"The U.S. Food and Drug Administration today approved Tecfidera (dimethyl fumarate) capsules to treat adults with relapsing forms of multiple sclerosis (MS).
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Depression and Suicide
EXTAVIA (interferon beta-1b) should be used with caution in patients with depression, a condition that is common in people with multiple sclerosis. Depression and suicide have been reported to occur with increased frequency in patients receiving interferon compounds, including interferon beta-1b. Patients treated with EXTAVIA (interferon beta-1b kit) should be advised to report immediately any symptoms of depression and/or suicidal ideation to their prescribing physicians. If a patient develops depression, cessation of EXTAVIA (interferon beta-1b kit) therapy should be considered.
In the four randomized controlled studies there were three suicides and eight suicide attempts among the 1532 patients in the interferon beta-1b treated groups compared to one suicide and four suicide attempts among the 965 patients in the placebo groups.
Injection Site Necrosis
Injection site necrosis (ISN) has been reported in 4% of patients in controlled clinical trials [see ADVERSE REACTIONS]. Typically, injection site necrosis occurs within the first four months of therapy, although post-marketing reports have been received of ISN occurring over one year after initiation of therapy. Necrosis may occur at a single or multiple injection sites. The necrotic lesions are typically three cm or less in diameter, but larger areas have been reported. Generally the necrosis has extended only to subcutaneous fat. However, there are also reports of necrosis extending to and including fascia overlying muscle. In some lesions where biopsy results are available, vasculitis has been reported. For some lesions debridement and, infrequently, skin grafting have been required.
As with any open lesion, it is important to avoid infection and, if it occurs, to treat the infection. Time to healing was varied depending on the severity of the necrosis at the time treatment was begun. In most cases healing was associated with scarring.
Some patients have experienced healing of necrotic skin lesions while interferon beta-1b therapy continued; others have not. Whether to discontinue therapy following a single site of necrosis is dependent on the extent of necrosis. For patients who continue therapy with EXTAVIA (interferon beta-1b kit) after injection site necrosis has occurred, EXTAVIA (interferon beta-1b kit) should not be administered into the affected area until it is fully healed. If multiple lesions occur, therapy should be discontinued until healing occurs.
Patient understanding and use of aseptic self-injection techniques and procedures should be periodically reevaluated, particularly if injection site necrosis has occurred.
Injection Site Reactions
In controlled clinical trials, injection site reactions occurred in 78% of patients receiving interferon beta-1b with injection site necrosis in 4%. Injection site inflammation (42%), injection site pain (16%), injection site hypersensitivity (4%), injection site necrosis (4%), injection site mass (2%), injection site edema (2%) and non-specific reactions were significantly associated with interferon beta-1b treatment . The incidence of injection site reactions tended to decrease over time. Approximately 69% of patients experienced the event during the first three months of treatment, compared to approximately 40% at the end of the studies.
Anaphylaxis has been reported as a rare complication of interferon beta-1b use. Other allergic reactions have included dyspnea, bronchospasm, tongue edema, skin rash and urticaria [see ADVERSE REACTIONS].
Flu-Like Symptom Complex
In controlled clinical trials, the rate of flu-like symptom complex was approximately 57%. The incidence decreased over time, with only 10% of patients reporting flu-like symptom complex at the end of the studies. The median duration of flu-like symptom complex in Study l was 7.5 days [see Clinical Studies].
In controlled clinical trials, leukopenia was reported in 18% of patients receiving interferon beta-1b, leading to a reduction of the dose of interferon beta-1b in some patients [see ADVERSE REACTIONS]. Monitoring of complete blood and differential white blood cell counts is recommended.
Hepatic Enzymes Elevations
In controlled clinical trials, elevations of SGPT to greater than five times baseline value were reported in 12% of patients receiving interferon beta-1b, and increase of SGOT to greater than five times baseline value were reported in 4% of patients receiving interferon beta-1b, leading to dose-reduction or discontinuation of treatment in some patients [see ADVERSE REACTIONS]. Monitoring of liver function tests is recommended.
In addition to those laboratory tests normally required for monitoring patients with multiple sclerosis, complete blood and differential white blood cell counts, platelet counts and blood chemistries, including liver function tests, are recommended at regular intervals (one, three, and six months) following introduction of EXTAVIA (interferon beta-1b kit) therapy, and then periodically thereafter in the absence of clinical symptoms. Thyroid function tests are recommended every six months in patients with a history of thyroid dysfunction or as clinically indicated. Patients with myelosuppression may require more intensive monitoring of complete blood cell counts, with differential and platelet counts.
