Version May 2024
Peginterferon alfa-2a may cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders. Monitor patients closely with periodic clinical and laboratory evaluations. Withdraw therapy in patients with persistently severe or worsening signs or symptoms of these conditions. In many, but not all, cases, these disorders resolve after stopping peginterferon alfa-2a therapy.
Chronic hepatitis B: SUBQ: 180 mcg once weekly for 48 weeks.
Missed dose: If within 2 days of the usual day of administration, administer dose as soon as possible then resume prior schedule; if >2 days after the usual day of administration then contact health care provider.
Essential thrombocythemia, advanced (off-label use): SUBQ: 90 mcg once weekly; adjust dose based on response or tolerance (doses ranged from 45 mcg once every 2 to 4 weeks to 90 mcg once weekly); continue as long as clinically benefiting (Quintás-Cardama 2009; Quintás-Cardama 2013).
Polycythemia vera, advanced (off-label use): SUBQ: 90 mcg once weekly; adjust dose based on response or tolerance (doses ranged from 45 mcg once every 2 to 4 weeks to 180 mcg once weekly); continue as long as clinically benefiting (Kiladjian 2008; Quintás-Cardama 2009; Quintás-Cardama 2013).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
CrCl ≥30 mL/minute: No dosage adjustment required.
CrCl <30 mL/minute: 135 mcg once weekly; monitor for toxicity
End-stage renal disease (ESRD) requiring hemodialysis: 135 mcg once weekly; monitor for toxicity. If severe adverse reactions or laboratory abnormalities occur, may reduce dose to 90 mcg once weekly until adverse reactions resolve; if intolerance persists after dosage adjustment, discontinue.
Hepatic impairment prior to initiation: Contraindicated in autoimmune hepatitis and hepatic decompensation (Child-Pugh >6 [class B and C]) in cirrhotic patients before treatment.
Hepatic impairment during treatment:
Note: Immediately discontinue therapy if hepatic decompensation (Child-Pugh ≥6 [class B and C]) is observed.
HBV:
ALT >5 x ULN: Consider decreasing dose to 135 mcg once weekly or temporarily discontinuing and monitor LFTs more frequently. If ALT continues to rise despite dose reduction or ALT increase is accompanied by increased bilirubin or hepatic decompensation, discontinue therapy immediately. Therapy may resume after ALT flare subsides.
ALT >10 x ULN: Consider discontinuing.
Dosage modifications for adverse reactions and/or toxicity:
HBV:
Based on hematologic parameters:
ANC 500 to <750/mm3: Decrease dose to 135 mcg once weekly.
ANC <500/mm3: Suspend therapy until ANC >1,000/mm3, then restart at 90 mcg once weekly; monitor ANC.
Platelet count 25,000 to <50,000/mm3: Decrease dose to 90 mcg once weekly.
Platelet count <25,000/mm3: Discontinue therapy.
Depression (severity based on DSM-IV criteria):
Mild depression: No dosage adjustment required; evaluate once weekly by visit/phone call. If depression remains stable, continue weekly visits. If depression improves, resume normal visit schedule. For worsening depression, discontinue or reduce dosage to 90 mcg or 135 mcg once weekly. Consider psychiatric consultation.
Moderate depression: Decrease to 90 mcg or 135 mcg once weekly; evaluate once weekly with an office visit at least every other week. If depression remains stable, consider psychiatric evaluation and continue with reduced dosing. If symptoms improve and remain stable for 4 weeks, resume normal visit schedule; continue reduced dosing or return to normal dose. For worsening depression, discontinue permanently and obtain immediate psychiatric consultation.
Severe depression: Discontinue permanently. Obtain immediate psychiatric consultation. Utilize follow-up psychiatric therapy as needed.
Refer to adult dosing.
(For additional information see "Pegylated interferon (peginterferon) alfa-2a: Pediatric drug information")
Chronic hepatitis B (CHB) (hepatitis B e antigen [HBeAg] positive): Children ≥3 years and Adolescents: SubQ: 104 mcg/m2 once weekly; maximum dose: 180 mcg/dose; duration of therapy: 48 weeks. Note: Dosing presented is mathematically equivalent to weekly dosing presented in manufacturer's labeling: 180 mcg/1.73 m2 x Body Surface Area (BSA); adolescents who reach their 18th birthday during treatment should remain on the pediatric regimen.
