Before methotrexate toxicity occurred, eGFR was available for many of the patients. Five patients (63%) had mild renal insufficiency (60–89 mL/min/1.73 m²) and three patients (38%) had moderate renal insufficiency (30–59 mL/min/1.73m²). At the time of admission, four patients had mild renal insufficiency, five patients had moderate renal insufficiency, and one patient had severe renal insufficiency with an eGFR of 9 mL/min/1.73m².
By comparison, the group of 150 patients with RA received 14.3 mg ± 4.9 mg of methotrexate a week. These patients used ARBs or ACEis and NSAIDs or COX-2 inhibitors at similar rates as the study group but were less likely to use diuretics (n=18) than the study group (n=5; P=0.01 Fisher’s exact test). The comparator group’s eGFR was 70 mL/min/1.73m², which was higher than that of the patients with methotrexate toxicity (median 61 [32–77] mL/min/1.73m²; P=0.0171). Eight (5%) of the patients from the comparator group had normal renal function, 105 (70%) had mild renal insufficiency, 35 (23%) had moderate renal insufficiency and one had an eGFR of 19 mL/min/1.73m².
Conclusion
These data show that life-threatening methotrexate reactions still occur. In the evaluated patients who were older than 70 and had prior mild to moderate renal function impairment, the risk of serious methotrexate toxicity was increased. In many of these patients, acute renal failure that may have improved by the time of hospital admission seemed to be the cause of methotrexate toxicity. While one patient was clinically suspected of accidental methotrexate overdose, researchers also found measurable levels in three other patients that suggest overdose. Compared with an RA population of similar age, the renal function of the study group was slightly worse, and the use of diuretics was more common in those with severe toxicity.
Reminders: When treating patients with low-dose methotrexate, liver and kidney disease should be excluded prior to use, as well as alcohol use.3 Chest radiograph and pregnancy testing should be obtained prior to starting treatment.
Physicians and other members of the healthcare team should obtain a patient’s complete blood count, and liver and kidney function tests prior to prescribing methotrexate. Monitor these levels throughout treatment. A complete blood count, creatinine and liver function tests should be assessed every two to four weeks during the first three months of treatment, every eight to 12 weeks for the following three to six months and every 12 weeks thereafter.
Methotrexate may cause bone marrow suppression, and hepatic and pulmonary disorders. Decreased clearance, drug-to-drug interactions and dosing errors are risk factors for toxicity.