Albumin (Human), USP
This product contains albumin, a derivative of human blood. Based on effective donor screening and product manufacturing processes, it carries an extremely remote risk for transmission of viral diseases. A theoretical risk for transmission of Creutzfeldt-Jakob disease (CJD) also is considered extremely remote. No cases of transmission of viral diseases or CJD have ever been identified for albumin.
Patient Counseling Information
All patients should be instructed to carefully read the supplied EXTAVIA Medication Guide. Patients should be cautioned not to change the dose or schedule of administration without medical consultation.
Advise patients that depression and suicidal ideation have been reported during the use of interferon beta-1b. Advise patients of the symptoms of depression or suicidal ideation, and instruct patients to report them immediately to their physician.
Injection Site Reactions, Including Necrosis
Advise patients that injection site reactions occur in most patients treated with interferon beta-1b, and that injection site necrosis may occur at one or multiple sites. 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 EXTAVIA (interferon beta-1b kit) therapy.
Allergic Reactions and Anaphylaxis
Advise patients of the symptoms of allergic reactions and anaphylaxis, and instruct patients to seek immediate medical attention if these symptoms occur.
Patients should be informed that flu-like symptoms are common following initiation of therapy with interferon beta-1b. In controlled clinical trials, antipyretics and analgesics were permitted for relief of these symptoms. In addition, gradual dose titration during initiation of interferon beta-1b treatment may reduce flu-like symptoms [see DOSAGE AND ADMINISTRATION].
Advise patients that EXTAVIA (interferon beta-1b kit) should not be used during pregnancy unless the potential benefit justifies the potential risk to the fetus [see Use in Special Population].
Instruction on Self-injection Technique and Procedures
Patients should be instructed in the use of aseptic technique when administering EXTAVIA (interferon beta-1b kit) . Appropriate instruction for reconstitution of EXTAVIA (interferon beta-1b kit) and methods of self-injection should be provided, including careful review of the EXTAVIA (interferon beta-1b kit) Medication Guide. The first injection should be performed under the supervision of an appropriately qualified health care professional.
Patients should be cautioned against the re-use of needles or syringes and instructed in safe disposal procedures. A puncture resistant container for disposal of used needles and syringes should be supplied to the patient along with instructions for safe disposal of full containers.
Patients should be advised of the importance of rotating areas of injection with each dose, to minimize the likelihood of severe injection site reactions, including necrosis or localized infection, (see Picking an Injection Site section of the Medication Guide).
Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenesis: Interferon beta-1b has not been tested for its carcinogenic potential in animals.
Mutagenesis: Interferon beta-1b was not genotoxic in the in vitro Ames bacterial test or the in vitro chromosomal aberration assay in human peripheral blood lymphocytes. Interferon beta-1b treatment of mouse BALBc-3T3 cells did not result in increased transformation frequency in an in vitro model of tumor transformation.
Impairment of fertility: Administration of interferon beta-1b (doses of up to 0.33 mg/kg) to normally cycling female rhesus monkeys had no apparent adverse effects on either menstrual cycle duration or associated hormonal profiles (progesterone and estradiol) when administered over three consecutive menstrual cycles. The highest dose tested is approximately 30 times the recommended human dose of 0.25 mg on a body surface area (mg/m2) basis. The potential for other effects on fertility or reproductive performance was not evaluated.
Use In Specific Populations
Pregnancy Category C: There are no adequate and well-controlled studies of interferon beta-1b in pregnant women; however, spontaneous abortions while on treatment were reported in four patients participating in the interferon beta-1b RRMS clinical trial. Interferon beta-1b should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
When interferon beta-1b (doses ranging from 0.028 to 0.42 mg/kg) was administered to pregnant rhesus monkeys throughout the period of organogenesis (gestation days 20 to 70), a dose-related abortifacient effect was observed. The low effect dose is approximately 3 times the recommended human dose of 0.25 mg on a body surface are (mg/m2) basis. A no-effect dose for embryo-fetal developmental toxicity in rhesus monkeys was not established.
It is not known whether interferon beta-1b is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from interferon beta-1b, a decision should be made to either discontinue nursing or discontinue the drug, taking into account the importance of drug to the mother.
Safety and efficacy in pediatric patients have not been established.
Clinical studies of interferon beta-1b did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently than younger patients.
Last reviewed on RxList: 9/16/2009
This monograph has been modified to include the generic and brand name in many instances.
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