A 37 y/o patient presents to your clinic with complaints of mouth sores and diarrhea. He's generally in good health but has felt sluggish recently. His past medical history is significant for moderate/severe rheumatoid arthritis (RA), which had been well controlled until recently. He was started on methotrexate by the rheumatologist during his clinic visit last week. His labs are normal except a slightly decreased Hct and WBC. His serum creatinine is WNL.

What's a likely cause of the patients' complaints? How would you treat this patient?

MTX is dosed once a WEEK when used for alternative conditions such as asthma, RA, inflammatory bowel disease, psoriasis, etc. There are more than a few reports of patients receiving MTX for these conditions as a DAILY dose instead of a WEEKLY dose. This could occur because of a prescribing error, dispensing error, or a misunderstanding of the dosing regimen by the patient. However it happens, a serious and potentially fatal overdose can occur. Deaths have resulted in some of these cases.

To treat such a patient:

-  Stop the drug.
-  Monitor labs and hydration. Dehydration can worsen MTX toxicity. Vigorous IV hydration and alkaline diuresis can help the body remove excess MTX.

-  Consider leucovorin if symptoms are severe. Dose - controversial. It is generally recommended that doses of Leucovorin equal to, or greater than, the ingested dose of methotrexate be given. Treatment may be guided by serum MTX levels. Folic acid is NOT an effective antidote.

-  The following guide has been recommended (MICROmedexÒ). This is probably better suited to 'rescue' doses of leucovorin after high dose MTX.

         MTX concentration      Hours Post-MTX          Dose of (x10(-6)M) Infusion Leucovorin

          1-0.1                                 24                             10-15 mg/m(2) Q6H for 12 doses

          1-5                                    24                             50 mg/m(2) Q6H until less than 1 x 10(-7)M

          5-10                                  24                             100 mg/m(2) Q6H until less than 1 x 10(-7)M

-  Myeloid stimulants (GM CSF) have been used in very severe cases.

REFERENCE

- Cohen MR. Beware of daily oral methotrexate dosing. Hospital Pharmacy 2002;37:586-7.