Methotrexate-related nausea and fatigue are an issue for many rheumatology patients who otherwise benefit from the treatment, but
Subcutaneous dosing is one option suggested by panel members, of the University of Rochester (N.Y.) and , of St. Vincent’s University Hospital, Dublin, who along with several other colleagues fielded questions during a discussion session at the Winter Rheumatology sponsored by the American College of Rheumatology.
“I like sub-Q,” agreed discussion moderator, of Brigham and Women’s Hospital, Boston. “But I actually would lower the dose sub-Q before I gave it because you actually may get a higher serum level,” he said, explaining that that may negate the benefits with respect to nausea.
His preferred approach, he said, is to either split dosing – for example, splitting a 20-mg dose into two 10-mg doses followed 10 hours later with Leucovorin (folinic acid) – or to give the full methotrexate dose at bedtime followed 10 hours later with Leucovorin.
“I use a lot of Leucovorin – a lot,” he noted.
For those patients who get nauseated at the mere mention of methotrexate, though, it’s probably best to try a different drug, he said.
Another approach, suggested by, of the Hospital for Special Surgery in New York, is to give Zofran (ondansetron) with methotrexate. Other suggestions included lowering the methotrexate dose and injecting the drug.
For fatigue, there has been some suggestion of a benefit with B-12 supplementation, panel members said. Dr. Bykerk noted some ongoing work that is demonstrating a benefit with sublingual B-12 for methotrexate intolerance in general, and it appears to allow for much higher methotrexate dosing, she said.
Early reports regarding those as-yet-unpublished data are, indeed, promising, Dr. Weinblatt said, noting that in his practice he has been using subcutaneous B-12 given at about 1,000 mcg 2 days before methotrexate and then on the day of methotrexate for patients with fatigue who are “failing Leucovorin, failing caffeine.”
Addressing fatigue and nausea in patients on methotrexate is important because, in his experience in appropriately monitored patients, it’s not serious adverse events, but rather fatigue and nausea, that most often lead to stopping methotrexate.
Dr. Weinblatt reported financial relationships with nearly 20 pharmaceutical companies. Dr. Bykerk reported financial relationships with Amgen, Brainstorm, Bristol-Myers Squibb, Pfizer, and Regeneron. Dr. Veale reported financial relationships with AbbVie, Janssen, Pfizer, Roche, and UCB. Dr. Ritchlin reported financial relationships with AbbVie, Amgen, Janssen, Lilly, Novartis, Pfizer, and UCB.