Peginterferon beta-1a is available through recombinant DNA technology. The drug is an amino acid glycoprotein that is covalently conjugated with a methoxy polyethylene glycol (PEG) molecule, which reduces clearance in vivo allowing for a more flexible dosing schedule when compared to interferon beta-1a products. Peginterferon beta-1a is indicated for the treatment of adults with relapsing forms of multiple sclerosis, including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease. Peginterferon beta-1a is administered every 14 days, compared to weekly or three times weekly dosage regimens with interferon beta-1a products. Peginterferon beta-1a, like other interferon beta-1a treatments, produces a significant relative reduction of annualized MS relapse rates and disability progression. Early treatment of MS with proper therapy may delay cognitive and physical disability. The interferon beta medications are generally considered the initial treatment options for pediatric patients with MS. Monitor closely for side effects; hepatic injury has been observed with use.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Injectable Administration
-Premedication with acetaminophen or ibuprofen may lessen the severity of flu-like symptoms that may be experienced during treatment.
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
-Allow pre-filled syringes or pens to warm to room temperature for about 30 minutes once removed from refrigeration. Avoid the use of external heat sources.
Intramuscular Administration
Intramuscular injection (Plegridy prefilled syringe for IM administration):
-Health care professionals should train patients in the proper technique for self-administering IM injections using the prefilled syringe. See the manufacturer's "Instructions for Use".
-Note that the protective rubber cover of the prefilled syringe for IM administration contains natural rubber latex and should not be handled by latex-sensitive individuals.
-Attach the needle to the single-use prefilled syringe.
-Choose an injection site on the left or right thigh. Do not inject into the same site for consecutive injections. Rotate injection sites with each injection to minimize injection site reactions, including tissue necrosis.
-Inject intramuscularly.
-After administration, dispose of the used syringe properly.
Subcutaneous Administration
Subcutaenous injection (Plegridy prefilled syringes and pens for subcutaneous administration, including starter packs):
-Health care professionals should train patients in the proper technique for self-administering subcutaneous injections using the prefilled pen or syringe. See the manufacturer's "Instructions for Use".
-Needles are pre-attached to the subcutaneous single-use pens or syringes.
-Choose an injection site on the back of the upper arms; abdomen; or front thighs. Do not inject into the same site for consecutive injections. Rotate injection sites to minimize injection site reactions, including tissue necrosis.
-Inject subcutaneously.
-After administration, dispose of the used syringe or pen properly.
Flu-like symptoms occur commonly patients treated with peginterferon beta-1a (47%). Symptoms of flu syndrome are most prominent at therapy initiation. Concurrent use of analgesics and/or antipyretics may help ameliorate flu-like symptoms on treatment days. Although flu-like symptoms are common, less than 1% of patients discontinued peginterferon beta-1a during clinical trials due to the symptoms. Additional adverse effects seen with peginterferon beta-1a include fever (45%), increases in body temperature (6%), chills (17%), myalgia (19%), arthralgia (11%), pain (5%), asthenia (13%), and hyperthermia (4%). Nausea (9%) and vomiting (5%) were also observed. Chills occurred in 36% of patients given peginterferon beta-1a intramuscularly and 27% of patients given peginterferon beta-1a subcutaneously during an open-label bioequivalence trial. Pain was reported in 22% of patients given peginterferon beta-1a intramuscularly compared to 14% of patients given the drug subcutaneously.
An injection site reaction occurred in 66% of patients given peginterferon beta 1-a subcutaneously during clinical trials. Injection site erythema was common, noted in 62% of those receiving the drug. Injection site pain and pruritus were also commonly reported in 15% and 13% of patients, respectively. Injection site edema (3%), warmth (3%), hematoma (3%), and rash (2%) were also observed. Pruritus was reported in 4% of patients. Injection site reactions including erythema, pain, pruritus, or edema occurred in 14% of patients given peginterferon beta-1a intramuscularly and 32% of patients who received peginterferon beta-1a subcutaneously during an open-label bioequivalence trial. Injection site pain occurred in 11% of patients given peginterferon beta-1a intramuscularly compared to 15% given the drug subcutaneously. Injection site erythema occurred in 2% of patients given the drug intramuscularly compared to 25% with subcutaneous use. Peginterferon beta-1a may cause tissue necrosis at the injection site. Injection site necrosis was observed in one of 1,468 patients treated with peginterferon beta-1a during clinical trials. Injection site abscesses and cellulitis have been reported during postmarketing use of interferon beta. Hospitalization for surgical drainage and intravenous antibiotics were required in some cases. Advise patients of the importance of injection site rotation and aseptic injection technique to minimize the risk of tissue necrosis; periodically evaluate patient understanding and use of aseptic self-injection techniques and procedures. Also, instruct patients to promptly report any break in the skin, which may be associated with blue-black discoloration, swelling, or fluid drainage. If tissue necrosis occurs, consider drug discontinuation based on the extent of necrosis. If continuation occurs, avoid administration of peginterferon beta-1a near the affected area until healing occurs. If multiple lesions occur, discontinue therapy until healing occurs or change injection site. Hypersensitivity reactions have also been reported. Anaphylaxis or other anaphylactoid reactions were rarely reported with peginterferon beta-1a during clinical trials and anaphylaxis has been reported during postmarketing experience. Serious allergic reactions including angioedema or urticaria occurred in less than 1% of patients. Discontinue the drug if a serious allergic reaction occurs.
Depression, suicidal ideation, and new or worsening psychiatric disorders such as psychosis have been reported to occur with increased frequency in patients receiving interferon compounds. In clinical trials with peginterferon beta-1a, adverse events related to depression or suicidal ideation in multiple sclerosis patients were similar between active drug and placebo groups (8%). Advise patients to immediately report any symptoms of depression and/or suicidal ideation to their healthcare professional. If a patient develops depression or other severe psychiatric symptoms, consider peginterferon beta-1a cessation.
Headache (44%) was reported with peginterferon beta-1a use during initial clinical trials. Headache occurred in 36% of patients given peginterferon beta-1a intramuscularly and 41% of patients given peginterferon beta-1a subcutaneously during an open-label bioequivalence trial. Seizures have been associated with the use of beta interferons, including peginterferon beta-1a. Seizures were reported in less than 1% of multiple sclerosis patients who received the drug during clinical trials. It is not known whether seizures were related to the effects of multiple sclerosis alone, to peginterferon beta-1a, or to a combination of both. Seizures in patients without a prior history have also been noted postmarketing.
Severe hepatic injury, including hepatic failure, hepatitis, and autoimmune hepatitis have been reported rarely with interferon beta use. Some cases of hepatic failure have required liver transplantation. Elevations of hepatic enzymes, hepatic injury, and noninfectious hepatitis have been observed with peginterferon beta-1a treatment. During clinical trials, elevations of ALT (6%), AST (4%), and GGT (3%) were observed. Elevations of ALT or AST more than 5 time ULN occurred in 2% and less than 1% of patients treated with peginterferon beta-1, respectively, compared to less than 1% of placebo-treated patients. Elevated hepatic enzymes in combination with hyperbilirubinemia occurred in 2 patients during clinical trials. Consider regular monitoring of hepatic function during treatment, and monitor patients for clinical symptoms of hepatic injury.
Decreases in peripheral blood counts in all cell lines, including rare cases of pancytopenia and severe thrombocytopenia, are known to be dose-related laboratory abnormalities associated with the use of interferons. Leukopenia was reported in 7% of patients who received peginterferon beta-1a during clinical trials compared to 1% of patients who received placebo. Lymphocytopenia, neutropenia, and thrombocytopenia each occurred in < 1% of patients. One serious case of neutropenia (neutrophils <= 0.5 x 109/L) and another serious case of thrombocytopenia (platelets <= 10 x 109/L) occurred. Recovery of cell counts occurred after drug discontinuation. Autoimmune idiopathic thrombocytopenia has also been observed. Consider regular monitoring of hematologic parameters and monitor patients for signs of hematological disorders during treatment.
Cases of congestive heart failure, cardiomyopathy, and cardiomyopathy with congestive heart failure have been reported with interferon beta therapy. In clinical trials with peginterferon beta-1a, the incidence of all cardiac adverse events was 7%. Closely monitor patients with cardiac disease for worsening of their clinical condition during treatment with peginterferon beta-1a.
In clinical trials of peginterferon beta-1a, neutralizing antibody formation was noted in < 1% of patients treated for 1 year. Approximately 7% of patients developed antibodies to PEG. The significance of the appearance of serum neutralizing activity is unknown. Comparison of the incidence of antibodies between interferon products may be misleading due to factors that affect testing of antibodies (e.g., sensitivity and specificity of the assay, handling, time of sample collection, concurrent medications, underlying medical conditions, etc.).
Autoimmune reactions have been associated with peginterferon beta-1a therapy including hyperthyroidism and hypothyroidism. The incidence of all autoimmune disorders during clinical trials was < 1%. Consider thyroid function monitoring if clinically appropriate. If patients develop an autoimmune disorder, consider drug discontinuation.
Menstrual irregularity, a reversible adverse effect, has been observed with interferon beta treatment and may occur with peginterferon beta-1a. Menorrhagia and metrorrhagia have also been reported in post-marketing experience.
Cases of thrombotic microangiopathy, including thrombotic thrombocytopenic purpura (TTP) and hemolytic-uremic syndrome (HUS), have been reported with interferon beta products. Cases have been reported several weeks to years after treatment initiation. Some cases have been fatal. Discontinue therapy if clinical symptoms and laboratory parameters consistent with thrombotic microangiopathy develop, and manage as appropriate.
Cases of pulmonary arterial hypertension (PAH), some requiring hospitalization, have been reported in patients treated with interferon beta products in the absence of other contributory factors. One reported case required a lung transplant. Cases of pulmonary hypertension have been reported at various time points during treatment, and may occur years after treatment initiation. Assess patients who develop unexplained symptoms (e.g., dyspnea or new or increasing fatigue) for PAH. Discontinue therapy if a diagnosis of PAH is confirmed, and manage as appropriate.
Peginterferon beta-1a is contraindicated for use in patients with a history of hypersensitivity to natural or recombinant interferon beta or peginterferon. Serious allergic reactions are rare complications of treatment with interferon beta; anaphylaxis has been reported with use of peginterferon beta-1a in the postmarketing setting.
Use peginterferon beta-1a with caution in patients with preexisting hepatic disease. Severe hepatic injury, including hepatitis, autoimmune hepatitis, and rare cases of severe hepatic failure, have been reported with interferon beta therapy. Elevation of liver function tests (LFTs) and bilirubin may occur. Asymptomatic elevation of hepatic transaminases has also been reported, and in some patients has recurred upon rechallenge with interferon beta. Cases of noninfectious hepatitis have been reported in the postmarketing setting with use of peginterferon beta-1a. Monitor patients for signs and symptoms of hepatic injury and monitoring of LFTs during peginterferon beta-1a treatment is advised. The potential hepatotoxicity risk of interferon beta therapies when used in combination with known hepatotoxic drugs or other products (e.g., ethanol ingestion) should be considered before their concurrent use.
Depression, suicidal ideation, and suicide occur more frequently in patients receiving interferon beta therapy than in patients receiving placebo. Advise patients to report immediately any symptom of depression or suicidal ideation to their healthcare provider. If a patient develops depression or other severe psychiatric symptoms, consider stopping treatment with peginterferon beta-1a.
Exercise caution when administering peginterferon beta-1a to patients with a pre-existing seizure disorder. Seizures are associated with use of interferon beta. Rarely, seizures were observed in clinical studies with peginterferon beta-1a.
Monitor patients with significant cardiac disease or pre-existing heart failure for worsening of their cardiac condition during initiation and continuation of treatment with peginterferon beta-1a. Congestive heart failure, cardiomyopathy, and cardiomyopathy with congestive heart failure may occur in patients receiving interferon beta therapies.
Patients with bone marrow suppression or who are receiving myelosuppressive therapy may be at increased risk of developing hematologic toxicity during peginterferon beta-1a therapy. Decreased peripheral blood counts in all cell lines are possible, including rare cases of pancytopenia and severe thrombocytopenia. Monitoring of complete blood cell counts, differential white blood cell counts, and platelet counts is recommended during therapy. Patients with bone marrow suppression may require more intensive monitoring of blood cell counts.
Cases of thrombotic microangiopathy, including thrombotic thrombocytopenic purpura (TTP) and hemolytic-uremic syndrome (HUS), have been reported with interferon beta products. Cases have been reported several weeks to years after treatment initiation. Some cases have been fatal. Discontinue therapy if clinical symptoms and laboratory parameters consistent with thrombotic microangiopathy develop, and manage as appropriate.
Use peginterferon beta-1a with caution in patients with pulmonary hypertension. Cases of pulmonary arterial hypertension (PAH), some requiring hospitalization, have been reported in patients treated with interferon beta products in the absence of other contributory factors. Assess patients who develop unexplained symptoms (e.g., dyspnea or new or increasing fatigue) for PAH. Discontinue therapy if a diagnosis of PAH is confirmed, and manage as appropriate. Cases of PAH have been reported at various time points during treatment, and may occur years after treatment initiation.
Autoimmune disease of multiple target organs has been reported during interferon beta therapy, including idiopathic thrombocytopenia, thyroid disease (hyperthyroidism or hypothyroidism), and rare cases of autoimmune hepatitis. Patients should be monitored for signs of these disorders. Consider thyroid function testing every 6 months in patients with a history of thyroid disease or as clinically indicated. If a patient develops a new autoimmune disorder, consider stopping peginterferon beta-1a.
Injection site reactions, including injection site tissue necrosis, abscess, and cellulitis, can occur with the use of peginterferon beta-1a. Some cases reported postmarketing required hospitalization for surgical drainage and intravenous antibiotics. Periodically evaluate patient understanding and use of aseptic self-injection techniques and procedures, particularly if injection site necrosis has occurred. Decisions to discontinue therapy following tissue necrosis at an injection site should be based on the extent of the necrosis. For patients who continue therapy, avoid administration near the affected area until it is fully healed. If multiple lesions occur, change injection site or discontinue peginterferon beta-1a until healing occurs.
