Introduction

A covalent conjugate of interferon beta-1a (recombinant DNA origin) and polyethylene glycol (PEG). Interferon beta-1a is an immunomodulatory agent.

Uses for Peginterferon Beta-1a (Systemic)

Multiple Sclerosis (MS)

Management of relapsing forms of MS, including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults.

Peginterferon beta-1a is one of several disease-modifying therapies used in the management of relapsing forms of MS. Although not curative, these therapies have all been shown to modify several measures of disease activity, including relapse rates, new or enhancing MRI lesions, and disability progression.

The American Academy of Neurology (AAN) recommends that disease-modifying therapy be offered to patients with relapsing forms of MS who have had recent relapses and/or MRI activity. Clinicians should consider adverse effects, tolerability, method of administration, safety, efficacy, and cost of the drugs in addition to patient preferences when selecting an appropriate therapy.

Peginterferon Beta-1a (Systemic) Dosage and Administration

General

Patient Monitoring

• Monitor liver function tests and for signs and symptoms of hepatic injury.

• Periodically evaluate patient's understanding and use of aseptic technique and proper procedures for self administration.

• Monitor patients with substantial cardiac disease for worsening of their condition upon initiation of therapy and during continued treatment with peginterferon beta-1a.

• Monitor complete blood cell counts (CBC), including differential WBC counts and platelets, during peginterferon beta-1a therapy. Also monitor for infections, bleeding, and symptoms of anemia. Patients with myelosuppression may require more intensive monitoring of blood cell counts.

• Monitor patients for any new or increasing fatigue or shortness of breath during therapy.

Premedication and Prophylaxis

• Prophylactic and concurrent use of analgesics and/or antipyretics may prevent or ameliorate flu-like symptoms associated with peginterferon beta-1a treatment.

Other General Considerations

• Peginterferon beta-1a may be self-administered after appropriate training is provided.

• Patients and/or their caregivers who administer peginterferon beta-1a in a home setting should be cautioned against reuse of syringes and needles, supplied with a puncture-resistant container for the safe disposal of such equipment after use, and instructed on the proper disposal of full disposal containers.

Administration

Administer by IM or sub-Q injection. Bioequivalence has been demonstrated between the 2 routes of administration.

The commercially available subcutaneous injection is supplied by the manufacturer as a prefilled pen or syringe with an attached needle, and the commercially available IM injection is supplied as a prefilled syringe with a separate needle.

Prior to administration, allow prefilled injection pens and syringes to reach room temperature (about 30 minutes); do not use external heat sources (e.g., hot water) to warm solution.

Switching between IM and sub-Q administration not evaluated; however, manufacturer states that if route of administration is switched (IM to sub-Q or vice-versa), it is not expected that repeat dosage titration is necessary.

Prefilled injection pens and syringes are for single use only; discard any unused portions.

IM Administration

Administer by IM injection every 14 days into the thigh. Rotate injections between the left and right thigh to minimize risk of injection site reactions.

Sub-Q Administration

Administer by sub-Q injection every 14 days into abdomen, back of upper arm, or thigh. Rotate injection sites to minimize risk of injection site reactions.

Dosage

Adults

Multiple Sclerosis

Sub-Q

To reduce the incidence and severity of flu-like symptoms, gradually titrate to recommended maintenance dosage of 125 mcg every 14 days according to schedule in Table 1.

For sub-Q injection, the Plegridy or Plegridy Pen Starter Pack, which contains a 63-mcg prefilled injection pen or syringe and a 94-mcg prefilled injection pen or syringe, is designed to be used during dosage titration.

IM

To reduce the incidence and severity of flu-like symptoms, gradually titrate to recommended maintenance dosage of 125 mcg every 14 days according to schedule in Table 2.

For IM injection, the Plegridy Titration Kit, which contains 2 colored titration clips, is designed to be used with the prefilled syringe for IM use during dosage titration. A yellow clip is used for dose 1 to provide 63 mcg of the drug and a purple clip is used for dose 2 to provide 94 mcg of the drug.

Special Populations

Hepatic Impairment

No specific dosage recommendations.

Renal Impairment

Manufacturer makes no specific dosage recommendations; results of a pharmacokinetic study suggest dosage adjustment not required.

Geriatric Patients

No specific dosage recommendations.

