Name: Methotrexate

Methotrexate Dosage


Take this medication exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.
The dose your doctor recommends may be based on the following:

  • the condition being treated
  • other medical conditions you have
  • other medications you are taking
  • how you respond to this medication
  • your weight
  • your height
  • your age
  • your gender

Methotrexate starting doses include the following. Dosage adjustment will be made gradually to achieve an optimal response.

  • RA is 7.5 mg of an oral (by mouth) formulation once weekly, or
    • 2.5 mg at 12 hour intervals for 3 doses given as a course once weekly
  • pJIA is 10 mg/m2 once weekly
  • psoriasis is 10 to 25 mg once weekly by mouth or as an injection into the muscle, just under the skin, or into the vein, or
    • 2.5 mg at 12 hour intervals for three doses
  • choriocarcinoma and similar trophoblastic diseases is 15 mg to 30 mg by mouth daily for a 5-day course. Such courses are usually repeated for 3 to 5 times as required.

For leukemia:

  • When used for induction, the recommended methotrexate tablet dose is 3.3 mg/m2 given daily.
  • Maintenance therapy is methotrexate tablets taken 2 times weekly by mouth in total weekly doses of 30 mg/m2.

For lymphoma:

  • Recommended dosage is 10 to 25 mg/day orally for 4 to 8 days. Lymphosarcomas in Stage III may respond to combined drug therapy with methotrexate given in doses of 0.625 to 2.5 mg/kg daily.

For mycosis fungoides (cutaneous T cell lymphoma):

  • Dosage in early stages is usually 5 mg to 50 mg once weekly. Methotrexate has also been administered twice weekly in doses ranging from 15 mg to 37.5 mg in those who have responded poorly to weekly therapy.


What is methotrexate (rheumatrex dose pack, trexall)?

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 other purposes not listed in this medication guide.

  • Colitis (Symptoms, Types, and Treatments)
  • Crohn's Disease
  • Granulomatosis with Polyangiitis (GPA or Wegener's Granulomatosis)
  • Juvenile Idiopathic Arthritis (Juvenile Rheumatoid Arthritis)
  • Lupus (Systemic Lupus Erythematosus or SLE)
  • NSAIDs (Nonsteroidal Antiinflammatory Drugs)
  • Psoriasis
  • Psoriatic Arthritis
  • Rheumatoid Arthritis (RA)
  • Ulcerative Colitis

Uses for Methotrexate

Breast Cancer

Treatment (alone or, more commonly, in combination chemotherapy) of breast cancer.a 262 265

First-line adjuvant chemotherapy in combination with other drugs (i.e., cyclophosphamide and fluorouracil, with or without hormonal therapy).166 167 168 169 170 171 172 173 174 175 178 179 182 185 186 187 267 An anthracycline-containing regimen is preferred in patients with node-positive disease.267

Some studies suggest a slight advantage for anthracycline-containing regimens in relapse-free and survival rates in both premenopausal and postmenopausal patients.274

Also used in patients with metastatic disease.267 274

Head and Neck Cancer

Palliative treatment (alone and in combination therapy) of recurrent or metastatic head and neck carcinoma.182 210 211 212 262 265 267

Frequently used in combination regimens with other antineoplastic agents (e.g., bleomycin, fluorouracil, vincristine).210

Combination therapy with cisplatin, methotrexate, bleomycin, and vincristine has been used for recurrent or metastatic squamous cell carcinoma of the head and neck.212

Further study needed to establish comparative benefit of methotrexate-containing regimens.210 212


Component of various chemotherapy regimens in palliative treatment of acute leukemias.a

Intrathecally for prophylaxis and treatment of meningeal leukemia.a 262 267

First-line therapy in combination with mercaptopurine for maintenance of drug-induced remissions of acute lymphoblastic leukemia (ALL).262 265 267

Has been used in high doses as a component of some alternative combination chemotherapy regimens for remission induction in ALL, but not generally considered a drug of choice for remission induction.267

Rarely effective alone for treatment of acute myeloblastic leukemia (AML);a has been used as an additional component in some chemotherapy regimens for induction or post-induction therapy of AML.a 267

Lung Cancer

Has been used in second-line therapy of recurrent small cell lung cancer.235 262 265 276

Although labeled for use in squamous cell type of non-small cell lung cancer,127 262 265 other agents are preferred.182 267


