VUMERITY Offers the Well-Understood Safety of dimethyl fumarate1

Contraindications

VUMERITY is contraindicated in patients

  • With known hypersensitivity to diroximel fumarate, dimethyl fumarate, or to any of the excipients of VUMERITY. Reactions may include anaphylaxis and angioedema
  • Taking dimethyl fumarate

Warnings and Precautions

Anaphylaxis and Angioedema1

Warning

  • Dimethyl fumarate can cause anaphylaxis and angioedema after the first dose or at any time during treatment

Signs and symptoms

  • Include difficulty breathing, urticaria, and swelling of the throat and tongue

Guidance

  • Patients should be instructed to discontinue VUMERITY and seek immediate medical care should they experience signs and symptoms of anaphylaxis and angioedema

Progressive Multifocal Leukoencephalopathy (PML)1

Warning

  • PML has occurred in patients with MS who have been treated with dimethyl fumarate

 

  • PML is an opportunistic viral infection of the brain caused by the JC virus (JCV) that typically only occurs in patients who are immunocompromised, and that usually leads to death or severe disability

Details

  • A fatal case of PML occurred in a patient who received dimethyl fumarate for 4 years while enrolled in a clinical trial
    • The patient experienced prolonged lymphopenia (lymphocyte counts predominantly <0.5x109 for 3.5 years) while taking dimethyl fumarate
  • PML has also occurred in patients taking dimethyl fumarate in the postmarketing setting in the presence of lymphopenia (<0.8x109/L) persisting for more than 6 months
  • While the role of lymphopenia in these cases is uncertain, the majority of cases occurred in patients with lymphocyte counts <0.5x109/L

Signs and symptoms

  • Diverse, progress over days to weeks
  • Include progressive weakness on one side of the body or clumsiness of limbs; disturbance of vision; and changes in thinking, memory, and orientation leading to confusion and personality changes
  • MRI findings may be apparent before clinical signs or symptoms

Guidance

  • At the first sign or symptom suggestive of PML, withhold VUMERITY and perform an appropriate diagnostic evaluation

For additional information, please see full Prescribing Information.

Lymphopenia1

Warning

  • VUMERITY may decrease lymphocyte counts

Details

  • In the MS placebo-controlled trials with dimethyl fumarate, mean lymphocyte counts decreased by approximately 30% during the first year of treatment with dimethyl fumarate and then remained stable
  • Four weeks after stopping dimethyl fumarate, mean lymphocyte counts increased but did not return to baseline
  • 6% of dimethyl fumarate patients and <1% of placebo patients experienced lymphocyte counts <0.5x109/L (lower limit of normal 0.91x109/L)
  • In controlled and uncontrolled clinical trials with dimethyl fumarate, 2% of patients experienced lymphocyte counts <0.5x109/L for at least six months, and in this group the majority of lymphocyte counts remained <0.5x109/L with continued therapy
  • Neither VUMERITY nor dimethyl fumarate has been studied in patients with preexisting low lymphocyte counts

Guidance

  • Obtain a CBC, including lymphocyte count, before initiating treatment with VUMERITY, 6 months after starting treatment, and then every 6 to 12 months thereafter, and as clinically indicated
  • Consider interruption of VUMERITY in patients with lymphocyte counts <0.5x109/L persisting for more than 6 months
  • Given the potential for delayed recovery of lymphocyte counts, continue to obtain lymphocyte counts until their recovery if VUMERITY is discontinued or interrupted due to lymphopenia
  • Restart VUMERITY based on individual and clinical circumstances

Liver Injury1

Warning

  • Clinically significant cases of liver injury have been reported in patients treated with dimethyl fumarate in the postmarketing setting
  • The onset has ranged from a few days to several months after initiation of treatment with dimethyl fumarate
  • None of the reported cases resulted in liver failure, liver transplant, or death. Some cases required hospitalization
  • The combination of new serum aminotransferase elevations with increased levels of bilirubin caused by drug-induced hepatocellular injury is an important predictor of serious liver injury that may lead to acute liver failure, liver transplant, or death in some patients

Signs and symptoms

  • Include elevation of serum aminotransferases to greater than 5-fold the upper limit of normal (ULN) and elevation of total bilirubin to greater than 2-fold the ULN

Guidance

  • Obtain serum aminotransferase, alkaline phosphatase, and total bilirubin levels prior to treatment with VUMERITY and during treatment, as clinically indicated
  • Discontinue VUMERITY if clinically significant liver injury induced by VUMERITY is suspected

Flushing1

Warning

  • VUMERITY may cause flushing. In clinical trials, 40% of patients treated with dimethyl fumarate experienced flushing
  • 3% of patients discontinued dimethyl fumarate for flushing and <1% had serious flushing symptoms that were not life-threatening but led to hospitalization

Signs and symptoms

  • Generally began soon after initiating dimethyl fumarate and usually improved or resolved over time
  • Include warmth, redness, itching, and/or burning sensation

Guidance

  • Taking VUMERITY with food may reduce the incidence of flushing
  • Alternatively, taking non-enteric coated aspirin (up to a dose of 325 mg) 30 minutes prior to VUMERITY dosing may reduce the incidence or severity of flushing
  • Advise patients to contact their healthcare provider if they experience persistent and/or severe flushing