Other Special Populations

Dosage adjustments based on body weight, gender, or age not required.

Contraindications

• Known hypersensitivity to natural or recombinant interferon beta or peginterferon, or any other ingredient in the formulation.

Warnings/Precautions

Hepatotoxicity

Possible elevations in hepatic aminotransferase concentrations (ALT and AST) and hepatic injury.

Hepatitis, autoimmune hepatitis, and rare cases of hepatic failure reported with interferon beta therapy.

Monitor patients for manifestations of hepatic injury; also monitor liver function tests. Consider discontinuance of drug if hepatic injury occurs.

Depression and Suicide

Depression, suicidal ideation, and suicide attempts possible. If depression or other serious psychiatric symptoms occur, consider discontinuing therapy.

Injection Site Reactions and Necrosis

Severe injection site reactions, including necrosis, injection site abscesses and cellulitis, reported. Hospitalization for surgical drainage and IV antibiotics has been required in some cases.

Local injection site reactions (e.g., erythema, pain, pruritus, edema) are common following sub-Q administration.

Periodically evaluate patient’s understanding and use of aseptic technique and proper procedures for self-administration, particularly if injection site necrosis has occurred.

Whether to discontinue therapy following a single site of necrosis depends on extent of necrosis. If therapy is continued, avoid injections near affected site until lesion has fully healed. If multiple lesions occur, change injection site or discontinue drug until healing occurs.

Cardiovascular Effects

Possible congestive heart failure and cardiomyopathy; monitor patients with substantial cardiac disease for worsening of their condition during initiation and continued treatment.

Hematologic Effects

Decreased peripheral blood cell counts in all cell lines, including rare cases of pancytopenia and severe thrombocytopenia, reported with interferon beta therapy.

Monitor CBCs, including WBC differential and platelet counts, during therapy. In addition, monitor patients for infections, bleeding, and symptoms of anemia. Patients with myelosuppression may require more intensive monitoring.

Thrombotic Microangiopathy

Thrombotic microangiopathy (TMA), including thrombotic thrombocytopenic purpura and hemolytic uremic syndrome, reported with interferon beta therapy and has been fatal in some cases.

If clinical manifestations and/or laboratory findings consistent with TMA occur, discontinue therapy and manage patient as clinically indicated.

Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) reported in the absence of other contributory factors. Many cases required hospitalization; one patient underwent lung transplant. PAH may occur at varying time points including several years after treatment initiation.

Assess new onset dyspnea or increasing fatigue for the potential development of PAH. If alternative causes ruled out and PAH diagnosis confirmed, discontinue therapy and manage as clinically indicated.

Autoimmune Diseases

Autoimmune diseases, including idiopathic thrombocytopenic purpura (ITP), hyperthyroidism, hypothyroidism, and autoimmune hepatitis, reported with interferon beta therapy.

If a new autoimmune disorder develops, consider discontinuing therapy.

Seizures

Seizures reported; use with caution in patients with preexisting seizure disorders.

Immunogenicity

Possible development of neutralizing antibodies to peginterferon beta-1a or PEG. Presence of anti-PEG antibodies does not appear to affect overall exposure or pharmacodynamic response to the drug following sub-Q administration.

Immunogenicity of peginterferon beta-1a given by IM injection not evaluated.

Sensitivity Reactions

Hypersensitivity

Anaphylaxis and other serious allergic reactions (e.g., angioedema, urticaria) reported rarely.

Discontinue therapy if a serious allergic reaction occurs.

Latex Sensitivity

The cover of the prefilled syringe for the IM injection contains natural rubber latex. Safety of using the prefilled syringe for IM injection not evaluated in individuals sensitive to latex.

Specific Populations

Pregnancy

Data from a large, population-based cohort study as well as other published studies conducted over several decades have not revealed a drug-associated risk of major birth defects with use of interferon beta during pregnancy. Findings concerning a potential risk for low birth weight or miscarriage with use of interferon beta during pregnancy have been inconsistent.

Animal reproduction studies not conducted to date with peginterferon beta-1a; however, studies using nonconjugated interferon beta in pregnant monkeys demonstrated some abortifacient activity, but no evidence of adverse effects on embryofetal development.

Lactation

Limited published information indicate that interferon beta-1a is distributed into human milk in low concentrations. It is not known whether peginterferon beta-1a affects milk production.