There are no data available on peginterferon beta-1a use during human pregnancy from well-controlled studies. Observational studies of interferon beta in women have generally not indicated a drug-associated risk of major birth defects. Increased risks for lower mean birth weight, shorter mean birth length, and preterm birth (less than 37 weeks) without spontaneous abortion were reported during a systemic review of 761 interferon-beta exposed pregnancies; no increased risk for congenital anomalies was found. The National Multiple Sclerosis Society consensus guidelines and the product labels recommend that women discontinue interferon beta therapy when trying to conceive and throughout gestation due to insufficient evidence regarding safety to the human fetus; however, most women who happen to conceive while taking interferon beta appear to have healthy newborns. If a patient does become pregnant while receiving interferon therapy, she should be made aware of the risks; discontinuation of interferon therapy during pregnancy is recommended. The risks and benefits of continuing interferon beta therapy during pregnancy require careful consideration of the patient's level of disease activity, personal preferences, and the potential fetal risks. Data from a large, multicenter trial of pregnant patients with multiple sclerosis (MS) suggest that patients have a decrease in the number and severity of MS relapses during pregnancy, despite discontinuation or lack of receipt of disease-modifying medications. In monkeys given interferon beta by subcutaneous injection every other day during early pregnancy, no teratogenic or other adverse effects on fetal development were observed; however, abortifacient activity was evident following 3 to 5 doses. The effects of peginterferon beta-1a during labor and delivery are unknown.
There are limited data regarding the use of peginterferon beta-1a during breast-feeding, and its excretion into human milk is unknown. Due to its poor oral bioavailability, any drug present in the breast milk is unlikely to be systemically absorbed by the nursing infant. The estimated relative infant dose would be 0.006% of the maternal interferon beta dose, according to one study. The Multiple Sclerosis Centre of Excellence on Reproduction and Child Health considers the various interferon beta products to be moderately safe for use during lactation since the molecular weight of the drug is likely to limit transfer to breast milk. Other reviews concur that peginterferon beta-1a is likely compatible with breast-feeding. Glatiramer and interferon beta-1b are potential alternatives to consider for the treatment of multiple sclerosis. However, the standard of care based is to have a mother start disease-modifying therapy of any type only after complete weaning of their infant. A discussion about the risks and benefits of postponing the resumption of interferon beta treatment in order to breast-feed is important, particularly for women who experience highly-active disease or who had active multiple sclerosis in the year prior to conception. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for peginterferon beta-1a and any potential adverse effects on the breast-fed infant.
The protective rubber cover of the peginterferon beta-1a prefilled syringe for intramuscular administration contains natural rubber latex. Patients with a latex hypersensitivity should not handle this product. Natural rubber latex may cause allergic reactions in sensitive individuals.
General dosing information
-Be sure to prescribe and dispense the right products based on administration route.
-Switching between the subcutaneous and intramuscular routes of administration has not been studied. It is not expected that dose titration should be repeated to ameliorate flu-like symptoms if switching between subcutaneous and intramuscular routes of administration.
For the treatment of relapsing forms of multiple sclerosis, including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease:
Intramuscular or Subcutaneous dosage:
Adults: 63 mcg subcutaneously on day 1, then 94 mcg subcutaneously on day 15, and then 125 mcg every 14 days starting on day 29.
Maximum Dosage Limits:
-Adults
125 mcg IM or subcutaneously once every 14 days.
-Geriatric
125 mcg IM or subcutaneously once every 14 days.
-Adolescents
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Increased drug exposure may occur in patients with severe renal impairment; however, specific guidelines for dosage adjustments in renal impairment are not available. Monitor patients for adverse reactions.
*non-FDA-approved indication
Abacavir: (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) can both cause hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART.
Abacavir; Dolutegravir; Lamivudine: (Moderate) Monitor for treatment-associated toxicities, especially hepatic decompensation, during coadministration of interferons (with or without ribavirin) and lamivudine. Dose reduction or discontinuation of interferon, ribavirin, or both should be considered if worsening clinical toxicities are observed, including hepatic decompensation (e.g., Child-Pugh score greater than 6). (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) can both cause hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART.
Abacavir; Lamivudine, 3TC: (Moderate) Monitor for treatment-associated toxicities, especially hepatic decompensation, during coadministration of interferons (with or without ribavirin) and lamivudine. Dose reduction or discontinuation of interferon, ribavirin, or both should be considered if worsening clinical toxicities are observed, including hepatic decompensation (e.g., Child-Pugh score greater than 6). (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) can both cause hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART.
