Class: Interferons
VA Class: AM800
Brands: Pegasys, PEG-Intron
May cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders.1 20 Patients should be closely monitored with periodic clinical and laboratory evaluations.1 20 Discontinue peginterferon alfa in patients with persistently severe or worsening signs or symptoms of these conditions.1 20 In many, but not all cases, these disorders resolve after the drug is discontinued.1 20
Concomitant use of ribavirin: ribavirin may cause birth defects and/or death of the fetus.1 20 Extreme care must be used to avoid pregnancy in females and in female partners of male patients.1 20 Ribavirin causes hemolytic anemia; this may result in worsening of cardiac disease.1 20 Ribavirin is genotoxic and mutagenic and should be considered a potential carcinogen.1 20
REMS:
FDA approved a REMS for peginterferon alfa to ensure that the benefits of a drug outweigh the risks. The REMS may apply to one or more preparations of peginterferon alfa and consists of the following: medication guide. See the FDA REMS page () or the ASHP REMS Resource Center ().
Introduction
Antiviral agent; contains interferon alfa (recombinant DNA origin) covalently bound to polyethylene glycol (PEG) monomethoxy ether.1 20 Available as peginterferon alfa-2a and peginterferon alfa-2b.1 20
Uses for Peginterferon Alfa
Chronic Hepatitis C Virus (HCV) Infection
Treatment of chronic HCV infection in adults with compensated liver disease; used alone or, preferably, in conjunction with oral ribavirin.1 3 7 10 15 20
Although peginterferon alfa has been effective when used alone in patients with compensated liver disease and histologic evidence of cirrhosis (Child-Pugh class A),20 28 higher rates of sustained virologic response and lower rates of relapse are achieved when used in conjunction with oral ribavirin.3 15
Peginterferon alfa in conjunction with oral ribavirin is considered the treatment of choice for treatment-naive patients (have not previously received interferon alfa therapy) and for previously treated patients† who fail to achieve a sustained virologic response following treatment with nonconjugated interferon alfa alone or in conjunction with oral ribavirin.3 15 16 18
Safety and efficacy of peginterferon alfa alone or in conjunction with oral ribavirin not established for treatment of chronic HCV infection in patients with advanced liver disease, patients coinfected with hepatitis B virus (HBV) infection, or in liver or other organ transplant recipients.1 20
Peginterferon alfa-2a (Pegasys) alone or in conjunction with oral ribavirin (Copegus) has been effective for treatment of chronic HCV infection in certain adults coinfected with HIV (i.e., those with stable HIV infection receiving stable antiretroviral therapy or antiretroviral therapy not required).20
Safety and efficacy of peginterferon alfa-2a (Pegasys) alone or in conjunction with oral ribavirin not established for treatment of chronic HCV infection in patients coinfected with HIV who have CD4+ T-cell counts <100/mm3.20 Safety and efficacy of peginterferon alfa-2b (PEG-Intron) used in conjunction with ribavirin not established in those with HCV and HIV coinfection.1
Treatment of chronic HCV infection is complex and rapidly evolving; a specialist should be consulted to obtain the most up-to-date information regarding patient selection criteria and preferred regimens.3 12
Peginterferon Alfa Dosage and Administration
General
Duration of Treatment of Chronic Hepatitis C Virus (HCV) Infection
Optimal duration of concomitant therapy with peginterferon alfa and oral ribavirin not established.3 19
HCV monoinfection: Some clinicians state that duration of therapy should depend on both the patient’s HCV genotype and baseline serum HCV RNA levels.3 19 These clinicians recommend a 24-week regimen for patients with HCV genotype 1 and baseline HCV RNA levels <2 million copies/mL, a 24-week regimen for those with HCV genotype 2 or 3 (regardless of their baseline serum HCV RNA levels), and a 48-week regimen for those with genotype 1 infections and baseline HCV RNA levels >2 million copies/mL.3 19 In one clinical study, sustained virologic response rates for patients with genotypes 2 and 3 were similar following 24 or 48 weeks of concomitant therapy with peginterferon alfa-2a and oral ribavirin, regardless of baseline HCV RNA levels.20