Component of combination chemotherapeutic regimens as first-line palliative therapy for high-grade Burkitt’s lymphoma or maintenance therapy for high-grade lymphoblastic non-Hodgkin’s lymphoma.262 265 267

Component of alternative combination chemotherapy regimens for treatment of intermediate-grade non-Hodgkin’s lymphomas (diffuse large cell, diffuse small cell, diffuse mixed, follicular large cell).267

Has been used intrathecally in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone with or without rituximab for first-line therapy of intermediate-grade non-Hodgkin’s lymphomas.267

Although radiation or topical therapy is generally used for treatment of localized histiocytic lymphoma, lymphosarcoma, and mycosis fungoides, chemotherapy may be useful in generalized stages of these diseases.a

First-line267 systemic chemotherapy for advanced cutaneous T-cell lymphoma (e.g., mycosis fungoides, Sézary syndrome).262 265 277

First-line therapy of primary CNS lymphoma.267

Hodgkin’s disease responds poorly to methotrexate.a


High-dose therapy, followed by leucovorin or levoleucovorin rescue, in combination chemotherapy regimens as adjunct to surgical resection or amputation of primary tumor in patients with nonmetastatic osteosarcoma262 263 264 267 270 (designated an orphan drug by FDA for this use).192

Also has been used as a component of adjunctive combination chemotherapy regimens in patients with metastatic osteosarcoma.270


Symptomatic control of severe, recalcitrant, disabling psoriasis that is not adequately responsive to other forms of therapy in carefully selected patients; not curative.a 262 265

Use only after diagnosis definitely established (e.g., biopsy, after dermatologic consultation).262 265

Rheumatoid Arthritis

Management of rheumatoid arthritis in adults whose symptoms progress despite an adequate regimen of NSAIAs.111 112 113 114 115 116 127 128 138 139 140 141 142 143 144 145 146 147 148 149 152 153 154 262 265

Management of active polyarticular-course juvenile rheumatoid arthritis in children who have had an insufficient therapeutic response to, or are intolerant of, an adequate trial of first-line therapy (i.e., full-dose NSAIAs).262 265 (See Pediatric Use under Cautions.)

One of several disease-modifying antirheumatic drugs (DMARDs) that can be used when DMARD therapy is appropriate.220 224

Substantially greater long-term efficacy than other DMARDs; used as the initial or anchor DMARD in many patients with rheumatoid arthritis.220 222 224 225 226 Also has been used in combination with other DMARDs.220 222 225 228 229 230 231 232 233 234

Use only as part of a comprehensive treatment program, including nondrug therapies (e.g., rest, physical therapy).127

No substantial evidence that methotrexate permanently arrests or reverses the underlying disease process,127 128 138 140 144 147 153 although disease progression is slowed in some patients.138 140 143 144 160 220

Trophoblastic Neoplasms

Treatment (with or without leucovorin) of trophoblastic neoplasms (choriocarcinoma, chorioadenoma destruens, hydatidiform mole) in women (except those with impaired renal or hepatic function or who have failed to respond to previous methotrexate therapy, in which case dactinomycin is used).a 262 265 268

Most effective in patients who have had disease for only a short period prior to initiation of chemotherapy, who have low initial gonadotropin concentrations, and who do not have metastases.a

First-line therapy with or without leucovorin in patients with nonmetastatic or good-prognosis metastatic gestational trophoblastic neoplasms.267 268

Component of combination chemotherapy regimen with dactinomycin and chlorambucil in patients with good-prognosis metastatic gestational trophoblastic neoplasms with refractory disease.268

In patients with poor-prognosis metastatic trophoblastic neoplasms, methotrexate in combination with etoposide, dactinomycin, vincristine, and cyclophosphamide (EMA-CO) is a standard treatment option.268 A dose-intensive regimen, EMA-CE, in which etoposide and cisplatin are substituted for vincristine and cyclophosphamide of the EMA-CO regimen, may offer additional benefits.268

Has been used prophylactically against malignant trophoblastic disease in patients with hydatidiform mole.a

Testicular choriocarcinomas are usually resistant to methotrexate alone; has been used as component of combination therapy in patients with metastatic tumors of the testes.a

Bladder Cancer

Used in combination regimens with vinblastine and cisplatin, with or without doxorubicin, as first- or second-line therapy267 for invasive and advanced bladder cancer†.182 205 206 207 208 209

