Pegasys ProClick

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Pegasys ProClick

Classes

Interferons for Hepatitis B and C
Interferons, Alpha

Administration

 
NOTE: Variations in dosage and adverse reactions exist among different subtypes of interferon alfa. Therefore, do not use different brands of interferon in a single treatment regimen. Also, the vials and prefilled syringes of peginterferon alfa-2a are not directly interchangeable. The same amount of drug will not be provided by equal volumes.
 
NOTE: Due to possible severe central nervous system reactions and severe hematologic reactions, baseline neuropsychiatric monitoring and complete blood count assessment of all patients are recommended. Pregnancy screening, liver function tests, serum creatinine, and thyroid function tests are also recommended prior to initiating therapy.
 
NOTE: Patients should be well hydrated before drug receipt, if clinically appropriate.

Injectable Administration

Administer subcutaneously. Do not inject intradermally, intramuscularly, or intravenously.
Only an individual trained in subcutaneous drug delivery should administer the injection. The initial injection should be given by a trained health care professional. A patient that is properly trained in subcutaneous injection technique may self-inject, if appropriate.
Premedication with acetaminophen or ibuprofen may decrease the incidence of administration-related reactions (i.e., fever). Bedtime administration may increase patient tolerance of therapy.
Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. The solution should be clear and colorless or a light yellow. Do not use if the solution has visible particles, flakes, color, or is cloudy.

Subcutaneous Administration

Do not use the vials and prefilled syringes interchangeably without noting the drug concentration difference. The volume to be administered will vary based on the product. All preparations are single-dose only; discard any unused solution.
180 mcg dose: 1 mL from 180 mcg/mL vial; 0.5 mL from 180 mcg/ 0.5 mL prefilled syringe.
135 mcg dose: 0.75 mL from 180 mcg/mL vial; 0.375 mL from 180 mcg/0.5 mL prefilled syringe.
90 mcg dose: 0.5 mL from 180 mcg/mL vial; 0.25 mL from 180 mcg/ 0.5 mL prefilled syringe.
 
Preparation of subcutaneous dosage immediately prior to injection:
Gently warm the refrigerated medicine to room temperature. Accomplish this by rolling the vial in the palms of your hands for about 1 minute prior to injection. Warm the syringe by placing it on a clean flat surface and waiting until it reaches room temperature. Wait for any condensation on the outside of the syringe to disappear prior to use.
Do not shake the vial or prefilled syringe as foaming may occur.
If using the vial, flip the plastic top off the vial and clean the rubber stopper with an alcohol pad. Obtain a sterile needle and syringe to withdraw and administer the drug solution. If needed, attach the needle to the end of the syringe. Pull the plunger back to the needed dosage mark on the syringe. While keeping the vial upright, insert the needle into the vial and slowly inject all the air into the airspace of the vial; DO NOT inject air into the fluid. Invert the vial and syringe to withdraw the needed amount of drug solution by slowly pulling the plunger back to the needed dosage mark on the syringe. The vials are single-use only; discard any unused portion.
For pediatric patients, prepare dose using ONLY the 180 mcg/mL vial. The weight-based dose should be drawn from the 180 mcg/mL vial using a sterile 1 mL tuberculin syringe.
If using the prefilled syringe, attach the needle by removing the rubber cap from the syringe barrel and placing the needle onto the end of the syringe barrel. Do not remove the clear needle shield until immediately before the injection of the product.
With the needle in the upright position, tap the syringe barrel lightly. Press the plunger slightly to eliminate any air bubbles that may be present. If using the prefilled syringe, you may need to push some medicine out of the syringe to deliver the correct amount. The prefilled syringe is marked for 90 mcg, 135 mcg, and 180 mcg dosage amounts. The edge of the plunger stopper needs to be on the correct dosage line.
 
Subcutaneous (SC) injection technique:
Clean the injection area (upper thigh or abdominal area beside the navel or waistline) with an alcohol swab. Choose a new location for each subsequent injection.
Pinch an area of skin and insert the needle with the bevel up subcutaneously as far as it will go by using a quick dart-like motion.
Release the skin and gently pull back on the syringe before delivering the drug to ensure it is not injected into a blood vessel. If blood appears in the barrel of the syringe, remove the needle and discard the syringe. Do not reuse syringes and needles. If no blood appears, slowly push down on the plunger to deposit the medicine.
After removal of the needle, place an alcohol swab over the injection site and press slightly.
Do not recap the needle. If using a syringe with a needle-stick protection device, place the free end of the orange cap on a flat surface and push down until the cap covers the needle. A click will be heard. Discard the syringe and needle into a sharps container.