Chronic hepatitis C (CHC): Note: Although FDA approved in pediatric patients ≥5 years of age, AASLD/IDSA guidelines do not recommend the use of interferon products for the treatment of hepatitis C in children 3 to 11 years (AASLD/IDSA 2018).
Children ≥5 years and Adolescents: SubQ: 104 mcg/m2 once weekly; maximum dose: 180 mcg/dose; in combination with ribavirin (Schwarz 2011); Note: Dosing presented is mathematically equivalent to weekly dosing presented in manufacturer's labeling: 180 mcg/1.73 m2 x BSA; adolescents who reach their 18th birthday during treatment should remain on the pediatric regimen.
Duration of therapy (based on genotype):
HCV genotype 1, 4, 5, 6: 48 weeks
HCV genotype 2, 3: 24 weeks
Note: Pharmacokinetic simulation and modeling (including 14 pediatric and 402 adult patients [accounting for 143 pediatric and 4,020 adult pharmacokinetic observations] from multiple clinical trials) has developed a simplified weight-band dosing for BSA ranges (see the following) to provide similar exposure to the 104 mcg/m2 (180 mcg/1.73 m2) weekly regimen; direct patient experience is lacking (Brennan 2016)
BSA 0.71 to 0.74 m2: 65 mcg/dose
BSA 0.75 to 1.08 m2: 90 mcg/dose
BSA 1.09 to 1.51 m2: 135 mcg/dose
BSA >1.51 m2: 180 mcg/dose
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Dosing adjustment for toxicity: Note: Pediatric dosing adjustments shown below correspond to the following doses in manufacturer's labeling: 78 mcg/m2 = 135 mcg/1.73 m2; 52 mcg/m2 = 90 mcg/1.73 m2; and 26 mcg/m2 = 45 mcg/1.73 m2 (Schwarz 2011).
Depression: CHB, CHC: Children ≥3 years and Adolescents:
Mild depression: No dosage adjustment required; evaluate once weekly by visit/phone call. If depression remains stable, continue weekly visits. If depression improves, resume normal visit schedule. If depression worsens after 8 weeks, consider psychiatric consultation; discontinue therapy or decrease dose to 78 mcg/m2 once weekly or a further dose reduction to 52 mcg/m2 once weekly.
Moderate depression: Decrease dose to 78 mcg/m2 once weekly or a further dose reduction to 52 mcg/m2 once weekly. Evaluate once weekly with an office visit at least every other week. After 8 weeks, if symptoms improve and remain stable for 4 weeks, resume normal visit schedule; may continue reduced dosing or return to normal dose. If depression remains stable, consider psychiatric evaluation and continue reduced dosing. If symptoms worsen, obtain immediate psychiatric consultation and discontinue therapy permanently.
Severe depression: Discontinue interferon treatment permanently. Obtain immediate psychiatric consultation and therapy necessary.
Hematologic toxicity: Note: For CHC, management dependent upon weeks of therapy
Neutropenia:
ANC 750 to 999/mm3:
CHB: Children ≥3 years and Adolescents: No dosage modification.
CHC: Children ≥5 years and Adolescents:
Week 1 to 2: Decrease dose to 78 mcg/m2 once weekly
Weeks 3 to 48: No modification
ANC 500 to 749/mm3:
CHB: Children ≥3 years and Adolescents: Decrease dose to 78 mcg/m2 once weekly
CHC: Children ≥5 years and Adolescents:
Week 1 to 2: Hold dose until ANC >750/mm3 then resume therapy at 78 mcg/m2 once weekly. Assess WBC 3 times weekly to verify ANC >750/mm3.