Use of leucovorin rescue or deletion of methotrexate is advised if methotrexate-containing regimens are being considered for the treatment of advanced or metastatic bladder cancer in patients with renal dysfunction, edema, pleural fluid collections, or ascites.205

Crohn’s Disease

Management of chronically active Crohn’s disease†.241 242 243 244 245 246 247 248 249 250 251 258 259 260

Ectopic Pregnancy

Used as an alternative to surgical management of ectopic pregnancy† in selected patients with small, unruptured tubal pregnancies.271 272 273

Multiple Sclerosis

Low-dose oral therapy has been used in patients with chronic progressive multiple sclerosis†.201 202 203 204

Psoriatic Arthritis

Has been used for its immunosuppressive and/or anti-inflammatory effects in treatment of psoriatic arthritis†.109 110

Cautions for Methotrexate


  • Pregnant women with psoriasis or rheumatoid arthritis; use in treatment of neoplastic diseases only when potential benefit outweighs risk to fetus.262 265 (See Boxed Warning.)

  • Nursing women.127 262 265

  • Excessive alcohol consumption, alcoholic liver disease, or other chronic liver disease in patients with psoriasis or rheumatoid arthritis.127 262 265

  • Overt or laboratory evidence of immunodeficiency syndromes in patients with psoriasis or rheumatoid arthritis.127 262 265

  • Preexisting blood dyscrasias (e.g., bone marrow hypoplasia, leukopenia, thrombocytopenia, clinically important anemia) in patients with psoriasis or rheumatoid arthritis.127 262 265

  • Known hypersensitivity to methotrexate.262 265



Also see Boxed Warnings.

Fetal/Neonatal Morbidity and Mortality

Fetal death and/or congenital anomalies reported.262 265 Exclude pregnancy before initiating treatment.262 265 Avoid pregnancy if either partner is receiving methotrexate; avoid pregnancy during therapy and for ≥3 months after therapy in male patients and for at least one ovulatory cycle after therapy in female patients.262 265 If used during pregnancy or patient becomes pregnant, apprise of potential fetal hazard.262 265

Sensitivity Reactions

Dermatologic and Sensitivity Reactions

Severe, occasionally fatal cutaneous or sensitivity reactions (e.g., toxic epidermal necrolysis, Stevens-Johnson syndrome, exfoliative dermatitis, skin necrosis, erythema multiforme) reported in pediatric and adult patients within days of receiving drug at various dosages, by various routes, and for various conditions.193 262 265

Erythematous rashes, pruritus, dermatitis, urticaria, folliculitis, photosensitivity, depigmentation, hyperpigmentation, petechiae, ecchymoses, telangiectasia, acne, furunculosis, and skin ulceration also reported.a 262 265

Lesions of psoriasis may be aggravated by concomitant exposure to ultraviolet radiation; possible “recall” radiation dermatitis and sunburn with methotrexate use.262 265

Major Toxicities

Hematologic Effects

Possible suppressed hematopoiesis, anemia, aplastic anemia, pancytopenia, leukopenia, neutropenia, and/or thrombocytopenia.262 265 Use with caution in patients with malignancy and preexisting hematopoietic impairment.262 265

Perform CBCs, including differential and platelet counts, at least weekly in patients with neoplastic disease and at least monthly in patients with psoriasis or rheumatoid arthritis.a 262 265

In patients with psoriasis or rheumatoid arthritis, discontinue if clinically important decrease in blood counts occurs and institute appropriate alternative therapy; in patients with neoplastic disease, continue only if potential benefit warrants risk of severe myelosuppression.a 262 265

If profound granulocytopenia and fever occur, observe patient closely and initiate broad-spectrum antibiotic therapy if there are signs of infection.a 262 265

Blood or platelet transfusions may be necessary in patients with severe myelosuppression.a

GI Effects

Risk of vomiting, diarrhea, or stomatitis resulting in dehydration; discontinue drug until recovery occurs.262 265 (See GI Toxicity in Boxed Warning.)