Abacavir; Lamivudine, 3TC; Zidovudine, ZDV: (Major) Use interferons and zidovudine together with caution. Closely monitor patients for treatment-associated toxicities, especially hematologic effects and hepatic decompensation, and manage as recommended for the individual therapies. Coadministration of alpha interferons may increase the hematologic toxicity of zidovudine. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) are also associated with hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. Interferon therapy may also reduce zidovudine clearance. (Moderate) Monitor for treatment-associated toxicities, especially hepatic decompensation, during coadministration of interferons (with or without ribavirin) and lamivudine. Dose reduction or discontinuation of interferon, ribavirin, or both should be considered if worsening clinical toxicities are observed, including hepatic decompensation (e.g., Child-Pugh score greater than 6). (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) can both cause hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART.
Alemtuzumab: (Major) Concomitant use of peginterferon beta-1a with alemtuzumab may increase the risk of immunosuppression. Avoid the use of these drugs together.
Atazanavir: (Moderate) The concomitant use of interferons and anti-retroviral protease inhibitors should be done with caution as both can cause hepatotoxicity. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation. Most protease inhibitors have been associated with episodes of liver toxicity. Cirrhotic chronic HCV infected patients co-infected with HIV receiving HAART and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. The HCV-HIV International Panel recommends the management of hepatotoxicity should be based on the knowledge of the mechanisms involved for each drug. Furthermore, they state that there are lower rates of liver-related mortality in coinfected patients taking HAART, even in those with end-stage liver disease, compared with patients not receiving HAART.
Atazanavir; Cobicistat: (Moderate) The concomitant use of interferons and anti-retroviral protease inhibitors should be done with caution as both can cause hepatotoxicity. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation. Most protease inhibitors have been associated with episodes of liver toxicity. Cirrhotic chronic HCV infected patients co-infected with HIV receiving HAART and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. The HCV-HIV International Panel recommends the management of hepatotoxicity should be based on the knowledge of the mechanisms involved for each drug. Furthermore, they state that there are lower rates of liver-related mortality in coinfected patients taking HAART, even in those with end-stage liver disease, compared with patients not receiving HAART.
Bictegravir; Emtricitabine; Tenofovir Alafenamide: (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) can both cause hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART.
Cabotegravir; Rilpivirine: (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and rilpivirine can both cause hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving antiretroviral agents and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART.
Chloroquine: (Moderate) Concurrent use of chloroquine and interferons is not recommended as there is an increased risk of retinal toxicity.
Clozapine: (Major) It is unclear if concurrent use of other drugs known to cause neutropenia (e.g., certain antineoplastic agents) increases the risk or severity of clozapine-induced neutropenia. Because there is no strong rationale for avoiding clozapine in patients treated with these drugs, consider increased absolute neutrophil count (ANC) monitoring and consult the treating oncologist.
Darunavir: (Moderate) The concomitant use of interferons and anti-retroviral protease inhibitors should be done with caution as both can cause hepatotoxicity. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation. Most protease inhibitors have been associated with episodes of liver toxicity. Cirrhotic chronic HCV infected patients co-infected with HIV receiving HAART and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. The HCV-HIV International Panel recommends the management of hepatotoxicity should be based on the knowledge of the mechanisms involved for each drug. Furthermore, they state that there are lower rates of liver-related mortality in coinfected patients taking HAART, even in those with end-stage liver disease, compared with patients not receiving HAART.
Darunavir; Cobicistat: (Moderate) The concomitant use of interferons and anti-retroviral protease inhibitors should be done with caution as both can cause hepatotoxicity. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation. Most protease inhibitors have been associated with episodes of liver toxicity. Cirrhotic chronic HCV infected patients co-infected with HIV receiving HAART and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. The HCV-HIV International Panel recommends the management of hepatotoxicity should be based on the knowledge of the mechanisms involved for each drug. Furthermore, they state that there are lower rates of liver-related mortality in coinfected patients taking HAART, even in those with end-stage liver disease, compared with patients not receiving HAART.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) The concomitant use of interferons and anti-retroviral protease inhibitors should be done with caution as both can cause hepatotoxicity. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation. Most protease inhibitors have been associated with episodes of liver toxicity. Cirrhotic chronic HCV infected patients co-infected with HIV receiving HAART and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. The HCV-HIV International Panel recommends the management of hepatotoxicity should be based on the knowledge of the mechanisms involved for each drug. Furthermore, they state that there are lower rates of liver-related mortality in coinfected patients taking HAART, even in those with end-stage liver disease, compared with patients not receiving HAART. (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) can both cause hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART.
Delavirdine: (Major) The concomitant use of interferons and anti-retroviral non-nucleoside reverse transcriptase inhibitors (NNRTIs) should be done with caution as both can cause hepatic damage. NNRTIs may cause liver damage in the context of hypersensitivity reactions or by direct toxic effects. Many studies demonstrate that nevirapine is more hepatotoxic than efavirenz. Underlying chronic HCV infection enhances the risk of developing liver enzyme elevations in patients receiving nevirapine. Overall, the HCV-HIV International Panel recommends the management of hepatotoxicity should be based on the knowledge of the mechanisms involved for each drug. Furthermore, they state that there are lower rates of liver-related mortality in coinfected patients taking HAART, even in those with end-stage liver disease, compared with patients not receiving HAART. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation.