Weeks 3 to 48: Decrease dose to 78 mcg/m2 once weekly
ANC 250 to 499/mm3:
CHB: Children ≥3 years and Adolescents: Hold dose until ANC ≥1,000/mm3, then resume dose at 52 mcg/m2 once weekly
CHC: Children ≥5 years and Adolescents:
Week 1 to 2: Hold dose until ANC >750/mm3 then resume dose at 52 mcg/m2 once weekly
Weeks 3 to 48: Hold dose until ANC >750/mm3 then resume dose at 78 mcg/m2 once weekly
ANC <250/mm3 or febrile neutropenia: CHB, CHC: Children ≥3 years and Adolescents: Discontinue treatment.
Thrombocytopenia:
Platelet count 25,000 to <50,000/mm3: CHB, CHC: Children ≥3 years and Adolescents: Decrease dose to 52 mcg/m2 once weekly.
Platelet count <25,000: CHB, CHC: Children ≥3 years and Adolescents: Discontinue treatment.
Children and Adolescents: There are no dosage adjustment provided in manufacturer's labeling; has not been studied; based on experience in adult patients, dosing adjustment suggested
Hepatic impairment prior to initiation: Contraindicated in autoimmune hepatitis, hepatic decompensation (Child-Pugh >6 [class B and C]) in cirrhotic patients before treatment, and hepatic decompensation with Child-Pugh ≥6 in cirrhotic HCV patients coinfected with HIV before treatment.
Hepatic impairment during therapy:
Persistent or increasing ALT elevations ≥5 times ULN but <10 times ULN:
CHB: Children ≥3 years and Adolescents: Decrease dose to 78 mcg/m2 once weekly; monitor ALT weekly to ensure stable or decreasing concentrations.
CHC: Children ≥5 years and Adolescents: Decrease dose to 78 mcg/m2once weekly; monitor ALT weekly; further reduce dose if necessary until stable or ALT decreases.
Persistent ALT values ≥10 times ULN: CHB, CHC: Children ≥3 years and Adolescents: Discontinue treatment.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults unless otherwise indicated.
>10%:
Dermatologic: Alopecia (children and adolescents: 6%; adults: 18% to 23%), pruritus (12%)
Endocrine & metabolic: Growth suppression (children and adolescents: decrease >15 percentiles: weight [11% to 29%], height [6% to 18%])
Gastrointestinal: Abdominal pain (children, adolescents, and adults: 15% to 17%), anorexia (16% to 17%), diarrhea (16%), nausea (children and adolescents: 9%; adults: ≤24%), vomiting (children, adolescents, and adults: ≤24%)
Hematologic & oncologic: Neutropenia (severe: 21%)
Hepatic: Increased serum alanine aminotransferase (children and adolescents: 10%; adults: 12% to 27%)
Immunologic: Antibody development (29%; neutralizing: 13%)
Local: Injection-site reaction (22%)
Nervous system: Anxiety (≤19%), asthenia (children and adolescents: 9%; adults: ≤56%), depression (18%), dizziness (children and adolescents: 6%; adults: 16%), fatigue (children and adolescents: 8%; adults: ≤56%), headache (children and adolescents: 21%; adults: 27% to 54%), insomnia (19%), irritability (≤19%), nervousness (≤19%), pain (11%), rigors (35%)
Neuromuscular & skeletal: Arthralgia (28%), myalgia (26% to 37%)
Respiratory: Cough (children and adolescents: 15%; adults: 4%), flu-like symptoms (children and adolescents: 14%)
Miscellaneous: Fever (children, adolescents, and adults: 37% to 54%)
1% to 10%:
Dermatologic: Dermatitis (8%), diaphoresis (6%), eczema (1%), skin rash (children, adolescents, and adults: 5% to 10%), xeroderma (4%)
Endocrine & metabolic: Hypothyroidism (3%), weight loss (4%)
Gastrointestinal: Decreased appetite (children and adolescents: 6%), xerostomia (6%)
Hematologic & oncology: Anemia (severe: 2%), lymphocytopenia (severe: 3%), thrombocytopenia (severe: 5%)
Hepatic: Increased serum aspartate aminotransferase (children and adolescents: 10%)
Nervous system: Lack of concentration (8%), memory impairment (5%), mood changes (3%)
Neuromuscular & skeletal: Back pain (9%)
Ophthalmic: Blurred vision (4%)
Respiratory: Dyspnea (4%; dyspnea on exertion: <1%), epistaxis (children and adolescents: 9%), nasopharyngitis (children and adolescents: 6%), upper respiratory tract infection (children and adolescents: 8%)
