methotrexate (Rx)Brand and Other Names:Trexall, Otrexup, more...Rasuvo

 
 
 

Dosing & Uses

AdultPediatric

Dosage 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)

tablet

  • 2.5mg
  • 5mg
  • 7.5mg
  • 10mg
  • 15mg
more...

Neoplasms

Antineoplastic dosage range: 30-40 mg/m²/week to 100-12,000 mg/m² with leucovorin rescue  

Trophoblastic neoplasms: 15-30 mg/day PO/IM for 5 days; may be repeated

Burkitt lymphoma, stage I/II: 10-25 mg/day PO for 4-8 days

Dosing considerations

  • Various dosing regimens exist; consult oncologist 

Meningeal Leukemia

12 mg intrathecally; not to exceed 15 mg/dose every 2-7 days; administer 1 additional dose after cell count on CSF returns to normal;

Dosing considerations

  • Administration at intervals less than 1 week may result in increased subacute toxicity
  • Use preservative-free methotrexate only; dilute to 1 mg/mL in preservative-free NS

Osteosarcoma

12 g/m² IV over 4 hours on weeks 4, 5, 6, 7, 11, 12, 15, 16, 29, 30, 44, and 45 after surgery in combination with other chemotherapy; leucovorin rescue  

If peak serum methotrexate <454 mcg/mL at end of initial infusion, dose may be increased to 15 g/m² in subsequent treatments 

Dosing considerations

  • High-dose therapy requires adequate hydration and urine alkalinization 
  • Delay methotrexate if severe myelosuppression, hepatotoxicity, mucositis, or pleural effusion present

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 as a single weekly dose, OR

2.5 mg PO q12hr for 3 sequential doses per week

Increase PO 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 (SC), initial dose: 7.5 mg as a single SC dose once weekly; adjust autoinjector dose by 2.5 mg increments as clinically required

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 (SC): 10-25 mg SC once weekly

Breast Cancer

40 mg/m&sup2 IV; days 1 and 8 every 4 weeks in combination with cyclophosphamide and fluoracil for 6-12 cycles

Head and Neck Cancer

40 mg/m&sup2 IV; once weekly until disease progression or unacceptable toxicity

Mycosis Fungoides (Cutaneous T-cell Lymphoma)

5-50 mg PO/IM once weekly or 15-37.5 mg twice weekly for who have responded poorly to weekly therapy

Dosing Modifications

Renal impairment

  • CrCl 10-50 mL/min: 50% of dose at normal dosing interval
  • CrCl <10 mL/min: Avoid use
  • Intermittent hemodialysis: 50% of dose at normal dosing interval
  • Continuous renal replacement therapy: 50% of dose at normal dosing interval

Hepatic impairment

  • Bilirubin 3.1-5.0 mg/dL or AST > 3 times ULN: Give 75% of dose
  • Bilirubin >5.0 mg/dL: Avoid use

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

Acute Lymphoblastic Leukemia (Orphan)

Orphan indication sponsor

  • Only for Children Pharmaceuticals; 35 bis rue Gay; Lusac, France

Myasthenia Gravis (Orphan)

Orphan designation for treatment of myasthenia gravis

Sponsor

  • Universtiy of Kanasa Medical Center; 3901 Rainbow Blvd, MSN 2012; Kanasa City , KS 66160

Dosage Forms & Strengths

injectable solution

  • 25mg/mL

powder for injection

  • 1g

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)

tablet

  • 2.5mg
  • 5mg
  • 7.5mg
  • 10mg
  • 15mg
more...