Adverse Reactions
Severe

neutropenia / Delayed / 5.0-12.0
anemia / Delayed / 2.0-8.0
eczema vaccinatum / Delayed / 1.0-5.0
suicidal ideation / Delayed / 0-1.0
coma / Early / 0-1.0
peptic ulcer / Delayed / 0-1.0
GI bleeding / Delayed / 0-1.0
pancreatitis / Delayed / 0-1.0
pulmonary embolism / Delayed / 0-1.0
aplastic anemia / Delayed / 0-1.0
lupus-like symptoms / Delayed / 0-1.0
thrombotic thrombocytopenic purpura (TTP) / Delayed / 0-1.0
interstitial nephritis / Delayed / 0-1.0
stroke / Early / 0-1.0
corneal erosion / Delayed / 0-1.0
seizures / Delayed / Incidence not known
bronchospasm / Rapid / Incidence not known
erythema multiforme / Delayed / Incidence not known
anaphylactic shock / Rapid / Incidence not known
Stevens-Johnson syndrome / Delayed / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known
exfoliative dermatitis / Delayed / Incidence not known
angioedema / Rapid / Incidence not known
myocardial infarction / Delayed / Incidence not known
pulmonary hypertension / Delayed / Incidence not known
bronchiolitis obliterans / Delayed / Incidence not known
autoimmune disease / Delayed / Incidence not known
papilledema / Delayed / Incidence not known
retinal hemorrhage / Delayed / Incidence not known
optic neuritis / Delayed / Incidence not known
retinal thrombosis / Delayed / Incidence not known
visual impairment / Early / Incidence not known
retinopathy / Delayed / Incidence not known
retinal detachment / Delayed / Incidence not known
macular edema / Delayed / Incidence not known
hepatic failure / Delayed / Incidence not known
red cell aplasia / Delayed / Incidence not known
pancytopenia / Delayed / Incidence not known
hearing loss / Delayed / Incidence not known

Moderate

lymphopenia / Delayed / 3.0-81.0
hypertriglyceridemia / Delayed / 20.0-36.0
antibody formation / Delayed / 3.0-29.0
elevated hepatic enzymes / Delayed / 1.0-27.0
depression / Delayed / 18.0-18.0
dyspnea / Early / 0-13.0
impaired cognition / Early / 8.0-8.0
thrombocytopenia / Delayed / 5.0-8.0
memory impairment / Delayed / 5.0-5.0
hypothyroidism / Delayed / 0-4.0
blurred vision / Early / 4.0-4.0
hyperthyroidism / Delayed / 0-3.0
psychosis / Early / 0-1.0
hallucinations / Early / 0-1.0
colitis / Delayed / 0-1.0
angina / Early / 0-1.0
diabetes mellitus / Delayed / 0-1.0
psoriasis / Delayed / 0-1.0
cholangitis / Delayed / 0-1.0
steatosis / Delayed / 0-1.0
peripheral neuropathy / Delayed / 0-1.0
bullous rash / Early / Incidence not known
dehydration / Delayed / Incidence not known
hypertension / Early / Incidence not known
chest pain (unspecified) / Early / Incidence not known
pneumonitis / Delayed / Incidence not known
hyperglycemia / Delayed / Incidence not known
hypoglycemia / Early / Incidence not known
hyperbilirubinemia / Delayed / Incidence not known

Mild

asthenia / Delayed / 8.0-65.0
fatigue / Early / 8.0-65.0
headache / Early / 21.0-64.0
fever / Early / 37.0-54.0
injection site reaction / Rapid / 22.0-45.0
myalgia / Early / 26.0-40.0
arthralgia / Delayed / 22.0-28.0
alopecia / Delayed / 6.0-28.0
vomiting / Early / 15.0-25.0
nausea / Early / 9.0-25.0
anorexia / Delayed / 6.0-24.0
anxiety / Delayed / 19.0-19.0
irritability / Delayed / 19.0-19.0
insomnia / Early / 19.0-19.0
pruritus / Rapid / 11.0-19.0
dizziness / Early / 6.0-16.0
weight loss / Delayed / 4.0-16.0
diarrhea / Early / 11.0-16.0
rash / Early / 5.0-15.0
abdominal pain / Early / 8.0-15.0
cough / Delayed / 4.0-15.0
infection / Delayed / 0-14.0
influenza / Delayed / 0-14.0
xerosis / Delayed / 4.0-10.0
emotional lability / Early / 3.0-9.0
epistaxis / Delayed / 9.0-9.0
back pain / Delayed / 9.0-9.0
pharyngitis / Delayed / 6.0-6.0
diaphoresis / Early / 6.0-6.0
xerostomia / Early / 4.0-6.0
dyspepsia / Early / 0-1.0
vesicular rash / Delayed / Incidence not known
urticaria / Rapid / Incidence not known
tongue discoloration / Delayed / Incidence not known

