Vumerity Disease Interactions

Serious cases of herpes zoster have occurred in patients treated with dimethyl fumarate (which has the same active metabolite as diroximel fumarate); patients should be monitored for signs/symptoms of herpes zoster while on diroximel fumarate. Other serious opportunistic infections have occurred with dimethyl fumarate, including cases of serious viral, fungal, and bacterial infections. Patients with signs/symptoms consistent with any of these infections should undergo prompt diagnostic evaluation and receive appropriate treatment. Withholding diroximel fumarate treatment in patients with herpes zoster or other serious infections until the infection has resolved should be considered.

Therapy with diroximel fumarate should be administered cautiously in patients with liver dysfunction; no studies have been conducted in these patients. Clinically significant cases of liver injury have been reported in patients treated with dimethyl fumarate (which has the same active metabolite as diroximel fumarate) in the postmarketing setting. Signs/symptoms of liver injury, including elevation of serum aminotransferases to greater than 5-fold the upper limit of normal and elevation of total bilirubin to greater than 2-fold the upper limit of normal have been observed; these abnormalities resolved upon treatment discontinuation. Serum aminotransferase, alkaline phosphatase, and total bilirubin levels should be obtained prior to and during treatment with diroximel fumarate, as clinically indicated; therapy should be discontinued if clinically significant liver injury induced by diroximel fumarate is suspected.

Diroximel fumarate may decrease lymphocyte counts. Neither diroximel fumarate nor dimethyl fumarate (same active metabolite) have been studied in patients with preexisting low lymphocyte counts; caution is advised in these patients. CBC (including lymphocyte count) should be obtained before initiating treatment with diroximel fumarate, 6 months after starting treatment, every 6 to 12 months thereafter, and as clinically indicated. Interruption of therapy in patients with lymphocyte counts less than 0.5 x 10(9)/L persisting for more than 6 months and withholding treatment from patients with serious infections until resolution should be considered. Caution is recommended and decisions about whether or not to restart diroximel fumarate should be individualized based on clinical circumstances.

Progressive multifocal leukoencephalopathy (PML) has occurred in patients with multiple sclerosis (MS) treated with dimethyl fumarate (which has the same active metabolite as diroximel fumarate); PML is an opportunistic viral infection of the brain caused by the John Cunningham virus (JC virus) that generally only occurs in immunocompromised patients and usually leads to death or severe disability. Caution and monitoring is advised in patients with MS. Diroximel fumarate should be withheld at the first sign/symptom suggestive of PML and an appropriate diagnostic evaluation should be performed.

Due to an increase in the exposure of a major metabolite (2-hydroxyethyl succinimide [HES]), the use of diroximel fumarate is not recommended in patients with moderate or severe renal dysfunction.