Use with extreme caution in presence of peptic ulcer disease or ulcerative colitis.262 265

Hepatic Effects

Possible hepatotoxicity; may be acute (increased serum aminotransferase concentrations) or chronic (fibrosis and cirrhosis).127 128 131 155 164 262 265

Chronic hepatotoxicity, potentially fatal, generally occurs after prolonged use (≥2 years) and after a total dose of ≥1.5 g.127 128 131 164 262 265

Risk of hepatotoxicity in patients with psoriasis appears to be related to cumulative dose and may be enhanced by alcoholism, obesity, diabetes, and advanced age.116 127 131 141 142 150 158 160 262 265 These risk factors also may apply to patients with rheumatoid arthritis;127 150 age at first use and duration of therapy also reported as risk factors in rheumatoid arthritis patients.262 265

Use with particular caution in patients with preexisting liver damage or hepatic impairment.262 265

Psoriasis: Perform liver function tests, including serum albumin, periodically prior to dosing, although results may be normal despite developing fibrosis or cirrhosis.116 127 131 138 141 142 147 148 262 265 Liver biopsy recommended before therapy or shortly after therapy initiation (2–4 months), at cumulative dose of 1.5 g, and after each additional 1–1.5 g.127 163 262 265 Usually discontinue drug if moderate fibrosis or any cirrhosis; repeat biopsy in 6 months if mild fibrosis.262 265 Continue use with caution if milder changes (e.g., fatty changes, low-grade portal inflammation).262 265

Rheumatoid arthritis: Prolonged, substantial abnormalities in liver function test results may precede appearance of hepatic fibrosis or cirrhosis; 127 262 265 perform liver function tests at baseline and at 4- to 8-week intervals.262 265 Pretreatment liver biopsy recommended if history of excessive alcohol consumption, persistently abnormal baseline liver function tests, or chronic hepatitis B or C infection.127 Perform liver biopsy during therapy if persistent liver function test abnormalities or serum albumin concentrations fall below normal (in setting of well-controlled rheumatoid arthritis).262 265 If liver biopsy shows mild changes (Roenigk grade I, II, or IIIa), continue therapy and monitoring; discontinue if persistently abnormal liver function tests, if biopsy shows moderate to severe changes (Roenigk grade IIIb or IV), or if patient refuses biopsy.262 265

Respiratory Effects

Potentially fatal119 127 154 pulmonary toxicity; can progress rapidly117 118 119 127 128 129 130 and may not be fully reversible.119 127 128 Adverse pulmonary effects (i.e., acute or chronic interstitial pneumonitis, pulmonary fibrosis) may occur at any dosage at any time during therapy.117 118 119 242 262 265

If manifestations (e.g., fever, cough [especially dry and nonproductive], dyspnea, chest pain, hypoxemia [possibly severe], radiographic evidence of pulmonary infiltrates [usually diffuse and/or alveolar])117 118 119 127 128 129 130 159 160 262 265 occur, discontinue and carefully evaluate, including exclusion of possible infectious causes.119 127 128 129 130

Management is mainly supportive and may include mechanical ventilation.119 128 129 130

Potentially fatal opportunistic infections (e.g., P. jiroveci pneumonia) reported; consider possibility of P. jiroveci pneumonia in patients who develop pulmonary symptoms.262 265

Renal Effects

May cause renal damage that may lead to acute renal failure.262 265

Nephrotoxicity is due principally to precipitation of methotrexate and 7-hydroxymethotrexate in the renal tubules.262 265

Careful attention to renal function, including adequate hydration, urine alkalinization, and measurement of methotrexate and Scr concentrations is essential.265

Perform renal function tests prior to and periodically during therapy (at 1- to 2-month intervals in patients with psoriasis or rheumatoid arthritis; more frequently in patients with neoplastic disease).a 262 265

If renal impairment develops during therapy, reduce dosage or discontinue drug until renal function is improved or restored.a 262 265

Immunosuppressive Effects

Consider immunosuppressive effects when evaluating use in patients in whom immune response may be important or essential.a (See Vaccines under Interactions.)

Usually contraindicated in patients with overt or laboratory evidence of immunodeficiency syndromes.a 262 265 (See Contraindications under Cautions.)

