Peginterferon Alfa (Antiviral) (Monograph)

Brand name: Pegasys
Drug class: Interferons

Introduction

Antiviral agent; contains interferon alfa (recombinant DNA origin) covalently bound to monomethoxy polyethylene glycol (PEG).

Uses for Peginterferon Alfa (Antiviral)

Chronic HBV Infection

Treatment of adults with hepatitis B e antigen (HBeAg)-positive or HBeAg-negative chronic HBV infection who have compensated liver disease and evidence of viral replication and liver inflammation.

Treatment of HBeAg-positive chronic HBV infection in non-cirrhotic pediatric patients ≥3 years of age with evidence of viral replication and elevations in serum ALT.

Efficacy and safety notestablished in patients with HBV coinfected with HCV or HIV.

The American Association for the Study of Liver Diseases (AASLD) has published guidelines for management of chronic HBV infection. The guidelines strongly recommend antiviral therapy in adults with immune-active chronic HBV infection (HBeAg negative or HBeAg positive) to decrease the risk of liver-related complications. Drugs of choice for initial treatment include peginterferon alfa, entecavir, tenofovir disoproxil fumarate (TDF), or tenofovir alafenamide (TAF).

Treatment of chronic HBV infection is complex and rapidly evolving; consult AASLD guidelines for the most updated information.

Chronic HCV Infection

Treatment of chronic HCV infection in adults and pediatric patients ≥5 years of age with compensated liver disease; used in conjunction with other hepatitis C antiviral agents in adults and in combination with ribavirin in pediatric patients ≥5 years of age.

Peginterferon alfa-2a monotherapy is only indicated for the treatment of patients with chronic HCV and compensated liver disease if there are contraindications or significant intolerance to other HCV antiviral drugs.

Peginterferon alfa-2a alone or in combination with ribavirin without additional HCV antiviral drugs is not recommended for treatment of patients with chronic HCV infection who previously failed therapy with an interferon-alfa.

Not recommended for treatment of chronic HCV infection in patients with solid organ transplants.

Also has been used in multiple-drug regimens for the treatment of chronic HCV infection in patients coinfected with HIV. However, guidance no longer recommends use of peginterferon-containing regimens to treat HCV infection, including in patients with HIV.

The Infectious Diseases Society of America (IDSA) and the American Association for the Study of Liver Diseases (AASLD) have published joint guidelines for the management of HCV infection. The guidelines strongly recommend universal treatment with direct-acting antiviral (DAA) drugs in most patients with acute or chronic HCV infection. Although peginterferon alfa has been used in conjunction with ribavirin in drug regimens that include an HCV DAA, peginterferon alfa is no longer recommended in the 2023 AASLD guidelines as part of an initial treatment regimen for HCV infection due to inferior efficacy rates compared with other DAA regimens.

Treatment of chronic HCV infection is complex and rapidly evolving; consult the AASLD and IDSA joint guidelines for the most updated information.

Acute HCV Infection

Has been used for treatment of acute HCV infection^{† [off-label]} in an attempt to prevent progression to chronic HCV infection; used alone or in conjunction with oral ribavirin.

Patients with acute HCV infection have higher treatment response rates than those with chronic HCV infection, and treatment of the acute infection can reduce risk that the disease will evolve to chronic infection.

Treat patients with acute HCV infection upon initial diagnosis without awaiting spontaneous resolution.

To date, there are insufficient data to support a particular regimen or treatment duration outside of a clinical trial. Because of their high efficacy and safety, the same regimens that are recommended for chronic HCV infection are recommended for acute HCV infection. Consultation with a specialist is advised to obtain the most up-to-date information regarding the treatment of acute HCV infection.

Hepatitis E Virus (HEV) Infection

Has been used alone or in conjunction with ribavirin for treatment of chronic HEV infection^{† [off-label]}.

Chronic HEV infection reported almost exclusively among immunocompromised individuals, including solid organ transplant recipients, patients receiving cancer chemotherapy, and HIV patients. Optimal treatment of chronic HEV infection not identified.

