Multiple sclerosis, relapsing: IM, SUBQ: Initial: 63 mcg on day 1; 94 mcg on day 15. Maintenance: 125 mcg every 14 days beginning on day 29. Note: Analgesics and/or antipyretics may help decrease flu-like symptoms during treatment.
Conversion between IM and SUBQ routes: Switching between routes has not been studied; however, repeating dose titration is not expected to be needed to decrease flu-like symptoms when switching routes, since bioequivalence has been demonstrated between IM and SUBQ administration.
There are no dosage adjustments provided in the manufacturer's labeling; use with caution in severe renal impairment (CrCl <30 mL/minute).
Hemodialysis: Partially removed (~24%) by hemodialysis
There are no dosage adjustments provided in the manufacturer's labeling; however, not metabolized extensively in the liver.
Refer to adult dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Pen-injector, Subcutaneous [preservative free]:
Plegridy: 125 mcg/0.5 mL (0.5 mL) [contains mouse (murine) and/or hamster protein]
Plegridy Starter Pack: 63 mcg/0.5 mL & 94 mcg/0.5 mL (1 mL) [contains mouse (murine) and/or hamster protein]
Solution Prefilled Syringe, Intramuscular [preservative free]:
Plegridy: 125 mcg/0.5 mL (0.5 mL)
Solution Prefilled Syringe, Subcutaneous:
Plegridy: 125 mcg/0.5 mL (0.5 mL) [contains mouse (murine) and/or hamster protein]
Plegridy Starter Pack: 63 mcg/0.5 mL & 94 mcg/0.5 mL (1 mL) [contains mouse (murine) and/or hamster protein]
No
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Subcutaneous:
Plegridy: 125 mcg/0.5 mL (0.5 mL)
Solution Therapy Pack, Subcutaneous:
Plegridy: 63 mcg/0.5 mL & 94 mcg/0.5 mL (1 mL)
Plegridy 125 mcg/0.5 mL prefilled syringe for intramuscular administration: FDA approved January 2021; anticipated availability currently unknown.
An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/125499s021lbl.pdf#page=20, must be dispensed with this medication.
A health care professional should provide preparation/administration training to patient or caregiver prior to the first dose. Allow product to warm to room temperature (~30 minutes) prior to administration; do not heat using external sources (eg, hot water).
IM: Administer IM in the thigh; rotate injection sites between left and right thigh.
SUBQ: Administer SUBQ in the abdomen, back of the upper arm, or thigh; rotate injection sites; do not inject into area where skin is red, irritated, bruised, infected, or scarred.
Multiple sclerosis, relapsing: Treatment of patients with relapsing forms of multiple sclerosis, including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease
Peginterferon beta-1a may be confused with interferon alfa-2b, interferon alfacon-1, interferon beta, interferon gamma-1b, peginterferon alfa-2a, peginterferon alfa-2b
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for adults.
>10%:
Dermatologic: Injection site pruritus (13%)
Local: Erythema at injection site (62%), injection site reaction (66%; severe: 3%), pain at injection site (15%)
Nervous system: Chills (17%), headache (44%)
Neuromuscular & skeletal: Arthralgia (11%), asthenia (13%), myalgia (19%)
Respiratory: Flu-like symptoms (47%)
Miscellaneous: Fever (45%)
1% to 10%:
Dermatologic: Pruritus (4%), rash at injection site (2%)
Endocrine & metabolic: Increased gamma-glutamyl transferase (3%)
Gastrointestinal: Nausea (9%), vomiting (5%)
Hematologic and oncologic: Decreased white blood cell count (<3 × 109/L: 7%)
Hepatic: Increased serum alanine aminotransferase (6%; >5 × ULN: 2%), increased serum aspartate aminotransferase (4%)
Immunologic: Antibody development (to PEG: 7%; neutralizing antibodies: <1%)
Local: Hematoma at injection site (3%), swelling at injection site (3%), warm sensation at injection site (3%)
Nervous system: Hyperthermia (4%), increased body temperature (6%), pain (5%)
<1%:
Dermatologic: Urticaria
Hematologic & oncologic: Pancytopenia, severe neutropenia, severe thrombocytopenia
Hepatic: Increased serum bilirubin
Hypersensitivity: Angioedema
Local: Tissue necrosis at injection site
Postmarketing:
Hematologic & oncologic: Hemolytic-uremic syndrome, thrombotic microangiopathy, thrombotic thrombocytopenic purpura
Hepatic: Hepatic injury (severe; including autoimmune hepatitis, hepatic failure, hepatitis)
Hypersensitivity: Anaphylaxis, severe hypersensitivity reaction
Hypersensitivity to natural or recombinant interferon beta or peginterferon, or any component of the formulation.
Documentation of allergenic cross-reactivity for interferons is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.
Canadian labeling: Additional contraindications (not in US labeling): Current severe depression and/or suicidal ideation.
Concerns related to adverse effects:
• Autoimmune disorders: Idiopathic thrombocytopenia, hyper- and hypothyroidism, and autoimmune hepatitis have been reported. Consider discontinuing treatment in patients who develop a new autoimmune disorder.
• Bone marrow suppression: May cause decreased peripheral blood cell counts in all cell lines, including rare instances of pancytopenia and severe thrombocytopenia. Monitor CBC with differential and platelets; monitor patients for infections, bleeding, and symptoms of anemia. Patients with preexisting myelosuppression may need more intensive monitoring.
• Hepatic effects: Severe hepatic injury, including hepatitis, autoimmune hepatitis, and severe hepatic failure (rare) have been reported; asymptomatic elevation of hepatic transaminases has also been reported and has recurred upon rechallenge. Monitor for signs and symptoms of hepatic injury.
