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Methotrexate Dosage

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Usual Adult Dose 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 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 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 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, subcutaneously, 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

Patients may be switched from oral methotrexate to weekly subcutaneous injections taking into account the increased bioavailability relative to the oral formulation.

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.

Subcutaneous injection for Polyarticular Juvenile Idiopathic Arthritis: 10 mg/m2 subcutaneously 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.

Renal Dose Adjustments

Avoid the use of methotrexate in patients with CrCl less than 10 mL/min.

CrCl greater than or equal to 10 less than 50 mL/min: Administer at 30% to 50% the recommended dose.
CrCl greater than or equal to 50 less than 60 mL/min: Administer at 70% the recommended dose.
CrCl greater than or equal to 60 less than 80 mL/min: Administer at 75% the recommended dose.

Liver Dose Adjustments

Data not available

Precautions

Methotrexate has the potential for serious toxicity. Toxic effects may be related in frequency and severity to dose or frequency of administration but have been seen at all doses.

The clinical pharmacology of methotrexate has not been well studied in older individuals. Due to diminished hepatic and renal function as well as decreased folate stores in this population, relatively low doses should be considered, and these patients should be closely monitored for early signs of toxicity.

Methotrexate should be used with extreme caution in the presence of debility.

Dialysis

Data not available

Other Comments

Cyclic combination therapy of methotrexate with other tumor drugs has been reported to be useful.

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