Peginterferon beta-1a

>10%

Injection site reactions (66%)

Injection site erythema (62%)

Influenzalike illness (47%)

Pyrexia (45%)

Headache (44%)

Myalgia (19%)

Chills (17%)

Asthenia (13%)

Injection site pruritus (13%)

Arthralgia (11%)

1-10%

Nausea (9%)

Depression (8%); not different from placebo

CHF, cardiomyopathy (7%); not different from placebo

Decreased WBCs (7%)

Increased ALT (6%)

Vomiting (5%)

Pain (5%)

Hyperthermia (4%)

Pruritus (4%)

Increased AST (4%)

Increased GGT (3%)

Injection site edema (3%)

Injection site warmth (3%)

Injection site hematoma (3%)

Injection site rash (2%)

Increased ALT, >5 x ULN (2%)

<1

Increased AST, >5 x ULN

Seizures

Anaphylaxis, angioedema, urticaria

Autoimmune disorders

Contraindications

History of hypersensitivity to natural or recombinant interferon beta or peginterferon

Cautions

Severe hepatic injury, including hepatitis, autoimmune hepatitis, and rare cases of severe hepatic failure, reported; monitor liver function tests and consider discontinuing if hepatic injury occurs

Depression, suicidal ideation, and suicide occur more frequently in patients receiving interferon beta than in patients receiving placebo; advise patients to report immediately any symptom of depression and consider discontinuing if depression occurs

Seizures are associated with the use of interferon beta (<1%)

Anaphylaxis and other allergic reactions reported (rare); discontinue if a serious allergic reaction occurs

Injection site reactions reported, including site necrosis; change injection site; if multiple injection lesions occur, discontinue until healing 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, and autoimmune hepatitis, have been reported

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

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements.

No drug interactions have been determined by the manufacturer. However, you should tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements. Not all drug interactions are known or reported and new drug interactions are continually being reported.

Use peginterferon beta-1a exactly as prescribed.

Peginterferon beta-1a comes in injectable form and is injected directly under the skin every 14 days.

If you miss a dose, take the missed dose as soon as you remember. If it is almost time for the next dose, skip the missed dose and take your next dose at the regular time. Do not take two doses of peginterferon beta-1a at the same time.

Avoid injecting this medicine into skin that is red, bruised, irritated, scarred, or infected.

• If you have an allergy to interferon beta-1a or any other part of peginterferon beta-1a.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.

This medicine may interact with other drugs or health problems.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this medicine with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of infection like fever, chills, very bad sore throat, ear or sinus pain, cough, more sputum or change in color of sputum, pain with passing urine, mouth sores, or wound that will not heal.
• Signs of low mood (depression), thoughts of killing yourself, nervousness, emotional ups and downs, thinking that is not normal, anxiety, or lack of interest in life.
• Signs of bleeding like throwing up blood or throw up that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; vaginal bleeding that is not normal; bruises without a reason or that get bigger; or any bleeding that is very bad or that you cannot stop.
• Signs of thyroid problems like a change in weight without trying, feeling nervous and excitable, feeling restless, feeling very weak, hair thinning, low mood (depression), neck swelling, not able to focus, not able to handle heat or cold, period (menstrual) changes, shakiness, or sweating.
• Shortness of breath, a big weight gain, or swelling in the arms or legs.
• Chest pain or pressure or a fast heartbeat.
• A heartbeat that does not feel normal.
• Seizures.
• Very bad dizziness or passing out.
• Feeling very tired or weak.
• Very bad and sometimes deadly liver problems have happened with peginterferon beta-1a. Call your doctor right away if you have signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.

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

Excretion

Urine (major)

Time to Peak

1 to 1.5 days

Half-Life Elimination

~78 hours (multiple sclerosis patients)

There are no dosage adjustments provided in the manufacturer's labeling.

Subcutaneous: Administer subcutaneously in the abdomen, back of the upper arm, or thigh; rotate injection sites; do not inject into area where skin is red, irritated, bruised or scarred.

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; adverse reactions in patients with severe renal impairment (CrCl <30 mL/minute); injection site reactions; signs/symptoms of thrombotic microangiopathy (eg, new-onset hypertension, thrombocytopenia, renal impairment).

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dose adjustment(s) may be required; however, no specific guidelines have been suggested.