Peginterferon Alfa-2a

Trade Names:PEGASYS- Injection 180 mcg

Pharmacology

Binds to specific receptors on cell surface and initiates a complex cascade of protein-protein interactions, leading to rapid activation of gene transcription. Interferon-stimulated genes regulate many biologic effects (eg, inhibition of viral replication of infected cells, inhibition of cell proliferation, immunomodulation).

Pharmacokinetics

Absorption

T _max is 72 to 96 h. Steady state is reached within 5 to 8 wk.

Elimination

Cl is 94 mL/h; t _½ is approximately 80 h.

Special Populations

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

AUC increased, but C _max did not.

Indications and Usage

Treatment of hepatitis B e antibody (HBeAg) positive and HBeAg negative chronic hepatitis B virus (HBV) in patients who have compensated liver disease and evidence of viral replication and liver inflammation; alone or in combination with ribavirin tablets for the treatment of chronic hepatitis C virus (HCV) in patients with compensated liver disease and those not treated previously with interferon alfa.

Unlabeled Uses

Chronic myelogenous leukemia, renal cell carcinoma.

Contraindications

Autoimmune hepatitis; patients with decompensated hepatic disease prior to or during treatment with interferon alfa-2a; hypersensitivity to any component of the product; because peginterferon alfa-2a contains benzyl alcohol, it is contraindicated in neonates and infants; in combination with ribavirin tablets, peginterferon is contraindicated in pregnancy; men whose female partner is pregnant; patients with hemoglobinopathies; hypersensitivity to any component of the ribavirin products.

Dosage and Administration

Subcutaneous 180 mcg (1 mL vial or 0.5 mL prefilled syringe) once weekly for 48 wk. For patients with hepatitis C, consider discontinuing therapy after 12 to 24 wk of therapy if patient has failed to demonstrate an early virologic response.

Subcutaneous Discontinue immediately if ALT increases are progressive despite dose reduction or accompanied by increased bilirubin or evidence of hepatic decompensation.

In patients with chronic HBV and elevations in ALT (greater than 5 × upper limits of normal [ULN]), monitor liver function more frequently and consider reducing the dose to 135 mcg or temporarily discontinuing treatment. After dose reduction or withholding therapy, treatment may be resumed after ALT flares subside. In patients with persistent, severe hepatitis B flares (ALT more than 10 × ULN), consider discontinuing therapy.

In patients with chronic HCV and progressive ALT increases above baseline values, reduce the dose to 135 mcg and monitor liver function more frequently. After dose reduction or withholding therapy, treatment may be resumed after ALT flares subside.

When dose reduction is required for moderate to severe adverse reactions, initial dose reduction to 135 mcg generally is 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 reactions.

For mild depression, continue dose at 180 mcg and evaluate patient once weekly until symptoms improve or worsen; for moderate depression, decrease dose to 135 mcg (in some cases, a dose reduction to 90 mcg may be needed) and evaluate patient once weekly until symptoms improve or worsen. If symptoms improve and are stable for 4 wk, continue reduced dose or return to normal dose. If symptoms worsen (severe depression), discontinue permanently and obtain immediate psychiatric consultation.

Dose reduction to 135 mcg is recommended if the neutrophil count is less than 750 cells/mm ³ . Suspend treatment in patients with an absolute neutrophil count below 500 cells/mm ³ until the count returns to more than 1,000 cells/mm ³ . Reinstitute therapy at 90 mcg and monitor the neutrophil count. A dose reduction to 90 mcg is recommended if the platelet count is less than 50,000 cells/mm ³ . Cessation of therapy is recommended when the platelet count is below 25,000 cells/mm ³ .

A dose reduction to 135 mcg is recommended in patients with end-stage renal disease requiring hemodialysis.