HCV monoinfection: Manufacturer of peginterferon alfa-2a (Pegasys) recommends a 48-week regimen for patients with HCV genotypes 1 or 4 and a 24-week regimen for those with HCV genotypes 2 or 3.20 This manufacturer and some clinicians recommend that discontinuance of therapy be considered after 12–24 weeks if there is no evidence of an early virologic response (i.e., undetectable HCV RNA levels or ≥2 log10 reduction in HCV RNA titer by 12 weeks).16 19 20
Manufacturer of peginterferon alfa-2b (PEG-Intron) recommends discontinuance of therapy if HCV RNA levels remain high after 6 months of PEG-Intron used with or without ribavirin.1
Safety and efficacy of peginterferon alfa therapy given for >48–52 weeks not established.1 20
Administration
Peginterferon alfa-2a (Pegasys) and peginterferon alfa-2b (PEG-Intron) are administered by sub-Q injection once weekly.1 20 When ribavirin is used concomitantly, ribavirin is given orally with food.1 20
Peginterferon alfa-2a and peginterferon alfa-2b 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.1 20
Patients and/or their caregivers who administer peginterferon alfa in a home setting should be carefully instructed in the proper administration of the drug (including aseptic techniques), cautioned against reuse of syringes and needles, and supplied with a puncture-resistant container for proper, safe disposal of such equipment (with instructions on proper disposal of full containers).1 20
Sub-Q Administration
Peginterferon Alfa-2a (Pegasys)
Peginterferon alfa-2a is administered undiluted.20 Vials and prefilled syringes are for single-use only; any unused portions should be discarded.20
Peginterferon Alfa-2b (PEG-Intron)
Peginterferon alfa-2b lyophilized powder for injection must be reconstituted prior to administration using only sterile water for injection provided by the manufacturer.1
Redipen prefilled dual-chamber cartridge containing lyophilized peginterferon alfa-2b and sterile water for injection: Hold upright and press the 2 halves together according to manufacturer’s directions.1 Gently invert to mix; do not shake.1 Attach the needle provided and calibrate dose according to manufacturer’s directions.1
Vials: Slowly add 0.7 mL of sterile water diluent provided by the manufacturer and gently swirl vial.1 No other drugs should be added to reconstituted solution.1
Dosage
Because there are differences in the potencies and in recommended dosages between the commercially available peginterferon alfa preparations, it is recommended that the peginterferon alfa preparation selected for the patient be used throughout the treatment regimen.20 Patients should be cautioned not to change brands of peginterferon alfa without consulting their clinician.20
Dosage of peginterferon alfa and/or ribavirin should be adjusted in patients who develop adverse neuropsychiatric (i.e., depression) or hematologic effects.1 20 (See Special Populations under Dosage and Administration.) If serious adverse effects or laboratory abnormalities occur during concomitant peginterferon alfa and oral ribavirin therapy, the dosage of one or both drugs should be modified or therapy discontinued, if appropriate, until the adverse reactions abate.1 20 If intolerance persists after dosage adjustments, both peginterferon alfa and oral ribavirin should be discontinued.20
Adults
Treatment of Chronic Hepatitis C Virus (HCV) Infection
Concomitant Therapy with Peginterferon Alfa-2a (Pegasys) and Ribavirin
Sub-Q
Adults with HCV monoinfection (without coexisting HIV infection): 180 mcg once weekly in conjunction with oral ribavirin (800 mg–1.2 g daily, depending on HCV genotype).20 29 (See Table.)
