One suicide and 4 attempted suicides were observed among 372 study patients during a 3-year period. All five patients received Betaseron (three in the 0.05 mg group and two in the 0.25 mg group). There were no attempted suicides in patients on study who did not receive Betaseron. Depression and suicide have been reported to occur in patients receiving interferon alfa, a related compound. Patients to be treated with Betaseron should be informed that depression and suicidal ideation may be a side effect of the treatment and should report these symptoms immediately to the prescribing physician. Patients exhibiting depression should be monitored closely and cessation of therapy should be considered.

Injection site necrosis (ISN) has been reported in 5% of patients in controlled clinical trials (see ADVERSE REACTIONS section). Typically, injection site necrosis occurs within the first 4 months of therapy, although post-marketing reports have been received of ISN occurring over 1 year after initiation of therapy. Necrosis may occur at single or multiple injection sites. The necrotic lesions are typically 3 cm or less in diameter, but larger areas have been reported. While necrosis has commonly extended only to subcutaneous fat, there are also reports of necrosis extending to and including fascia overlaying muscle. In some lesions where biopsy results are available, vasculitis has been reported. For some lesions debridement and infrequently, skin grafting has been required.

As with any open lesion, it is important to avoid infection and if it occurs, to treat the infection. Time to healing has 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 after injection site necrosis has occurred, Betaseron 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.

General

Patients should be instructed in injection techniques to assure the safe self-administration of Betaseron. (See PATIENT INFROMATION: Betaseron.)

Information to patients

Instruction on self-injection technique and procedures.

Patients should be instructed in the use of aseptic technique when administering Betaseron. Appropriate instruction for reconstitution of Betaseron and self-injection should be given including careful review of the Betaseron Patient INFORMATION sheet. If possible, 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 or necrosis (see PATIENT INFORMATION: Rotating Injection Sites ).

Patients should be cautioned not to change the dosage or the schedule of administration without medical consultation.

Awareness of adverse reactions.

Serious adverse reactions associated with the use of Betaseron have been reported including depression and injection site necrosis (see

WARNINGS

Patients should immediately report symptoms of depression or suicidal ideation to their physician. The symptoms of depression should be closely monitored by a physician.

Injection site necrosis was reported in 5% of patients in a controlled MS trial. If the patient experiences any break in the skin, which may be associated with blue-black discoloration, swelling, or drainage of fluid from the injection site, the patient should be advised to promptly contact their physician prior to continuing their Betaseron therapy.

Other injection site reactions occurred in eighty-five percent of patients in the controlled MS trial, at one or more times during therapy. There was redness, pain, swelling and discoloration. In general, these were transient and did not require discontinuation of therapy, but the nature and severity of all reported reactions should be carefully assessed (see ADVERSE REACTIONS section).

Flu-like symptoms are common following initiation of therapy with Betaseron. In the controlled MS clinical trial, acetaminophen was permitted for relief of fever or myalgia (see ADVERSE REACTIONS section).

Patients should be cautioned about the abortifacient potential of Betaseron (see Pregnancy - Teratogenic Effects).

Laboratory Tests

The following laboratory tests are recommended prior to initiating Betaseron therapy and at periodic intervals thereafter: hemoglobin, complete and differential white blood cell counts, platelet counts and blood chemistries including liver function tests. In the controlled MS trial, patients were monitored every 3 months. The study protocol stipulated that Betaseron therapy be discontinued in the event the absolute neutrophil count fell below 750/mm³. When the absolute neutrophil count had returned to a value greater than 750/mm³, therapy could be restarted at a 50% reduced dose. No patients were withdrawn or dose reduced for neutropenia or lymphopenia.

Similarly, if hepatic transaminase (SGOT/SGPT) levels exceeded 10 times the upper limit of normal, or if the serum bilirubin exceeded 5 times the upper limit of normal, therapy was discontinued. In each instance during the controlled MS trial, hepatic enzyme abnormalities returned to normal following discontinuation of therapy. When measurements had decreased to below these levels, therapy could be restarted at a 50% dose reduction, if clinically appropriate. Two patients were dose reduced for increased liver enzymes; one continued on treatment and one was ultimately withdrawn.

Drug Interactions

See DRUG INTERACTIONS section.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis: The carcinogenic potential of Betaseron was evaluated by studying its effect on the morphological transformation of the mammalian cell line BALBc-3T3. No significant increases in transformation frequency were noted. No carcinogenicity data are available in animals or humans.

Betaseron^® (Interferon beta-1b) was not mutagenic when assayed for genotoxicity in the Ames bacterial test in the presence or absence of metabolic activation.

Impairment of Fertility: Studies in rhesus monkeys at doses up to 0.33 mg/kg/day (32 times the recommended human dose based on body surface area comparison*) in normally cycling rhesus female monkeys had no apparent adverse effects on the menstrual cycle or on associated hormonal profiles (progesterone and estradiol) when administered over 3 consecutive menstrual cycles. The extrapolability of animal doses to human doses is not known. Effects of Betaseron on normal cycling human females are not known. *body surface dose based on 70 kg female

Pregnancy

Teratogenic Effects: Pregnancy Category C: Betaseron was not teratogenic at doses up to 0.42 mg/kg/day in rhesus monkeys, but demonstrated a dose-related abortifacient activity when administered at doses ranging from 0.028 mg/kg/day (2.8 times the recommended human dose based on body surface area comparison) to 0.42 mg/kg/day (40 times the recommended human dose based on body surface area comparison). The extrapolability of animal doses 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 MS clinical trial. Betaseron 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, 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 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, a decision should be made as to whether either to discontinue nursing or discontinue the drug, taking into account the importance of drug to the mother.

Pediatric Use

Safety and efficacy in children under 18 years of age have not been established.

Bookmark this page: