What dose of MTX is used to treat Rheumatoid Arthritis and what toxicities are associated with its use?
Dosage: 7.5 to 25 mg orally, subcutaneous, or intramuscular weekly. The absorption of oral and parenteral MTX is equivalent at doses <15 mg/week. At higher doses, parenteral MTX gives serum levels 30% higher than oral MTX. At oral doses above 15 mg/week, better absorption is obtained if the oral dose is split (within a 24-hour period) or the parenteral form is used.
- • Oral MTX is available in 2.5-mg tablets and Trexall is available in 5.0-, 7.5-, 10-, and 15-mg tablets. Most rheumatologists favor using only 2.5-mg tablets to reduce the risk of dosing confusion. The cost of 40 pills is approximately $95/month (“cash price”). There has been recent cost variability due to intermittent shortages of oral generic MTX.
- • Subcutaneous MTX (generic) is supplied as a solution of 25 mg/mL (supplied in 2-mL and 10-mL vials). The patient must draw up the correct dose (2.5 mg/0.1 mL). MTX solution can be with or without preservative. At the doses used in rheumatology, patients can take either type. Preservative-free solution can be used if there are injection site reactions. The cost of two 2-mL vials (i.e., 1 month of therapy) is $30 to $40.
- • Fixed-dose individual syringes (Otrexup, Rasuvo) for subcutaneous injection are supplied as single dose, autoinjectors (0.4 mL) with prefilled doses of 10, 15, 20, or 25 mg. The cost of four 25-mg syringes is $475 to $650/month.
Folic acid 1 mg/day should always be given with MTX, and the dose can be increased to 2 to 5 mg/day if symptoms of toxicity (mouth sores) develop. Folinic acid (leucovorin) 5 mg given as one dose 24 hours after weekly dose of MTX can sometimes help mouth sores even if folic acid fails.
- • Oral ulcers: this may be prevented with the use of folic acid. Some patients may benefit from vitamin A 8000 IU/day.
- • Photosensitivity.
- • Hepatic toxicity: folic acid and subcutaneous dosing may reduce this side effect. Concern has lessened with further experience, and routine liver biopsy is not recommended. Obesity and diabetes mellitus increase fat in the liver and chance of MTX hepatotoxicity.
- • Hematologic toxicity: this includes leukopenia, thrombocytopenia, pancytopenia, and megaloblastic anemia. This is less likely to occur if renal function is normal.
- • Pneumonitis: pulmonary toxicity from MTX can be myriad. In true pneumonitis, it is critical to eliminate infectious causes such as Pneumocystis jiroveci pneumonia, and if MTX is felt to be the causative agent, it must be stopped and not restarted. The mortality rate upon rechallenge is up to 50%.
- • Flu-like symptoms: these include nausea, fatigue, fever, chills, myalgias, and are called “MTX flu”. Some patients may have less of these symptoms if dextromethorphan 30 mg given with MTX and 30 mg 8 to 12 hours later (Mucinex-DM).
- • Worsening nodulosis (5%) and leukocytoclastic vasculitis.
- • Lymphomas: when a patient on MTX is diagnosed with Epstein–Barr virus-positive lymphoma, the treatment of the lymphoma is to stop the MTX. The lymphoma may resolve completely without chemotherapy in some patients.
- • Teratogenicity: category X drug during pregnancy.