Peginterferon Alfa (Antiviral) Dosage and Administration

General

Pretreatment Screening

• Question patients regarding prior history of drug abuse.

• Perform baseline ophthalmologic examination.

• Screen all patients for HIV.

• Perform standard hematological (i.e., complete blood count) and biochemical laboratory tests; evaluate liver and renal function.

• Perform pregnancy testing for women of childbearing potential.

• Perform ECG in patients with preexisting cardiac abnormalities (when used in combination with ribavirin).

Patient Monitoring

• Perform hematologic testing at 2 and 4 weeks and biochemical testing at 4 weeks. Additional testing should be performed periodically during therapy.

• Closely monitor hepatic function and clinical status during therapy. Monitor renal function.

• Monitor all patients for evidence of depression and other psychiatric symptoms.

• Monitor patients closely for the development or aggravation of existing autoimmune, ischemic, and infectious disorders.

• In patients with preexisting ophthalmologic disorders (e.g., diabetic or hypertensive retinopathy), perform periodic ophthalmologic examinations during therapy.

• In women of childbearing potential, perform pregnancy testing monthly during combination therapy and for 6 months after discontinuing therapy.

Administration

Administer by sub-Q injection once weekly.

Administer into thigh or abdomen. Avoid areas of the navel and waistline. Rotate injection sites.

May be self-administered if the clinician determines that the patient and/or their caregiver are competent to prepare and safely administer the drug after appropriate training and with medical follow-up as necessary.

Carefully instruct patients and/or caregivers who administer peginterferon alfa-2a in the home setting on proper administration of the drug (including aseptic techniques) and safe disposal of syringes and needles.

Allow the vial and prefilled syringe to reach room temperature and for condensation on the outside of the prefilled syringe to disappear before administration; do not shake.

Solution should be clear and colorless to light yellow; do not use if solution is discolored or cloudy or if particulates are present.

Vials and prefilled syringes are for single-use only; discard any unused portions.

Dosage

Pediatric Patients

Treatment of Chronic HBV Infection

Peginterferon Alfa-2a (Pegasys)

Sub-Q

Children ≥3 years of age: 180 mcg/1.73 m² × BSA once weekly (maximum dose of 180 mcg). Recommended treatment duration is 48 weeks.

Maintain recommended pediatric dosage through the entire duration of therapy in patients who turn 18 years of age during therapy.

Treatment of Chronic HCV Infection

Concomitant Peginterferon Alfa-2a (Pegasys) and Oral Ribavirin

Sub-Q

Children ≥5 years of age: 180 mcg/1.73 m² × BSA once weekly (maximum dose of 180 mcg) in conjunction with oral ribavirin.

Recommended treatment duration is 24 weeks for HCV genotype 2 or 3 and 48 weeks for other HCV genotypes.

Patients who initiate treatment prior to their 18th birthday should maintain the recommended pediatric dosage (not the adult dosage) through the completion of therapy

Adults

Treatment of Chronic HBV Infection

Peginterferon Alfa-2a (Pegasys)

Sub-Q

180 mcg once weekly for 48 weeks.

Treatment of Chronic HCV Infection without HIV Coinfection

Peginterferon Alfa-2a (Pegasys) and Concomitant Antiviral Treatment

Sub-Q

Adults with HCV monoinfection (without coexisting HIV infection): 180 mcg once weekly in conjunction with other HCV antiviral agents. Recommended treatment duration depends on HCV genotype. (See Table 1.)

If peginterferon alfa-2a is used in combination with other antiviral drugs for chronic HCV infection, 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.

If peginterferon alfa-2a and ribavirin are used without other HCV antiviral drugs, the recommended duration of therapy is 48 weeks.

If peginterferon alfa-2a and ribavirin are used without other HCV antiviral drugs, the recommended duration of therapy is 24 weeks.

For treatment of HCV genotype 1 with peginterferon alfa-2a in combination with ribavirin or alone, discontinuance of therapy is recommended if HCV RNA levels have not decreased ≥2 log₁₀ from baseline at week 12 or are still detectable after 24 weeks of treatment.

Peginterferon Alfa-2a (Pegasys) Monotherapy

Sub-Q

180 mcg once weekly for 48 weeks.