Use with extreme caution in presence of active infection.a 262 265

Hypogammaglobulinemia reported rarely.262 265

Neurologic Effects

Leukoencephalopathy reported following IV administration in patients who had received craniospinal irradiation; chronic leukoencephalopathy also reported in patients receiving repeated high-dose therapy with leucovorin rescue even without cranial irradiation.262

Severe neurotoxic effects, manifested mainly by focal or generalized seizures, reported with increased frequency in pediatric patients with ALL who received intermediate-dose IV therapy (1 g/m2);193 262 leukoencephalopathy and/or microangiopathic calcifications usually were observed in diagnostic imaging procedures of symptomatic patients.193

A transient acute neurologic syndrome observed in patients receiving high-dosage regimens; exact cause unknown.262 Manifestations of this stroke-like encephalopathy may include confusion, hemiparesis, transient blindness, seizures, and coma.262

Intrathecal Administration

Possible acute chemical arachnoiditis manifested by headache, back pain, nuchal rigidity, and/or fever; subacute myelopathy manifested by paraparesis/paraplegia involving one or more spinal nerve roots; chronic leukoencephalopathy (may be progressive and fatal) manifested by confusion, irritability, somnolence, ataxia, dementia, and occasionally seizures and coma; and increased CSF pressure.127

Systemic toxicity also may occur following intrathecal administration.a 262

Inadvertent intrathecal overdosage has occurred;101 102 103 symptoms generally include CNS effects (i.e., headache, nausea, vomiting, seizure, acute toxic encephalopathy),262 although in some cases, no symptoms were reported.262 Death has occurred following intrathecal overdose; in these cases, cerebellar herniation associated with increased intracranial pressure and acute toxic encephalopathy also reported.262

Accidental intrathecal overdosage may require intensive systemic support, high-dose systemic leucovorin (intrathecal leucovorin contraindicated), alkaline diuresis, and rapid CSF drainage and ventriculolumbar perfusion.262

Focal leukemic involvement of the CNS may not respond to intrathecal methotrexate and may best be treated with radiation therapy.a

General Precautions

Adequate Patient Evaluation and Monitoring

Therapeutic response is not likely without some evidence of toxicity.a Severity of toxic reactions may be increased when used in combination with other antineoplastic agents and/or radiation therapy.a

Closely monitor patients with complete hematologic studies, urinalysis, renal function tests, liver function tests, and chest radiographs.a 262 265 (See Major Toxicities under Cautions.)

If serious toxicity occurs, reduce dosage or discontinue and institute appropriate corrective measures (e.g., use of leucovorin calcium, acute intermittent hemodialysis with a high-flux dialyzer).265

Third-Space Compartments

Exits slowly from third-space compartments (e.g., pleural effusions, ascites), resulting in prolonged elimination and unexpected toxicity in patients with substantial third-space accumulations.a 265 Evacuation of fluid recommended before treatment; monitor plasma methotrexate concentrations.265

Specific Populations


Category X.262 (See Fetal/Neonatal Morbidity and Mortality in Boxed Warning and under Cautions.)


Distributed into milk.262 Contraindicated in nursing women because of risk to nursing infant.127 262 265

Pediatric Use

Safety and efficacy established only for cancer chemotherapy or polyarticular-course juvenile rheumatoid arthritis.262 265

In clinical studies, safety in pediatric patients 2–16 years of age with juvenile rheumatoid arthritis was similar to that observed in adults with rheumatoid arthritis.262 265

Severe neurotoxic effects (e.g., focal or generalized seizures) reported in pediatric patients with ALL who received intermediate-dose IV therapy (1 g/m2).193 262 (See Neurologic Effects under Cautions.)

Preparations containing benzyl alcohol preservative not recommended in neonates because of toxicity.262

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults; select dosage with caution due to greater frequency of decreased hepatic and renal function and folate stores and of concomitant disease and drug therapy (i.e., that interfere with renal function or methotrexate or folate metabolism) observed in the elderly.262 265

Occurrence of bone marrow suppression, thrombocytopenia, and pneumonitis may increase with age.262 265

Closely monitor geriatric patients for early signs of hepatic, bone marrow, and renal toxicity; certain toxicities may be reduced by folate supplementation.262 265 Scr may overestimate renal function in geriatric patients; consider more accurate methods (i.e., Clcr). Serum methotrexate concentrations may be helpful.262 265

Hepatic Impairment

Contraindicated in patients with psoriasis or rheumatoid arthritis who have alcoholic liver disease or other chronic liver disease.262 265 Use with extreme caution, if at all, in patients with malignant disease who have preexisting liver damage or impaired hepatic function.a

Renal Impairment

Usually contraindicated.a

Debilitated Patients

Use with extreme caution.265

Common Adverse Effects

Ulcerative stomatitis, leukopenia, nausea, abdominal distress, malaise, undue fatigue, chills, fever, dizziness, decreased resistance to infection.262 265

