PEGYLATION—THE PROCESS THAT ALLOWS FOR AN INCREASE IN INTERFERON BETA CIRCULATION TIME¹

Important Safety Information

• PLEGRIDY is contraindicated in patients with a history of hypersensitivity to natural or recombinant interferon beta or peginterferon, or any other component of the formulation.
• 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 PLEGRIDY in clinical studies. The incidence of elevations of ALT and AST above 5 times the upper limit of normal was 2% in PLEGRIDY-treated patients (1% placebo) and was <1% in PLEGRIDY-treated patients (<1% placebo), respectively. Monitor liver function tests and patients for signs of hepatic injury. Consider discontinuation of PLEGRIDY if hepatic injury occurs.
• Depression, suicidal ideation, and suicide occur more frequently in patients receiving interferon beta than in patients receiving placebo. The overall incidence of adverse events related to depression and suicidal ideation was 8% in both the PLEGRIDY and placebo groups. The incidence of serious events was similar and less than 1% in both groups. Advise patients to report immediately any symptom of depression or suicidal ideation. If a patient develops depression or other severe psychiatric symptoms, consider stopping treatment with PLEGRIDY.
• Seizures are associated with the use of interferon beta. The incidence of seizures in clinical studies was less than 1% in patients receiving PLEGRIDY and placebo. Exercise caution when administering PLEGRIDY to patients with a seizure disorder.
• 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. Discontinue PLEGRIDY if a serious allergic reaction occurs.
• Injection site reactions, including injection site necrosis, can occur with the use of subcutaneous interferon beta. The incidence of injection site reactions (e.g., injection site erythema, pain, pruritus, or edema) was 66% in the PLEGRIDY group (3% were severe) and 11% in the placebo group (0% were severe). One patient out of 1468 patients who received PLEGRIDY experienced injection site necrosis. Decisions to discontinue therapy following necrosis at a single injection site should be based on the extent of the necrosis. If therapy is continued, avoid administration of PLEGRIDY near the affected area until it is fully healed. If multiple lesions occur, discontinue PLEGRIDY until healing occurs.
• Congestive heart failure, cardiomyopathy, and cardiomyopathy with congestive heart failure occur in patients receiving interferon beta. The incidence of cardiovascular events was 7% in both PLEGRIDY and placebo treatment groups. Monitor patients with significant cardiac disease for worsening of their cardiac condition during initiation and continuation of treatment with PLEGRIDY.
• Interferon beta can cause decreased peripheral blood counts in all cell lines, including rare instances of pancytopenia and severe thrombocytopenia. Decreases in white blood cell counts below 3.0 x 10⁹/L occurred in 7% of patients receiving PLEGRIDY and in 1% receiving placebo. 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. Monitor patients for infections, bleeding, and symptoms of anemia. Monitor complete blood cell counts, differential white blood cell counts, and platelet counts during treatment with PLEGRIDY. Patients with myelosuppression may require more intensive monitoring of blood cell counts.
• Cases of thrombotic microangiopathy (TMA), including thrombotic thrombocytopenic purpura and hemolytic uremic syndrome, some fatal, have been reported several weeks to years after starting interferon beta products. Discontinue PLEGRIDY if clinical symptoms and laboratory findings consistent with TMA occur, and manage as clinically indicated.
• Autoimmune disorders of multiple target organs including idiopathic thrombocytopenia, hyper- and hypothyroidism, and autoimmune hepatitis have been reported with interferon beta. The incidence of autoimmune disorders was less than 1% in both PLEGRIDY and placebo treatment groups. If patients develop a new autoimmune disorder, consider stopping PLEGRIDY.
• The most common adverse reactions (incidence greater than 10% and at least 2% more than placebo) associated with PLEGRIDY treatment are injection site erythema, influenza-like illness, pyrexia, headache, myalgia, chills, injection site pain, asthenia, injection site pruritus, and arthralgia. 
• Encourage patients who become pregnant while taking PLEGRIDY to enroll in the PLEGRIDY pregnancy registry by calling 1-866-810-1462 or visiting https://www.plegridypregnancyregistry.com/.

Indication