"The U.S. Food and Drug Administration today approved Tecfidera (dimethyl fumarate) capsules to treat adults with relapsing forms of multiple sclerosis (MS).
MS is a chronic, inflammatory, autoimmune disease of the central nervous system"...
Depression And Suicide
REBIF (interferon beta-1a) should be used with caution in patients with depression, a condition that is common in people with multiple sclerosis. Depression, suicidal ideation, and suicide attempts have been reported to occur with increased frequency in patients receiving interferon compounds, including REBIF. In addition, there have been postmarketing reports of suicide in patients treated with REBIF. Patients should be advised to report immediately any symptoms of depression and/or suicidal ideation to the prescribing physician. If a patient develops depression, cessation of treatment with REBIF should be considered.
Severe liver injury, including some cases of hepatic failure requiring liver transplantation, has been reported rarely in patients taking REBIF. Symptoms of liver dysfunction began from one to six months following the initiation of REBIF. If jaundice or other symptoms of liver dysfunction appear, treatment with REBIF should be discontinued immediately due to the potential for rapid progression to liver failure.
Asymptomatic elevation of hepatic transaminases (particularly SGPT) is common with interferon therapy [see ADVERSE REACTIONS]. REBIF should be initiated with caution in patients with active liver disease, alcohol abuse, increased serum SGPT ( > 2.5 times ULN), or a history of significant liver disease. Also, the potential risk of REBIF used in combination with known hepatotoxic products should be considered prior to REBIF administration, or when adding new agents to the regimen of patients already on REBIF. Reduction of REBIF dose should be considered if SGPT rises above 5 times the upper limit of normal. The dose may be gradually re-escalated when enzyme levels have normalized [see Laboratory Tests and DOSAGE AND ADMINISTRATION].
Anaphylaxis And Other Allergic Reactions
Anaphylaxis has been reported as a rare complication of REBIF use. Other allergic reactions have included skin rash and urticaria, and have ranged from mild to severe without a clear relationship to dose or duration of exposure. Several allergic reactions, some severe, have occurred after prolonged use. Discontinue REBIF if anaphylaxis occurs.
Injection Site Reactions including Necrosis
In controlled clinical trials, injection site reactions occurred more frequently in REBIF-treated patients (92% in the 44 mcg group and 89% in the 22 mcg group) than in placebo-treated patients (39%) and at a higher frequency in REBIF treated patients (83%) than in AVONEX-treated patients (28%). Injection site necrosis also occurred more frequently in REBIF-treated patients (3% in the 44 mcg group and 1% in the 22 mcg group) than in placebo-treated patients (0) during the two years of therapy. All events resolved with conservative management.
Injection site reactions including injection site pain, erythema, edema, cellulitis, abscess, and necrosis have been reported in the postmarketing setting. Some occurred more than 2 years after initiation of REBIF. Necrosis occurred at single and at multiple injection sites. Some cases of injection site necrosis required treatment with intravenous antibiotics and surgical intervention (debridement and skin grafting).
Patient understanding and use of aseptic self-injection techniques and procedures should be periodically evaluated, particularly if injection site necrosis has occurred. Patients should be advised of the importance of rotating sites of injection with each dose and not reusing syringes. Patients should be advised against injecting an area which is inflamed, edematous, erythematous, ecchymotic, or has any other signs of infection. These signs should be reported to a healthcare professional immediately.
Decreased Peripheral Blood Counts
Decreased peripheral blood counts in all cell lines, including pancytopenia, have been reported in REBIF-treated patients. In controlled clinical trials, leukopenia occurred at a higher frequency in REBIF-treated patients (36% in 44 mcg group and 28% in 22 mcg group) than in placebo-treated patients (14%) and at a higher frequency in REBIF-treated patients (6%) compared to the AVONEX-treated patients ( < 1%). Thrombocytopenia and anemia occurred more frequently in 44 mcg REBIF-treated patients (8% and 5%, respectively) than in placebo-treated patients (2% and 3%, respectively). In a pooled analysis of 7 placebo controlled trials with REBIF doses of 22 mcg or 44 mcg, the rate of pancytopenia (in subjects with normal baseline values who developed laboratory values less than the lower limit of normal for all 3 hematology parameters simultaneously) was higher in the total REBIF group (5.5 per 1000 subject-year) than in the placebo group (1.2 per 1000 subject-year). Patients should be monitored for symptoms or signs of decreased blood counts. Monitoring of complete blood and differential white blood cell counts is also recommended [see DOSAGE AND ADMINISTRATION and Laboratory Tests].
Caution should be exercised when administering REBIF to patients with pre-existing seizure disorders. Seizures have been temporally associated with the use of beta interferons, including REBIF, in clinical trials and in postmarketing reports.