Dolutegravir; Lamivudine: (Moderate) Monitor for treatment-associated toxicities, especially hepatic decompensation, during coadministration of interferons (with or without ribavirin) and lamivudine. Dose reduction or discontinuation of interferon, ribavirin, or both should be considered if worsening clinical toxicities are observed, including hepatic decompensation (e.g., Child-Pugh score greater than 6).
Dolutegravir; Rilpivirine: (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and rilpivirine can both cause hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving antiretroviral agents and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART.
Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Moderate) Monitor for treatment-associated toxicities, especially hepatic decompensation, during coadministration of interferons (with or without ribavirin) and lamivudine. Dose reduction or discontinuation of interferon, ribavirin, or both should be considered if worsening clinical toxicities are observed, including hepatic decompensation (e.g., Child-Pugh score greater than 6).
Efavirenz: (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and efavirenz can both cause hepatotoxicity. Cirrhotic chronic HCV infected patients co-infected with HIV receiving HAART and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) can both cause hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and efavirenz can both cause hepatotoxicity. Cirrhotic chronic HCV infected patients co-infected with HIV receiving HAART and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Monitor for treatment-associated toxicities, especially hepatic decompensation, during coadministration of interferons (with or without ribavirin) and lamivudine. Dose reduction or discontinuation of interferon, ribavirin, or both should be considered if worsening clinical toxicities are observed, including hepatic decompensation (e.g., Child-Pugh score greater than 6). (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and efavirenz can both cause hepatotoxicity. Cirrhotic chronic HCV infected patients co-infected with HIV receiving HAART and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) can both cause hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) can both cause hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART.
Emtricitabine: (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) can both cause hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) can both cause hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and rilpivirine can both cause hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving antiretroviral agents and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) can both cause hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and rilpivirine can both cause hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving antiretroviral agents and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART.
Emtricitabine; Tenofovir alafenamide: (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) can both cause hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART.
Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) can both cause hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART.
Entecavir: (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) can both cause hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART.
Fosamprenavir: (Moderate) The concomitant use of interferons and anti-retroviral protease inhibitors should be done with caution as both can cause hepatotoxicity. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation. Most protease inhibitors have been associated with episodes of liver toxicity. Cirrhotic chronic HCV infected patients co-infected with HIV receiving HAART and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. The HCV-HIV International Panel recommends the management of hepatotoxicity should be based on the knowledge of the mechanisms involved for each drug. Furthermore, they state that there are lower rates of liver-related mortality in coinfected patients taking HAART, even in those with end-stage liver disease, compared with patients not receiving HAART.
Indinavir: (Moderate) The concomitant use of interferons and anti-retroviral protease inhibitors should be done with caution as both can cause hepatotoxicity. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation. Most protease inhibitors have been associated with episodes of liver toxicity. Cirrhotic chronic HCV infected patients co-infected with HIV receiving HAART and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. The HCV-HIV International Panel recommends the management of hepatotoxicity should be based on the knowledge of the mechanisms involved for each drug. Furthermore, they state that there are lower rates of liver-related mortality in coinfected patients taking HAART, even in those with end-stage liver disease, compared with patients not receiving HAART.
Lamivudine, 3TC: (Moderate) Monitor for treatment-associated toxicities, especially hepatic decompensation, during coadministration of interferons (with or without ribavirin) and lamivudine. Dose reduction or discontinuation of interferon, ribavirin, or both should be considered if worsening clinical toxicities are observed, including hepatic decompensation (e.g., Child-Pugh score greater than 6).
Lamivudine, 3TC; Zidovudine, ZDV: (Major) Use interferons and zidovudine together with caution. Closely monitor patients for treatment-associated toxicities, especially hematologic effects and hepatic decompensation, and manage as recommended for the individual therapies. Coadministration of alpha interferons may increase the hematologic toxicity of zidovudine. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) are also associated with hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. Interferon therapy may also reduce zidovudine clearance. (Moderate) Monitor for treatment-associated toxicities, especially hepatic decompensation, during coadministration of interferons (with or without ribavirin) and lamivudine. Dose reduction or discontinuation of interferon, ribavirin, or both should be considered if worsening clinical toxicities are observed, including hepatic decompensation (e.g., Child-Pugh score greater than 6).
Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Monitor for treatment-associated toxicities, especially hepatic decompensation, during coadministration of interferons (with or without ribavirin) and lamivudine. Dose reduction or discontinuation of interferon, ribavirin, or both should be considered if worsening clinical toxicities are observed, including hepatic decompensation (e.g., Child-Pugh score greater than 6).