<1%: Gastrointestinal: Dyspepsia
Frequency not defined (may include combination with ribavirin):
Cardiovascular: Angina pectoris, cardiac arrhythmia, pulmonary embolism
Endocrine & metabolic: Hyperthyroidism, increased serum triglycerides
Gastrointestinal: Cholangitis, colitis, gastrointestinal hemorrhage, pancreatitis, peptic ulcer
Hematologic & oncologic: Aplastic anemia, thrombotic thrombocytopenic purpura
Hepatic: Liver steatosis
Nervous system: Aggressive behavior, coma, hallucination, lethargy, neurological signs and symptoms (including homicidal ideation, suicidal ideation, suicidal tendencies), peripheral neuropathy, psychiatric disturbance
Neuromuscular & skeletal: Myositis
Ophthalmic: Corneal ulcer
Postmarketing (any population):
Cardiovascular: Acute myocardial infarction, chest pain, hypertension, supraventricular cardiac arrhythmia
Dermatologic: Exfoliative dermatitis, Stevens-Johnson syndrome, vesicobullous reaction
Endocrine & metabolic: Dehydration, diabetes mellitus, hyperglycemia, hypoglycemia
Gastrointestinal: Tongue discoloration
Hematologic & oncologic: Pure red cell aplasia
Immunologic: Autoimmune disease (including rheumatoid arthritis, sarcoidosis, systemic lupus erythematosus), graft rejection (kidney, liver)
Infection: Limb abscess, infection (including bacterial infection, fungal infection, viral infection)
Nervous system: Cerebral ischemia, cerebrovascular hemorrhage, seizure
Ophthalmic: Macular edema, optic neuritis, papilledema, retinal cotton-wool spot, retinal detachment, retinal hemorrhage, retinal thrombosis, retinopathy, vision loss
Otic: Auditory impairment, hearing loss
Hypersensitivity reactions (eg, urticaria, angioedema, bronchoconstriction, anaphylaxis, Stevens-Johnson syndrome) to peginterferon alfa-2a, other alfa interferons, or any component of the formulation; autoimmune hepatitis; hepatic decompensation in cirrhotic patients (Child-Pugh score >6, class B and C) before treatment; hepatic decompensation with Child-Pugh score ≥6 in cirrhotic CHC coinfected with HIV before treatment; neonates and infants (due to benzyl alcohol component)
Combination therapy with peginterferon alfa-2a and ribavirin is also contraindicated in pregnancy; men whose female partners are pregnant; patients with hemoglobinopathies (ie, thalassemia major, sickle cell disease); coadministration with didanosine
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to E. coli-derived products; history of autoimmune disease; severe psychiatric disorder or history of severe psychiatric disorder; uncontrolled thyroid disorder; breastfeeding
Concerns related to adverse effects:
• Bone marrow suppression: Causes bone marrow suppression, including potentially severe cytopenias; alfa interferons may (rarely) cause aplastic anemia. Ribavirin may potentiate these effects. When used in combination with ribavirin, use caution with baseline neutrophil count <1,500/mm3, platelet count <90,000/mm3 or hemoglobin <10 g/dL. Discontinue therapy (at least temporarily) if ANC <500/mm3 or platelet count <25,000/mm3. Severe neutropenia and thrombocytopenia may occur with a greater incidence in HIV coinfected patients than monoinfected patients. Obtain CBC before treatment and monitor routinely during therapy.
• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery or driving).
• Dermatologic effects: Serious cutaneous reactions, including vesiculobullous eruptions, Stevens-Johnson syndrome, and exfoliative dermatitis, have been reported with use, with or without ribavirin therapy; discontinue with signs or symptoms of severe skin reactions.
• Gastrointestinal effects: Gastrointestinal hemorrhage, ulcerative and hemorrhagic/ischemic colitis (may be fatal) have been observed with interferon alfa treatment; may be severe and/or life-threatening; discontinue immediately if symptoms of colitis (eg, abdominal pain, bloody diarrhea, and/or fever) develop. Colitis generally resolves within 1 to 3 weeks of discontinuation.