HCV Genotype | Pegasys Dosage | Ribavirin Dosage | Duration |
|---|---|---|---|
1,4 | 180 mcg | 500 mg twice daily in those weighing <75 kg or 600 mg twice daily in those weighing ≥75 kg | 48 weeks |
2,3 | 180 mcg | 400 mg twice daily | 24 weeks |
5,6 | Data insufficient to make dosage recommendations | Data insufficient to make dosage recommendations |
Adults with HCV and HIV coinfection: 180 mcg once weekly in conjunction with oral ribavirin (800 mg daily in 2 doses) for 48 weeks, regardless of HCV genotype.20
Concomitant Therapy with Peginterferon Alfa-2b (PEG-Intron) and Ribavirin
Sub-Q
1.5 mcg/kg once weekly1 3 in conjunction with oral ribavirin (400 mg twice daily).1 3 30
The appropriate volume of reconstituted PEG-Intron to be administered in conjunction with oral ribavirin is based on the solution strength used and the patient’s weight as suggested in the following table, and may be adjusted according to the patient’s response and tolerance.1
Redipen or Vial Strength (mcg per 0.5 mL) | Weight (kg) | Once Weekly Dose (mcg) | Volume of PEG-Intron to Administer (mL) |
|---|---|---|---|
50 | <40 | 50 | 0.5 |
80 | 40–50 | 64 | 0.4 |
80 | 51–60 | 80 | 0.5 |
120 | 61–75 | 96 | 0.4 |
120 | 76–85 | 120 | 0.5 |
150 | >85 | 150 | 0.5 |
Monotherapy with Peginterferon Alfa-2a (Pegasys)
Sub-Q
Adults with monoinfection (without coexisting HIV infection): 180 mcg once weekly for 48 weeks.20
Adults with HIV coinfection: 180 mcg once weekly for 48 weeks.20
Monotherapy with Peginterferon Alfa-2b (PEG-Intron)
Sub-Q
1 mcg/kg once weekly for 1 year.1 The appropriate volume of reconstituted peginterferon alfa-2b is based on the solution strength used and the patient’s weight as suggested in the following table, and may be adjusted according to the patient’s response and tolerance.1
Redipen or Vial Strength (mcg per 0.5 mL) | Weight (kg) | Once Weekly Dose (mcg) | Volume of PEG-Intron to Administer (mL) |
|---|---|---|---|
50 | ≤45 | 40 | 0.4 |
50 | 46–56 | 50 | 0.5 |
80 | 57–72 | 64 | 0.4 |
80 | 73–88 | 80 | 0.5 |
120 | 89–106 | 96 | 0.4 |
120 | 107–136 | 120 | 0.5 |
150 | 137–160 | 150 | 0.5 |
Special Populations
Hepatic Impairment
Treatment of Chronic Hepatitis C Virus (HCV) Infection
Peginterferon Alfa-2a (Pegasys)
Sub-Q
In patients with progressive ALT increases above baseline values, decrease Pegasys dosage to 135 mcg once weekly.20 If increases in ALT concentrations progress despite dosage reduction or are accompanied by increased bilirubin or evidence of hepatic decompensation, immediately discontinue the drug.20
Renal Impairment
Treatment of Chronic Hepatitis C Virus (HCV) Infection
Peginterferon Alfa-2a (Pegasys)
Sub-Q
Patients with end-stage renal disease requiring hemodialysis: Reduce dosage to 135 mcg once weekly.20 Monitor closely for signs and symptoms of interferon toxicity.20
Peginterferon Alfa-2b (PEG-Intron)
Sub-Q
Patients with moderate renal impairment (Clcr 30–50 mL/minute): Reduce dosage by 25%.1
Patients with severe renal impairment (Clcr10–29 mL/minute): Reduce dosage by 50%.1
Discontinue if renal function decreases during treatment.1
Geriatric Patients
Cautious dosage selection because of age-related decreases in renal function.20 (See Renal Impairment under Dosage and Administration.) Use peginterferon alfa with caution in those with Clcr <50 mL/minute; concomitant oral ribavirin should not be used in those with Clcr <50 mL/minute.1 20
Patients Who Develop Depression during Treatment
In patients who develop mild mental depression, usual dosage of Pegasys or PEG-Intron may be continued if the patient is evaluated once weekly (by office visit and/or phone).1 20
If a patient develops moderate depression, dosage should be reduced and the patient evaluated once weekly (office visit at least every other week).1 20 If a patient develops moderate depression while receiving Pegasys, reduce dosage to 135 mcg daily (a reduction to 90 mcg daily may be needed in some cases).20 If the patient develops moderate depression while receiving PEG-Intron, reduce dosage by 50% for at least 4–8 weeks.1 If symptoms improve with the reduced dosage and remain stable for 4 weeks, reduced dosage can be continued or dosage can be increased to the usual dosage.1 20
