Tecfidera® (dimethyl fumarate) delayed-release capsules,
for oral use
Brief Summary of Full Prescribing Information
1 INDICATIONS AND USAGE
TECFIDERA is indicated for the treatment of patients with relapsing
forms of multiple sclerosis.
2 DOSAGE AND ADMINISTRATION
2. 1 Dosing Information
The starting dose for TECFIDERA is 120 mg twice a day orally. After
7 days, the dose should be increased to the maintenance dose of
240 mg twice a day orally. Temporary dose reductions to 120 mg
twice a day may be considered for individuals who do not tolerate
the maintenance dose. Within 4 weeks, the recommended dose of
240 mg twice a day should be resumed. Discontinuation of
TECFIDERA should be considered for patients unable to tolerate
return to the maintenance dose. The incidence of flushing may be
reduced by administration of TECFIDERA with food. Alternatively,
administration of non-enteric coated aspirin (up to a dose of 325 mg)
30 minutes prior to TECFIDERA dosing may reduce the incidence or
severity of flushing [see Clinical Pharmacology ( 12. 3)].
TECFIDERA should be swallowed whole and intact. TECFIDERA
should not be crushed or chewed and the capsule contents should not
be sprinkled on food. TECFIDERA can be taken with or without food.
2. 2 Blood Test Prior to Initiation of Therapy
Obtain a complete blood cell count (CBC) including lymphocyte count
before initiation of therapy [see Warnings and Precautions ( 5. 3)].
3 DOSAGE FORMS AND STRENGTHS
TECFIDERA is available as hard gelatin delayed-release capsules
containing 120 mg or 240 mg of dimethyl fumarate. The 120 mg
capsules have a green cap and white body, printed with “BG- 12
120 mg” in black ink on the body. The 240 mg capsules have a green
cap and a green body, printed with “BG- 12 240 mg” in black ink on
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 [see Warnings
and Precautions ( 5. 1)].
5 WARNINGS AND PRECAUTIONS
5. 1 Anaphylaxis and Angioedema
TECFIDERA can cause anaphylaxis and angioedema after the first
dose or at any time during treatment. Signs and symptoms have
included difficulty breathing, urticaria, and swelling of the throat and
tongue. Patients should be instructed to discontinue TECFIDERA
and seek immediate medical care should they experience signs and
symptoms of anaphylaxis or angioedema.
5. 2 Progressive Multifocal Leukoencephalopathy
Progressive multifocal leukoencephalopathy (PML) 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. A fatal case
of PML occurred in a patient who received TECFIDERA for 4
years while enrolled in a clinical trial. During the clinical trial, the
patient experienced prolonged lymphopenia (lymphocyte counts
predominantly <0.5x109/L for 3. 5 years) while taking TECFIDERA
[see Warnings and Precautions ( 5. 3)]. The patient had no other
identified systemic medical conditions resulting in compromised
immune system function and had not previously been treated with
natalizumab, which has a known association with PML. The patient
was also not taking any immunosuppressive or immunomodulatory
PML has also occurred 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.
At the first sign or symptom suggestive of PML, withhold TECFIDERA
and perform an appropriate diagnostic evaluation. MRI findings may
be apparent before clinical signs or symptoms. Typical symptoms
associated with PML are diverse, progress over days to weeks, and
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.
TECFIDERA may decrease lymphocyte counts. In the MS
placebo controlled trials, mean lymphocyte counts decreased by
approximately 30% during the first year of treatment with TECFIDERA
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
less than 0.5x109/L persisting for more than six 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. Consider withholding
treatment from patients with serious infections until resolution.
Decisions about whether or not to restart TECFIDERA should be
individualized based on clinical circumstances.
TECFIDERA may cause flushing (e.g., warmth, redness, itching, and/
or burning sensation). In clinical trials, 40% of TECFIDERA treated
patients experienced flushing. Flushing symptoms generally began
soon after initiating TECFIDERA and usually improved or resolved
over time. In the majority of patients who experienced flushing,
it was mild or moderate in severity. Three percent (3%) of patients
discontinued TECFIDERA for flushing and <1% had serious flushing
symptoms that were not life-threatening but led to hospitalization.
Administration of TECFIDERA with food may reduce the incidence
of flushing. Alternatively, administration of non-enteric coated aspirin
(up to a dose of 325 mg) 30 minutes prior to TECFIDERA dosing
may reduce the incidence or severity of flushing [see Dosing and
Administration ( 2. 1) and Clinical Pharmacology ( 12. 3)].
6 ADVERSE REAC TIONS
The following important adverse reactions are described elsewhere in
labeling: Anaphylaxis and Angioedema ( 5. 1), Progressive multifocal
leukoencephalopathy ( 5. 2), Lymphopenia ( 5. 3), Flushing ( 5.4) [see
Warnings and Precautions].
6. 1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions,
adverse reaction rates observed in clinical trials of a drug cannot be
directly compared to rates in the clinical trials of another drug and may
not reflect the rates observed in clinical practice.
The most common adverse reactions (incidence ≥10% and ≥2%
more than placebo) for TECFIDERA were flushing, abdominal pain,
diarrhea, and nausea.
Adverse Reactions in Placebo-Controlled Trials
In the two well-controlled studies demonstrating effectiveness,
1529 patients received TECFIDERA with an overall exposure of 2244
person-years [see Clinical Studies ( 14)].
The adverse reactions presented in the table below are based
on safety information from 769 patients treated with TECFIDERA
240 mg twice a day and 771 placebo-treated patients.
Table 1: Adverse Reactions in Study 1 and 2 reported for
TECFIDERA 240 mg BID at ≥2% higher incidence than placebo
Flushing 40 6
Abdominal pain 18 10
Diarrhea 14 11
Nausea 12 9
Vomiting 9 5
Pruritus 8 4
Rash 8 3
Albumin urine present 6 4