• Hepatic effects: Hepatic decompensation and death have been associated with the use of alpha interferons including Pegasys, in cirrhotic chronic hepatitis C patients; patients coinfected with HIV and receiving antiretroviral therapy have shown an increased risk. Monitor hepatic function closely during use; discontinue immediately if decompensation occurs (Child-Pugh score >6) in monoinfected patients and (Child-Pugh score ≥6, class B and C) in patients coinfected with HIV. Instruct patients to avoid alcohol; may increase hepatic effects.
• Hypersensitivity reactions: Severe acute hypersensitivity reactions (eg, urticaria, angioedema, bronchoconstriction, anaphylaxis) have been reported; prompt discontinuation and management is recommended.
• Neuropsychiatric disorders: [US Boxed Warning]: May cause or exacerbate life-threatening neuropsychiatric disorders; monitor closely; discontinue treatment with worsening or persistently severe signs/symptoms of neuropsychiatric disorders. In most cases these effects were reversible following discontinuation, but not all cases. Neuropsychiatric adverse effects include depression, suicidal ideation, suicide attempt, homicidal ideation, drug overdose, and relapse of drug addiction, and may occur in patients with or without a prior history of psychiatric disorder. Avoid use in severe psychiatric disorders; use with extreme caution in patients with a history of depression.
• Ophthalmic effects: Decreased or loss of vision and retinopathy, including macular edema, optic neuritis, papilledema, retinal hemorrhages, retinal detachment (serous), cotton wool spots, and retinal artery or vein thrombosis, may occur or be aggravated during treatment; if any ocular symptoms occur during use, a complete eye exam should be performed promptly. Prior to use, all patients should have a visual exam and patients with preexisting disorders (eg, diabetic or hypertensive retinopathy) should have exams periodically during therapy. Discontinue if new or worsening ophthalmologic disorders occur.
• Pancreatitis: Pancreatitis, including fatal cases, has been observed with alfa interferon and ribavirin therapy. Withhold treatment for suspected pancreatitis; discontinue therapy for confirmed pancreatitis.
• Pulmonary effects: May cause or aggravate dyspnea, pulmonary infiltrates, pneumonia, bronchiolitis obliterans, interstitial pneumonitis, pulmonary hypertension, and sarcoidosis, which may result in potentially fatal respiratory failure; may recur upon rechallenge with interferons. Monitor closely. Discontinue with pulmonary infiltrates or evidence of impaired pulmonary function. Use with caution in patients with pulmonary dysfunction or a history of pulmonary disease.
Disease-related concerns:
• Autoimmune disease: [US Boxed Warning]: May cause or exacerbate autoimmune disorders; monitor closely; discontinue treatment in patients with worsening or persistently severe signs/symptoms of autoimmune disease. In most cases these effects were reversible following discontinuation, but not all cases. Thyroiditis, thrombotic thrombocytopenic purpura, immune thrombocytopenia (formerly known as idiopathic thrombocytopenic purpura), rheumatoid arthritis, interstitial nephritis, systemic lupus erythematosus, myositis, hepatitis, and psoriasis have been reported with interferon therapy; use with caution in patients with autoimmune disorders.
• Cardiovascular disease: Use with caution in patients with prior cardiovascular disease; hypertension, supraventricular arrhythmias, chest pain, and MI have been observed with treatment. Patients with a history of significant or unstable cardiac disease should not receive combination treatment with ribavirin.
• Diabetes: Use with caution in patients with diabetes mellitus; hyper/hypoglycemia have been reported; may require adjustments in antidiabetic medications; discontinue if unable to effectively manage diabetes with medication.
• Hepatitis B: In hepatitis B patients, flares (transient and potentially severe increases in serum ALT) may occur during or after treatment; more frequent monitoring of LFTs and a dose reduction are recommended. Discontinue immediately if ALT elevation continues despite dose reduction or if increased bilirubin or hepatic decompensation occur.