If a patient develops severe depression, permanently discontinue Pegasys or PEG-Intron and provide immediate psychiatric consultation.1 20
Patients Who Develop Hematologic Effects during Therapy
Dosage of Pegasys should be decreased to 135 mcg once weekly in patients with ANC <750/mm3;20 withhold the drug in those with ANC <500/mm3.20 If ANC increases to >1000/mm3,20 Pegasys may be resumed at a dosage of 90 mcg once weekly with close monitoring.20 If platelet counts decrease to <50,000/mm3, reduce Pegasys dosage to 90 mcg once weekly;20 discontinue the drug in those with platelet counts <25,000/mm3.20
Although usual dosage of Pegasys can be continued in patients with abnormal decreases in hemoglobin concentrations, concomitant oral ribavirin dosage should be decreased to 600 mg daily (200 mg every morning and 400 every evening) if hemoglobin concentrations decrease to <10 g/dL in patients with no preexisting cardiovascular disease or if hemoglobin concentrations decrease by ≥2 g/dL during any 4-week period in patients with a history of stable cardiovascular disease.20 29 Concomitant oral ribavirin should be permanently discontinued if hemoglobin concentrations decrease to <8.5 g/dL in patients with no preexisting cardiovascular disease or if hemoglobin concentrations fall to <12 g/dL after 4 weeks of reduced ribavirin dosage in patients with a history of stable cardiovascular disease.20
Dosage of PEG-Intron should be decreased by 50% in patients who have leukocyte counts <1500/mm3, neutrophil counts <750/mm3, or platelet counts <80,000/mm3; usual dosage of oral ribavirin can be continued in these patients.1 In those with hemoglobin concentrations <10 g/dL, usual dosage of PEG-Intron can be continued but oral ribavirin dosage should be decreased by 200 mg daily.1 Both peginterferon alfa-2b and oral ribavirin should be permanently discontinued in patients who have hemoglobin concentrations <8.5 g/dL, leukocyte counts <1000/mm3, neutrophil counts <500/mm3, or platelet counts <50,000/mm3.1 For patients with preexisting stable cardiovascular disease, PEG-Intron dosage should be decreased by 50% and ribavirin dosage decreased by 200 mg daily if hemoglobin concentrations decrease more than 2 g/dL during any 4-week period; both drugs should be permanently discontinued if hemoglobin concentrations fall to <12 g/dL after 4 weeks of such reduced dosages.1
Cautions for Peginterferon Alfa
Contraindications
Hypersensitivity to peginterferon alfa or any ingredient in the formulation.1 20
Autoimmune hepatitis.1 20
Use of peginterferon alfa-2a (Pegasys) in cirrhotic patients with chronic HCV monoinfection (without coexisting HIV infection) who have hepatic decompensation (Child-Pugh score >6; class B and C) prior to or during treatment.20
Use of peginterferon alfa-2a (Pegasys) in cirrhotic patients with chronic HCV infection who are coinfected with HIV and have hepatic decompensation (Child-Pugh score ≥6) prior to or during treatment.20
Use of peginterferon alfa-2a (Pegasys) in neonates and infants (this preparation contains benzyl alcohol).20
Use of concomitant ribavirin in pregnant women; men whose female partners are pregnant; patients with hemoglobinopathies (e.g., thalassemia major, sickle-cell anemia); patients with Clcr <50 mL/minute; or known hypersensitivity to ribavirin or any ingredient in the formulation.1
Warnings/Precautions
Warnings
Concomitant Oral Ribavirin
The usual cautions, precautions, and contraindications associated with oral ribavirin therapy should be observed when the drug is used concomitantly with peginterferon alfa.1 20
Ribavirin may cause fetal harm; if oral ribavirin is used in conjunction with peginterferon alfa, extreme care must be taken to avoid pregnancy in female patients and in female partners of male patients.1 20
Consider that the primary toxicity of ribavirin is hemolytic anemia, that the drug may potentiate neutropenia induced by peginterferon alfa, and can result in worsening of cardiac disease.1 20
Neuropsychiatric Effects
