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Rebif (Interferon Beta-1a) - Warnings and Precautions

 
 



WARNINGS

DEPRESSION

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® . 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.

HEPATIC INJURY

A case of fulminant hepatic failure requiring liver transplantation in a patient who initiated Rebif® therapy while taking another potentially hepato-toxic medication has been reported from a non-U.S. postmarking source. Symptomatic hepatic dysfunction, primarily presenting as jaundice, has been reported as a rare complication of Rebif® use. 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. Dose reduction should be considered if SGPT rises above times the upper limit of normal. The dose may be gradually re-escalated when enzyme levels have normalized. Treatment with Rebif® should be stopped if jaundice or other clinical symptoms of liver dysfunction appear.

ANAPHYLAXIS

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.

ALBUMIN (HUMAN)

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.

PRECAUTIONS

GENERAL

Caution should be exercised when administering Rebif® to patients with pre-existing seizure disorders. Seizures have been associated with the use of beta interferons. A relationship between occurrence of seizures and the use of Rebif® has not been established. Leukopenia and new or worsening thyroid abnormalities have developed in some patients treated with Rebif® (see ADVERSE REACTIONS). Regular monitoring for these conditions is recommended (see PRECAUTIONS: Laboratory Tests).

INFORMATION FOR PATIENTS

All patients should be instructed to read the Rebif® Medication Guide supplied to them. Patients should be cautioned not to change the dosage or the schedule of administration without medical consultation.

Patients should be informed of the most common and the most severe adverse reactions associated with the use of Rebif® (see WARNINGS and ADVERSE REACTIONS). Patients should be advised of the symptoms associated with these conditions, and to report them to their physician.

Female patients should be cautioned about the abortifacient potential of Rebif® (see PRECAUTIONS: Pregnancy).

Patients should be instructed in the use of aseptic technique when administering Rebif® . Appropriate instruction for self-injection or injection by another person should be provided, including careful review of the Rebif® Medication Guide. If a patient is to self-administer Rebif® , the physical and cognitive ability of that patient to self-administer and properly dispose of syringes should be assessed. The initial injection should be performed under the supervision of an appropriately qualified health care professional. Patients should be advised of the importance of rotating sites of injection with each dose, to minimize the likelihood of severe injection site reactions or necrosis. 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 instructed in the technique and importance of proper syringe disposal and be cautioned against reuse of these items.

LABORATORY TESTS

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. Thyroid function tests are recommended every 6 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.

DRUG INTERACTIONS

No formal drug interaction studies have been conducted with Rebif® . Due to its potential to cause neutropenia and lymphopenia, proper monitoring of patients is required if Rebif® is given in combination with myelosuppressive agents.

CARCINOGENESIS, MUTAGENESIS, IMPAIRMENT OF FERTILITY

Carcinogenesis:    No carcinogenicity data for Rebif® are available in animals or humans.

Mutagenesis:    Rebif® was not mutagenic when tested in the Ames bacterial test and in an in vitro cytogenetic assay in human lymphocytes in the presence and absence of metabolic activation.

Impairment of Fertility:    No studies have been conducted to evaluate the effects of Rebif® on fertility in humans. In studies in normally cycling female cynomolgus monkeys given daily sc injections of Rebif® 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. The validity of extrapolating doses used in animal studies to human doses is not established. In male monkeys, the same doses of Rebif® had no demonstrable adverse effects on sperm count, motility, morphology, or function.

Pregnancy Category C

Rebif® treatment has been associated with significant increases in embryolethal or abortifacient effects in cynomolgus monkeys administered doses approximately 2 times the cumulative weekly human dose (based on either body weight or surface area) either during the period of organogenesis (gestation day 21-89) or later in pregnancy. There were no fetal malformations or other evidence of teratogenesis noted in these studies. These effects are consistent with the abortifacient effects of other type I interferons. There are no adequate and well-controlled studies of Rebif® in pregnant women. However, in Studies 1 and 2, there were 2 spontaneous abortions observed and 5 fetuses carried to term among 7 women in the Rebif® groups. If a woman becomes pregnant or plans to become pregnant while taking Rebif® , she should be informed about the potential hazards to the fetus, and discontinuation of Rebif® should be considered.

A pregnancy registry has been established to monitor pregnancy outcomes of women exposed to Rebif® while pregnant. Health care providers are encouraged to register patients on line at rebifpregnancyregistry.com or by calling MS LifeLines at 1-877-44-REBIF (1-877-447-3243).

NURSING MOTHERS

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.

Pediatric Use:    The safety and effectiveness of Rebif® in pediatric patients have not been studied.

Geriatric Use:    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.

Page last updated: 2006-09-09

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