Dosing Hepatic Impairment

There are no dosage adjustments provided in the manufacturer’s labeling; use with caution in patients with impaired hepatic function or preexisting hepatic damage. The following adjustments have been recommended (Floyd 2006):

Bilirubin 3.1 to 5 mg/dL or transaminases >3 times ULN: Administer 75% of dose

Bilirubin >5 mg/dL: Avoid use

Dosing Obesity

ASCO Guidelines for appropriate chemotherapy dosing in obese adults with cancer (excludes leukemias): Utilize patient’s actual body weight (full weight) for calculation of body surface area- or weight-based dosing, particularly when the intent of therapy is curative; manage regimen-related toxicities in the same manner as for nonobese patients; if a dose reduction is utilized due to toxicity, consider resumption of full weight-based dosing with subsequent cycles, especially if cause of toxicity (eg, hepatic or renal impairment) is resolved (Griggs 2012).


In children, doses ≥12 g/m2 are associated with a high emetic potential; doses ≥250 mg/m2 (IV) in adults and children are associated with moderate emetic potential (Dupuis 2011). Antiemetics may be recommended to prevent nausea and vomiting.

Methotrexate may be administered orally, IM, IV, intrathecally, or SubQ; IV administration may be as slow push (10 mg/minute), bolus infusion, or 24-hour continuous infusion (route and rate of administration depend on indication and/or protocol; refer to specific references). Must use preservative-free formulation for intrathecal or high-dose methotrexate administration.

Specific dosing schemes vary, but high doses should be followed by leucovorin calcium rescue to prevent toxicity.

Oral solution: Ensure accuracy when dispensing and administering to prevent dosing errors. A calibrated oral syringe/dosing cup that can measure and deliver the prescribed dose accurately should be used; do not use a household teaspoon or tablespoon to measure dose.

Otrexup and Rasuvo are autoinjectors for once weekly subcutaneous use in the abdomen or thigh; patient may self-administer after appropriate training. All schedules should be continually tailored to the individual patient. An initial test dose may be given prior to the regular dosing schedule to detect any extreme sensitivity to adverse effects.

Dietary Considerations

Some products may contain sodium.

Important information

Methotrexate is not usually taken every day. You must use the correct dose 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.

Methotrexate dosing information

Usual Adult Dose of Methotrexate for Acute Lymphoblastic Leukemia:

Induction: 3.3 mg/m2/day orally or IM (in combination with prednisone 60 mg/m2).

Maintenance (during remission): 15 mg/m2 IM or orally twice a week.
Alternate remission dosing: 2.5 mg/kg IV every 14 days.

Usual Adult Dose of Methotrexate for Choriocarcinoma:

15 to 30 mg IM or orally daily for 5 days. Repeat courses 3 to 5 times with a rest period of greater than or equal to 1 week between courses, until any manifesting toxic symptoms subside.

Effectiveness of therapy is ordinarily evaluated by 24 hour quantitative analysis of urinary chorionic gonadotropin (hCG), which generally will return to normal or less than 50 intl units/24 hours usually after the third or fourth course and usually followed by a complete resolution of measurable lesions in 4 to 6 weeks. One to two courses of methotrexate after normalization of hCG is usually recommended.

Usual Adult Dose of Methotrexate for Trophoblastic Disease:

15 to 30 mg IM or orally daily for 5 days. Repeat courses 3 to 5 times with a rest period of greater than or equal to 1 week between courses, until any manifesting toxic symptoms subside.

Effectiveness of therapy is ordinarily evaluated by 24 hour quantitative analysis of urinary chorionic gonadotropin (hCG), which generally will return to normal or less than 50 intl units/24 hours usually after the third or fourth course and usually followed by a complete resolution of measurable lesions in 4 to 6 weeks. One to two courses of methotrexate after normalization of hCG is usually recommended.

Usual Adult Dose of Methotrexate for Lymphoma:

For Burkitt's tumor in Stages I-II: 10 to 25 mg orally once a day for 4 to 8 days

Malignant lymphoma in Stage III: 0.625 to 2.5 mg/kg orally daily as a part of combination chemotherapy.

Treatment in all stages usually consists of several courses of the drug interposed with 7 to 10 day rest periods.