General Advice

• For subcutaneous administration only. Not for intradermal, IM, IV, or intra-arterial administration.
• Administer in abdomen or thigh.
• Solution should be colorless to light yellow. Do not administer if particulate matter or discoloration is noted.
• Warm refrigerated solution by gently rolling vial or prefilled syringe in palms of hands for about 1 min. Do not shake.
• Use only 1 dose/vial. Do not re-enter vial. Discard any unused portions. Do not save unused solution for later administration.
• If patient develops flu-like symptoms (eg, arthralgia, chills, fatigue, fever, headache, myalgia, rigors, sweating), administer drug in the evening and give nonnarcotic analgesics as prescribed.

Storage/Stability

Store in refrigerator (36° to 46°F). Do not freeze or shake. Protect from light.

Drug Interactions

Methadone levels may be elevated 10% to 15%. The clinical importance of this increase is not known.

The risk of treatment-associated toxicity (eg, hepatic decompensation) may be increased. Coadministration of ritonavir and didanosine is not recommended. The risk of neutropenia or anemia may be increased with coadministration of zidovudine.

Theophylline plasma levels may be elevated, increasing the risk of adverse reactions.

Laboratory Test Interactions

None well documented.

Adverse Reactions

CNS

Fatigue/asthenia (56%); headache (54%); pyrexia (37%); insomnia, irritability/anxiety/nervousness (19%); depression (18%); dizziness (16%); concentration impairment (8%); memory impairment (5%); mood alteration (3%).

Dermatologic

Alopecia (23%); pruritus (12%); dermatitis (8%); sweating increased (6%); rash (5%); dry skin (4%); eczema (1%).

EENT

Blurred vision (4%); hearing impairment or loss (postmarketing).

Endocrine

Hypothyroidism (3%).

GI

Nausea/vomiting (24%); anorexia (17%); diarrhea (16%); abdominal pain (15%); dry mouth (6%).

Hematologic-Lymphatic

Neutropenia (21%); thrombocytopenia (5%); lymphopenia (3%); anemia (2%).

Lab Tests

Decreased neutrophils (95%); decreased lymphocytes (81%); decreased platelets (52%); elevated triglycerides (at least 50%); elevated ALT (27%, HBV); decreased Hgb below 12 g/dL (17%); binding antibodies to interferon alfa-2a assessed by ELISA assay (9%); hypothyroidism (4%); elevated ALT (HCV), hyperthyroidism (1%).

Local

Injection site reaction (22%).

Metabolic-Nutritional

Weight decrease (4%).

Musculoskeletal

Myalgia (37%); rigors (35%); arthralgia (28%); back pain (9%).

Respiratory

Cough, dyspnea (4%).

Miscellaneous

Pain (11%).

Precautions

Pregnancy

Category C . Category X when used with ribavirin.

Lactation

Undetermined.

Children

Safety and efficacy not established.

Elderly

Use with caution because of increased likelihood of decreased renal function. Consider monitoring renal function.

Hypersensitivity

Severe acute hypersensitivity reactions, including anaphylaxis, have been rarely observed during alpha interferon and ribavirin therapy.

Renal Function

Use with caution in patients with CrCl less than 50 mL/min; adjust dose accordingly.

Hepatic Function

Exacerbations of hepatitis during HBV treatment are characterized by transient and potentially severe increases in serum ALT (greater than 10 × ULN). If ALT increases are progressive despite reduction of dose, or are accompanied by increased bilirubin or evidence of hepatic decompensation, immediately discontinue treatment.

Fertility

May impair fertility in women.

Special Risk Patients

Safety and efficacy not established for the treatment of HCV in patients who are liver or other organ transplant recipients, coinfected with HBV, coinfected with HIV with a CD4+ cell count less than 100 cells/mcL, or who have had prior alpha interferon treatment failures with or without ribavirin.

Hazardous Tasks

May cause confusion, dizziness, fatigue, and somnolence.

Autoimmune disorders

Development or exacerbation of autoimmune disorders, including idiopathic thrombocytopenic purpura, interstitial nephritis, myositis, psoriasis, and SLE, may occur. Use with caution in patients with autoimmune disorders.