Potentially fatal neuropsychiatric events (suicide, suicidal and homicidal ideation, depression, relapse of drug addiction/overdose, aggressive behavior) have occurred during and after peginterferon alfa therapy in patients with and without a previous psychiatric disorder.1 20
Use with extreme caution in patients with a history of psychiatric disorders.1 20 Monitor all patients for evidence of depression and other psychiatric symptoms.1 20
Dosage reduction recommended in patients who develop mild or moderate depression while receiving the drug.1 (See Patients Who Develop Depression During Therapy under Dosage and Administration.)
Discontinue immediately and provide appropriate psychiatric intervention if severe depression and/or other psychiatric conditions (e.g., psychoses, hallucinations, bipolar disorder, mania) occur.1 20
Infectious Complications
Serious bacterial infections, including some fatalities, have been observed in patients treated with alfa interferons including peginterferon alfa-2a.20 Some of these may have been related to neutropenia induced by the drug.20
Discontinue peginterferon alfa in patients who develop severe infection and institute appropriate anti-infectives.20
Myelosuppression
Thrombocytopenia and neutropenia are dose-limiting toxicities.1 20 Severe cytopenias may occur; aplastic anemia has been reported rarely.1 20 Concomitant oral ribavirin may potentiate neutropenia and lymphopenia induced by interferon alfa.1 20
Severe thrombocytopenia and neutropenia occurs more frequently in patients coinfected with chronic HCV and HIV than in those not coinfected with HIV and may result in serious infections or bleeding.20
Perform CBCs prior to and routinely during peginterferon alfa therapy.1 20 Adjust dosage or discontinue drug if necessary.1 20 (See Patients Who Develop Hematologic Effects During Therapy under Dosage and Administration.)
Use with caution in patients with baseline neutrophil counts <1500/mm3, with baseline platelet counts <90,000/mm3, baseline hemoglobin <10 g/dL, or a baseline risk of severe anemia (e.g., spherocytosis, history of GI bleeding).20
Cardiovascular Effects
Clinically important cardiovascular effects (e.g., hypotension, arrhythmia, tachycardia, cardiomyopathy, angina pectoris, and myocardial infarction) may occur.1 20
Patients with preexisting cardiac abnormalities should receive ECGs before initiation of therapy.1 20 Use with caution and with close monitoring in those with a history of myocardial infarction and arrhythmic disorders.1 20
Patients with a history of clinically important or unstable cardiac disease should not receive concomitant oral ribavirin.1 20
Hepatic Failure
Patients with chronic HCV infection and cirrhosis may be at risk of hepatic decompensation and death during interferon alfa (including peginterferon alfa) therapy.20 Such patients who are coinfected with HIV and receiving highly active antiretroviral therapy (HAART) in conjunction with interferon alfa-2a therapy (with or without ribavirin) appear to be at increased risk for development of hepatic decompensation compared with patients not receiving HAART.20
Closely monitor clinical status and hepatic function.20 Immediately discontinue peginterferon alfa if decompensation (Child-Pugh score ≥6) occurs.20
Endocrine and Metabolic Effects
Thyroid dysfunction (e.g., hypothyroidism, hyperthyroidism) and hyperglycemia have occurred.1 20 Patients with hypothyroidism, hyperthyroidism, or diabetes mellitus whose disease cannot be effectively treated should not receive peginterferon alfa.1 20
Autoimmune Disease
Development or exacerbation of autoimmune disease (e.g., thyroiditis, thrombocytopenia, rheumatoid arthritis, interstitial nephritis, systemic lupus erythematosus, psoriasis) has been reported.1 20
Use with caution in patients with preexisting autoimmune disorders.1 20
Pulmonary Effects
Potentially life-threatening dyspnea, pneumonia, bronchiolitis obliterans, pulmonary infiltrates, interstitial pneumonitis, and sarcoidosis have been reported.1 20
Discontinue peginterferon alfa and oral ribavirin therapy in patients who develop pulmonary infiltrates or pulmonary function impairment.1 20 Recurrence of respiratory failure has occurred with interferon rechallenge, and patients should be closely monitored if therapy is resumed.1
