Peginterferon Alfa-2a

A to Z Drug Facts

 Action Binds to specific receptors on cell surface and initiates a complex sequence of intracellular events (eg, inhibition of viral replication and inhibition of cell proliferation).

Absorption: T_max is 72 to 96 hr. Steady-state is reached within 5 to 8 wk.

Elimination: Cl is approximately 94 mL/hr; t_½ is approximately 80 hr.

Elderly: AUC increased but C_max did not.

Renal function impairment: Cl decreased 25% to 45% in those with end-stage renal disease undergoing hemodialysis.

 Indications Treatment of chronic hepatitis C in patients with compensated liver disease and not treated previously with interferon alfa.

 Contraindications Autoimmune hepatitis; decompensated hepatic disease prior to or during treatment with interferon alfa-2a; hypersensitivity to any component of the product.

 Route/Dosage

Adults: SC 180 mcg (1 mL) once weekly for 48 wk.

Dose reduction

Adverse reactions: When dose reduction is required for moderate to severe adverse reactions, initial dose reduction to 135 mcg is generally adequate; however, in some cases, a dose reduction to 90 mcg may be needed. The dose may be re-escalated following improvement of the adverse reaction. Hematologic toxicity: Dose reduction to 135 mcg of peginterferon alfa-2a is recommended if the neutrophil count is less than 750 cells/mm³. Suspend treatment in patients with an absolute neutrophil count below 500 cells/mm³ until the count returns to more than 1000 cells/mm³. Reinstitute therapy at 90 mcg of peginterferon alfa-2a and monitor the neutrophil count.

A dose reduction to 90 mcg of peginterferon alfa-2a is recommended if the platelet count is less than 50,000 cells/mm³. Cessation of therapy is recommended when the platelet count is below 25,000 cells/mm³. Renal function impairment: A dose reduction to 135 mcg of peginterferon alfa-2a is recommended in patients with end-stage renal disease requiring hemodialysis. Hepatic function impairment: A dose reduction to 90 mcg of peginterferon alfa-2a is recommended in patients with progressive ALT increases above baseline values. Discontinue peginterferon alfa-2a immediately if ALT increases are progressive despite dose reduction or accompanied by increased bilirubin or evidence of hepatic decompensation.

 Interactions

Theophylline: Plasma concentrations of theophylline may be elevated, increasing the risk of side effects.

 Lab Test Interferences None well documented.

 Adverse Reactions

CARDIOVASCULAR: Arrhythmia; endocarditis. CNS: Depression, irritability, anxiety; headache; insomnia; dizziness; concentration impairment; memory impairment; suicidal ideation. DERMATOLOGIC: Alopecia; pruritus; sweating; dermatitis; rash. EENT: Corneal ulcer. GI: Nausea; anorexia; diarrhea; abdominal pain; dry mouth; vomiting; peptic ulcer; GI bleeding; pancreatitis; colitis. HEMATOLOGIC: Neutropenia; thrombocytopenia. HEPATIC: Hepatic dysfunction; fatty liver; cholangitis. METABOLIC: Diabetes mellitus. RESPIRATORY: Pneumonia; interstitial pneumonitis; pulmonary embolism. OTHER: Flu-like symptoms; myalgia; arthralgia; back pain; fatigue; pyrexia; rigors; injection-site reaction; pain; asthenia; suicide; autoimmune phenomena; peripheral neuropathy; coma; myositis; cerebral hemorrhage.

 Precautions

Pregnancy: Category C. Lactation: Undetermined. Children: Safety and efficacy not established. Elderly patients: Use with caution because of increased likelihood of decreased renal function. Autoimmune disorders: Use with caution. Bone marrow toxicity: Bone marrow function may be suppressed. Cardiovascular disorders: Use with caution in patients with preexisting cardiac disease, including hypertension, supraventricular arrhythmias, chest pain, and MI. Colitis: Fatal and nonfatal ischemic and hemorrhagic colitis have been observed. Discontinue use immediately in patients who develop symptoms. Endocrine disorders: May cause or aggravate hypothyroidism and hyperthyroidism. Hyperglycemia, hypoglycemia, and diabetes mellitus have occurred during treatment with peginterferon alfa-2a; therefore, patients with these conditions at baseline, who cannot be effectively treated by medication, should not begin peginterferon alfa-2a therapy. Patients who develop these conditions during treatment and cannot be controlled by medication may require discontinuation of peginterferon alfa-2a therapy. Ophthalmologic disorders: Decreased or loss of vision, retinopathy including macular edema, retinal hemorrhage, cotton wool spots, and retinal artery or vein obstruction have been observed. Pancreatitis: Fatal and nonfatal pancreatitis has been observed. Discontinue use in patients who develop symptoms. Pulmonary disorders: Dyspnea, pulmonary infiltrates; pneumonia, bronchiolitis obliterans, interstitial pneumonitis, and sarcodosis have been associated with use. Renal impairment: Use with caution and adjust dose accordingly. Special risk patients: May cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders.