Boxed Warning
Alcoholism, bipolar disorder, depression, driving or operating machinery, encephalopathy, mania, neurologic events, peripheral neuropathy, psychiatric event, psychosis, seizure disorder, seizures, substance abuse, suicidal ideation

Alpha interferons, including peginterferon alfa-2a, may cause or aggravate a psychiatric event or disorder. Patients should be monitored closely with periodic clinical and laboratory evaluations. It is recommended to monitor and evaluate for these conditions every 3 weeks during the first 8 weeks of treatment and every 6 months thereafter and for at least 6 months after the last dose. Permanently discontinue peginterferon alfa-2a therapy for homicidal or suicidial ideation, aggressive behavior towards others, severe depression, or other severe or persistent psychiatric symptoms; institute psychiatric intervention and follow-up as appropriate. In many, but not all cases, these disorders may resolve after stopping therapy. Patients should be warned to report changes in moods or behaviors, depression, suicidal ideation or other symptoms promptly to their health care provider. Any patient with a history of substance abuse (e.g., alcoholism), encephalopathy, depression or severe psychiatric disorder (e.g., bipolar disorder, mania, psychosis) should receive peginterferon alfa-2a with extreme caution, since these conditions may worsen or relapse. Former drug addicts may fall back into drug addiction or overdose. Although dose reduction or cessation of therapy may lead to resolution of the symptoms, depression or other psychiatric symptoms may persist and suicides have occurred even after withdrawing therapy, and continued psychiatric intervention may be needed. Neurologic events have also been reported with use. Because dizziness and drowsiness are common, patients should also be warned against driving or operating machinery until they know how peginterferon alfa-2a therapy will affect them. EEG abnormalities and seizures have been reported in post-market use and peginterferon alfa-2a should be used with caution in patients with a pre-existing seizure disorder. Peripheral neuropathy has been reported when alpha interferons were given in combination with telbivudine. In one clinical trial, an increased risk and severity of peripheral neuropathy was observed with the combination use of telbivudine and peginterferon alfa-2a as compared to telbivudine alone. The safety and efficacy of telbivudine in combination with interferons for the treatment of chronic hepatitis B have not been demonstrated.

Infection

Alpha interferons, including peginterferon alfa-2a, may cause or aggravate fatal or life-threatening infections. Serious and severe infections (bacterial infection, viral infection, or fungal infection), some fatal, have been reported during treatment with alpha interferons, including peginterferon alfa-2a. Suppression of the bone marrow due to peginterferon alfa-2a increases the risk for serious infections, but such infections may also occur in the absence of decreased neutrophil counts. Patients should be monitored closely with baseline and periodic monitoring and clinical and laboratory evaluations. While fever may be associated with the flu-like syndrome reported commonly during interferon therapy, other causes of high or persistent fever must be ruled out, particularly in patients with reduced neutrophil counts. Appropriate anti-infective therapy should be started immediately and discontinuation of peginterferon alfa-2a therapy should be considered.

Autoimmune disease, idiopathic thrombocytopenic purpura (ITP), psoriasis, rheumatoid arthritis, systemic lupus erythematosus (SLE), thrombotic thrombocytopenic purpura (TTP)

Peginterferon alfa-2a should be used with caution in patients with a history of autoimmune disease. Peginterferon alfa-2a is contraindicated for use in patients with autoimmune hepatitis. Development or exacerbation of autoimmune diseases (e.g., myositis, hepatitis, thrombotic thrombocytopenic purpura (TTP), immune thrombocytopenic purpura (ITP), thyroiditis, thrombocytopenia, rheumatoid arthritis, interstitial nephritis, systemic lupus erythematosus (SLE), or psoriasis) has been observed in patients receiving alpha interferons. Patients should be monitored closely with periodic clinical and laboratory evaluations. Peginterferon alfa-2a should be discontinued in patients with persistently severe or worsening signs or symptoms of these conditions. In many, but not all cases, these disorders resolve after stopping peginterferon alfa-2a.