Ulcerative and Hemorrhagic Colitis
Potentially life-threatening ulcerative and hemorrhagic/ischemic colitis has been observed within 12 weeks of initiation of interferon alfa treatment.1 20
Discontinue immediately in patients who develop signs and symptoms of colitis (e.g., abdominal pain, bloody diarrhea, fever); colitis usually resolves within 1–3 weeks of discontinuance of interferon alfa therapy.1 20
Pancreatitis
Potentially life-threatening pancreatitis has occurred in patients receiving interferon alfa therapy.1 20
Discontinue in patients with suspected pancreatitis; permanently discontinue if diagnosis of pancreatitis is established.1 20
Ocular Effects
Decrease or loss of vision, retinal artery or vein thrombosis, retinal hemorrhages and cotton-wool spots, optic neuritis, and papilledema are induced or aggravated by peginterferon alfa or other interferon alfa preparations.1 20
Perform baseline ophthalmologic examinations prior to initiation of peginterferon alfa therapy and periodically thereafter in patients with preexisting ophthalmologic disorders (e.g. diabetic or hypertensive retinopathy).1 20 Any patient who develops ocular symptoms should receive a prompt and complete eye examination.1 20
Discontinue therapy in patients who develop new or worsening ophthalmologic disorders.1 20
Sensitivity Reactions
Hypersensitivity Reactions
Serious acute hypersensitivity reactions (urticaria, angioedema, bronchoconstriction, anaphylaxis) and cutaneous eruptions (Stevens-Johnson syndrome, toxic epidermal necrolysis) have been observed rarely with interferon alfa with or without concomitant oral ribavirin.1 20
If a hypersensitivity reaction occurs, discontinue peginterferon alfa and oral ribavirin immediately and provide appropriate supportive and symptomatic care.1 20 Transient rash does not necessitate interruption of treatment.1
General Precautions
Laboratory Monitoring
Assess organ system functions, including renal, hepatic, and hematopoietic, prior to and during peginterferon alfa therapy (with or without concomitant oral ribavirin).1 20
Periodically monitor triglyceride concentrations.1
In clinical studies, CBCs and chemistries (liver function tests, uric acid) were measured at 1, 2, 4, 6, and 8 weeks or 2, 4, 8, or 12 weeks after initiation of therapy and then every 4-6 weeks or more frequently if abnormalities were found.1 20 In addition, TSH was measured every 12 weeks.1 20
Pregnancy screening tests should be performed in all women of childbearing potential prior to initiation of treatment; in those receiving concomitant oral ribavirin, pregnancy tests should be repeated once monthly during and for 6 months after discontinuing therapy.1 20
Antibody Formation
As with other interferon alfa therapies, neutralizing antibodies may develop in patients receiving peginterferon alfa.1 20
Specific Populations
Pregnancy
Category C when used alone.1 20 Category X when used with ribavirin.1 20
Pregnancy registry at 800-593-2214 to monitor pregnancy outcomes of female patients and female partners of male patients exposed to ribavirin.1 20 29 30
Lactation
Not known whether peginterferon alfa is distributed into milk.1 20 Discontinue nursing or the drug.1 20
Pediatric Use
Safety and efficacy not established in children <18 years of age.1 20
Peginterferon alfa-2a (Pegasys) contraindicated in neonates and infants;20 each mL contains 10 mg of benzyl alcohol as a preservative.20 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.20 21 22 23 24 25 26
Geriatric Use
Experience in those 65 years of age and older insufficient to determine whether they respond differently than younger adults.1 20
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.20 Use with caution.1 20
Because geriatric patients may have decreased renal function and because patients with renal impairment may be at increased risk of drug-induced toxicity, monitor closely and adjust dosage accordingly.20
Hepatic Impairment
Use with caution; dosage adjustments may be required.20 (See Hepatic Impairment under Dosage and Administration.)