 Administration/Storage

• For SC administration only. Not for intradermal, IM, or IV administration.
• Do not administer if particulate matter or discoloration noted.
• If severe adverse reactions develop, dosage adjustment or discontinuation of therapy may be appropriate.
• Use only 1 dose/vial. Do not re-enter vial. Discard any unused portions. Do not save unused solution for later administration.
• Store unused vials in refrigerator (36° to 46°F). Do not freeze or shake. Protect from light.

 Assessment/Interventions

• Obtain patient history, including drug history and any known allergies. Note evidence of decompensated liver disease or diagnosis of autoimmune hepatitis. Note history of psychiatric disorders, autoimmune disorders, cardiac disease, thyroid disease, diabetes, or previous treatment with alpha interferon.
• Ensure that the following laboratory tests are performed and reviewed prior to beginning therapy and periodically thereafter during the 48 wk of therapy: platelet count; hemoglobin; absolute neutrophil count; liver enzymes and bilirubin; serum creatinine or creatinine clearance; TSH.
• Ensure that all patients have an ophthalmic examination prior to beginning therapy and that patients with preexisting ophthalmic disorders (eg, diabetic or hypertensive retinopathy) receive periodic ophthalmic examinations during therapy.
• Monitor patient for life-threatening neuropyschiatric reactions (eg, depression, suicidal ideation, suicidal attempt). If noted, inform health care provider immediately.
• Assess patient for GI, CV, HEMA, respiratory, and DERM side effects. If noted and significant inform health care provider.
• If patient experiences adverse CNS symptoms, implement safety precautions such as lowering bed, putting side rails up, and supervising ambulation.
• Assess for flu-like symptoms (eg, fever, rigors, headache, fatigue, arthralgia, myalgia, chills, sweating). If such symptoms occur, administer drug in the evening and give nonnarcotic analgesics as prescribed.
• Implement infection control measures if WBC drops; implement bleeding precautions if platelet count drops.
• Reduce dose 25% if absolute neutrophil count is less than 750/mm³.
• Reduce dose 50% if platelet count is less than 50,000/mm³.
• Suspend therapy if absolute neutrophil count is less than 500/mm³ or if platelet count is less than 25,000/mm³.
• Reduce dose 25% in patient with end-stage renal disease on hemodialysis.
• Reduce dose 50% in patient with progressive ALT increases above baseline values. Discontinue therapy if ALT increases progress in spite of dose reduction or if hepatic decompensation or increased bilirubin are noted.
• Reduce dose 25% if moderate to severe adverse reactions occur. Further reduce dose to 50% if adverse reactions persist. Discontinue therapy if the reaction does not become tolerable at the reduced dose.
• Ensure that women of child bearing potential is using effective contraception during therapy.

 Patient/Family Education

• Explain name, dose, action, and potential side effects of drug. If patient will be administering at home, review “Medication Guide” with the patient. Ensure that the patient understands how to store, prepare, and administer the dose, and dispose of used equipment and supplies.
• Teach patient infection control and bleeding precautions.
• Advise patient that drug may cause confusion, drowsiness, or dizziness and to use caution while driving or performing other activities requiring mental alertness.
• Advise women of childbearing potential to use effective contraception during treatment.
• Instruct women to contact health care provider if pregnant, planning to become pregnant, or breastfeeding.
• Advise patient that it is not known if this drug will prevent transmission of hepatitis C to others nor is it known if it can prevent cirrhosis, liver failure, or liver cancer that may develop as a result of hepatitis C infection.
• Advise patient to report any of the following: signs or feelings of depression; persistent fever; sore throat; unusual bleeding or bruising; stomach pain; bloody diarrhea; rapid or irregular pulse; difficulty breathing.
• Instruct patient to not take any prescription or OTC medications or dietary supplements unless advised by the health care provider.
• Advise patient that follow-up visits and lab tests will be required to monitor therapy; keep appointments.

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Copyright © 2003 Facts and Comparisons
David S. Tatro
A to Z Drug Facts