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), 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
  • 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

Meningeal Leukemia

<1 year: 6 mg intrathecally (IT) every 2-5 days

1-2 years: 8 mg IT every 2-5 days

2-3 years: 10 mg IT every 2-5 days

≥3 years: 12 mg IT every 2-5 days

Dosing considerations

  • Use preservative-free methotrexate for injection only
  • Dilute to 1 mg/mL in preservative-free 0.9% NaCl

Acute Lymphoblastic Leukemia (Orphan)

Oral solution

Orphan designation for treatment of acute lymphoblastic leukemia in pediatric patients (0 through 16 years of age)

Sponsor

  • Silvergate Pharmaceuticals, Inc; 6251 Greenwood Plaza Blvd, Suite 101;Greenwood Village, CO 80111

Renal Impairment

CrCl 10-50 mL/min/1.73mm²: 50% dose

CrCl<10 mL/min/1.73 mm²: 30% dose

Next

Interactions

Interaction Checker

methotrexate and

No Results

     
     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

            Sort by :  
             activity indicator 
            Previous
            Next

            Adverse Effects

            >10%

            Arachnoiditis with intrathecal administration

            Subacute toxicity with intrathecal administration (paralysis of extremities, cranial nerve palsy, seizure or coma)

            Demyelinating encephalopathy with cranial irradiation or other systemic chemotherapy

            Reddening of skin

            Hyperuricemia

            Ulcerative stomatitis

            Glossitis

            Gingivitis

            Nausea and vomiting

            Diarrhea

            Anorexia

            Intestinal perforation

            Mucositis (dose-dependent)

            Leukopenia

            Thrombocytopenia

            Renal failure

            Azotemia

            Nephropathy

            Pharyngitis

            1-10%

            Alopecia

            Photosensitivity

            Rash

            Abdominal distress

            Malaise

            Fatigue

            Chills, fever

            Decreased resistance to infection

            Gastrointestinal hemorrhage

            Myelosuppression

            Disorders of lung, interstitial pneumonia (acute, chronic)

            Atrophy of liver, cirrhosis, hepatic fibrosis or necrosis, elevated liver function tests, hepatic failure

            Previous
            Next

            Warnings

            Black Box Warnings

            For use in life threatening neoplastic disease or patients with psoriasis or rheumatoid arthritis with severe recalcitrant disabling disease, not adequately responsive to other forms of therapy

            Deaths reported with use of methotrexate in the treatment of malignancy, psoriasis, and rheumatoid arthritis

            Monitor patients closely for bone marrow, liver, lung and kidney toxicities

            Inform patients of risks involved; patient should be under a physician’s care throughout therapy

            High dose regimens recommended for osteosarcoma requires meticulous care; high dose regimens are investigational; therapeutic advantage not established

            Not recommended for women of childbearing potential, due to teratogenic activity, unless benefit-risk ratio is acceptable

            May cause fetal death or congenital abnormalities; use is contraindicated in pregnant women

            Methotrexate formulations or diluents containing preservatives should not be used for intrathecal or high-dose therapy

            May cause renal damage leading to acute renal failure, especially in high doses

            Elimination is reduced in impaired renal function, ascites, or pleural effusions; reduce dose and monitor carefully for toxicity

            Bone marrow suppression, aplastic anemia, and GI toxicity reported with high doses and concurrent administration of NSAIDs

            Any dose level or route of administration may cause severe and potentially fatal dermatologic reactions

            Tumor lysis syndrome may occur in patients with high tumor burden

            Administer therapy under supervision of physician experienced in use of antimetabolite therapy

            Diarrhea and ulcerative stomatitis may necessitate interruption of therapy; otherwise hemorrhagic enteritis and death from intestinal perforation may occur

            Methotrexate has been associated with acute and potentially fatal chronic hepatotoxicity; acutely, liver enzyme elevations are common but are usually transient and asymptomatic and not predictive of subsequent hepatic disease; periodic liver biopsies are recommended for psoriatic patients receiving long-term therapy

            Low-dose methotrexate has been associated with development of malignant lymphomas

            Immune suppression may lead to potentially fatal opportunistic infections

            May cause potentially fatal pneumonitis at any time during therapy even at low doses and is not fully reversible; pulmonary symptoms (especially a dry, non-productive cough) may require interruption of therapy and careful investigation

            Concomitant use with radiotherapy may increase risk of soft tissue necrosis and osteonecrosis

