Generic name: Methotrexate

Brand name: Otrexup, Rasuvo, Trexall, Xatmep

Classification:
PHARMACOTHERAPEUTIC: Folate antagonist (Antimetabolite)
CLINICAL: Antineoplastic, antirheumatic disease-modifying, immunosuppressant

Mode of action:
Competes with enzymes necessary to reduce folic acid to tetrahydrofolic acid, a component essential to DNA synthesis, repair, and
cellular replication.
Therapeutic Effect: Inhibits DNA, protein synthesis. Possesses anti-inflammatory and immune-modulating activity.

Ordered dose and frequency:

Suggested dose (by manufacturer):

TABLETS (RHEUMATREX, TREXALL)
Adults. 2.5 mg every 12 hr for 3 doses/wk, increased as ordered by 2.5 mg/wk. Alternatively, 7.5 mg once weekly.
Maximum: 30 mg/wk.
I.V. OR I.M INJECTION (METHOTREXATE SODIUM), SUBCUTANEOUS INJECTION (OTREXUP PFS, RASUVO, REDITREX)
Adults. 10 to 25 mg as a single dose weekly. I.V. injection rate dependent upon dose. Follow manufacturer instructions.
Maximum: 30 mg weekly.
TABLETS (RHEUMATREX, TREXALL)
Adults. 2.5 every 12 hr for 3 doses/wk, increased as ordered by 2.5 mg/wk. Alternatively, 7.5 mg once weekly.
Maximum: 20 mg/wk.
SUBCUTANEOUS INJECTION (OTREXUP PFS, RASUVO, REDITREX TREXALL)
Adults. 7.5 mg once weekly, then gradually increased to achieve an optimal response.
Maximum: 20 mg/wk.
ORAL SOLUTION (XATMEP), I.M. INJECTION (METHOTREXATE SODIUM), SUBCUTANEOUS INJECTION (OTREXUP PFS,
RASUVO, REDITREX), TABLETS (RHEUMATREX, TREXALL)
Children ages 2 to 16. Initial: 10 mg/m2 once weekly, increased gradually, as needed
Indication:
Oncology Uses
ALERT: Refer to individual specific protocols for optimum dosage, sequence of administration.
Head/Neck Cancer
PO, IV, IM: ADULTS, ELDERLY: 40 mg/ m2 once wkly. Continue until disease progression or unacceptable toxicity
Breast Cancer
IV: ADULTS, ELDERLY: 40 mg/m2 days 1 and 8 q4wks in combination with cyclophosphamide and fluorouracil.
Mycosis Fungoides
IM, PO: ADULTS, ELDERLY: 5–50 mg once wkly or 15–37.5 mg twice wkly.
Rheumatoid Arthritis (RA)
PO: ADULTS: Initially, 10–15 mg once wkly. May increase by 5 mg q2–4wks to a maximum dose of 20–30 mg once weekly.
SQ/IM: Initially, 7.5 mg/wk. Adjust dose gradually to optimal response.
ELDERLY: Initially, 5–7.5 mg/wk.
Maximum: 20 mg/wk. Juvenile
Rheumatoid Arthritis (JRA)
PO, IM, SQ: CHILDREN: Initially, 10 mg/ m2 once wkly, then 20–30 mg/m2/wk as a single dose.
Psoriasis
PO: ADULTS, ELDERLY: Initially, 10–25 mg once wkly or 2.5–5 mg q12h for 3 doses once wkly. IM/SQ: 10–25 mg once
wkly. Adjust dose gradually to optimal response. Titrate to lowest effective dose.
Dosage in Renal Impairment
Creatinine Clearance Reduce Dose to
61–80 mL/min 75% of normal
51–60 mL/min 70% of normal
10–50 mL/min 30–50% of normal
Less than 10 mL/min Avoid use

Dosage in Hepatic Impairment

Use caution.
Contraindication:

For all conditions: Breastfeeding, hypersensitivity to methotrexate or its components, pregnancy; For treatment of psoriasis or
rheumatoid arthritis: alcoholism; alcoholic liver disease; chronic liver disease; laboratory evidence or overt immunodeficiency
syndromes; preexisting blood dyscrasias such as bone marrow hypoplasia, leukopenia, significant anemia, or thrombocytopenia

Cautions: Peptic ulcer, ulcerative colitis, preexisting myelosuppression, history of chronic hepatic disease, alcohol consumption,
obesity, diabetes, hyperlipidemia, use with other hepatotoxic medications, concomitant use of proton pump inhibitors. Use of
NSAIDs or aspirin with lower methotrexate doses for rheumatoid arthritis

Side effects:
Frequent (10%–3%): Nausea, vomiting, stomatitis, burning/erythema at psoriatic site (in pts with psoriasis).
Occasional (3%– 1%): Diarrhea, rash, dermatitis, pruritus, alopecia, dizziness, anorexia, malaise, headache, drowsiness, blurred
vision.

