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Depression and Suicide

Betaseron (interferon beta-1b) (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 Betaseron (interferon beta-1b) . Patients treated with Betaseron (interferon beta-1b) 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 Betaseron (interferon beta-1b) therapy should be considered.

In the four randomized controlled studies there were three suicides and eight suicide attempts among the 1532 patients in the Betaseron (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 Betaseron (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 Betaseron (interferon beta-1b) after injection site necrosis has occurred, Betaseron (interferon beta-1b) 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.

Anaphylaxis

Anaphylaxis has been reported as a rare complication of Betaseron (interferon beta-1b) use. Other allergic reactions have included dyspnea, bronchospasm, tongue edema, skin rash and urticaria (see ADVERSE REACTIONS).

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.

Information for Patients

All patients should be instructed to carefully read the supplied Betaseron (interferon beta-1b) Medication Guide. Patients should be cautioned not to change the dose or schedule of administration without medical consultation.

Patients should be made aware that serious adverse reactions during the use of Betaseron (interferon beta-1b) have been reported, including depression and suicidal ideation, injection site necrosis, and anaphylaxis (see WARNINGS). Patients should be advised of the symptoms of depression or suicidal ideation and be told to report them immediately to their physician. Patients should also be advised of the symptoms of allergic reactions and anaphylaxis.

Patients should be advised 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 Betaseron (interferon beta-1b) therapy.

Patients should be informed that flu-like symptoms are common following initiation of therapy with Betaseron (interferon beta-1b) . In the controlled clinical trials, antipyret-ics and analgesics were permitted for relief of these symptoms. In addition, gradual dose titration during initiation of Betaseron (interferon beta-1b) treatment may reduce flu-like symptoms (see DOSAGE AND ADMINISTRATION).

Female patients should be cautioned about the abortifacient potential of Betaseron (interferon beta-1b) (see PRECAUTIONS, Pregnancy-Teratogenic effects).

Instruction on Self-injection Technique and Procedures

Patients should be instructed in the use of aseptic technique when administering Betaseron (interferon beta-1b) . Appropriate instruction for reconstitution of Betaseron (interferon beta-1b) and methods of self-injection should be provided, including careful review of the Betaseron (interferon beta-1b) 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).

Laboratory Tests

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 Betaseron (interferon beta-1b) 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 monitoringof complete blood cell counts, with differential and platelet counts.

Carcinogenesis, Mutagenesis, and Impairment of Fertility

Carcinogenesis: Interferon beta-1b has not been tested for its carcinogenic potential in animals.

Mutagenesis: Betaseron (interferon beta-1b) was not mutagenic when assayed for genotoxicity in the Ames bacterial test in the presence or absence of metabolic activation. Interferon beta-1b was not mutagenic to human peripheral blood lymphocytes in vitro, in the presence or absence of metabolic inactivation. Betaseron (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: Studies in normally cycling, female rhesus monkeys at doses up to 0.33 mg/kg/day (32 times the recommended human dose based on body surface area, body surface dose based on 70 kg female) 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 validity of extrapolating doses used in animal studies to human doses is not known. Effects of Betaseron (interferon beta-1b) on normally cycling human females are not known.

Pregnancy-Teratogenic effects

Pregnancy Category C: Betaseron (interferon beta-1b) was not teratogenic at doses up to 0.42 mg/kg/day when given to pregnant female rhesus monkeys on gestation days 20 to 70. However, a dose related abortifacient activity was observed in these monkeys when Interferon beta-1b was administered at doses ranging from 0.028 mg/kg/day to 0.42 mg/kg/day (2.8 to 40 times the recommended human dose based on body surface area comparison). The validity of extrapolating doses used in animal studies to human doses is not known. Lower doses were not studied in monkeys. Spontaneous abortions while on treatment were reported in patients (n=4) who participated in the Betaseron (interferon beta-1b) RRMS clinical trial. Betaseron (interferon beta-1b) given to rhesus monkeys on gestation days 20 to 70 did not cause teratogenic effects; however, it is not known if teratogenic effects exist in humans. There are no adequate and well-controlled studies in pregnant women. If the patient becomes pregnant or plans to become pregnant while taking Betaseron (interferon beta-1b) , the patient should be apprised of the potential hazard to the fetus and it should be recommended that the patient discontinue therapy.

Nursing Mothers

It is not known whether Betaseron (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 Betaseron (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.

Pediatric Use

Safety and efficacy in pediatric patients have not been established.

Geriatric Use

Clinical studies of Betaseron (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: 6/26/2008
This monograph has been modified to include the generic and brand name in many instances.