Potential for methotrexate exposure through contamination during parenteral use as an immunosuppressant.
BACKGROUND
To evaluate whether the risk of methotrexate (MTX) exposure through skin contamination using parenteral doses of 25 mg warrants special oncology handling precautions during administration.


METHODS
We conducted a study with six human volunteers deliberately exposed to an entire dose of 25 mg MTX solution on their skin for 30 min. Serum levels of MTX were measured at baseline, 2, 4, 8, 12 and 24 h as well as serum homocysteine at baseline and 24 h after clinical exposure. Twenty-four-hour urinary excretion of MTX and possible local or systemic signs of toxicity were also recorded.


RESULTS
All MTX serum concentrations were less than 0.02 micromol/L within the 24-h period. This is 500 times below the recommended serum concentration for which folinic acid supplementation is recommended. There was also no significant increase in homocysteine level to suggest MTX toxicity. The only adverse effects were mild local dermal reactions in three female volunteers.


CONCLUSIONS
Deliberate skin contamination and possible inhalation of a 25 mg MTX solution failed to show significant or quantifiable serum and urine concentrations to suggest MTX toxicity. Precautions to prevent contact with MTX designed for oncology protocols are unnecessary for our rheumatology patients or their carers using these much lower immunosuppressant doses for autoimmune diseases.
Wong
L S
LS
Department of Clinical Pharmacology and Toxicology, Canberra Hospital, Canberra, Australian Capital Territory, Australia. wlsan@yahoo.com
Tymms
K E
KE
Buckley
N A
NA
D000328:Adult; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D007263:Infusions, Parenteral / Q000009:adverse effects / Q000379:methods; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage* / Q000009:adverse effects* / Q000097:blood; D008875:Middle Aged; D012869:Skin Absorption / Q000187:drug effects / Q000502:physiology
D007166:Immunosuppressive Agents; D008727:Methotrexate