• Hypersensitivity: Anaphylaxis and other serious allergic reactions (eg, angioedema, urticaria) may occur (rare); discontinue therapy if a serious allergic reaction occurs and institute appropriate supportive therapy.
• Injection-site reactions: Injection-site reactions have occurred, including pain, erythema, edema, pruritus, cellulitis, abscess, and necrosis. Necrosis may occur at single and multiple sites. Some reactions have occurred ≥2 years after initiation with use of other interferon beta products; reactions typically resolve with conservative treatment (antibiotics or surgical intervention may be required). Patient and/or caregiver competency in injection technique should be confirmed and periodically reevaluated. Do not inject into affected area until completely healed; if multiple lesions occur, discontinue use until they are fully healed.
• Neuropsychiatric disorders: Depression, suicidal ideation and suicide have been reported; monitor for symptoms of depression and suicidal ideation; consider discontinuing treatment with development of depression or other severe psychiatric symptoms.
• Thrombotic microangiopathy: Thrombotic microangiopathy (TMA), including thrombotic thrombocytopenic purpura (TTP) or hemolytic uremic syndrome (HUS), has been reported (some fatal) with interferon beta products. Cases have been reported several weeks to years after initiating therapy. Monitor for new-onset hypertension, thrombocytopenia, renal impairment; discontinue use in patients who develop TMA and manage appropriately (Hunt 2014; Mahe 2013).
Disease-related concerns:
• Cardiovascular disease: Congestive heart failure (CHF), cardiomyopathy, and cardiomyopathy with CHF may occur in patients receiving interferon beta. Monitor patients with significant cardiac disease for worsening of their cardiac condition during initiation and continuation of therapy.
• Renal impairment: Use with caution in severe renal impairment; increased drug exposure may occur; monitor for adverse reactions.
• Seizures: May cause seizures; use with caution in patients with a seizure disorder.
Dosage form specific issues:
• Latex: The protective rubber cover of the IM prefilled syringe may contain latex.
• Product variability: Due to differences in dosage, patients should not change brands of interferon.
None known.
Cladribine: May enhance the adverse/toxic effect of Interferons (Beta). Specifically, the risk for lymphopenia may be increased. Risk X: Avoid combination
Pegloticase: May diminish the therapeutic effect of PEGylated Drug Products. Risk C: Monitor therapy
Pegvaliase: PEGylated Drug Products may enhance the adverse/toxic effect of Pegvaliase. Specifically, the risk of anaphylaxis or hypersensitivity reactions may be increased. Risk C: Monitor therapy
Zidovudine: Interferons may enhance the adverse/toxic effect of Zidovudine. Interferons may decrease the metabolism of Zidovudine. Risk C: Monitor therapy
In general, disease modifying therapies for multiple sclerosis (MS) are stopped prior to a planned pregnancy except in females at high risk of MS activity (AAN [Rae-Grant 2018]). Consider use of agents other than peginterferon beta-1a for females at high risk of disease reactivation who are planning a pregnancy. Delaying pregnancy is recommended for females with persistent high disease activity; when disease modifying therapy is needed in these patients, other agents are preferred (ECTRIMS/EAN [Montalban 2018]).
Information related to the use of peginterferon beta-1a in pregnancy is limited (MacDonald 2018). Based on available data, an increased risk of major birth defects following maternal use of interferon beta products has not been observed; data related to low birth weight or miscarriage are inconsistent.
In general, disease-modifying therapies for multiple sclerosis (MS) are not initiated during pregnancy, except in females at high risk of MS activity (AAN [Rae-Grant 2018]). When disease-modifying therapy is needed in these patients, other agents are preferred (ECTRIMS/EAN [Montalban 2018]).
It is not known if peginterferon beta-1a is present in breast milk; however, interferon beta-1a is present in breast milk following use of other products.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother.
CBC with differential and platelets, transaminase levels; signs and symptoms of hepatic injury, hypersensitivity, infections, bleeding, new onset autoimmune disorders, psychiatric disorders (including depression and/or suicidal ideation), new onset/worsening cardiovascular disease; signs/symptoms of injection-site reactions; signs/symptoms of thrombotic microangiopathy (eg, new-onset hypertension, thrombocytopenia, renal impairment).
Interferon beta differs from the naturally occurring human protein by a single amino acid substitution and the lack of carbohydrate side chains; alters the expression and response to surface antigens and can enhance immune cell activities. Properties of interferon beta that modify biologic responses are mediated by cell surface receptor interactions; mechanism in the treatment of multiple sclerosis is unknown.
Distribution: Vd: 481 L
Metabolism: Not extensively metabolized in the liver
Half-life elimination: ~78 hours (multiple sclerosis patients)
Time to peak: 1 to 1.5 days
Excretion: Urine (major)
Renal function impairment: Renal impairment can increase the Cmax and AUC for peginterferon beta-1a. The half-life was 53, 49, and 82 hours in patients with mild, moderate, and severe renal impairment, respectively.
Solution Pen-injector (Plegridy Starter Pack Subcutaneous)
63 & 94 mcg/0.5 mL (per mL): $8,906.04
Solution Pen-injector (Plegridy Subcutaneous)
125 mcg/0.5 mL (per 0.5 mL): $4,453.02
Solution Prefilled Syringe (Plegridy Intramuscular)
125 mcg/0.5 mL (per 0.5 mL): $4,453.02
Solution Prefilled Syringe (Plegridy Starter Pack Subcutaneous)
63 & 94 mcg/0.5 mL (per mL): $8,906.04
Solution Prefilled Syringe (Plegridy Subcutaneous)
125 mcg/0.5 mL (per 0.5 mL): $4,453.02
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.