Consider developmental and health benefits of breast-feeding along with the mother’s clinical need for peginterferon beta-1a and potential adverse effects on the breast-fed infant from the drug or underlying maternal condition.

Pediatric Use

Safety and efficacy not established in pediatric patients.

Geriatric Use

Insufficient data to determine whether geriatric patients ≥65 years of age respond differently to peginterferon beta-1a than younger adults.

Renal Impairment

Because of possibility of increased drug exposure, monitor patients with severe renal impairment for adverse effects.

Systemic exposure not affected in patients with end-stage renal disease undergoing hemodialysis.

Common Adverse Effects

Injection site erythema, flu-like symptoms, pyrexia, headache, myalgia, chills, injection site pain, asthenia, injection site pruritus, arthralgia.

General

Patient Monitoring

• Monitor liver function tests and for signs and symptoms of hepatic injury.

• Periodically evaluate patient's understanding and use of aseptic technique and proper procedures for self administration.

• Monitor patients with substantial cardiac disease for worsening of their condition upon initiation of therapy and during continued treatment with peginterferon beta-1a.

• Monitor complete blood cell counts (CBC), including differential WBC counts and platelets, during peginterferon beta-1a therapy. Also monitor for infections, bleeding, and symptoms of anemia. Patients with myelosuppression may require more intensive monitoring of blood cell counts.

• Monitor patients for any new or increasing fatigue or shortness of breath during therapy.

Premedication and Prophylaxis

• Prophylactic and concurrent use of analgesics and/or antipyretics may prevent or ameliorate flu-like symptoms associated with peginterferon beta-1a treatment.

Other General Considerations

• Peginterferon beta-1a may be self-administered after appropriate training is provided.

• Patients and/or their caregivers who administer peginterferon beta-1a in a home setting should be cautioned against reuse of syringes and needles, supplied with a puncture-resistant container for the safe disposal of such equipment after use, and instructed on the proper disposal of full disposal containers.

Administration

Administer by IM or sub-Q injection. Bioequivalence has been demonstrated between the 2 routes of administration.

The commercially available subcutaneous injection is supplied by the manufacturer as a prefilled pen or syringe with an attached needle, and the commercially available IM injection is supplied as a prefilled syringe with a separate needle.

Prior to administration, allow prefilled injection pens and syringes to reach room temperature (about 30 minutes); do not use external heat sources (e.g., hot water) to warm solution.

Switching between IM and sub-Q administration not evaluated; however, manufacturer states that if route of administration is switched (IM to sub-Q or vice-versa), it is not expected that repeat dosage titration is necessary.

Prefilled injection pens and syringes are for single use only; discard any unused portions.

IM Administration

Administer by IM injection every 14 days into the thigh. Rotate injections between the left and right thigh to minimize risk of injection site reactions.

Sub-Q Administration

Administer by sub-Q injection every 14 days into abdomen, back of upper arm, or thigh. Rotate injection sites to minimize risk of injection site reactions.

Dosage

Adults

Multiple Sclerosis

Sub-Q

To reduce the incidence and severity of flu-like symptoms, gradually titrate to recommended maintenance dosage of 125 mcg every 14 days according to schedule in Table 1.

For sub-Q injection, the Plegridy or Plegridy Pen Starter Pack, which contains a 63-mcg prefilled injection pen or syringe and a 94-mcg prefilled injection pen or syringe, is designed to be used during dosage titration.

IM

To reduce the incidence and severity of flu-like symptoms, gradually titrate to recommended maintenance dosage of 125 mcg every 14 days according to schedule in Table 2.

For IM injection, the Plegridy Titration Kit, which contains 2 colored titration clips, is designed to be used with the prefilled syringe for IM use during dosage titration. A yellow clip is used for dose 1 to provide 63 mcg of the drug and a purple clip is used for dose 2 to provide 94 mcg of the drug.

Special Populations

Hepatic Impairment

No specific dosage recommendations.

Renal Impairment

Manufacturer makes no specific dosage recommendations; results of a pharmacokinetic study suggest dosage adjustment not required.

Geriatric Patients

No specific dosage recommendations.

Other Special Populations

Dosage adjustments based on body weight, gender, or age not required.

No formal drug interaction studies to date.