Lopinavir; Ritonavir: (Moderate) The concomitant use of interferons and anti-retroviral protease inhibitors should be done with caution as both can cause hepatotoxicity. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation. Most protease inhibitors have been associated with episodes of liver toxicity. Cirrhotic chronic HCV infected patients co-infected with HIV receiving HAART and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. The HCV-HIV International Panel recommends the management of hepatotoxicity should be based on the knowledge of the mechanisms involved for each drug. Furthermore, they state that there are lower rates of liver-related mortality in coinfected patients taking HAART, even in those with end-stage liver disease, compared with patients not receiving HAART.
Nelfinavir: (Moderate) The concomitant use of interferons and anti-retroviral protease inhibitors should be done with caution as both can cause hepatotoxicity. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation. Most protease inhibitors have been associated with episodes of liver toxicity. Cirrhotic chronic HCV infected patients co-infected with HIV receiving HAART and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. The HCV-HIV International Panel recommends the management of hepatotoxicity should be based on the knowledge of the mechanisms involved for each drug. Furthermore, they state that there are lower rates of liver-related mortality in coinfected patients taking HAART, even in those with end-stage liver disease, compared with patients not receiving HAART.
Nevirapine: (Major) The concomitant use of interferons and nevirapine should be done with caution as both can cause hepatotoxicity. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation. Nevirapine may cause liver damage in the context of hypersensitivity reactions or by direct toxic effects. Cirrhotic chronic HCV infected patients co-infected with HIV receiving HAART and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. Patients with signs or symptoms of hepatitis, or with increased transaminases combined with rash or other systemic symptoms, must discontinue nevirapine and seek medical evaluation immediately.
Nirmatrelvir; Ritonavir: (Moderate) The concomitant use of interferons and anti-retroviral protease inhibitors should be done with caution as both can cause hepatotoxicity. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation. Most protease inhibitors have been associated with episodes of liver toxicity. Cirrhotic chronic HCV infected patients co-infected with HIV receiving HAART and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. The HCV-HIV International Panel recommends the management of hepatotoxicity should be based on the knowledge of the mechanisms involved for each drug. Furthermore, they state that there are lower rates of liver-related mortality in coinfected patients taking HAART, even in those with end-stage liver disease, compared with patients not receiving HAART.
Ocrelizumab: (Moderate) Ocrelizumab has not been studied in combination with other immunosuppressive or immune modulating therapies used for the treatment of multiple sclerosis, such as peginterferon beta-1a. Concomitant use of ocrelizumab with peginterferon beta-1a may increase the risk of immunosuppression.
Ofatumumab: (Moderate) Concomitant use of ofatumumab with peginterferon beta-1a may increase the risk of immunosuppression. Ofatumumab has not been studied in combination with other immunosuppressive or immune modulating therapies used for the treatment of multiple sclerosis, such as peginterferon beta-1a. Consider the duration and mechanism of action of drugs with immunosuppressive effects when switching therapies for multiple sclerosis patients.
Ozanimod: (Moderate) Concomitant use of ozanimod with peginterferon beta-1 may increase the risk of immunosuppression. Ozanimod has not been studied in combination with other immunosuppressive or immune modulating therapies used for the treatment of multiple sclerosis.
Pexidartinib: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with peginterferon beta-1a. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
Pretomanid: (Major) Avoid coadministration of pretomanid with peginterferon beta-1a, especially in patients with impaired hepatic function, due to increased risk for hepatotoxicity. Monitor for evidence of hepatotoxicity if coadministration is necessary. If new or worsening hepatic dysfunction occurs, discontinue hepatotoxic medications.
Protease inhibitors: (Moderate) The concomitant use of interferons and anti-retroviral protease inhibitors should be done with caution as both can cause hepatotoxicity. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation. Most protease inhibitors have been associated with episodes of liver toxicity. Cirrhotic chronic HCV infected patients co-infected with HIV receiving HAART and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. The HCV-HIV International Panel recommends the management of hepatotoxicity should be based on the knowledge of the mechanisms involved for each drug. Furthermore, they state that there are lower rates of liver-related mortality in coinfected patients taking HAART, even in those with end-stage liver disease, compared with patients not receiving HAART.
Rilpivirine: (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and rilpivirine can both cause hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving antiretroviral agents and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART.
Riluzole: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and peginterferon beta-1a. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Ritonavir: (Moderate) The concomitant use of interferons and anti-retroviral protease inhibitors should be done with caution as both can cause hepatotoxicity. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation. Most protease inhibitors have been associated with episodes of liver toxicity. Cirrhotic chronic HCV infected patients co-infected with HIV receiving HAART and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. The HCV-HIV International Panel recommends the management of hepatotoxicity should be based on the knowledge of the mechanisms involved for each drug. Furthermore, they state that there are lower rates of liver-related mortality in coinfected patients taking HAART, even in those with end-stage liver disease, compared with patients not receiving HAART.