Usual Adult Dose for Meningeal Leukemia:

12 mg/m2 intrathecally every 2 to 5 days until the cell count of the CSF returns to normal. At this point, one additional dose is advisable. Administration at intervals of less than 1 week may result in increased subacute toxicity.

Usual Adult Dose for Mycosis Fungoides:

2.5 to 10 mg PO daily or 50 mg IM once a week or 25 mg IM twice a week.

Usual Adult Dose for Osteosarcoma:

Initial Dose: 12 g/m2 intravenously as a 4 hour infusion (in combination with other chemotherapeutic agents). If this dose is not adequate to achieve a peak serum concentration of 1000 micromolar at the end of the infusion, the dose may be increased to 15 g/m2.

Treatments may occur at 4, 5, 6, 7, 11, 12, 15, 16, 29, 30, 44, and 45 weeks after surgery.

If the patient is vomiting or unable to tolerate oral medication, leucovorin should be added to this regimen at the same dose and schedule as the methotrexate.

Usual Adult Dose for Psoriasis:

Single Dose: 10 to 25 mg/week orally, IM, or IV until adequate response is achieved.
Divided Dose: 2.5 mg orally, IM, or IV every 12 hours for 3 doses once a week.
Maximum weekly dose: 30 mg.

Usual Adult Dose for Rheumatoid Arthritis:

Single dose: 7.5 mg orally weekly.
Divided dose: 2.5 mg orally every 12 hours for 3 doses once a week.
Maximum weekly dose: 20 mg.

Usual Adult Dose for Neoplastic Diseases:

I.V.: Range is wide from 30-40 mg/m2/week to 100-12,000 mg/m2 with leucovorin rescue

Usual Pediatric Dose for Acute Lymphocytic Leukemia:

100 mg/m2 over 1 hour followed by a 35 hour infusion delivering 900 mg/m2/day.

Usual Pediatric Dose for Dermatomyositis:

15 to 20 mg/m2 orally once weekly.

Usual Pediatric Dose for Meningeal Leukemia:

less than 4 months: 3 mg/dose intrathecally.
greater than or equal to 4 months less than 1 year: 6 mg/dose intrathecally.
greater than or equal to 1 year less than 2 years: 8 mg/dose intrathecally.
greater than or equal to 2 years less than 3 years: 10 mg/dose intrathecally.
greater than or equal to 3 years: 12 mg/dose intrathecally.

The dose may be administered every 2 to 5 days until CSF counts return to normal followed by a dose administered once weekly for 2 weeks and monthly thereafter. Administration at intervals of less than 1 week may result in increased subacute toxicity.

Usual Pediatric Dose for Neoplastic Diseases:

7.5 to 30 mg/m2 IM or orally every 2 weeks.
Alternate dosing: 10 to 18,000 mg/m2 IV bolus or continuous infusion over 6 to 42 hours.

Usual Pediatric Dose for Rheumatoid Arthritis:

5 to 15 mg/m2 IM or orally once weekly.

Usual Pediatric Dose for Solid Tumors:

less than 12 years: 12000 mg/m2 IV.
greater than or equal to 12 years: 8000 mg/m2 IV.
Maximum dose: 18 grams.

What other drugs will affect methotrexate?

Many drugs can interact with methotrexate. Not all possible interactions are listed here. Tell your doctor about all your medications and any you start or stop using during treatment with methotrexate, especially:

  • azathioprine;

  • leucovorin;

  • phenytoin;

  • probenecid;

  • theophylline;

  • an antibiotic or sulfa drugs;

  • isotretinoin, retinol, tretinoin;

  • NSAIDs (non-steroidal anti-inflammatory drugs) - ibuprofen (Advil, Motrin), naproxen (Aleve), celecoxib, diclofenac, indomethacin, meloxicam, and others; or

  • salicylates - aspirin, Nuprin Backache Caplet, Kaopectate, KneeRelief, Pamprin Cramp Formula, Pepto-Bismol, Tricosal, Trilisate, and others.

This list is not complete and many other drugs can interact with methotrexate. This includes prescription and over-the-counter medicines, vitamins, and herbal products. Give a list of all your medicines to any healthcare provider who treats you.

In Summary

Commonly reported side effects of methotrexate include: increased liver enzymes. See below for a comprehensive list of adverse effects.