            Contraindications

            Pregnancy: Do not use due to potential for fetal death and teratogenic effects

            Nursing: Do not use due to potential for serious adverse effects in infants

            Alcoholism, alcoholic liver disease, or other chronic liver disease

            Immunodeficiency syndromes

            Preexisting blood dyscrasias such as bone marrow hypoplasia, leukopenia, thrombocytopenia, or significant anemia

            Hypersensitivity: Do not use with known hypersensitivity; severe reactions have been observed with use

            Cautions

            Only for use by physicians experienced in antimetabolite therapy

            For intrathecal and high-dose methotrexate therapy, use preservative-free formulation; preserved formulation of methotrexate is not for intrathecal or high dose therapy; contains benzyl alcohol

            Elderly patients: monitor closely for early signs of hepatic, bone marrow, and renal toxicity

            Response in 3-6 weeks; patient may continue to improve for another 12 weeks or more

            Elimination reduced with renal impairment, ascites, or pleural effusions; monitor closely for renal, bone marrow, lung, or liver toxicity

            Taking with folic acid 1 mg/day PO may significantly reduce liver toxicity

            Dermatologic toxicity: severe, potentially fatal skin reactions have been reported; psoriatic lesions may also be aggravated by UV radiation and sunburns may be recalled or worsened

            Good oral care recommended (risk of mucositis)

            Use extreme caution with active infection, peptic ulceration, and ulcerative colitis

            Immunizations: May be ineffective during therapy and live virus vaccines are not recommended due to risk of infection

            Ectopic pregnancy: Ideally, human chorionic gonadotropin should be <5000 International Units/L and sonogram normal

            Acute and chronic hepatoxicity: Acutely, liver enzyme elevations are common but are usually transient and asymptomatic and not predictive of subsequent hepatic disease; periodic liver biopsies are recommended for psoriatic patients receiving long-term therapy; should not be used in patient with alcoholism, alcoholic liver disease, or other chronic liver disease

            Pulmonary toxicity: Pulmonary fibrosis, pulmonary interstitial infiltrates, and lung disease may occur acutely at any time during therapy (weekly doses >7.5 mg) but are fully reversible; symptoms (especially dry cough) may necessitate interruption of treatment and investigation

            Methotrexate clearance rates vary widely and are generally decreased at higher doses

            Glucarpidase is indicated for treatment of toxic methotrexate concentrations in patients with delayed methotrexate clearance due to impaired renal function (refer to the glucarpidase prescribing information); if glucarpidase used, do not administer leucovorin within two hours before or after dose of glucarpidase because leucovorin is a substrate for glucarpidase; there are published case reports of intravenous and intrathecal glucarpidase treatment to hasten clearance of methotrexate in cases of overdose

            GI toxicity: Diarrhea or ulcerative stomatitis warrants discontinuance of therapy (risk of hemorrhagic enteritis or intestinal perforation)

            Bone marrow suppression: May cause anemia, aplastic anemia, pancytopenia, leukopenia, neutropenia, and/or thrombocytopenia; use caution in patients with preexisting hematopoietic impairment and with concomitant use of NSAIDs; a significant drop in blood counts warrants discontinuation of therapy

            May impair fertility, cause oligospermia, and menstrual dysfunction; exclude pregnancy before initiating treatment

            Neurotoxicity: May cause neurotoxicity, including strokelike encephalopathy, seizures, leukoencephalopathy, and myelopathy

            Nephrotoxicity: Risk of acute renal failure especially at high doses

            Caution should be used while driving or operating machinery due to risk of dizziness and fatigue 

            Previous
            Next

            Pregnancy & Lactation

            Pregnancy category: X

            Lactation: Drug excreted in breast milk; do not nurse

            Pregnancy Categories

            A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA:Information not available.

            more...
            Previous
            Next

            Pharmacology

            Mechanism of Action

            Inhibits dihydrofolic acid reductase; inhibits purine and thymidylic acid synthesis, which in turn interferes with DNA synthesis, repair, and cellular replication; cell cycle specific for S phase of cycle