• Infectious disorders: [US Boxed Warning]: May cause or aggravate infectious disorders; monitor closely; discontinue treatment in patients with worsening or persistently severe signs/symptoms of infectious disorders. In most cases these effects were reversible following discontinuation, but not all cases. Serious and severe infections (bacterial, viral, and fungal), some fatal, have been reported with treatment. Interferon therapy is commonly associated with flu-like symptoms, including fever; rule out other causes/infection with persistent or high fever.
• Ischemic disorders: [US Boxed Warning]: May cause or aggravate ischemic disorders and hemorrhagic cerebrovascular events; monitor closely; discontinue treatment in patients with worsening or persistent ischemia. In most cases these effects were reversible following discontinuation, but not all cases. Has been reported in patients without risk factors for stroke.
• Renal impairment: Use with caution in patients with renal dysfunction (CrCl <30 mL/minute); dosage adjustment recommended; monitor for signs/symptoms of toxicity (dosage adjustment required if toxicity occurs).
• Seizure disorders: Clinical practice chronic hepatitis B treatment guidelines do not recommend use in patients with uncontrolled seizures (AASLD [Terrault 2016]).
• Thyroid disorders: Use with caution in patients with preexisting thyroid disease; thyroid disorders (hyper- or hypothyroidism) or exacerbations have been reported; discontinue if unable to effectively manage with medication.
Special populations:
• Older adult: Use with caution in the elderly; certain adverse effects (eg, neuropsychiatric, cardiac, flu-like reactions) may be more severe.
• Pediatric: Growth velocity (height and weight) was decreased in children with or without combination treatment with ribavirin, during the length of treatment. In clinical studies, decreases were noted in weight and height for age z-scores and normative growth curve percentiles. Following treatment, rebound growth and weight gain occurred in most patients; however, a small percentage did not. For most children with hepatitis C, posttreatment recovery in growth at 2 years posttreatment was maintained to 6 years posttreatment. In children with hepatitis B at 5 years posttreatment, the percentage of children with a decrease of more than 15 percentiles from baseline was 29% for weight and 18% for height. Growth should be closely monitored in children during therapy and posttreatment until growth catch-up has occurred.
Dosage form specific issues:
• Benzyl alcohol and derivatives: Some dosage forms may contain benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol with caution in neonates. See manufacturer's labeling.
• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.
• Product variability: Due to differences in dosage, patients should not change brands of interferon without the concurrence of their health care provider.
Other warnings/precautions:
• Appropriate use: Hepatitis B: Hepatitis B genotypes A and B are more likely to achieve HBeAg and HBsAg loss with peg-interferon than non-A/B genotypes. For patients with hepatitis B coinfected with hepatitis delta virus, pegylated interferon is the only effective therapy (AASLD [Terrault 2016]).
Inhibition of growth velocity in pediatric patients may occur; in clinical trials, growth suppression of ≥15 percentiles on the normal growth curve was reported for weight in 43% of pediatric patients and for height in 25% of patients after 48 weeks of therapy. At the two-year follow-up after treatment, most children had returned to their baseline growth curve percentile; monitor growth at baseline and during therapy.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, Subcutaneous:
Pegasys: 180 mcg/mL (1 mL) [contains benzyl alcohol, polysorbate 80]
Solution, Subcutaneous [preservative free]:
Pegasys ProClick: 180 mcg/0.5 mL (0.5 mL [DSC]) [contains benzyl alcohol, polysorbate 80]
Solution Prefilled Syringe, Subcutaneous:
Pegasys: 180 mcg/0.5 mL (0.5 mL) [contains benzyl alcohol, polysorbate 80]
Solution Prefilled Syringe, Subcutaneous [preservative free]:
Pegasys: 180 mcg/0.5 mL (0.5 mL [DSC]) [contains benzyl alcohol, polysorbate 80]
No
Solution (Pegasys Subcutaneous)
180 mcg/mL (per mL): $1,336.10
Solution Prefilled Syringe (Pegasys Subcutaneous)
180 mcg/0.5 mL (per 0.5 mL): $1,336.11
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Subcutaneous:
Pegasys: 180 mcg/0.5 mL (0.5 mL) [contains benzyl alcohol, polysorbate 80]
SubQ: Administer in the abdomen or thigh. Rotate injection site. Administration should be done on the same day and at approximately the same time each week.
