Parenteral Manual

Methotrexate

Disclaimer: Official controlled document is the CHEO online copy. It is the responsibility of user to ensure that any paper copy version is the same as the online version before use.

Alternate Name(s): 
AMETHOPTERIN, MTX
Classification: 
Antimetabolite, Folic Acid Antagonist, Antineoplastic - CYTOTOXIC
Original Date: 
August 2005
Revised Date: 
June 2015
Indications: 
  • Acute lymphoblastic leukemia     
  • Osteosarcoma       
  • Non-Hodgkin's lymphomas
  • Non-malignant disorders (eg. psoriasis, rheumatoid arthritis)

THIS MEDICATION IS TO BE ADMINISTERED BY A CHEMO-TRAINED NURSE FOR ALL ONCOLOGY PATIENTS IN ORDER TO ENSURE PROTOCOL VALIDATION AND ONCOLOGY CARE MANAGEMENT.  FOR NON-ONCOLOGY PATIENTS, IT CAN BE ADMINISTERED SUBCUTANEOUSLY BY ANY NURSE WHO HAS KNOWLEDGE OF PROPER CYTOTOXIC HANDLING POLICIES AND PROCEDURES.  PLEASE CONTACT YOUR EDUCATOR IF YOU HAVE ANY QUESTIONS.

Reconstitution and Stability: 
  • Store at room temperature
  • Available as a 25 mg/mL solution for IV use
  • Available as a non-preserved 10 mg/mL for intrathecal injection
  • Stable for 72 hours in dextrose/saline combinations +/- bicarbonate
  • Stable in syringes for 14 days
  • Intrathecal preparations expire after 8 hours due to concern for sterility
  • Protect IV infusions from light. (Use brown biohazard bag; do not have to wrap buretrol or tubing.)  Light sensitivity is increased by dilution and combination with sodium bicarbonate.
Compatibility: 
  • Solutions Compatible: D5W, 0.9% NaCl and combinations
  • Additive/Above Cassette Compatible: no information
  • Y-site Compatible: allopurinol, cytarabine, dexamethasone, diphenhydramine (Benadryl), fludarabine, fluorouracil, furosemide, heparin, hydromorphone, lorazepam, methylprednisolone, metoclopramide, morphine, ondansetron, potassium chloride, ranitidine, sodium bicarbonate

Incompatible: chlorpromazine, droperidol, idarubicin, midazolam, propofol

 

 

 

Administration: 

(For approved routes of administration by nursing personnel, refer to Policy for the Administration of Intravenous Medications.)

SC YES
IM YES, alternate limb weekly
IV Direct YES, chemotherapy trained RN only
Usual dilution: undiluted (25 mg/mL) into freely running IV solution
Infusion time: 2 to 5 minutes
IV Intermittent Infusion

Yes

Usual dilution: depends on protocol (usual < 25 mg/mL); up to 500 mg/m2 may be given undiluted via syringe pump

Infusion time: depends on protocol; undiluted may be given over 10-15 minutes

IV Continuous Infusion YES
Usual dilution: depends on protocol (usual < 25 mg/mL)
Intrathecal YES, physician or Clinical Nurse Specialist in Oncology only
Dosage: 

(For neonatal dosages, refer to Neonatal IV Drug Manual.)

Acute Lymphoblastic Leukemia

  • 1-5 g/m2 IV over 24 hours Q 3-4 weeks
  • dose decreased by 50% in children with Trisomy 21

Osteosarcoma

  • 12 g/m2 IV over 4 hours (Maximum dose is 20 g)
  • GFR must be > 60 mL/min/1.73 m2

Intrathecal:  Usually dosed according to age

  • <1 year old  =  6 mg IT
  • <2 years old = 8 mg IT
  • <3 years old = 10 mg IT
  • >3 years old = 12 mg IT
  • >9 years old = 15 mg IT (depending on protocol, some will have a 12 mg IT maximum dose)

- Dose must be held for ALT >20 x upper limit of normal
** Dosage may differ according to protocol

Potential hazards of parenteral administration: 

Immediate (within a few minutes to hours):

  • Nausea, vomiting, (moderately low to moderately high emetogenic potential, dose dependent)
  • Diarrhea and abdominal distress (especially with large doses)
  • Chills, fever, dizziness
  • Seizures with large doses
  • Intrathecal - backache, fever, meningismus, headache, seizures
  • NON-VESICANT

Intermediate (within a few days)

  • Ulcerative stomatitis
  • Malaise, undue fatigue
  • Elevation of liver enzymes, jaundice
  • Nephrotoxicity with high doses - see below
  • Dermatologic and sensitivity reactions (rash, skin peeling with large doses)
  • Photosensitivity

Delayed (within a few days to weeks)

  • Myelosuppression, nadir: 7-13 days
  • Immunosuppression
  • Alopecia
  • Other: allergic pneumonitis, osteoporosis, leukoencephalopathy, stroke-like encepalopathy

*Treatment for unusual side effects are available through the study chair identified on the front page of the protocol and/or pharmacy

Notes: 
  • Methotrexate has many clinically significant drug interactions (ie. cotrimoxazole [Septra], NSAIDS, phenytoin, thiazide diuretics, warfarin, ascorbic acid [Vitamin C], omeprazole)
  • Careful monitoring of patient's hematological status, liver and renal function is necessary before, during and after treatment
  • Use with caution in children with a third space (ascites, effusions, edema)

For patients receiving high dose methotrexate (>1 g/m2):

  • Monitor creatinine
  • Alkalinize urine with PO/IV sodium bicarbonate (may be added to methotrexate infusion bag), ensure urine pH is greater than 7 for up to 48 hours post-dose
  • Maintain hydration prior to, during, and after high-dose administration
  • Monitor methotrexate levels after high-dose therapy beginning 24 hours after start of infusion
  • For doses requiring leucovorin rescue, make sure total rescue is in stock prior to starting treatment
  • Leucovorin rescue required for all doses > 300 mg/m2
  • Must use non-preserved solutions for doses > 5 g/m2

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