Methotrexate

Drug Data

Classification

Generic Name Methotrexate

Pharmacologic Class Folic acid antagonist

Trade Name Folex Minimum Dose 7.5 mg 1 tab BID

Therapeutic Class Antimetabolite. Antineoplastic, Antipsoriatic, Antirheumatic

Maximum Dose 15 mg 1 tab q6˚

Pregnancy Risk Factor X

Contents Methotrexate Availability and color

- Tablets- 2.5, 5, 7.5 10, 15mg - Powder for injection- 20 mg, 1 g per vial - Injection- 25 mg/mL

Routes of administration Oral Intramuscular Intravenous

Mechanism of Action Inhibits folic acid reductase, leading to inhibition of DNA synthesis and inhibition of cellular replication; selectively affects the most rapidly dividing cells (neoplastic and psoriatic cells) Pharmacokinetics A: Rapidly absorbed from the GI tract at low doses, higher doses are less well absorbed. Rapidly and completely absorbed after IM doses. D: Tissues and extracellular fluids; crosses the blood-brain barrier and placenta; enters breast milk. Small amounts in saliva and breast milk. 50% bound to plasma proteins. Bound as polyglutamate conjugates, bound drug may remain in the body for several mth, particularly in the liver. M: Partly by intestinal flora. Does not undergo significant metabolism at low dose therapy; 7-hydroxy metabolite is detected at high-doses. E: Primarily via urine; small amounts in bile, feces. Rout e Oral IM IV

Onse t Varie s Rapi d Rapi d

Peak 1-2 hr 0.5-1 hr 0.5-1 hr

Indication General Indications - Burkitt's lymphoma - Acute lymphoblastic leukaemia - Choriocarcinoma - Mycosis fungoides - Psoriasis - Rheumatoid arthritis - Crohn's disease - Osteosarcoma - Breast cancer - Advanced lymphosarcoma - Acute lymphoblastic leukaemia - Choriocarcinoma - Acute lymphoblastic leukaemia - Mycosis fungoides - Crohn's disease - Psoriasis - Meningeal leukaemia - Hydatidiform mole

Duratio n Unknow n Unknow n Unknow n

Contraindication s Concentrations - Pregnancy - Lactation - Alcoholism - Chronic liver disease - Immune deficiencies - Blood dyscrasias - Hypersensitivity Precaution - Renal disease - Infection - Peptic ulcer - Ulcerative colitis - Debility Drug interaction Drug to drug - Potentially serious to fatal reactions when given with NSAID’s - Risk for toxicity with alcohol - Increased risk of toxicity with salicylates, probenecid, sulfonamides - Decreased serum levels and therapeutic effects of digoxin - May decrease theophylline clearance

Adverse Reaction

Nursing Responsibilities

CNS: Headache, drowsiness, blurred vision, aphasia, hemiparesis, paresis, seizures, fatigue, malaise, dizziness Dermatologic: Erythematous rashes, pruritus, urticaria, photosensitivity, depigmentation, alopecia, ecchymosis, telangiectasia, acne, furunculosis GI: Ulcerative stomatitis, gingivitis, pharyngitis, anorexia, nausea, vomiting, diarrhea, hematemesis, melena, GI ulceration, bleeding, enteritis, hepatic toxicity GU: Renal failure, effects on fertility Hematologic: Severe bone marrow depression, increased susceptibility to infection Hypersensitivity: Anaphylaxis, sudden death Respiratory: Interstitial pneumonitis, chronic interstitial obstructive pulmonary disease Other: Chills and fever, metabolic changes, cancer

Before - Observe 15 rights in drug administration. - Assess for contraindications of the drug. - Arrange for tests to evaluate CBC, urinalysis, renal and liver function tests, and chest X-ray before therapy. - Ensure that patient is not pregnant before administering. - Prepare a calendar of treatment days.

Source: Karch, Amy: 2009 Lippincott’s Nursing Drug Guide, p. 769

Source: Karch, Amy: 2009 Lippincott’s Nursing Drug Guide, p. 769

Drug to food - none reported

Drug Half Life 3-15 hr

Source: Karch, Amy: 2009 Lippincott’s Nursing Drug Guide, p. 767768

Source: http://www.keele.ac.uk/ Karch, Amy: 2009 Lippincott’s Nursing Drug Guide, p. 767

Source: http://mims.com.ph/, Karch, Amy: 2009 Lippincott’s Nursing Drug Guide, p. 768

Source: http://mims.com.ph/

Source: Karch, Amy: 2009 Lippincott’s Nursing Drug Guide, p. 769

During - Arrange for tests to evaluate CBC, urinalysis, renal and liver function tests, and chest X-ray during therapy. - Do not administer any other medications containing alcohol. - Arrange for adequate hydration during therapy to reduce risk of hyperuricemia. - Arrange to have leucovrin readily available as antidote for methotrexate overdose. - Instruct to use contraceptives during therapy. After - Arrange for tests to evaluate CBC, urinalysis, renal and liver function tests, and chest X-ray several weeks after therapy. - Instruct to report black tarry stools, fever, chills, sore throat, unusual bleeding or bruising, cough or shortness of breath, darkened or bloody urine, abdominal, flank or joint pain, jaundice symptoms, mouth sores. - Arrange for an antiemetic if nausea and vomiting is severe. - Reduce dosage or discontinue if renal failure occurs. - Arrange for frequent, regular medical check-ups.