Use monotherapy only if there are contraindications or significant intolerance to other HCV antiviral drugs.

Treatment of Chronic HCV Infection with HIV Coinfection

Peginterferon Alfa-2a (Pegasys) and Concomitant Antiviral Treatment

Sub-Q

180 mcg subcutaneously once weekly.

If peginterferon alfa-2a is used in combination with other antiviral drugs, refer to the prescribing information of the other HCV antiviral drugs for the recommended dosage and duration of the entire treatment regimen (including peginterferon alfa-2a).

If peginterferon alfa-2a and ribavirin are used without other HCV antiviral drugs, the recommended duration of therapy is 48 weeks (regardless of HCV genotype).

Treatment of Acute HCV Infection† [off-label]

Peginterferon Alfa-2a (Pegasys)

Sub-Q

Some experts recommend 180 mcg once weekly for 24 weeks.

Treat upon initial diagnosis without awaiting spontaneous resolution. Pangenotypic regimens are recommended if HCV genotyping is unavailable or if concern of exposure to more than 1 genotype exists. Using the same regimens to treat acute/recent HCV as for chronic HCV infection also simplifies management, as defining acute HCV may be clinically challenging.

If response not obtained, some experts recommend retreatment with standard of care for chronic HCV infection.

Dosage Modification for Toxicity

Adjust dosage of peginterferon alfa-2a in patients who develop adverse neuropsychiatric (i.e., depression) or hematologic effects, or other serious adverse effects or laboratory abnormalities.

Depression

If mild depression occurs in an adult or pediatric patient receiving peginterferon alfa-2a, continue usual dosage of the drug, but evaluate patient once weekly (by office visit and/or phone) during the initial 4–8 weeks. After 8 weeks of therapy, if depression severity remains stable, continue weekly evaluations. If depression severity worsens, consider psychiatric consultation and discontinue peginterferon alfa-2a or reduce dosage to 135 mcg in adults (135 mg/1.73 m² × BSA for pediatric patients) or 90 mcg once weekly for adults (90 mcg/1.73 m² × BSA for pediatric patients).

If moderate depression develops, reduce dosage of the drug to 135 mcg in adults (135 mg/1.73 m² × BSA for pediatric patients) or 90 mcg in adults (90 mcg/1.73 m² × BSA for pediatric patients) once weekly and evaluate patient once weekly (office visit at least every other week). After 8 weeks of therapy, if depression severity remains stable, consider psychiatric consultation and continue reduced dosing. If symptoms improve with the reduced dosage and remain stable for 4 weeks, resume normal visit schedule and continue reduced dosage or increase to usual dosage. If depression severity worsens, obtain immediate psychiatric consultation and permanently discontinue peginterferon alfa-2a.

If severe depression develops, permanently discontinue peginterferon alfa-2a and obtain immediate psychiatric consultation; psychiatric therapy is necessary.

Hematologic Effects

Decrease dosage of peginterferon alfa-2a to 135 mcg once weekly in adults with an ANC of 500 to <750 cells/mm³. If ANC is <500 cells/mm³, discontinue peginterferon alfa-2a until ANC >1000 cells/mm³; resume the drug at a dosage of 90 mcg once weekly with ANC monitoring. Decrease peginterferon alfa-2a dosage to 90 mcg once weekly in adults with platelet counts of 25,000 to <50,000 cells/mm³, but discontinue therapy in those with platelet counts <25,000 cells/mm³. Consult manufacturer's prescribing information for more specific recommendations regarding dosage modification for hematologic effects.

If a pediatric patient receiving peginterferon alfa-2a develops neutropenia (ANC <1000 cells/mm³) or decreased platelet counts (<50,000 cells/mm³), dosage modification or discontinuance of therapy may be recommended depending on severity of hematologic effect and type of hepatitis being treated. Consult manufacturer's prescribing information for more specific recommendations regarding dosage modification for hematologic effects.