Bone marrow toxicity

Bone marrow function may be suppressed; severe cytopenias may occur. Severe neutropenia and thrombocytopenia occur with greater incidence in patients coinfected with HIV. Reduce dose in patients with hematologic abnormalities.

CV disorders

Chest pain, hypertension, MI, and supraventricular arrhythmias have been reported during treatment; use with caution in patients with preexisting cardiac disease.

Colitis

Fatal and nonfatal ulcerative and hemorrhagic/ischemic colitis have been observed within 12 wk of starting alpha interferon treatment. Discontinue use immediately in patients who develop abdominal pain, bloody diarrhea, and fever.

Endocrine disorders

May cause or aggravate hypothyroidism and hyperthyroidism. Hyperglycemia, hypoglycemia, and diabetes mellitus have occurred during treatment with peginterferon alfa-2a; therefore, do not begin peginterferon alfa-2a therapy in patients with these conditions at baseline who cannot be effectively treated by medication. Patients who develop these conditions during treatment and cannot be controlled by medication may require discontinuation of peginterferon alfa-2a therapy.

Hepatic failure

Patients with chronic hepatitis C with cirrhosis or cirrhosis and coinfected with HIV and receiving highly active antiretroviral therapy may be at risk of hepatic decompensation and death when treated with alpha interferons; immediately discontinue treatment if hepatic decompensation (Child-Pugh score 6 or greater) is observed.

Ophthalmologic disorders

Decrease or loss of vision, retinopathy including macular edema, retinal artery or vein thrombosis, retinal hemorrhages and cotton wool spots, optic neuritis, and papilledema have been observed; discontinue therapy in patients who develop new or worsening ophthalmologic disorders.

Pancreatitis

Fatal and nonfatal cases of pancreatitis have been observed. Discontinue use in patients who develop symptoms.

Pulmonary disorders

Dyspnea, pulmonary infiltrates, pneumonia, bronchiolitis obliterans, interstitial pneumonitis, and sarcoidosis may be induced or aggravated; discontinue therapy in patients who develop persistent or unexplained pulmonary infiltrates or pulmonary function impairment.

Overdosage

Symptoms

Elevated liver enzymes, fatigue, neutropenia, thrombocytopenia.

Patient Information

• If patient will be administering at home, review Medication Guide with the patient. Ensure the patient understands how to store, prepare, and administer the dose, and dispose of used equipment and supplies.
• Advise patient to take prescribed dose once a week, on the same day each week, and at approximately the same time.
• Advise patient that if a dose is missed and remembered within 2 days of when the dose should have been taken, to inject the missed dose as soon as remembered and take the next dose as regularly scheduled. Instruct patient to discuss with health care provider if more than 2 days passed and to not double the dose.
• Advise patient that flu-like symptoms (arthralgia, chills, fatigue, fever, headache, myalgia, rigors, sweating) are not uncommon and if such symptoms occur, to try administering the drug in the evening and using nonnarcotic analgesics as advised by health care provider.
• Advise patient not to switch between prefilled syringes and vials without talking with health care provider. Equal volumes of liquid from prefilled syringes and vials do not contain the same amount of peginterferon alfa-2a.
• Caution patient not to change or stop taking the dose unless advised by health care provider.
• Caution patient not to switch brands of interferon without talking with health care provider.
• 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 until tolerance is determined.
• Advise women of childbearing potential and men with female partners of childbearing potential of teratogenic and embryocidal risk of concurrent treatment with ribavirin; advise them to use 2 forms of effective contraception during and for 6 mo following treatment with ribavirin, and of the need for routine monthly pregnancy tests.
• Advise patient that it is not known if this drug, alone or in combination with ribavirin, will prevent transmission of hepatitis C to others or 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: anxiety, bleeding or unusual bruising, bloody diarrhea, change in vision, difficulty breathing, irritability, persistent fever, rapid or irregular pulse, severe chest pain, signs or feelings of depression, sore throat, stomach or lower back pain, suicidal ideation.

Copyright © 2009 Wolters Kluwer Health.