In addition to those laboratory tests normally required for monitoring patients with multiple sclerosis, blood cell counts and liver function tests are recommended at regular intervals (1, 3, and 6 months) following introduction of REBIF therapy and then periodically thereafter in the absence of clinical symptoms. Patients with myelosuppression may require more intensive monitoring of complete blood cell counts, with differential and platelet counts [see DOSAGE AND ADMINISTRATION and Decreased Peripheral Blood Counts]. New or worsening thyroid abnormalities have developed in some patients treated with REBIF. Thyroid function tests are recommended every 6 months in patients with a history of thyroid dysfunction or as clinically indicated.
Patient Counseling Information
See FDA-approved patient labeling (Medication Guide).
Inform patients of the availability of a Medication Guide, and instruct them to read the Medication Guide prior to taking REBIF. Instruct patients to take REBIF only as prescribed.
Depression and Suicide
Advise patients that depression, suicidal ideation, and suicide have been reported during the use of REBIF. Inform patients of the symptoms of depression and suicidal ideation and instruct patients to immediately report any of these symptoms to their healthcare provider [see WARNINGS AND PRECAUTIONS].
Advise patients that severe liver injury, including hepatic failure, has been reported with the use of REBIF. Educate patients about the symptoms of hepatic injury and instruct patients to report them immediately to their healthcare provider [see WARNINGS AND PRECAUTIONS].
Anaphylaxis and Other Allergic Reactions
Advise patients of the symptoms of allergic reactions and anaphylaxis, and instruct patients to seek immediate medical attention if these symptoms occur [see WARNINGS AND PRECAUTIONS].
Injection Site Reactions including Necrosis
Advise patients that injection site reactions occur in most patients treated with REBIF and that injection site necrosis may occur [see WARNINGS AND PRECAUTIONS]. Instruct patients to promptly report any break in the skin, which may be associated with blue-black discoloration, swelling, or drainage of fluid from the injection site, prior to continuing their REBIF therapy.
To minimize the likelihood of injection site reactions, inform patients of the importance of rotating injection sites with each dose and the use of aseptic injection technique [see DOSAGE AND ADMINISTRATION]. Advise patients not to re-use needles or syringes and instruct patients on safe disposal procedures. Provide appropriate instruction for self-injection of REBIF and REBIF Rebidose, including careful review of the REBIF Medication Guide.
Decreased Peripheral Blood Counts
Advise patients that they may develop a lowering of their peripheral blood counts, including their white blood counts, red blood counts, and platelets, and that their blood counts will be checked during therapy with REBIF. Inform patients that they may be more likely to get infections, anemia, or be at risk for bleeding, and that they should contact their healthcare provider if they develop symptoms of these adverse reactions [see WARNINGS AND PRECAUTIONS].
Instruct patients to report seizures immediately to their healthcare provider [see WARNINGS AND PRECAUTIONS].
Inform patients that flu-like symptoms are common following initiation of therapy with REBIF. Advise patients that concurrent use of analgesics and/or antipyretics may help reduce flu-like symptoms on treatment days [see DOSAGE AND ADMINISTRATION].
Risk in Pregnancy
Advise patients that REBIF should not be used during pregnancy unless the potential benefit justifies the potential risk to the fetus [see Use In Specific Populations]. Therefore, inform patients that if a pregnancy is considered, or does occur, the risks and benefits of continuing REBIF should be discussed with their healthcare provider.
Carcinogenesis, Mutagenesis, Impairment Of Fertility
REBIF has not been tested for carcinogenic potential in animals.
Interferon beta was negative in an in vitro bacterial reverse mutation (Ames) assay and an in vitro cytogenetic assay in human lymphocytes in the presence and absence of metabolic activation.
Impairment of Fertility
In studies in normally cycling female cynomolgus monkeys given daily subcutaneous injections of interferon beta for six months at doses of up to 9 times the recommended weekly human dose (based on body surface area), no effects were observed on either menstrual cycling or serum estradiol levels. In male monkeys, the same doses of interferon beta had no demonstrable adverse effects on sperm count, motility, morphology, or function.
Use In Specific Populations
Pregnancy Category C
There are no adequate and well-controlled studies in pregnant women. REBIF should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
In a study in pregnant cynomolgus monkeys, interferon beta was administered daily (intramuscular doses approximately 1, 2, and 7 times the maximum recommended cumulative weekly human dose, based on body surface area) either throughout the period of organogenesis or later in pregnancy (gestation day 90 to term). No adverse effects on embryofetal development were observed; however, the possibility of adverse effects cannot be ruled out because of the small number of animals tested (six per dose group at each developmental period).
It is not known whether REBIF is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when REBIF is administered to a nursing woman.
Safety and effectiveness in pediatric patients have not been established.
Clinical studies of REBIF did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently than younger subjects. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy.
Last reviewed on RxList: 5/12/2014
This monograph has been modified to include the generic and brand name in many instances.
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