Special Populations

Hepatic Impairment

When used for treatment of chronic HBV infection in adults with elevated plasma ALT concentrations (>5 times ULN), monitor hepatic function more frequently and consider either reducing dosage to 135 mcg once weekly or temporarily discontinuing treatment. Resume treatment after ALT flares subside. If ALT increases are persistent or severe (>10 times ULN), consider discontinuance of treatment. If ALT increases are progressive despite dosage reduction or are accompanied by increased bilirubin concentrations or evidence of hepatic decompensation, discontinue peginterferon alfa-2a therapy immediately.

When used for treatment of chronic HCV infection in adults with progressive ALT increases above baseline values, reduce dosage to 135 mcg once weekly and monitor hepatic function more frequently. Resume treatment after ALT flares subside. If ALT increases are progressive despite dosage reduction or are accompanied by increased bilirubin concentrations or evidence of hepatic decompensation, discontinue peginterferon alfa-2a immediately.

In pediatric patients with chronic HBV infection, modify dosage to 135 mcg/1.73 m²x BSA if persistent or increasing elevations of ALT are ≥5, but <10 times the ULN. Monitor weekly ALT level to ensure it is stable or decreasing. If persistent ALT ≥10 times the ULN occurs, discontinue treatment.

In pediatric patients with chronic HCV infection, modify dosage to 135 mcg/1.73 m²x BSA if persistent or increasing elevations of ALT are ≥5, but <10 times the ULN. Monitor weekly, reduce dosage further if necessary, until stable or ALT level decreases. If persistent ALT ≥10 times the ULN occurs, discontinue treatment.

Renal Impairment

When peginterferon alfa-2a is used in adults, those with Cl_crof 30–50 mL/minute can receive the usual dosage of 180 mcg once weekly, but reduce dosage to 135 mcg once weekly in those with Cl_cr <30 mL/minute, including those with end-stage renal disease requiring hemodialysis.

May reduce dosage in adults to 90 mcg once weekly if severe adverse reactions or laboratory abnormalities occur until adverse reactions abate; if intolerance persists, discontinue the drug. Dosage recommendations for peginterferon alfa-2a in pediatric patients with renal impairment are not available.

Geriatric Patients

Select dosage with caution because of age-related decreases in renal function.

Cautions for Peginterferon Alfa (Antiviral)

Contraindications

• Known hypersensitivity reactions (e.g., urticaria, angioedema, bronchoconstriction, anaphylaxis, Stevens-Johnson syndrome) to interferon alfas, including peginterferon alfa-2a, or any ingredient in the formulation.

• Autoimmune hepatitis.

• Hepatic decompensation (Child-Pugh score >6, class B and C) in cirrhotic patients prior to treatment.

• Hepatic decompensation (Child-Pugh score ≥6) in cirrhotic patients with chronic HCV infection who are coinfected with HIV prior to treatment.

• Use in neonates and infants (this preparation contains benzyl alcohol).

• When used in combination with other HCV antivirals, the contraindications applicable to those agents are applicable to combination therapy.

• Concomitant use of ribavirin and peginterferon alfa-2a is contraindicated in women who are pregnant and men whose female partners are pregnant.

Warnings/Precautions

Warnings

Risk of Serious Disorders

May cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders. (See Boxed Warning.)

Monitor closely with periodic clinical and laboratory evaluations; discontinue therapy in patients with persistently severe or worsening signs or symptoms of these disorders.

Other Warnings/Precautions

Pregnancy: Use with Ribavirin

Ribavirin may cause birth defects and/or fetal death. Female patients or female partners of male patients must avoid pregnancy while taking peginterferon alfa-2a and ribavirin combination therapy. Do not initiate ribavirin therapy unless a confirmed negative pregnancy test has been obtained immediately prior to initiation of therapy. Women of childbearing potential and male partners of females of childbearing potential must use 2 forms of effective contraception during treatment and for at least 6 months after treatment has concluded. Perform routine monthly pregnancy tests during this time.

Neuropsychiatric Reactions

Life-threatening or fatal neuropsychiatric reactions (e.g., suicide, suicidal and homicidal ideation, depression, relapse of drug addiction, drug overdose) may occur in patients receiving peginterferon alfa-2a therapy. These reactions can occur in patients with and without previous psychiatric illness. Neuropsychiatric adverse events observed with interferon alfas include aggressive behavior, psychoses, hallucinations, bipolar diorder, and mania.

