient response or intolerance to an adequate trial of first-line therapy including full dose NSAIDs Initial: 7.5 mg PO/IV/IM as a single weekly dose, OR 2.5 mg PO q12hr for 3 sequential doses per week Increase dose to optimum response; single dose not to exceed 20 mg/week PO (increased risk of bone marrow suppression); reduce to lowest possible effective dose Otrexup (SC): If used as initial therapy, start at lowest available dose (ie, 10 mg SC qWeek) Rasuvo or RediTrex (SC), initial dose: 7.5 mg as a single SC dose once weekly; adjust autoinjector dose by 2.5 mg increments as clinically required Administer folic acid or folinic acid to reduce the risk of methotrexate adverse reactions Psoriasis For symptomatic control of severe, recalcitrant, disabling psoriasis in adults not adequately responsive to other forms of therapy; use only with established diagnosis (by biopsy and/or after dermatologic consultation) Initial: 10-25 mg weekly in single PO/SC/IM/IV dose; not to exceed 30 mg/wk Gradually adjust dose to achieve to optimal clinical response; use lowest dose and longest rest period possible with return to conventional topical therapy encouraged Trexall: May give weekly dose divided as 2.5 mg PO q12hr for 3 sequential doses Otrexup (SC): If used as initial therapy, start a lowest available dose (ie, 10 mg SC qWeek) Rasuvo or RediTrex (SC): 10-25 mg SC once weekly Administer folic acid or folinic acid to reduce the risk of methotrexate adverse reactions Dosage Modifications Renal impairment Methotrexate elimination reduced with CrCl <90 mL/min Patients with renal impairment are at increased risk for adverse effects; carefully monitor for toxicity Follow recommendations to promote methotrexate elimination and decrease risk of acute kidney injury and other methotrexate toxicities in patients who are receiving intermediate- or high-dose regimens Some patients may require dose reduction or, in some cases, discontinuation Hepatic impairment Safety in patients with hepatic impairment is unknown Patients with hepatic impairment may be at increased risk for adverse reactions based on methotrexate elimination characteristics Consider dose reduction or discontinuing with hepatic impairment as appropriate Dosing Considerations Otrexup and Rasuvo (SC injections) are not indicated for neoplastic disease If switching from PO to SC (Otrexup, Rasuvo), consider higher bioavailability with SC compared with PO (see Pharmacology Absorption section) Ectopic Pregnancy (Off-label) 50 mg/m² IM; measure serum hCG levels on days 4 and 7; may repeat dose on day 7 if necessary If hCG levels decrease <15% between days 4 and 7, administer methotrexate 50 mg/m² IM; if hCG ≥15% between days 4 and 7, discontinue treatment and measure hCG weekly until reaching nonpregnant levels Myasthenia Gravis (Orphan) Orphan designation for treatment of myasthenia gravis Orphan Sponsor University of Kansas Medical Center; 3901 Rainbow Blvd, MSN 2012; Kansas City, KS 66160 Proliferative Vitreoretinopathy (Orphan) Orphan designation for prevention of proliferative vitreoretinopathy (PVR) Orphan Sponsor Helio Vision, Inc; 1000 Winter Street, 4th Floor; Waltham, Massachusetts 02451 Ectopic Pregnancy (Orphan) Orphan designation for treatment of ectopic pregnancy Orphan sponsor Antares Pharma, Inc; Princeton Crossroads Corporate Center; 100 Princeton South Suite 300; Ewing, New Jersey 08628 Dosage Forms & Strengths injectable solution 25mg/mL powder for injection 1g/vial (25mg/mL when reconstituted) SC autoinjector (Otrexup) 7.5mg/0.4mL 10mg/0.4mL 12.5mg/0.4mL 15mg/0.4mL 17.5mg/0.4mL 20mg/0.4mL 22.5mg/0.4mL 25mg/0.4mL SC autoinjector (Rasuvo) 2.5mg/0.05mL (delivers doses between 7.5 mg and 30 mg in 2.5 mg increments) SC prefilled syringe (RediTrex) 7.5mg/0.3mL 10mg/0.4mL 12.5mg/0.5mL 15mg/0.6mL 17.5mg/0.7mL 20mg/0.8mL 22.5mg/0.9mL 25mg/mL tablet 2.5mg 5mg 7.5mg 10mg 15mg oral solution, ready-to-use (Xatmep) 2.5mg/mL Polyarticular Juvenile Idiopathic Arthritis Management of active polyarticular juvenile idiopathic arthritis (pJIA) in children who have had an insufficient response or intolerance to an adequate trial of first-line therapy including full dose NSAIDs Initial: 10 mg/m² PO/IM/SC qWeek If switching from PO to SC (Otrexup, Rasuvo, RediTrex), consider higher bioavailability with SC compared with PO (see Pharmacology Absorption section) Dosing Considerations (PJIA) Data with doses up to 30 mg/m²/wk in children exist, although there are too few published studies to assess how doses >20 mg/m²/wk might affect the risk of serious toxicity in children, especially bone marrow suppression Experience does suggest, however, that children receiving 20 to 30 mg/m²/wk (0.65-1 mg/kg/wk) may have better absorption and fewer GI side effects if methotrexate is administered either IM or SC Administer folic acid or folinic acid to reduce the risk of methotrexate adverse reactions Meningeal Leukemia Indicated for prophylaxis and treatment of meningeal leukemia in adult and pediatric patients Use preservative-free methotrexate for intrathecal (IT) injection Treatment: Dose may be given at intervals of ≥2 days up to twice weekly; however, administration at intervals of <1 week may result in increased subacute toxicity Prophylaxis: Administered no more than once weekly Patients with Down syndrome: Administer leucovorin rescue with methotrexate IT Age-based dosing <1 year: 6 mg IT 1 to <2 years: 8 mg IT 2 to <3 years: 10 mg IT 3 to <9 years: 12 mg IT ≥9 years: 12-15 mg IT Acute Lymphoblastic Leukemia Indicated for treatment of pediatric patients with acute lymphoblastic