Exacerbation of cirrhosis-related neutropenia and thrombocytopenia is a risk associated with use of interferon alfa.28
Renal Impairment
Use peginterferon monotherapy with caution and under close medical supervision in patients with Clcr <50 mL/minute; dosage adjustments may be required.1 20 (See Renal Impairment under Dosage and Administration.)
Concomitant oral ribavirin should not be used in those with Clcr <50 mL/minute.1 20
Race
For reasons as yet unknown, response rates have been lower in black and Hispanic patients and higher in Asian patients compared with white patients.1 4 20 Although black patients had a higher proportion of poor prognostic factors compared with white patients, experience with these patients was insufficient to allow meaningful conclusions about differences in response rates after adjusting for these prognostic factors.1
Common Adverse Effects
Flu-like symptoms (fatigue/asthenia, headache, myalgia, pyrexia, rigors);1 7 20 neuropsychiatric effects (insomnia, depression, anxiety/emotional lability/irritability);1 20 hematologic effects (neutropenia, thrombocytopenia).1 20
Interactions for Peginterferon Alfa
May inhibit CYP1A2.20
Drugs Metabolized by Hepatic Microsomal Enzymes
Pharmacokinetic interactions unlikely with drugs that are substrates of CYP 2C9, 2C19, 2D6, or 3A4.20
Specific Drugs
Drug | Interaction | Comments |
|---|---|---|
Antiretrovirals, nucleoside reverse transcriptase inhibitors (NRTIs) | Possible increased risk of potentially fatal hepatic decompensation in cirrhotic patients with chronic HCV coinfected with HIV who are receiving peginterferon alfa (with or without ribavirin) and antiretroviral regimens that include NRTIs20 Didanosine: Fatal hepatic failure and peripheral neuropathy, pancreatitis, and symptomatic hyperlactatemia/lactic acidosis reported when used concomitantly with HCV regimens that include ribavirin20 Zidovudine: Possible increased risk of severe neutropenia (ANC <500/mm3) and severe anemia (hemoglobin <8 g/dL) if used concomitantly with peginterferon alfa and ribavirin20 | If used in patients coinfected with HIV who are receiving NRTIs, closely monitor for toxicities;20 if worsening toxicities are observed, consider discontinuing or reducing dosage of peginterferon and/or ribavirin;20 if decompensation occurs (Child-Pugh score ≥6), discontinue20 Didanosine: Concomitant use with HCV treatment regimens that include ribavirin not recommended20 |
Methadone | Possible increased methadone concentrations1 20 | Clinical importance unknown1 20 Monitor for signs and symptoms of methadone toxicity1 20 |
Ribavirin | Possible additive hematologic toxicity (neutropenia, anemia);1 8 20 no evidence of pharmacokinetic interaction8 20 Ribavirin can reduce phosphorylation of lamivudine, stavudine, and zidovudine; no evidence of pharmacokinetic or pharmacodynamic interaction when ribavirin used concomitantly with these drugs in patients coinfected with HCV and HIV20 | Concomitant oral ribavirin should not be used in those with Clcr <50 mL/minute1 20 If ribavirin used with peginterferon alfa in HCV patients coinfected with HIV, consider additional interactions related to concomitant use of ribavirin and NRTIs20 |
Theophylline | Possible increased theophylline AUC20 | Monitor plasma theophylline concentrations; adjust dosage if needed20 |
Peginterferon Alfa Pharmacokinetics
Absorption
Bioavailability
Following sub-Q administration of peginterferon alfa-2b, the mean absorption half-life is 4.6 hours.1 After multiple dosing of peginterferon alfa-2a or 2b, there is an increase in bioavailability.1 20
Maximal serum concentrations of peginterferon alfa-2b and peginterferon alfa-2a occur within 15–441 and 72–96 hours20 , respectively. Steady-state serum levels of peginterferon alfa-2a are attained within 5–8 weeks of once weekly dosing.20