Saquinavir: (Moderate) The concomitant use of interferons and anti-retroviral protease inhibitors should be done with caution as both can cause hepatotoxicity. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation. Most protease inhibitors have been associated with episodes of liver toxicity. Cirrhotic chronic HCV infected patients co-infected with HIV receiving HAART and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. The HCV-HIV International Panel recommends the management of hepatotoxicity should be based on the knowledge of the mechanisms involved for each drug. Furthermore, they state that there are lower rates of liver-related mortality in coinfected patients taking HAART, even in those with end-stage liver disease, compared with patients not receiving HAART.
Stavudine, d4T: (Major) Patients receiving stavudine with interferons (with or without ribavirin) should be closely monitored for treatment-associated toxicities, especially hepatic decompensation. Cirrhotic chronic HCV infected patients co-infected with HIV receiving HAART and alpha interferons appear to be at increased risk for hepatic decompensation compared to patients not receiving HAART. Additionally, stavudine has been associated with fatal and nonfatal lactic acidosis and hepatomegaly with or without steatosis and should be used cautiously in patients with hepatic disease. Discontinuation of stavudine should be considered as medically appropriate. Dose reduction or discontinuation of interferon, ribavirin, or both should also be considered if worsening clinical toxicities are observed, including hepatic decompensation (e.g., Child-Pugh score greater than 6).
Tipranavir: (Moderate) The concomitant use of interferons and anti-retroviral protease inhibitors should be done with caution as both can cause hepatotoxicity. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation. Most protease inhibitors have been associated with episodes of liver toxicity. Cirrhotic chronic HCV infected patients co-infected with HIV receiving HAART and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. The HCV-HIV International Panel recommends the management of hepatotoxicity should be based on the knowledge of the mechanisms involved for each drug. Furthermore, they state that there are lower rates of liver-related mortality in coinfected patients taking HAART, even in those with end-stage liver disease, compared with patients not receiving HAART.
Vigabatrin: (Major) Vigabatrin is associated with vision loss. The drug should not be used with interferons, which are associated with a potential for serious ophthalmic effects (e.g., retinopathy, optic neuritis, visual impairment), unless the benefit of treatment clearly outweighs the risks.
Zidovudine, ZDV: (Major) Use interferons and zidovudine together with caution. Closely monitor patients for treatment-associated toxicities, especially hematologic effects and hepatic decompensation, and manage as recommended for the individual therapies. Coadministration of alpha interferons may increase the hematologic toxicity of zidovudine. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) are also associated with hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. Interferon therapy may also reduce zidovudine clearance.
Interferon beta suppresses proliferation of myelin-basic protein-specific T-cells and inhibits the expression of pro-inflammatory cytokines including interleukin-17, osteopontin, and INF-G, which is believed to be a major factor responsible for triggering the autoimmune reaction leading to multiple sclerosis (MS). Additionally, formation of anti-inflammatory cytokines, such as interleukin-10, is induced. T-cell migration across the blood-brain barrier is inhibited. These actions protect neurons from demyelination. Interferon beta has also been found to increase production of nerve growth factor (NGF), which promotes oligodendrocyte survival and differentiation and axonal recovery. This may have a favorable effect on remyelination.
Peginterferon beta-1a is administered subcutaneously or intramuscularly. Doses are administered once every 14 days. The drug is primarily excreted renally. Extensive metabolism in the liver does not occur. The half-life is approximately 78 hours in multiple sclerosis patients.
Affected cytochrome P450 isoenzymes and drug transporters: None known
-Route-Specific Pharmacokinetics
Intramuscular Route
The pharmacokinetics of 125 mcg single dose of peginterferon beta-1a administered intramuscularly and subcutaneously are similar.
Subcutaneous Route
After a 125 mcg subcutaneous dose in multiple sclerosis patients, maximum peginterferon beta-1a serum concentrations were reached between 1 to 1.5 days. The drug did not accumulate in serum after multiple subcutaneous doses of 125 mcg every 14 days in healthy subjects.
-Special Populations
Renal Impairment
Following peginterferon beta-1a administration, the mean increases in AUC were 30%, 40%, and 53% for patients with mild, moderate, or severe renal impairment, respectively, compared to normal subjects. The mean increases in Cmax were 27%, 26%, and 42% for patients with mild, moderate, or severe renal impairment, respectively, compared to normal subjects. Subjects with end stage renal disease requiring hemodialysis 2 to 3 times weekly had similar AUC and Cmax values to normal subjects. A hemodialysis session removed approximately 24% of circulating drug.