Use with extreme caution in any patient with a history of depression. Monitor all patients receiving the drug for evidence of depression and other psychiatric symptoms. Advise patients to report any sign or symptom of depression or suicidal ideation to their clinician. In severe cases, therapy should be immediately discontinued and psychiatric intervention instituted.

Cardiovascular Disorders

Hypertension, supraventricular arrhythmia, chest pain, and MI reported.

Use with caution in patients with preexisting cardiovascular disease.

Because cardiac disease may be worsened by ribavirin-associated anemia, patients with a history of clinically important or unstable cardiac disease should not receive oral ribavirin in combination with peginterferon alfa-2a.

Myelosuppression

Suppresses bone marrow function and may cause severe cytopenias; aplastic anemia reported rarely. Concomitant oral ribavirin may potentiate neutropenia and lymphopenia induced by alfa interferons, including peginterferon alfa-2a.

Severe thrombocytopenia and neutropenia occur more frequently in patients coinfected with HIV than in those not coinfected with HIV; serious infections or bleeding may occur.

Use concomitant peginterferon alfa-2a and oral ribavirin with caution in patients with baseline neutrophil counts <1500 cells/mm³, baseline platelet counts <90,000 cells/mm³, or baseline hemoglobin <10 g/dL.

Perform CBCs prior to and routinely during therapy. Adjust dosage or discontinue drug if necessary.

Autoimmune Disease

Development or exacerbation of autoimmune disease (e.g., thyroiditis, thrombotic or idiopathic thrombocytopenic purpura, rheumatoid arthritis, myositis, interstitial nephritis, hepatitis, systemic lupus erythematosus, psoriasis) reported.

Use peginterferon alfa-2a with caution in patients with autoimmune disorders.

Endocrine and Metabolic Effects

May cause or aggravate hypothyroidism or hyperthyroidism. Hyperglycemia, hypoglycemia, and diabetes mellitus also reported.

Patients with hypothyroidism, hyperthyroidism, or diabetes mellitus at baseline whose disease cannot be effectively treated with medication should not receive peginterferon alfa-2a.

If these conditions develop during peginterferon alfa-2a therapy and cannot be effectively controlled with pharmacologic therapy, drug discontinuance may be necessary.

Ocular Effects

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 are induced or aggravated by peginterferon alfa-2a or other interferon alfa preparations.

Perform baseline ophthalmologic examination in all patients prior to initiation of peginterferon alfa-2a therapy. Perform ophthalmologic examinations periodically during treatment in those with preexisting ophthalmologic disorders (e.g., diabetic or hypertensive retinopathy).

Perform prompt and complete eye examination in any patient who develops ocular symptoms.

Discontinue peginterferon alfa-2a in patients who develop new or worsening ophthalmologic disorders.

Cerebrovascular Disorders

Ischemic and hemorrhagic cerebrovascular events reported with alfa interferons, including peginterferon alfa-2a. Such events have occurred in patients with few or no reported risk factors for stroke, including patients <45 years of age. Estimates of frequency and causal relationship not established.

Hepatic Failure and Hepatitis Exacerbations

Patients with chronic HCV infection and cirrhosis may be at risk of hepatic decompensation and death during interferon alfa (including peginterferon alfa-2a) therapy. Cirrhotic HCV patients coinfected with HIV receiving highly active antiretroviral therapy (HAART) in conjunction with interferon alfa therapy (with or without oral ribavirin) appear to be at increased risk for development of hepatic decompensation compared with patients not receiving HAART. In reported cases, patients were receiving HAART that included nucleoside reverse transcriptase inhibitors (abacavir, didanosine, lamivudine, zidovudine).

Closely monitor clinical status and hepatic function during therapy. Immediately discontinue peginterferon alfa-2a and ribavirin if hepatic decompensation (Child-Pugh score ≥6) occurs.

