Leflunomide tablets have undergone a label change related to the addition of peripheral neuropathy as a warning.6 There have been cases of peripheral neuropathy reported in patients receiving leflunomide, and most have recovered following discontinuation of the agent. Some patients, however, have had persistent symptoms. Patients that are older than age 60 years, are diabetic, and/or are receiving concomitant neurotoxic medications, may be at an increased the risk for developing peripheral neuropathy. If a patient taking leflunomide develops peripheral neuropathy, the therapy should be discontinued. Utilization of the leflunomide drug elimination procedure may be necessary.7
A recent study in Gastroenterology found that proton pump inhibitors (PPIs), which are often prescribed along with nonsteroidal antiinflammatory drugs (NSAIDs), may exacerbate NSAID-induced injury within the small intestine.8 This study evaluated the effects of omeprazole or lansoprazole for nine days on celecoxib- and naproxen-induced intestinal bleeding and ulceration in a rat model. The hematocrit was also measured. Both PPIs aggravated NSAID-induced intestinal ulceration and bleeding. Enteric microbial shifts occurred, which may provide a partial mechanism for this drug-induced effect.
Labeling of tacrolimus capsules have been updated to reflect the occurrence of cases of pure red cell aplasia (PRCA).9 Individuals at increased risk include those with parvovirus B19 infection, underlying disease, or use of concomitant drugs also associated with the development of PRCA. Consider drug discontinuation if PRCA occurs.
The labels for TNF-α inhibitors were updated in September to include a new warning related to the risk of developing serious and sometimes fatal infections from Legionella or Listeria.10 In a similar manner in 2008, the product labels were updated to reflect the risk of developing histoplasmosis and other invasive fungal infections. According to the FDA (from Adverse Events Reporting System data, 1999–2010), there were 80 reports of patients who developed Legionella pneumonia following the use of TNF-α inhibitors. Fourteen of these patients died. (See the October 2011 issue of Drug Safety Quarterly, available at www.rheumatology.org in the “Publications” menu, for more information.)
TNF-α inhibitors may be associated with a slight increase in the development of nonmelanoma skin cancers.11 This is according to Mariette et al following their meta-analysis in a recent issue of Annals of Rheumatic Diseases.12 There were 21 full-text articles and 8 abstracts that met their inclusion criteria. Certolizumab pegol and golimumab were not included in this analysis. In addition, Amari et al. found similar results in an observational study in 20,648 RA patients.13 They identified an incidence of nonmalignant skin cancer as 18.9/100 patient-years in those that received TNF-α inhibitors compared to 12.7/100 patient-years in those that received nonbiologic disease-modifying antirheumatic drugs. These authors note that this should prompt rheumatologists and other clinicians to carefully and systemically screen all patients that receive TNF-α inhibitors for precancerous lesions and skin cancer.