Trade Names:PEGASYS- Injection 180 mcg
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).
T max is 72 to 96 h. Steady state is reached within 5 to 8 wk.
Cl is 94 mL/h; t ½ is approximately 80 h.
Cl decreased 25% to 45% in those with end-stage renal disease undergoing hemodialysis.Elderly
AUC increased, but C max did not.
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.
Chronic myelogenous leukemia, renal cell carcinoma.
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.
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.Hepatic Function ImpairmentAdults
Subcutaneous Discontinue immediately if ALT increases are progressive despite dose reduction or accompanied by increased bilirubin or evidence of hepatic decompensation.Chronic HBV
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.Chronic HCV
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.Dose reductionAdverse reactions
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.Depression
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.Hematologic toxicity
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 .Renal function impairment
A dose reduction to 135 mcg is recommended in patients with end-stage renal disease requiring hemodialysis.
Store in refrigerator (36° to 46°F). Do not freeze or shake. Protect from light.
Methadone levels may be elevated 10% to 15%. The clinical importance of this increase is not known.Nucleoside reverse transcriptase inhibitors (eg, didanosine, zidovudine)
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
Theophylline plasma levels may be elevated, increasing the risk of adverse reactions.
None well documented.
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%).
Alopecia (23%); pruritus (12%); dermatitis (8%); sweating increased (6%); rash (5%); dry skin (4%); eczema (1%).
Blurred vision (4%); hearing impairment or loss (postmarketing).
Nausea/vomiting (24%); anorexia (17%); diarrhea (16%); abdominal pain (15%); dry mouth (6%).
Neutropenia (21%); thrombocytopenia (5%); lymphopenia (3%); anemia (2%).
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%).
Injection site reaction (22%).
Weight decrease (4%).
Myalgia (37%); rigors (35%); arthralgia (28%); back pain (9%).
Cough, dyspnea (4%).
WarningsAutoimmune, infectious, ischemic, and neuropsychiatric disorders
Interferons may cause or aggravate these fatal or life-threatening disorders. Persistent, severe, or worsening signs or symptoms may necessitate discontinuation of therapy. Closely monitor patients with periodic clinical and laboratory evaluations.Use with ribavirin
May cause birth defects and/or death of the fetus. Extreme care must be taken to avoid pregnancy in female patients and in female partners of male patients. Ribavirin causes hemolytic anemia, which may result in a worsening of cardiac disease. Ribavirin is genotoxic and mutagenic and should be considered a potential carcinogen.
Obtain standard hematologic and biochemical laboratory tests for all patients before beginning therapy. After initiating therapy, obtain hematologic tests at 2 and 4 wk, biochemical tests at 4 wk, and then periodically thereafter during therapy. Increase frequency of monitoring if abnormalities are noted. Pregnancy screening for women of childbearing potential must be performed before starting therapy and monthly during combination therapy and for 6 mo following discontinuation of therapy. Monitor all patients for evidence of depression and other psychiatric symptoms. Perform ophthalmic examination before starting therapy in all patients and periodically during treatment in patients with preexisting ophthalmic disorders (eg, diabetic or hypertensive retinopathy).
Category C . Category X when used with ribavirin.
Safety and efficacy not established.
Use with caution because of increased likelihood of decreased renal function. Consider monitoring renal function.
Severe acute hypersensitivity reactions, including anaphylaxis, have been rarely observed during alpha interferon and ribavirin therapy.
Use with caution in patients with CrCl less than 50 mL/min; adjust dose accordingly.
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.
May impair fertility in women.
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.
May cause confusion, dizziness, fatigue, and somnolence.
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 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.
Chest pain, hypertension, MI, and supraventricular arrhythmias have been reported during treatment; use with caution in patients with preexisting cardiac disease.
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.
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.
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.
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.
Fatal and nonfatal cases of pancreatitis have been observed. Discontinue use in patients who develop symptoms.
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.
Elevated liver enzymes, fatigue, neutropenia, thrombocytopenia.
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