Patients with chronic HBV infection may experience HBV exacerbations (characterized by transient and potentially severe increases in ALT) during treatment. Marked transaminase flares during peginterferon alfa-2a treatment have been accompanied by other liver test abnormalities. If ALT flares occur, monitor liver function more frequently and consider dosage reduction. Immediately discontinue treatment if ALT increases are progressive despite dosage reduction or are accompanied by increased bilirubin concentrations or evidence of hepatic decompensation.

Pulmonary Effects

May aggravate or induce potentially severe and life-threatening dyspnea, pneumonia, bronchiolitis obliterans, pulmonary infiltrates, interstitial pneumonitis, pulmonary hypertension, and sarcoidosis.

Discontinue peginterferon alfa-2a combination therapy in patients who develop pulmonary infiltrates or pulmonary function impairment. Recurrence of respiratory failure has occurred with interferon rechallenge; closely monitor patients who resume peginterferon alfa-2a therapy.

Infectious Complications

Serious and severe infections (bacterial, viral, fungal), including some fatalities, reported in patients treated with alfa interferons, including peginterferon alfa-2a.

While fever may be associated with the flu-like syndrome commonly reported during interferon therapy, rule out other causes of high or persistent fever, particularly in patients with neutropenia.

Initiate appropriate anti-infective therapy immediately and consider discontinuing peginterferon alfa-2a in patients who develop severe infections.

Colitis

Ulcerative and hemorrhagic/ischemic colitis, sometimes fatal, reported within 12 weeks of initiation of interferon alfa treatment.

Discontinue peginterferon alfa-2a immediately in patients who develop signs and symptoms of colitis (e.g., abdominal pain, bloody diarrhea, fever); colitis usually resolves within 1–3 weeks after discontinuance of interferon alfa therapy.

Pancreatitis

Pancreatitis, sometimes fatal, has occurred in patients receiving interferon alfa and ribavirin therapy.

Discontinue peginterferon alfa-2a and ribavirin in patients with signs and symptoms suggestive of pancreatitis; permanently discontinue the drugs if diagnosis of pancreatitis is established.

Hypersensitivity

Serious acute hypersensitivity reactions (e.g., urticaria, angioedema, bronchoconstriction, anaphylaxis) reported during interferon alfa and ribavirin therapy. If such a reaction occurs, discontinue peginterferon alfa-2a and ribavirin and provide appropriate medical treatment immediately.

Serious dermatologic reactions, including vesiculobullous eruptions, reactions in the spectrum of Stevens-Johnson syndrome (erythema multiforme major) with varying degrees of skin and mucosal involvement, and exfoliative dermatitis (erythroderma), reported in patients receiving peginterferon alfa-2a with and without ribavirin. Discontinue therapy if signs or symptoms of severe skin reactions occur.

Immunogenicity

Neutralizing antibodies may develop in patients receiving alfa interferons, including peginterferon alfa-2a.

Clinical and pathologic importance of development of serum neutralizing antibodies unknown. No apparent correlation of antibody development to clinical response or adverse events.

Organ Transplant Recipients

As with other alfa interferons, liver and renal graft rejections have been reported when peginterferon alfa-2a was used in organ transplant recipients.

Safety and efficacy not established in patients with liver or other transplants.

Specific Populations

Pregnancy

No adequate and well-controlled studies of peginterferon alfa-2a to inform a drug-associated risk. Based on animal reproduction studies, can cause fetal harm and assumed to have abortifacient potential.

Combination treatment with ribavirin is contraindicated in pregnant women and in the male partners of women who are pregnant as significant teratogenic and/or embryocidal effects have been demonstrated in all animal species exposed to ribavirin.

Lactation

Not known whether peginterferon alfa-2a is distributed into human milk. Effects of the drug on breastfed infants and on milk production also not known. Consider the developmental and health benefits of breastfeeding along with the mother's clinical need for peginterferon alfa-2a and any potential adverse effects on the breastfed child from the drug or underlying maternal condition.