Distribution
Extent
Not known whether peginterferon alfa-2a and peginterferon alfa-2b cross the placenta or are distributed into milk.1 20
Elimination
Elimination Route
Renal elimination accounts for 30% of the clearance of peginterferon alfa-2b.1
Half-life
The elimination half-lives of peginterferon alfa-2a and peginterferon alfa-2b are 80 and 40 hours, respectively.1 20
Special Populations
Patients with end stage renal disease undergoing hemodialysis: 25–45% reduction in clearance of peginterferon alfa-2a.20
Renal clearance of peginterferon alfa-2b reduced by 17% in moderate renal impairment (Clcr 30–49 mL/minute) and by 44% in severe renal impairment (Clcr 10–29 mL/minute).1
Stability
Storage
Parenteral
Injection (Pegasys)
2–8°C.20 Do not freeze or shake; protect from light.20 Vials and prefilled syringes are for single use only; discard any unused portions.20
For Injection (PEG-Intron)
Redipen prefilled dual-chamber cartridge containing lyophilized peginterferon alfa-2b and sterile water for injection: 2–8°C.1 Should be used immediately following reconstitution, but may be stored for up to 24 hours at 2–8°C; freezing should be avoided.1 Discard unused portion; do not reuse Redipen.1
Vials: 25°C (may be exposed to 15–30°C).1 Should be used immediately following reconstitution, but may be stored for up to 24 hours at 2–8°C; freezing should be avoided.1 Once reconstituted vial has been entered, any unused portions should be discarded and should not be pooled.1
Actions and Spectrum
Mechanisms of antiviral activity have not been fully elucidated.1 20 Interferons with antiviral activity appear to bind to specific membrane receptors on cell surfaces and initiate a complex sequence of intracellular events, including induction of certain enzymes, suppression of cell proliferation, various immunomodulating activities, and inhibition of viral replication in virus-infected cells.1 20
Advice to Patients
Advise patients receiving peginterferon alfa (alone or in conjunction with oral ribavirin) about appropriate use of the drugs and the expected benefits and risks.1 20
Caution patients not to change brands of peginterferon alfa without consulting their clinician.20
Advise patients it is not known whether use of peginterferon alfa (alone or in conjunction with oral ribavirin) will prevent transmission of HCV infection to others; also not known whether the drug(s) will cure hepatitis C or prevent long-term sequelae (cirrhosis, liver failure, liver cancer).1 20
Importance of remaining well hydrated, especially during initial treatment.1 20 If taking concomitant oral ribavirin, importance of taking the drug with food.1 20
Importance of reporting any sign or symptom of depression or suicidal ideation to clinician.1 20 Advise patients that the drug may need to be immediately discontinued and psychiatric intervention instituted in severe cases.1 20
Advise patients that laboratory evaluations are required before starting and periodically during treatment.1 20
Caution patients that dizziness, confusion, somnolence, and fatigue may occur and to avoid driving or operating machinery.1 20
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal products.1 20
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1
Advise patients of the teratogenic/embryocidal risks associated with concomitant oral ribavirin and the necessity of females of childbearing potential and male patients with female partners of childbearing age practicing effective contraception during and for 6 months after ribavirin therapy.1 20
Importance of advising patients of other important precautionary information.1 (See Cautions.)
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