SubQ: Do not shake vial, prefilled syringe, or autoinjector. For pediatric doses, the 180 mcg/mL vial should be used and doses withdrawn using a 1 mL tuberculin syringe. Allow syringe, autoinjector, or vial to reach room temperature before use. The vial may be warmed by gently rolling in the palms of the hand for ~1 minute. Allow the autoinjector to come to room temperature on its own for ~20 minutes; do not warm autoinjector any other way. Lay the prefilled syringe on a flat clean service and wait ~3 minutes, allowing it to reach room temperature; if condensation water remains on the outside of the syringe, let syringe set until it disappears.
Administer SubQ in the abdomen or thigh. Rotate injection site. Discard unused solution. Administration should be done on the same day and at approximately the same time each week.
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Pegasys: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/103964s5276lbl.pdf#page=37
Chronic hepatitis B: Treatment of adults with hepatitis B e antigen (HBeAg)-positive and HBeAg-negative chronic hepatitis B virus (HBV) infection who have compensated liver disease and evidence of viral replication and liver inflammation; treatment of pediatric patients ≥3 years of age with HBeAg-positive chronic HBV infection who are non-cirrhotic and have evidence of viral replication and elevations of serum alanine aminotransferase.
Essential thrombocythemia, advanced; Polycythemia vera, advanced
Inhibits CYP1A2 (weak)
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Aldesleukin: Interferons (Alfa) may enhance the adverse/toxic effect of Aldesleukin. In particular, risks of myocardial and renal toxicity may be increased by this combination. Management: Consider using lower doses to minimize toxicity of this combination. Only coadminister aldesleukin and interferons (alfa) in patients in whom potential benefits outweigh the risk of severe toxicity. Monitor renal and cardiac function closely if combined. Risk D: Consider therapy modification
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy
Chloramphenicol (Systemic): Myelosuppressive Agents may enhance the myelosuppressive effect of Chloramphenicol (Systemic). Risk X: Avoid combination
Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy
CloZAPine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of CloZAPine. Risk C: Monitor therapy
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider therapy modification
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination
Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination
Fezolinetant: CYP1A2 Inhibitors (Weak) may increase the serum concentration of Fezolinetant. Risk X: Avoid combination
Fluorouracil Products: Interferons (Alfa) may increase the serum concentration of Fluorouracil Products. Risk C: Monitor therapy
Methadone: Interferons (Alfa) may increase the serum concentration of Methadone. Risk C: Monitor therapy
Olaparib: Myelosuppressive Agents may enhance the myelosuppressive effect of Olaparib. Risk C: Monitor therapy
Pegloticase: May diminish the therapeutic effect of PEGylated Drug Products. Risk C: Monitor therapy
Pegvaliase: PEGylated Drug Products may enhance the adverse/toxic effect of Pegvaliase. Specifically, the risk of anaphylaxis or hypersensitivity reactions may be increased. Risk C: Monitor therapy
Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Ribavirin (Oral Inhalation): Interferons (Alfa) may enhance the adverse/toxic effect of Ribavirin (Oral Inhalation). Hemolytic anemia has been observed. Risk C: Monitor therapy
Ribavirin (Systemic): Interferons (Alfa) may enhance the adverse/toxic effect of Ribavirin (Systemic). Hemolytic anemia has been observed. Risk C: Monitor therapy
Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider therapy modification
Telbivudine: Peginterferon Alfa-2a may enhance the adverse/toxic effect of Telbivudine. Specifically, the risk for peripheral neuropathy may be increased. Risk X: Avoid combination
Theophylline Derivatives: CYP1A2 Inhibitors (Weak) may increase the serum concentration of Theophylline Derivatives. Risk C: Monitor therapy
TiZANidine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of TiZANidine. Management: Avoid these combinations when possible. If combined use is necessary, initiate tizanidine at an adult dose of 2 mg and increase in 2 to 4 mg increments based on patient response. Monitor for increased effects of tizanidine, including adverse reactions. Risk D: Consider therapy modification
Vitamin K Antagonists (eg, warfarin): Interferons (Alfa) may enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy
Zidovudine: Interferons may enhance the adverse/toxic effect of Zidovudine. Interferons may decrease the metabolism of Zidovudine. Risk C: Monitor therapy
Verify pregnancy status prior to administration in patients who could become pregnant. Disruption of the normal menstrual cycle was observed in animal studies. Patients who could become pregnant should use effective contraception during treatment.