Females and Males of Reproductive Potential

Females of reproductive potential must undergo pregnancy testing before initiation of treatment with peginterferon alfa-2a alone or in combination with ribavirin or with other HCV drugs. Females of reproductive potential and female partners of male patients receiving peginterferon alfa-2a in combination with ribavirin must have a routine pregnancy test performed monthly during treatment and for at least 6 months following treatment.

Peginterferon alfa-2a can cause disruption of the menstrual cycle based on its mechanism of action and studies in female monkeys. No female fertility study performed.

Advise females of reproductive potential to use effective contraception during peginterferon alfa-2a therapy (without ribavirin). Female patients and female partners of male patients must avoid pregnancy while taking peginterferon alfa-2a and ribavirin. Advise females of reproductive potential and their male partners to use 2 forms of effective contraception during combined interferon alfa-2a and ribavirin therapy and for at least 6 months after the last dose.

Pediatric Use

Efficacy and safety established for treatment of chronic HCV infection in pediatric patients 5 to 17 years of age and treatment of chronic HBV infection in pediatric patients 3 to 17 years of age.

Adverse effects reported in pediatric patients generally similar to those reported in adults. In addition, growth inhibition (delay in weight and height increases compared with baseline) reported in pediatric patients receiving peginterferon alfa-2a and oral ribavirin for chronic HCV infection and peginterferon alfa-2a for chronic HBV infection.

Contraindicated in neonates and infants; each vial contains 10 mg and each prefilled syringe contains 5 mg of benzyl alcohol as a preservative. Although a causal relationship has not been established, administration of injections preserved with benzyl alcohol has been associated with toxicity (e.g., neurologic) in neonates and infants, which is sometimes fatal.

Geriatric Use

Younger patients have higher virologic response rates than older patients. Experience in patients ≥65 years of age insufficient to determine whether they respond differently than younger adults.

Adverse reactions related to alfa interferons, such as CNS, cardiac, and systemic (e.g., flu-like) effects, may be more severe in geriatric patients than in younger adults. Use with caution.

Because geriatric patients may have decreased renal function and because patients with renal impairment may be at increased risk of drug-induced toxicity, carefully select dosage and consider monitoring renal function. Reduce dosage if Cl_cr <30 mL/minute.

Hepatic Impairment

Chronic HBV patients may be at risk for transient acute exacerbations (flares) of HBV infection.

Chronic HCV patients with cirrhosis may be at risk of hepatic decompensation and death. Closely monitor clinical status and hepatic function; immediately discontinue treatment if decompensation (Child-Pugh score ≥6) occurs.

If elevated plasma ALT concentrations occur, monitor hepatic function more frequently; consider dosage adjustments or discontinuance of therapy, if necessary.

Renal Impairment

Use with caution and close clinical and laboratory monitoring (particularly for Cl_crand decreased hemoglobin) in patients with any degree of renal impairment.

Dosage adjustment required if Cl_cr <30 mL/minute. Data not available regarding use in pediatric patients with renal impairment.

Common Adverse Effects

Common adverse effects in adults (>40%): Fatigue/asthenia, pyrexia, myalgia, headache.

Common adverse effects observed in pediatric patients are similar to those reported in adults.

Drug Interactions

Drugs Metabolized by Hepatic Microsomal Enzymes

Inhibits CYP1A2. Potential pharmacokinetic interactions with drugs metabolized by CYP1A2; interactions unlikely with drugs metabolized by CYP isoenzymes 2C9, 2C19, 2D6, or 3A4.

Specific Drugs

Peginterferon Alfa (Antiviral) Pharmacokinetics

Absorption

Bioavailability

Peak serum concentrations occur 72–96 hours following sub-Q administration. In adults receiving doses of 90–270 mcg, there is a nonlinear, dose-related increase in peak serum concentrations and AUC. With once-weekly dosing, steady-state serum concentrations attained within 5–8 weeks.

Special Populations

Children 2–8 years of age with HCV infection: Time to reach steady-state serum concentrations is approximately 12 weeks. Steady-state trough concentrations in children receiving BSA-adjusted dosing are similar to those in adults, but AUC values predicted to be 25–70% higher than those reported in adults receiving fixed doses of 180 mcg.