Usual Adult Dose for Burkitt's Tumor

-Burkitt's tumor Stages I to II: 10 to 25 mg orally once a day for 4 to 8 days
-Burkitt's tumor Stage III: Methotrexate is commonly given concomitantly with other antitumor agents
-Duration of therapy: All stages usually require several courses of therapy interposed with 7 to 10 day rest periods
-Lymphosarcoma Stage III: 0.625 to 2.5 mg/kg orally daily as a part of combination chemotherapy

-Burkitt's tumor

Usual Adult Dose for Psoriasis

Single Dose: 10 to 25 mg/week orally, IM, IV, or subcutaneously until adequate response is achieved
Divided Dose: 2.5 mg orally every 12 hours for 3 doses once a week
Maximum dose: 30 mg/week

-Once optimal clinical response has been achieved, each dosage schedule should be reduced to the lowest possible amount of drug and to the longest possible rest period.
-The use of MTX may permit the return to conventional topical therapy, which should be encouraged.

Use: For the symptomatic control of severe, recalcitrant, disabling psoriasis that is not adequately responsive to other forms of therapy, but only when the diagnosis has been established, as by biopsy and/or after dermatologic consultation. It is important to ensure that a psoriasis "flare" is not due to an undiagnosed concomitant disease affecting immune responses.

Usual Pediatric Dose for Meningeal Leukemia

-Less than 1 year old: 6 mg intrathecally every 2 to 5 days until the cell count of the CSF returns to normal; at this point, one additional dose is advisable
-One year old: 8 mg intrathecally every 2 to 5 days until the cell count of the CSF returns to normal; at this point, one additional dose is advisable
-Two years old: 10 mg intrathecally every 2 to 5 days until the cell count of the CSF returns to normal; at this point, one additional dose is advisable
-Three years and older: 12 mg intrathecally every 2 to 5 days until the cell count of the CSF returns to normal; at this point, one additional dose is advisable

-Administration at intervals of less than 1 week may result in increased subacute toxicity.
-The preserved formulations of this drug contain benzyl alcohol and must not be used for intrathecal or high dose therapy.

Use: Treatment and prophylaxis of meningeal leukemia


This drug is dialyzable via hemodialysis using a high flux dialyzer; however, no dose adjustment guidelines have been reported.


  • There are significant risks associated with the use of methotrexate and your physician should fully inform you of the risks before starting treatment. During treatment, you should be monitored regularly.
  • Carefully read dosage instructions. For psoriasis and rheumatoid arthritis, methotrexate is usually prescribed WEEKLY, not daily. If your label instructs you to take it daily, double check with your doctor that these are the correct instructions.
  • Report any instance of a dry, nonproductive cough to your doctor for further investigation.
  • Also report any instances of fever, unusual bleeding or bruising, loss of appetite, clay-colored stools, yellowing of the skin or eyes, swelling, diarrhea, skin reactions, vomiting, or mouth ulcers to your doctor.
  • Keep up a good level of hydration while taking methotrexate. If you become dehydrated, methotrexate may need to be temporarily discontinued until you have recovered.
  • Continued treatment with methotrexate may depend on the results of blood, kidney function, and other tests.
  • Keep up fluid levels while taking methotrexate; do not allow yourself to become dehydrated.
  • May make your skin more sensitive to the sun. Cover up and wear sunblock on exposed areas of skin when outside.
  • Do not take any over-the-counter NSAIDs including aspirin while you are on methotrexate unless your doctor permits this. Also, ask your doctor before taking any vitamin supplements or other medications purchased over-the-counter, or before receiving immunizations.
  • You may be at an increased risk of infection while taking methotrexate so avoid crowded areas and people who are unwell if you can. Wash your hands often.
  • Take good care of your mouth to help prevent mouth sores. Use a soft toothbrush and a mouthwash.
  • Avoid drinking alcohol or keep alcohol intake to a minimum while taking methotrexate.
  • If you are a woman with child-bearing potential, you should always use a reliable form of contraception while you are taking methotrexate. Your doctor may request that you take a pregnancy test before starting methotrexate. Methotrexate may also cause changes in your menstrual cycle. Men taking methotrexate should continue to use condoms for at least three months after stopping methotrexate.
  • Tell other healthcare providers that you are taking methotrexate. You should not receive any live vaccines while taking methotrexate.
  • If you are caring for somebody who is taking methotrexate, wear gloves when cleaning up body fluids or handling contaminated laundry or diapers, because methotrexate can transfer into urine, feces, and vomit. Wash any soiled items separately.