5.1 Hepatic Injury
Severe hepatic injury, including hepatitis, autoimmune hepatitis, and rare cases of severe hepatic failure, have been reported with interferon beta. Asymptomatic elevation of hepatic transaminases has also been reported, and in some patients has recurred upon rechallenge with interferon beta.
Elevations in hepatic enzymes and hepatic injury have been observed with the use of PLEGRIDY in clinical studies. The incidence of increases in hepatic transaminases was greater in patients taking PLEGRIDY than in those taking placebo. The incidence of elevations of alanine aminotransferase above 5 times the upper limit of normal was 1% in placebo-treated patients and 2% in PLEGRIDY-treated patients. The incidence of elevations of aspartate aminotransferase above 5 times the upper limit of normal was less than 1% in placebo-treated patients and less than 1% in PLEGRIDY-treated patients. Elevations of serum hepatic transaminases combined with elevated bilirubin occurred in 2 patients. Both cases resolved following discontinuation of PLEGRIDY.
Monitor patients for signs and symptoms of hepatic injury.
5.2 Depression and Suicide
Depression, suicidal ideation, and suicide occur more frequently in patients receiving interferon beta than in patients receiving placebo.
In clinical studies, the overall incidence of adverse events related to depression and suicidal ideation in multiple sclerosis patients was 8% in both the PLEGRIDY and placebo groups. The incidence of serious events related to depression and suicidal ideation was similar and less than 1% in both groups.
Advise patients to report immediately any symptom of depression or suicidal ideation to their healthcare provider. If a patient develops depression or other severe psychiatric symptoms, consider stopping treatment with PLEGRIDY.
5.3 Seizures
Seizures are associated with the use of interferon beta.
The incidence of seizures in multiple sclerosis clinical studies was less than 1% in patients receiving PLEGRIDY and placebo.
Exercise caution when administering PLEGRIDY to patients with a seizure disorder.
5.4 Anaphylaxis and Other Allergic Reactions
Anaphylaxis and other serious allergic reactions are rare complications of treatment with interferon beta.
Less than 1% of PLEGRIDY-treated patients experienced a serious allergic reaction such as angioedema or urticaria. Those who did have serious allergic reactions recovered promptly after treatment with antihistamines or corticosteroids.
Discontinue PLEGRIDY if a serious allergic reaction occurs.
5.5 Injection Site Reactions
Injection site reactions, including injection site necrosis, can occur with the use of subcutaneous interferon beta.
In clinical studies, the incidence of injection site reactions (e.g., injection site erythema, pain, pruritus, or edema) was 66% in the PLEGRIDY group and 11% in the placebo group; the incidence of severe injection site reactions was 3% in the PLEGRIDY group and 0% in the placebo group. One patient out of 1468 patients who received PLEGRIDY in clinical studies experienced injection site necrosis. The injury resolved with standard medical treatment.
Decisions to discontinue therapy following necrosis at a single injection site should be based on the extent of the necrosis. For patients who continue therapy with PLEGRIDY after injection site necrosis has occurred, avoid administration of PLEGRIDY near the affected area until it is fully healed. If multiple lesions occur, discontinue PLEGRIDY until healing occurs.
5.6 Congestive Heart Failure
Congestive heart failure, cardiomyopathy, and cardiomyopathy with congestive heart failure occur in patients receiving interferon beta.
In clinical studies, the incidence of cardiovascular events was 7% in both PLEGRIDY and placebo treatment groups. No serious cardiovascular events were reported in the PLEGRIDY group.
Monitor patients with significant cardiac disease for worsening of their cardiac condition during initiation and continuation of treatment with PLEGRIDY.
5.7 Decreased Peripheral Blood Counts
Interferon beta can cause decreased peripheral blood counts in all cell lines, including rare instances of pancytopenia and severe thrombocytopenia.
In clinical studies, decreases in white blood cell counts below 3.0 x 109/L occurred in 7% of patients receiving PLEGRIDY and in 1% receiving placebo. There is no apparent association between decreases in white blood cell counts and an increased risk of infections or serious infections. The incidence of clinically significant decreases in lymphocyte counts (below 0.5 x 109/L), neutrophil counts (below 1.0 x 109/L), and platelet counts (below 100 x 109/L) were all less than 1% and similar in both placebo and PLEGRIDY groups. Two serious cases were reported in patients treated with PLEGRIDY: one patient (less than 1%) experienced severe thrombocytopenia (defined as a platelet count less than or equal to 10 x 109/L), and another patient (less than 1%) experienced severe neutropenia (defined as a neutrophil count less than or equal to 0.5 x 109/L). In both patients, cell counts recovered after discontinuation of PLEGRIDY. Comp