Pediatric patients with HBV infection: AUC values in pediatric patients receiving BSA-adjusted dosing are comparable to AUC values in adults receiving 180-mcg doses.

Adults >62 years of age: Peak serum concentrations similar to those in adults <62 years of age, but AUC increased compared with those <62 years of age receiving 180-mcg doses.

Distribution

Extent

Not known whether peginterferon alfa-2a is distributed into human milk.

Elimination

Half-life

Mean terminal half-life after sub-Q dosing in HCV patients is 160 hours (range: 84–353 hours).

Stability

Storage

Parenteral

Injection

Vials or prefilled syringes (Pegasys): 2–8°C; do not leave out of refrigerator for >24 hours. Protect from light; do not freeze or shake. For single use only; discard any unused portion.

Actions and Spectrum

• Covalent conjugate of recombinant alfa-2a interferon with a single branched bis-monomethoxy polyethylene glycol (PEG) chain.

• Induces the innate antiviral immune response by binding to the human type 1 interferon receptor and initiating a sequence of intracellular events (receptor dimerization, activation of multiple intracellular signal transduction pathways initially mediated by the JAK/STAT pathway).

Advice to Patients

• Advise patients to read the FDA-approved patient labeling (Medication Guide and Instructions for Use).

• Patients receiving peginterferon alfa-2a alone or in combination with an approved HCV antiviral drug should be directed in its appropriate use, informed of the benefits and risks associated with treatment, and referred to FDA-approved patient labeling.

• Inform patients that ribavirin must not be used by women who are pregnant or by men whose female partners are pregnant. Ribavirin therapy should not be initiated until a report of a negative pregnancy test has been obtained immediately before starting therapy. Advise female patients of childbearing potential and male patients with female partners of childbearing potential of the fetal risks and instruct these patients to use 2 forms of effective contraception during ribavirin therapy and for 6 months after treatment discontinuation. Routine monthly pregnancy tests must be performed during this time.

• Advise patients to notify their healthcare provider immediately in the event of a pregnancy. To monitor maternal and fetal outcomes of pregnant women exposed to ribavirin, the Ribavirin Pregnancy Registry has been established. Patients should be encouraged to register by calling 1-800-593-2214.

• Inform patients that flu-like symptoms (e.g., tiredness, weakness, fever, chills, muscle aches, joint pain, headache) are very common with therapy. Also inform patients that some of these symptoms may be decreased by injecting peginterferon alfa-2a in the evening. Inform patients which over-the-counter (OTC) medicines can be taken to help prevent or decrease symptoms.

• Advise patients that laboratory evaluations are required before starting therapy and periodically thereafter. Instruct patients to remain well hydrated, especially during the initial stages of treatment.

• Question patients about prior history of drug abuse before initiating peginterferon alfa-2a as relapse of drug addiction and drug overdoses have been reported in patients treated with interferons.

• Inform patients that it is not known if therapy with peginterferon alfa-2a will prevent transmission of hepatitis B infection to others or prevent cirrhosis, liver failure, or liver cancer that might result from hepatitis B virus infection.

• Inform patients that the effect of treatment of hepatitis C infection on transmission is not known, and that appropriate precautions to prevent transmission of the hepatitis C virus during treatment or in the event of treatment failure should be taken.

• Caution patients who develop dizziness, confusion, somnolence, and fatigue to avoid driving or operating machinery.

• Advise patients to avoid drinking alcohol to reduce the chance of further injury to the liver.

• Advise patients not to switch to another brand of interferon without consulting their healthcare provider.

• Advise patients to take their prescribed dose on the same day and at approximately the same time each week. Advise patients that if they miss a dose, but remember within 2 days, to take their missed dose as soon as they remember and then to take their next dose on the day they normally do. If they remember when more than 2 days have passed, advise patients to consult their healthcare provider. Patients should also be advised to consult their healthcare provider if the full dose is not received (e.g., leakage around the injection site).

• Instruct patients on preparation and administration of peginterferon alfa-2a, including aseptic technique. Appropriate training for preparation using the vial and prefilled syringe must be given by a healthcare provider.

• Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.

• Inform patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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