If used in combination with ribavirin, all warnings related to the use of ribavirin and contraception should be followed. Refer to the ribavirin monograph for additional information.
Alfa interferon is endogenous to normal amniotic fluid (Lebon 1982); however, placenta perfusion studies note exogenous interferon alfa does not cross the placenta (Waysbort 1993). The US Department of Health and Human Services perinatal HIV guidelines recommend against the use of peginterferon-alfa during pregnancy because of its antigrowth and antiproliferative effects (HHS [perinatal] 2023). Animal reproduction studies have demonstrated abortifacient effects.
Peginterferon alfa-2a in combination with ribavirin is contraindicated in pregnant patients or patients whose partners are pregnant. Combination therapy with ribavirin may cause birth defects and death in an unborn child. All warnings related to the use of ribavirin and pregnancy should be followed. Refer to the ribavirin monograph for additional information.
Interferon alfa is endogenous to breast milk. Breast milk samples obtained from a lactating mother prior to and after administration of interferon alfa-2b showed that interferon alfa is present in breast milk and administration of the medication did not significantly affect endogenous levels (Kumar 2000).
Due to the potential for serious adverse reactions in the breastfed infant, the manufacturer recommends a decision be made to discontinue breastfeeding or to discontinue the drug, considering the importance of treatment to the mother.
Manufacturer's labeling:
Clinical studies tested as follows:
Pediatric patients: Hematologic and biochemical assessments were made at weeks 1, 3, 5, and 8, and then every 4 weeks thereafter; TSH measured every 12 weeks.
Adults: CBC (including hemoglobin, WBC, and platelets) and chemistries (including liver function tests and uric acid) measured at weeks 1, 2, 4, 6, and 8, and then every 4-6 weeks (more frequently if abnormal); TSH measured every 12 weeks.
In addition, the following baseline values were used as entrance criteria in adults:
Platelet count ≥90,000/mm3 (as low as 75,000/mm3 in patients with cirrhosis).
ANC ≥1,500/mm3
Serum creatinine <1.5 times ULN
TSH and T4 within normal limits or adequately controlled
CD4+ cell count ≥200 cells/mm3 or CD4+ cell count ≥100 cells/mm3
Prior to treatment, pregnancy screening should occur for women of childbearing age who are receiving treatment or who have male partners who are receiving treatment. In combination therapy with ribavirin, pregnancy tests should continue monthly up to 6 months after discontinuation of therapy. Evaluate for depression and other psychiatric symptoms before and during therapy; baseline eye examination and periodically in patients with baseline disorders; baseline echocardiogram in patients with cardiac disease. In children, growth velocity and weight should be monitored during and periodically after combination therapy is discontinued.
Alternate recommendations ( AASLD [Terrault 2016] ): Chronic Hepatitis B:
During therapy: CBC (monthly to every 3 months); TSH (every 3 months); monitor for autoimmune, ischemic, neuropsychiatric, and infectious complications.
Alpha interferons are a family of proteins, produced by nucleated cells that have antiviral, antiproliferative, and immune-regulating activity. There are 16 known subtypes of alpha interferons. Interferons interact with cells through high affinity cell surface receptors. Following activation, multiple effects can be detected including induction of gene transcription. Interferons inhibit cellular growth, alter the state of cellular differentiation, interfere with oncogene expression, alter cell surface antigen expression, increase phagocytic activity of macrophages, and augment cytotoxicity of lymphocytes for target cells.
Half-life elimination: Terminal: 50-160 hours; increased with renal dysfunction
Time to peak, serum: 72 to 96 hours
Altered kidney function: Clearance is decreased 43% in patients with severe renal impairment (CrCl <30 mL/minute).
Pediatric: Clearance was nearly 4-fold lower in children 2 to 8 years of age.
Older adult: AUC is increased in patients >62 years of age.
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