leukemia (ALL) as part of a multi-phase, combination chemotherapy regimen IV: Varies from 10-5,000 mg/m2; dose varies and depends disease state, patient risk category, concurrent drugs used, phase of treatment and response to treatment Oral solution (Xatmep): 20 mg/m2 PO qWeek Use leucovorin rescue in accordance with high-dose methotrexate IV regimen guidelines Non-Hodgkin Lymphoma Indicated for treatment of adults and pediatric patients with Non-Hodgkin lymphoma (NHL) Recommended dosage varies; refer to specific institutional protocol See leucovorin rescue protocols for intermediate- and high-dose methotrexate regimens Combination with other antineoplastics Range 10-8,000 mg/m2 IV Part of combination chemotherapy regimen: 1,000-3,000 mg/m2 IV infusion over 24 hr followed by leucovorin rescue in accordance with high-dose methotrexate regimen guidelines Single agent Cutaneous forms of NHL: 5-75 mg IV CNS-directed therapy Single agent: 8,000 mg/m2 IV infusion over 4 hr Combination with immunochemotherapy: 3,000-8,000 mg/m2 IV infusion followed by leucovorin rescue in accordance with high-dose methotrexate regimen guidelines Osteosarcoma Indicated for adults and pediatric patients with osteosarcoma as part of a combination chemotherapy regimen 12 g/m2 IV over 4 hr on weeks 4, 5, 6, 7, 11, 12, 15, 16, 29, 30, 44, and 45 after surgery in combination with other chemotherapy Not to exceed 20 g/dose Administer leucovorin rescue in accordance with high-dose methotrexate regimen guidelines If peak serum methotrexate <454 mcg/mL at end of initial infusion, dose may be increased to 15 g/m2 in subsequent treatments Dosage Modifications Renal impairment Methotrexate elimination reduced with CrCl <90 mL/min Patients with renal impairment are at increased risk for adverse effects; carefully monitor for toxicity Follow recommendations to promote methotrexate elimination and decrease risk of acute kidney injury and other methotrexate toxicities in patients who are receiving intermediate- or high-dose regimens Some patients may require dose reduction or, in some cases, discontinuation Hepatic impairment Safety in patients with hepatic impairment is unknown Patients with hepatic impairment may be at increased risk for adverse reactions based on methotrexate elimination characteristics Consider dose reduction or discontinuing with hepatic impairment as appropriate Dosing Considerations May impair fertility, cause oligospermia, and menstrual dysfunction; exclude pregnancy before initiating treatment Otrexup and Rasuvo (SC injections) are not indicated for neoplastic disease If switching from PO to SC (Otrexup, Rasuvo), consider higher bioavailability with SC compared with PO (see Pharmacology Absorption section) 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 Leucovorin rescue Administer leucovorin rescue doses ≥500 mg/m2 (ie, high-dose) Consider leucovorin rescue for doses 100 to <500 mg/m2 (ie, intermediate-dose) Supportive care For high-dose regimens, the following are recommended; also consider for intermediate-dose regimens Monitor serum creatinine, electrolytes, at baseline and at least daily during therapy Administer IV fluids starting before first dose and continue throughout treatment to maintain hydration and urine output Alkalinize urine starting before first dose and continue throughout treatment to maintain urine pH ≥7 Monitor methotrexate concentrations at least daily and adjust hydration and leucovorin dosing as needed Glucarpidase: Administer in patients with toxic plasma methotrexate concentrations (>1 micromole/L) and delayed methotrexate clearance owing to impaired renal function Monitor closely for early signs of bone marrow suppression, and renal or hepatic toxicity Interaction CheckerEnter a drug name and methotrexateNo Results No Interactions Found Interactions FoundContraindicatedSerious - Use AlternativeSignificant - Monitor CloselyMinorAll Interactions Sort By: SeverityName Contraindicated (10)acitretinacitretin, methotrexate. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated. Risk of additive hepatotoxicity.influenza virus vaccine quadrivalent, intranasalmethotrexate decreases effects of influenza virus vaccine quadrivalent, intranasal by pharmacodynamic antagonism. Contraindicated. Immunization with live virus vaccines is generally not recommended.measles mumps and rubella vaccine, livemethotrexate decreases effects of measles mumps and rubella vaccine, live by pharmacodynamic antagonism. Contraindicated. Immunization with live virus vaccines is generally not recommended.measles, mumps, rubella and varicella vaccine, livemethotrexate decreases effects of measles, mumps, rubella and varicella vaccine, live by pharmacodynamic antagonism. Contraindicated. Immunization with live virus vaccines is generally not recommended.rotavirus oral vaccine, livemethotrexate decreases effects of rotavirus oral vaccine, live by pharmacodynamic antagonism. Contraindicated. Immunization with live virus vaccines is generally not recommended.smallpox (vaccinia) vaccine, livemethotrexate decreases effects of smallpox (vaccinia) vaccine, live by pharmacodynamic antagonism. Contraindicated. Immunization with live virus vaccines is generally not recommended.typhoid vaccine livemethotrexate decreases effects of typhoid vaccine live by pharmacodynamic antagonism. Contraindicated. Immunization with live virus vaccines is generally not recommended.varicella virus vaccine livemethotrexate decreases effects of varicella virus vaccine live by pharmacodynamic antagonism. Contraindicated. Immunization with