peginterferon beta-1a (Rx)

>10%

IM

• Chills (36%)
• Headache (36-41%)
• Pain (22%)
• Injection site pain (11%)

SC

• Injection site erythema (25-62%)
• Influenza like illness (47%)
• Pyrexia (45%)
• Headache (41%)
• Chills (17-27%)
• Injection site pain (15%)
• Asthenia (13%)
• Injection site pruritus (13%)

1-10%

IM

• Injection site erythema (2%)

SC

• Body temperature increased (6%)
• ALT increased (6%)
• Pain (5%)
• AST increased (4%)
• Pruritus (4%)
• Hyperthermia (4%)
• Gamma-glutamyl-transferase increased (3%)
• Injection site edema (3%)
• Injection site warmth (3%)
• Injection site hematoma (3%)
• Injection site rash (2%)

Postmarketing Reports

Serious hypersensitivity reactions (eg, anaphylaxis)

Injection site reactions including necrosis

Noninfectious hepatitis

Pulmonary arterial hypertension

Contraindications

Hypersensitivity to natural or recombinant interferon beta or peginterferon, or any other excipients

Cautions

Depression, suicidal ideation, and suicide may occur; advise patients to report immediately any symptom of depression and consider discontinuing if depression occurs

Congestive heart failure and/or cardiomyopathy reported (7% in both peginterferon beta-1a- and placebo-treated patients)

Decreased peripheral blood counts reported in all cell lines, including rare instances of pancytopenia and severe thrombocytopenia; monitor for symptoms of infections, bleeding, and anemia; monitor CBC counts, differential WBC counts, and platelet counts

Autoimmune disorders of multiple target organs, including idiopathic thrombocytopenia, hyper- and hypothyroidism reported

Severe hepatic injury, including hepatitis, autoimmune hepatitis, and rare cases of severe hepatic failure, reported; cases of noninfectious hepatitis in postmarketing setting also reported; monitor patients for signs and symptoms of hepatic injury

In patients with renal impairment, monitor for adverse reactions because of increased systemic exposure

Cases of thrombotic microangiopathy, including thrombotic thrombocytopenic purpura and hemolytic uremic syndrome, some fatal, reported; some cases have been reported several weeks to years after starting interferon beta products; discontinue therapy if clinical symptoms and laboratory findings consistent with TMA occur, and manage as clinically indicated

Pulmonary arterial hypertension

• Cases of pulmonary arterial hypertension (PAH) reported; PAH has occurred in patients treated with interferon beta products in absence of other contributory factors; many of reported cases required hospitalization, including one case with interferon beta in which the patient underwent a lung transplant
• PAH has developed at various time points after initiating therapy with interferon beta products and may occur several years after starting treatment
• Patients who develop unexplained symptoms (eg, dyspnea, new or increasing fatigue) should be assessed for PAH; if alternative etiologies ruled out and diagnosis of PAH confirmed, discontinue treatment and manage as clinically indicated

Serious allergic reactions

• Serious allergic reactions (eg, angioedema, urticaria) reported
• Treat allergic reaction appropriately and promptly with antihistamines or corticosteroids
• Discontinue if a serious allergic reaction occurs
• Protective rubber cover of prefilled syringe for IM administration contains natural rubber latex; avoid IM use in patients that allergic or sensitive to latex; safety of prefilled syringes in latex-sensitive individuals not studied

Injection site reactions

• Injection site reactions, including injection site necrosis, can occur with the use of interferon beta products; in controlled clinical trials, injection site reactions (eg, injection site pain, bruising or erythema) reported; reactions included injection site inflammation (6%), injection site pain (8%), injection site mass (<1%), nonspecific reactions
• Injection site abscesses and cellulitis and injection site necrosis reported in postmarketing setting with interferon beta products; 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
• Whether to discontinue therapy following a single site of necrosis is dependent on extent of necrosis; for patients who continue therapy after injection site necrosis has occurred, avoid administration of the drug into the affected area until it is fully healed; if multiple lesions occur, change injection site or discontinue therapy until healing occurs

Hepatic injury

• Severe hepatic injury, including hepatitis, autoimmune hepatitis, and rare cases of severe hepatic failure, reported
• Elevated hepatic enzymes and hepatic injury reported; recurred in some patients upon rechallenge
• Monitor for signs and symptoms of hepatic injury

Pregnancy

There is pregnancy exposure registry that monitors pregnancy outcomes in women exposed to drug during pregnancy; encourage patients to enroll by calling 1-866-810-1462 or visiting https://www.plegridypregnancyregistry.com/.

Data from large population-based cohort study, as well as other published studies over several decades, have not identified drug-associated risk of major birth defects with use of interferon beta products during early pregnancy; findings regarding potential risk for low birth weight or miscarriage with use of interferon beta products in pregnancy have been inconsistent; in a study in pregnant monkeys, administration of interferon beta during pregnancy resulted in an increased rate of abortion

Lactation

Limited published literature has described the presence of interferon beta-1a products in human milk at low levels; there are no data on effects of interferon beta-1a on milk production

Consider developmental and health benefits of breastfeeding along with mother’s clinical need for drug and any potential adverse effects on breastfed infant from therapy or from underlying maternal condition

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

The exact mechanism by which peginterferon beta-1a exerts its effects in patients with multiple sclerosis is unknown; interferons are thought to alter response to surface antigen and may enhance immune cell activities

Absorption

Does not accumulate in serum after multiple doses

Peak plasma concentration: 280 pg/mL

Peak plasma time: 1-1.5 days

AUC over 14 day interval: 34.8 ng•hr/mL

Distribution

481 L

Metabolism

Not extensively metabolized in the liver

Elimination

Half-life: 78 hr

Steady state clearance: 4.1 L/hr

Excretion: Mostly in urine

SC or IM Preparation

Remove from refrigerator and allow to warm to room temperature (~30 min) before injection (do not use external heat sources, such as warm water)

SC or IM Administration

May be administered SC or IM

Use analgesics and/or antipyretics prophylactically or concurrently to prevent/ameliorate flulike symptoms associated with treatment

Train the proper technique for self-administering injections via SC or IM

Advise to check injection site for redness, swelling, and tenderness 2 hr after administering

Prefilled syringes and pens are for single-use only; discard after use

Sites of injection

• SC: Rotate injection sites between abdomen, back of upper arms, and thighs
• IM: Rotate injection sites between left and right thigh

Storage

Prefilled pen or syringes

• Store in closed original carton to protect from light until ready for injection
• Refrigerate between 2-8ºC (36-46ºF)
• Do not freeze; discard if frozen
• If refrigeration unavailable, store at 2-25ºC (36-77ºF) for up to 30 days; can be removed from, and returned to, a refrigerator if necessary; not to exceed a total combined time out of refrigeration of 30 days at 2-25ºC (36-77ºF)
• IM prefilled syringe contains natural rubber latex