Adverse effects:

CNS: Aphasia, cerebral thrombosis, chills, dizziness, drowsiness, fatigue, fever, headache, hemiparesis, leukoencephalopathy,
malaise, paresis, seizures
CV: Chest pain, deep vein thrombosis, hypotension, pericardial effusion, pericarditis, thromboembolism
ENDO: Gynecomastia
EENT: Blurred vision, conjunctivitis, gingivitis, glossitis, pharyngitis, stomatitis, transient blindness, tinnitus
GI: Abdominal pain, anorexia, cirrhosis, diarrhea, elevated liver enzymes, enteritis, GI bleeding and ulceration, hepatitis,
hepatotoxicity, nausea, pancreatitis, vomiting.
GU: Cystitis, hematuria, infertility, menstrual dysfunction, nephropathy, renal failure, tubular necrosis, vaginal discharge
HEME: Anemia, aplastic anemia, leukopenia, neutropenia, pancytopenia, thrombocytopenia
MS: Arthralgia, dysarthria, myalgia, stress fracture
RESP: Dry nonproductive cough, dyspnea, interstitial pneumonitis, pneumonia, pulmonary fibrosis or failure, pulmonary infiltrates
SKIN: Acne, alopecia, altered skin pigmentation, ecchymosis, erythema multiforme, exfoliative dermatitis, furunculosis, necrosis,
photosensitivity, pruritus, psoriatic lesions, rash, Stevens–Johnson syndrome, telangiectasia, toxic epidermal necrolysis, ulceration,
urticaria
Other: Anaphylaxis, increased risk of infection, lymphadenopathy, lymphoproliferative disease

Drug interaction:

bone marrow depressants: Possibly increased bone marrow depression

chloramphenicol, nonabsorbable broad spectum antibiotics, tetracycline: Possibly decreased methotrexate absorption
co-trimoxazole: Possibly increased bone marrow suppression
folic acid: Possibly decreased effectiveness of methotrexate.
hepatotoxic drugs: Increased risk of hepatotoxicity.
NSAIDs, penicillins, phenylbutazone, phenytoin, probenecid, salicylates, sulfonamides: Increased risk of methotrexate toxicity
theophylline: Possibly increased risk of theophylline toxicity
vaccines: Risk of disseminated infection with live-virus vaccines, risk of suppressed response to killed-virus vaccines

Nursing responsibilities (at least 10):

• Follow facility policy for preparing and handling drug; parenteral form poses a risk of carcinogenicity, mutagenicity, and
teratogenicity. Avoid skin contact.
• Use only preservative-free formulation of methotrexate when administering high-dose therapy.
• Monitor results of CBC, chest x-ray, liver and renal function tests, and urinalysis before and during treatment.
• Administer subcutaneous injection into patient’s abdomen or thigh. Increase patient’s fluid intake to 2 to 3 L daily, unless
contraindicated, to reduce the risk of adverse GU reactions.
• Assess patient for bleeding and infection.

WARNING Expect renal impairment to severely alter drug elimination.

• Be aware that high doses of methotrexate can impair renal elimination by forming crystals that obstruct urine flow. To
prevent drug precipitation, alkalinize patient’s urine with sodium bicarbonate tablets, as ordered.
• Follow standard precautions because drug can cause immunosuppression.
• Be aware that if patient becomes dehydrated from vomiting, prescriber should be notified, and expect to withhold drug until
patient recovers.
• Be aware that if patient receives high doses of drug, leucovorin should be kept readily available as antidote.
 • Be aware that methotrexate resistance may develop with prolonged use.

Bibliography (at least 3 references; APA format):

Saunders. (2020). Nursing Drug Handbook (P. 956)

Jones & Bartlett. (2021). Nurse’s Drug Handbook (P.1706)