            May inhibit rapid proliferation of epithelial cells in skin

            Absorption

            Bioavailability (PO): 60% at PO doses <30 mg/m², bioavailability is significantly less at doses >80 mg/m²

            Bioavailability (SC, Otrexup): 17, 13, 31, and 36% greater than PO methotrexate at doses of 10, 15, 20, and 25 mg respectively

            AUC (SC, Rasuvo): 35%, 49%, 51%, and 68% greater than PO methotrexate at doses of 7.5 mg, 15 mg, 22.5 mg, and 30 mg respectively

            Peak plasma time: PO, 1-2 hr; IM, 30-60 min

            Distribution

            Protein bound: 50%

            Vd: Initial, 0.18 L/kg; steady-state, 0.4-0.8 L/kg

            Metabolism

            Metabolized by liver and intracellularly

            Metabolites: Polyglutamated forms

            Elimination

            Half-life: Psoriasis, rheumatoid arthritis, and low-dose cancer treatment, 3-10 hr; high-dose treatment, 8-15 hr

            Excretion: Urine (80-100% within 24 hr), feces (small amounts)

            Previous
            Next

            Administration

            IV Incompatibilities

            Additive: Bleomycin

            Syringe: Droperidol, metoclopramide (may be compatible at low concentrations of metoclopramide)

            Y-site: Chlorpromazine, dexamethasone sodium phosphate(?), droperidol(?), gemcitabine, idarubicin, ifosfamide, midazolam, nalbuphine, promethazine, propofol

            IV/IM Preparation

            Reconstitute with D5W or NS: 20-mg vial, up to 25 mg/mL; 1-g vial, up to 50 mg/mL 

            May dilute further for IV infusion

            IV/IM Administration

            Administer by IM, IV push, or IV infusion

            Regular IV given with no more than 25 mg/mL

            IV push: Administered at 10 mg/min

            IV infusion (usually >100 mg): Administered over 30 minutes to 4 hours, or according to institutional protocol

            High-dose therapy (uses 1-g vial): Administered over 4 hours

            Specific dosing schemes vary, but high doses should be followed by leucovorin 24 hours after initiation of therapy to prevent toxicity

            IT Administration

            Do not use preservative-containing drug

            For meningeal leukemia, intrathecal administration is mandatory because CSF penetration is poor

            Before administration, equal volume of CSF is usually withdrawn; administer drug only if easy flow of blood-free CSF is noted

            SC Administration

            Otrexup is a single-dose auto-injector available in doses between 10 to 25 mg (in 5-mg increments) for once-weekly SC use only

            Rasuvo is a single-dose auto-injector available in doses between 7.5 and 30 mg (in 2.5-mg increments) for once-weekly SC use only

            Use another formulation in patients who require PO, IM, IV, intra-arterial, or IT dosing

            Visually inspect for particulate matter and discoloration prior to administration; do not use if seal is broken

            Administer SC in abdomen or thigh

            May self-inject if determined appropriate by a physician and have received proper training on preparation and administration; a trainer device is available

            Handling and disposal consistent with recommendation for cytotoxic drugs

            Storage

            Store intact vials at room temperature

            Protect from light

            Previous
            Next

            Images

            Previous
            Next

            Formulary

            FormularyPatient Discounts

            To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

            Adding plans allows you to:

            • View the formulary and any restrictions for each plan.
            • Manage and view all your plans together – even plans in different states.
            • Compare formulary status to other drugs in the same class.
            • Access your plan list on any device – mobile or desktop.

            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
            Add or Remove Plans
            Plans for
            Select State:
            Non-Medicare PlansMedicare Plans

            Select a box to add or remove a plan.

            Select a class to view formulary status for similar drugs

            Additional Offers
            Email to Patient

            From:

            To:

            The recipient will receive more details and instructions to access this offer.

            By clicking send, you acknowledge that you have permission to email the recipient with this information.

            Email Forms to Patient

            From:

            To:

            The recipient will receive more details and instructions to access this offer.

            By clicking send, you acknowledge that you have permission to email the recipient with this information.

            Previous
             
             
             
            All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.