PLEGRIDY has a well-established safety profile1

Safety of PLEGRIDY versus placebo was assessed in year 1 of ADVANCE (Study 1). Safety experience in year 2 of ADVANCE and its 2-year safety extension (Study 2) were consistent with the experience in year 1 of ADVANCE. Cumulatively, 1468 patients received PLEGRIDY in the 2 studies over 4 years.

Contraindications

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

Warnings and Precautions

Hepatic injury

Warning

  • 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

Details

  • 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

Guidance

  • Monitor patients for signs and symptoms of hepatic injury

Depression and suicide

Warning

  • Depression, suicidal ideation, and suicide occur more frequently in patients receiving interferon beta than in patients receiving placebo

Details

  • 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

Guidance

  • 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

Anaphylaxis and other allergic reactions

Warning

  • Serious allergic reactions are rare complications of treatment with interferon beta; anaphylaxis has been reported with use of PLEGRIDY in the postmarketing setting

Details

  • Less than 1% of PLEGRIDY-treated patients experienced a serious allergic reaction such as angioedema or urticaria
  • The rubber tip cap of the PLEGRIDY prefilled syringe for intramuscular administration contains natural rubber latex, which may cause allergic reactions and should not be handled by latex-sensitive individuals

Guidance

  • Discontinue PLEGRIDY if a serious allergic reaction occurs

Injections site reactions including necrosis

Injection site reactions, including injection site necrosis, can occur with the use of interferon beta, including PLEGRIDY.

Clinical study experience

  • In clinical studies of subcutaneous PLEGRIDY, the incidence of injection site reactions (eg, injection site erythema, pain, pruritus, or edema) was 66% in the PLEGRIDY group and 11% in the placebo group
    • Incidence of severe injection site reactions was 3% in the PLEGRIDY group and 0% in the placebo group
    • 1 patient out of 1468 patients who received PLEGRIDY experienced injection site necrosis. The injury resolved with standard medical treatment
  • In a single clinical study of healthy volunteers comparing single doses of intramuscular and subcutaneous PLEGRIDY, the incidence of injection site reactions (e.g., injection site erythema, pain, pruritus, or edema) was 14% in the intramuscular PLEGRIDY group and 32% in the subcutaneous PLEGRIDY group
  • Injection site abscesses and cellulitis have been reported in the postmarketing setting with use of interferon beta. Some cases required treatment with hospitalization for surgical drainage and intravenous antibiotics
  • Periodically evaluate patient understanding and use of aseptic self-injection techniques and procedures, particularly if injection site necrosis has occurred

Guidance

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.

Congestive heart failure

Warning

  • Congestive heart failure, cardiomyopathy, and cardiomyopathy with congestive heart failure occur in patients receiving interferon beta

Details

  • Incidence of cardiovascular events was 7% in both PLEGRIDY and placebo treatment groups
  • No serious cardiovascular events were reported in the PLEGRIDY group

Guidance

  • Monitor patients with significant cardiac disease for worsening of their cardiac condition during initiation and continuation of treatment with PLEGRIDY

Decreased peripheral blood counts

Warning

  • Interferon beta can cause decreased peripheral blood counts in all cell lines, including rare instances of pancytopenia and severe thrombocytopenia

Details

  • 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
    • 2 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
  • Compared to placebo, there were no significant differences in red blood cell counts in patients treated with PLEGRIDY

Guidance

  • 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

Thrombotic microangiopathy

Warning

  • Cases of thrombotic microangiopathy (TMA), including thrombotic thrombocytopenic purpura and hemolytic uremic syndrome, some fatal, have been reported with interferon beta products

Details

  • Cases have been reported several weeks to years after starting interferon beta products

Guidance

  • Discontinue PLEGRIDY if clinical symptoms and laboratory findings consistent with TMA occur, and manage as clinically indicated

Autoimmune disorders

Warning

  • Autoimmune disorders of multiple target organs including idiopathic thrombocytopenia, hyper- and hypothyroidism, and autoimmune hepatitis have been reported with interferon beta

Details

  • In clinical studies, the incidence of autoimmune disorders was less than 1% in both PLEGRIDY and placebo treatment groups

Guidance

  • If patients develop a new autoimmune disorder, consider stopping PLEGRIDY

Seizures

Warning

  • Seizures are associated with the use of interferon beta

Details

  • The incidence of seizures in multiple sclerosis clinical studies was less than 1% in patients receiving PLEGRIDY and placebo

Guidance

  • Exercise caution when administering PLEGRIDY to patients with a seizure disorder