Dosing and uses of Pegasys (peginterferon alfa 2a)
Adult dosage forms and strengths
vial for single use
- 180mcg/mL
prefilled syringe for single use
- 180mcg/0.5mL
autoinjector for single use
- 135mcg/0.5mL
- 180mcg/0.5mL
Chronic Hepatitis C
Indicated as part of a combination regimen with other hepatitis C virus (HCV) antiviral drugs, is indicated for the treatment of adults with chronic hepatitis C (CHC) with compensated liver disease
180 mcg SC once weekly
Treatment duration (CHC)
- If used in combination with other antiviral drugs for CHC, refer to the prescribing information of the other HCV antiviral drugs for the recommended dosage of the other HCV antiviral drugs and duration of the entire treatment regimen
- Genotypes 1, 4: 48 weeks if PEG-INF-alfa-2a and ribavirin are used without other HCV antiviral drugs
- Genotypes 2, 3: 24 weeks if PEG-INF-alfa-2a and ribavirin are used without other HCV antiviral drugs
- Genotypes 5, 6: Insufficient data to recommend use
- PEG-INF-alfa-2a monotherapy: 48 weeks
- HIV coinfection: 48 weeks if PEG-INF-alfa-2a and ribavirin are used without other HCV antiviral drugs (regardless of HCV genotype)
Dosing Considerations (CHC)
- PEG-INF-alfa-2a monotherapy is only indicated for the treatment of patients with CHC with compensated liver disease if there are contraindications or significant intolerance to other HCV antiviral drugs
- PEG-INF-alfa-2a alone or in combination with ribavirin without additional HCV antiviral drugs is not recommended for treatment of patients with CHC who previously failed therapy with an interferon-alfa
- Not recommended for treatment of patients with CHC who have had solid organ transplantation
Chronic Hepatitis B
Indicated for the treatment of adults with HBeAg-positive and HBeAg-negative chronic hepatitis B infection who have compensated liver disease and evidence of viral replication and liver inflammation
180 mcg SC once weekly for 48 weeks
Dosage modifications
Neutropenia
- ANC <750 cells/mm³: Reduce dose to 135 mcg SC once weekly
- ANC <500 cells/mm³: Discontinue treatment until ANC values return to >1000 cells/mm³ and then reinstitute at 90 mcg SC once weekly; monitor ANC
Thrombocytopenia
- Platelet <50,000 cells/mm³: Reduce dose to 90 mcg SC once weekly
- Platelets <25,000 cells/mm³: Discontinue
Increased ALt
- If ALT increases are progressive despite dose reduction or accompanied by increased bilirubin or evidence of hepatic decompensation, therapy should be immediately discontinued
- Chronic hepatitis C: If ALT increases above baseline values, reduce dose to 135 mcg/week and perform more frequent monitoring of liver function; after dosage reduction or withholding, therapy can be resumed after ALT flares subside
- Chronic hepatitis B (ALT >5 xULN): Monitor LFTs more frequently; consider reducing the dosage to 135 mcg/week or temporarily discontinuing treatment; after dosage reduction or withholding, therapy can be resumed after ALT flares subside
- Consider discontinuing in adults with persistent, severe hepatitis B flares (ALT >10 xULN)
Renal impairment
- CrCl 30-50 mL/min: 180 mcg once weekly
- CrCl <30 mL/min (including patients on hemodialysis): 135 mcg once weekly
- If severe adverse reactions or laboratory abnormalities develop, dose can be reduced to 90 mcg once weekly until adverse reactions abate
- If intolerance persists after dosage adjustment, discontinued
Depression
- Mild: No dosage change; if severity increases after 8 wk, discontinue or decrease dose and consider psychiatric consult
- Moderate: Decrease dose; if severity increases after 8 wk, discontinue permanently and obtain immediate psychiatric consult
- Severe: Discontinue permanently and obtain immediate psychiatric consult
Administration
Administer by SC injection once weekly in abdomen or thigh
Chronic Myelogenous Leukemia (Orphan)
Orphan indication sponsor
- Hoffman-La Roche Inc; 340 Kingsland St; Nutley, NJ 07110-1199
Renal Cell Carcinoma (Orphan)
Orphan indication sponsor
- Hoffman-La Roche Inc; 340 Kingsland St; Nutley, NJ 07110-1199
Pediatric dosage forms and strengths
vial for single use
- 180mcg/mL
prefilled syringe for single use
- 180mcg/0.5mL
autoinjector for single use
- 135mcg/0.5mL
- 180mcg/0.5mL
Chronic Hepatitis C
Indicated in combination with ribavirin for treatment of chronic hepatitis C of children aged ≥5 yr with CHC and compensated liver disease
