TECFIDERA Has a Well-Understood Safety Profile1

Contraindications

TECFIDERA is contraindicated in patients with known hypersensitivity to dimethyl fumarate or to any of the excipients of TECFIDERA. Reactions have included anaphylaxis and angioedema.

Warnings and precautions

Anaphylaxis and Angioedema1

Warning

  • Can occur after the first dose or anytime during treatment with TECFIDERA

Signs and symptoms

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

Guidance 

  • Discontinue TECFIDERA and seek immediate medical care

Progressive Multifocal Leukoencephalopathy (PML)1

Warning

  • Has occurred in patients with MS treated with TECFIDERA
  • 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 TECFIDERA for 4 years while enrolled in a clinical trial
    • Patient experienced prolonged lymphopenia (lymphocyte counts predominantly <0.5x109/L for 3.5 years) while taking TECFIDERA
  • PML has also occurred in the postmarketing setting in the presence of lymphopenia (<0.9x109/L)
  • While the role of lymphopenia in these cases is uncertain, the PML cases have occurred predominantly in patients with lymphocyte counts <0.8x109/L persisting for more than 6 months

Signs and symptoms

  • Diverse and 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 TECFIDERA and perform an appropriate diagnostic evaluation

For additional information, please see full Prescribing Information.

Herpes Zoster and Other Serious Opportunistic Infections1

Warning

  • Serious cases of herpes zoster have occurred with TECFIDERA, including disseminated herpes zoster, herpes zoster ophthalmicus, herpes zoster meningoencephalitis, and herpes zoster meningomyelitis 
  • These events may occur at any time during treatment 
  • Other serious opportunistic infections have occurred with TECFIDERA, including cases of serious viral (herpes simplex virus, West Nile virus, cytomegalovirus), fungal (Candida and Aspergillus), and bacterial (Nocardia, Listeria monocytogenes, Mycobacterium tuberculosis) infections
  • These infections have been reported in patients with reduced absolute lymphocyte counts (ALC) as well as in patients with normal ALC
  • These infections have affected the brain, meninges, spinal cord, gastrointestinal tract, lungs, skin, eye, and ear

Guidance

  • Monitor patients for signs and symptoms of herpes zoster
  • Patients with symptoms and signs consistent with any of the serious opportunistic infections should undergo prompt diagnostic evaluation and receive appropriate treatment
  • Consider withholding TECFIDERA treatment in patients with herpes zoster or other serious infections until the infection has resolved

 

Lymphopenia1,2

TECFIDERA-Lymphocyte-Counts
TECFIDERA-Lymphocyte-Counts

Warning

  • TECFIDERA may decrease lymphocyte counts 

Details

  • During the first year in clinical trials, mean lymphocyte counts decreased by approximately 30% and then remained stable
  • Four weeks after stopping TECFIDERA, mean lymphocyte counts increased but did not return to baseline
  • 6% of TECFIDERA 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, 2% of patients experienced lymphocyte counts <0.5x109/L for at least 6 months, and in this group, the majority of lymphocyte counts remained <0.5x109/L with continued therapy
  • TECFIDERA has not been studied in patients with pre-existing low lymphocyte counts

Guidance

  • Obtain a CBC, including lymphocyte count, before initiating treatment with TECFIDERA, 6 months after starting treatment, and then every 6 to 12 months thereafter, and as clinically indicated
  • Consider interruption of TECFIDERA 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 TECFIDERA is discontinued or interrupted due to lymphopenia
  • Restart TECFIDERA based on individual and clinical circumstances

Liver Injury1

Warning

  • Clinically significant cases of liver injury have been reported in patients treated with TECFIDERA in the postmarketing setting
  • The onset has ranged from a few days to several months after initiation of treatment with TECFIDERA
  • 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 TECFIDERA and during treatment, as clinically indicated
  • Discontinue TECFIDERA if clinically significant liver injury induced by TECFIDERA is suspected

Flushing1,2

TECFIDERA Incidence of Flushing Events chart
TECFIDERA Incidence of Flushing Events chart

Warning

  • May occur during treatment with TECFIDERA. In clinical trials, 40% experienced flushing
  • 3% of patients discontinued TECFIDERA because of flushing and <1% had serious flushing symptoms that were not life-threatening but led to hospitalization

Signs and symptoms

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

Guidance

  • Taking TECFIDERA with food may help with flushing
    • A high-fat, high-calorie meal did not affect overall exposure to TECFIDERA
  • Alternatively, taking non-enteric coated aspirin (up to a dose of 325 mg) 30 minutes prior to TECFIDERA dosing may reduce the incidence and severity of flushing
  • Advise patients to contact their healthcare provider if they experience persistent and/or severe flushing

*Flushing consists of the preferred terms of flushing and hot flush. Other related symptoms consist of the preferred terms of erythema, generalized erythema, burning sensation, skin burning sensation, feeling hot, and hyperemia.

A high-fat, high-calorie meal did not affect the overall exposure to MMF, a TECFIDERA metabolite, but decreased the maximal plasma concentration and increased the time until this concentration was reached. A high-fat, high-calorie meal reduced the incidence of flushing by approximately 25%.