<5 years: Safety and efficacy not established
≥5 years: 180 mcg/1.73 m² SC qWeek with daily ribavirin
Treatment duration
- Genotypes 2, 3: 24 weeks
- Genotypes 1, 4: 48 weeks
- Patients who initiate treatment prior to their 18th birthday should maintain the recommended pediatric dosage (not the adult dosage) through the completion of therapy
- Refer to ribavirin prescribing information for dose and duration
Dosage modifications
Neutropenia
- ANC 750-999 cells/mm³: Immediately decrease dose to 135 mcg/1.73 m² x BSA (weeks 1-2); no modification if this occurs during weeks 3-48
- ANC 500-749 cells/mm³: Delay or hold treatment until >750 cells/mm³ then resume dose at 135 mcg/1.73 m² x BSA (weeks 1-2) or immediately decrease dose to 135 mcg/1.73 m² x BSA (weeks 3-48)
- ANC 250-499 cells/mm³: Delay or hold treatment until >750 cells/mm³ then resume dose at 90 mcg/1.73 m² x BSA (weeks 1-2) or 135 mcg/1.73 m² x BSA (weeks 3-48)
- ANC <250 cells/mm³ (or febrile neutropenia): Discontinue
Thrombocytopenia
- Platelets <50,000 cells/mm³: Decrease dose to 90 mcg/1.73 m² x BSA SC once weekly
Increased ALt
- ALT ≥5 to <10 xULN: Decrease dose to 135 mcg/1.73 m² x BSA SC once weekly; monitor weekly, reduce dosage further if necessary until stable or ALT level decreases
- Persistent ALT ≥10 x ULN: Discontinue
Depression
- Mild: No dosage change; if severity increases after 8 wk, discontinue or decrease dose and consider psychiatric consult
- Moderate: Decrease dose; if severity increases after 8 wk, discontinue permanently and obtain immediate psychiatric consult
- Severe: Discontinue permanently and obtain immediate psychiatric consult
Administration
Administer by SC injection once weekly in abdomen or thigh
Pegasys (peginterferon alfa 2a) adverse (side) effects
>10%
Fatigue (24% to 67% )
Headache (27% to 54% )
Fever (24% to 54% )
Myalgia (26% to 51% )
Influenza-like illness (25% to 47% )
Rigor (25% to 47% )
Neutropenia (21% to 40% )
Anxiety (19% to 33% )
Feeling nervous (19% to 33% )
Irritability (19% to 33% )
Diarrhea (11% to 31% )
Injection site inflammation (10% to 31% )
Insomnia (19% to 30% )
Arthralgia (22% to 28% )
Alopecia (18% to 28% )
Abdominal pain (8% to 26% )
Nausea and vomiting (5% to 25% )
Loss of appetite (16% to 24% )
Injection site reaction (22% to 23% )
Dizziness (13% to 23% )
Depression (18% to 20% )
Pruritus (12% to 19% )
Dermatitis (8% to 16% )
Weight decreased (4% to 16% )
Lymphocytopenia (Severe) (5% to 14% )
Anemia (2% to 14%)
Lymphocyte count abnormal (3% to 14% )
Dyspnea (4% to 13% )
1-10%
Reduced concentration (8% to 10% )
Cough (4% to 10% )
Dry skin (4% to 10% )
Rash (5% to 8% )
Thrombocytopenia (5% to 8% )
Bacterial infectious disease (3% to 5% )
Severe bacterial infection (1-3%)
<1%
Angina
Cardiac dysrhythmia
Aggressive behavior
Cerebral hemorrhage
Cerebral ischemia
Coma
Drug Abuse
Peripheral neuropathy
Psychotic disorder
Suicide
Diabetes mellitus
Colitis
Gastrointestinal hemorrhage
Pancreatitis
Peptic ulcer disease
Aplastic anemia
Thrombotic thrombocytopenic purpura
Abnormal liver function
Cholangitis
Liver failure
Steatosis of liver
Myositis
Corneal ulcer
Pulmonary embolism
Frequency not defined
Myocardial infarction
Erythroderma (rare)
Stevens-Johnson syndrome (rare)
Hypo/hyperthyroidism
Hypo/hyperglycemia
Anemia (severe)
Cytopenia (severe)
Autoimmune disease (rare)
Hypersensitivity reaction (severe)
Serous retinal detachment
Pulmonary infiltrates
Liver graft rejection and renal graft rejection
Postmarketing Reports
Pure red cell aplasia
Hearing impairment
Hearing loss
Tongue pigmentation
Dehydration
Serious skin reactions
Seizures
Liver graft rejection and renal graft rejection
Warnings
Black box warnings
Alfa interferons cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders
Monitor closely with periodic clinical and laboratory evaluations
Discontinue drug if persistently severe or worsening signs or symptoms of the above conditions are present; disorders typically resolve after stopping therapy
Contraindications
Known hypersensitivity reactions (eg, urticaria, angioedema, bronchoconstriction, anaphylaxis, Stevens-Johnson) syndrome to alpha interferons
Autoimmune hepatitis Hepatic decompensation (Child-Pugh score >6 [class B and C]) in cirrhotic patients before treatment with or without HIV coinfection
Neonates and infants (contains benzyl alcohol); associated with an increased incidence of neurologic and other complications which are sometimes fatal in neonates and infants
When used in combination with other HCV antiviral drugs, the contraindications applicable to those agents are applicable to combination therapies
Combination treatment with ribavirin is contraindicated in women who are pregnant and men whose female partners are pregnant
Cautions
Ribavirin may cause birth defects and/or death of the exposed fetus; patients must avoid pregnancy (female patients or female partners of male patients) while taking PEG-INF-alfa-2a and ribavirin combination therapy
Life-threatening or fatal neuropsychiatric reactions may manifest and include suicide, suicidal ideation, homicidal ideation, depression, relapse of drug addiction, and drug overdose; these reactions may occur with and without history of previous psychiatric illness
Hypertension, supraventricular arrhythmias, chest pain, and myocardial infarction reported; caution with pre-existing cardiovascular disease
Suppresses bone marrow function and may result in severe cytopenias; ribavirin may potentiate the neutropenia and lymphopenia induced by alpha interferons; rare occurrences of aplastic anemia observed
Development or exacerbation of autoimmune disorders including myositis, hepatitis, thrombotic thrombocytopenic purpura, idiopathic thrombocytopenic purpura, psoriasis, rheumatoid arthritis, interstitial nephritis, thyroiditis, and systemic lupus erythematosus reported
May cause or aggravate endocrine disorders including hypothyroidism, hyperthyroidism, hyperglycemia, hypoglycemia, and diabetes mellitus
Alpha interferons may induce or exacerbate ophthalmic disorders including decrease or loss of vision, retinopathy including macular edema, retinal artery or vein thrombosis, retinal hemorrhages and cotton wool spots, optic neuritis, papilledema and serous retinal detachment
Patients with CHC with cirrhosis may be at risk of hepatic decompensation and death when treated with alpha interferons
Exacerbations of hepatitis during hepatitis B therapy are not uncommon and are characterized by transient and potentially severe increases in serum ALt
Dyspnea, pulmonary infiltrates, pneumonia, bronchiolitis obliterans, interstitial pneumonitis, pulmonary hypertension and sarcoidosis, some resulting in respiratory failure and/or patient deaths, may be induced or aggravated by alpha interferons
Serious and severe infections (bacterial, viral, or fungal), some fatal, have been reported during treatment with alpha interferons
Ulcerative and hemorrhagic/ischemic colitis, sometimes fatal, have been observed within 12 weeks of starting alpha interferon treatment
Pancreatitis, sometimes fatal, has occurred during alpha interferon and ribavirin treatment
Severe acute hypersensitivity reactions (eg, urticaria, angioedema, bronchoconstriction, and anaphylaxis) observed
Pediatric patients treated with PEG-INF-alfa-2a plus ribavirin showed a delay in weight and height increases after 48 weeks of therapy compared with baseline; after 2 yr follow-up, most children had returned to baseline normative growth curve percentiles for weight and height
Peripheral neuropathy has been reported when alpha interferons were given in combination with telbivudine
Growth inhibition observed in pediatric subjects 5 -17 years of age receiving peginterferon alfa-2a plus ribavirin thearpy combination for up to 48 weeks
Pregnancy and lactation
Pregnancy category: C (monotherapy); X (with ribavirin)
Lactation: Unknown if distributed in human breast milk; because of the potential for adverse reactions from the drugs in nursing infants, a decision must be made whether to discontinue nursing or discontinue the drug
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.
Pharmacology of Pegasys (peginterferon alfa 2a)
Mechanism of action
Recombinant alfa-2a interferon w/ polyethylene glycol (PEG) side chain
Immunomodulatory cytokine that enhances phagocytic activity of macrophages and cytotoxic activity of lymphocytes for target cells
Pharmacokinetics
Half-Life: 80 hr
Peak Plasma Time: 72-96 hr
Total Body Clearance: 94 mL/hr
Metabolism: Conjugation w/ polyethylene glycol slows metabolism
Enzymes Inhibited: CYP1A2