Angina, cardiac arrhythmias, cardiac disease, cardiomyopathy, cerebrovascular disease, coronary artery disease, hypertension, myocardial infarction, stroke

Ischemic and other cerebrovascular and cardiovascular events (e.g., hypertension, supraventricular arrhythmias, cardiomyopathy, chest pain, unstable angina pectoris, myocardial infarction, stroke) have been observed in patients treated with peginterferon alfa-2a. Some events occurred in patients with few or no reported risk factors. The drug should be used cautiously in patients with cardiac disease (including coronary artery disease) or cerebrovascular disease. Common adverse effects of peginterferon alfa-2a such as fever and chills may exacerbate preexisting cardiac conditions. Patients with a history of myocardial infarction and cardiac arrhythmias should be closely monitored, with baseline and periodic monitoring and clinical and laboratory evaluations. An electrocardiogram (ECG) is recommended prior to initiating therapy in such patients. Ischemic and hemorrhagic cerebrovascular events (e.g., strokes) have been observed in patients treated with interferon alfa-based therapies, including peginterferon alfa-2a. Events occurred in patients with few or no reported risk factors for stroke, including patients less than 45 years of age. Because these are spontaneous reports, estimates of frequency cannot be made, and a causal relationship between interferon alfa-based therapies and these events is difficult to establish. Peginterferon alfa-2a should be discontinued in patients with persistently severe or worsening signs or symptoms of these conditions. In many, but not all cases, these disorders resolve after stopping peginterferon alfa-2a. Because cardiac disease may be worsened by ribavirin-induced hemolytic anemia, patients with a history of significant or unstable cardiac disease should not receive combination therapy with ribavirin.

Contraception requirements, pregnancy, pregnancy testing, use with ribavirin

There are no adequate and well-controlled studies evaluating use of peginterferon alfa-2a in pregnant women. Peginterferon alfa-2a should be assumed to have abortifacient potential based on studies in pregnant Rhesus monkeys, which showed a statistically significant increase in abortions. No teratogenic effects were seen in the offspring delivered at term. Peginterferon alfa-2a monotherapy may be administered to women of childbearing potential only after a confirmed negative pregnancy test. Advise female patients to use effective contraception requirements during therapy. Ribavirin use with peginterferon alfa-2a poses additional risks during pregnancy, and clinicians should be fully aware of the contraindications, as well as the proper use and monitoring for ribavirin therapy. Peginterferon alfa-2a use with ribavirin is contraindicated in women who are pregnant and men whose female partners are pregnant. Ribavirin may cause birth defects and death of the unborn child (intrauterine fetal death), and is genotoxic and mutagenic. Extreme care must be taken to avoid pregnancy in female patients and in female partners of male patients if ribavirin is prescribed. Females drug recipients and female partners of male drug recipients must undergo pregnancy testing before starting peginterferon alfa-2a and ribavirin combination therapy, every month while being treated, and every month for the 6 months after treatment is discontinued. Contraceptive requirements exist for both males and females of childbearing potential in whom both ribavirin and peginterferon alfa-2a are prescribed. Both men and women of childbearing potential must use 2 forms of effective contraception during treatment and for 6 months after combination treatment discontinuation. If a female or the female sexual partner of a treated male becomes pregnant while taking peginterferon alfa-2a and ribavirin or within 6 months after discontinuation of treatment, the healthcare provider should be informed right away. The Ribavirin Pregnancy Registry (1-800-593-2214) should be contacted.

Common Brand Names

Pegasys

Dea Class

Rx

Description

Covalent conjugate of recombinant interferon alfa-2a with PEG
Used to treat chronic HCV infections in patients 5 years and older, and chronic HBV infections in patients 3 years and older
Improved tolerability when compared with interferon alfa-2a

Dosage And Indications
For the treatment of chronic hepatitis C infection in patients with compensated liver disease.
NOTE: The vials and prefilled syringes are not directly interchangeable. The same amount of drug will not be provided by equal volumes. The 1 mL vial and the 0.5 mL prefilled syringe both provide 180 mcg peginterferon alfa-2a.
NOTE: Patients who have failed other alfa interferon treatments, must receive peginterferon alfa-2a in combination with BOTH ribavirin AND an HCV direct-acting antiviral (DAA).
NOTE: Safety and efficacy have not been established in patients who are liver or other organ transplant recipients, are coinfected with hepatitis B, or are coinfected with HIV with a CD4 cell count less than 100 cells/mm3.
For the treatment of chronic hepatitis C as monotherapy.
NOTE: Monotherapy is not recommended unless there are contraindications or substantial intolerance to other HCV antiviral therapies. The efficacy of peginterferon alfa-2a is enhanced when used in combination with other HCV therapies.
Subcutaneous dosage Adults WITHOUT HIV coinfection

180 mcg subcutaneously once weekly for 48 weeks. Consider treatment discontinuation if there is not at least a 2 log10 reduction in HCV RNA from baseline by 12 weeks or if the HCV RNA is detectable after 24 weeks.

For the treatment of chronic hepatitis C in combination with ribavirin alone. Subcutaneous dosage Adults WITHOUT HIV coinfection

180 mcg subcutaneously once weekly plus daily ribavirin for 24 or 48 weeks depending upon the viral genotype. For genotypes 1 or 4, a treatment duration of 48 weeks is recommended. For HCV genotypes 2 or 3, a treatment duration of 24 weeks is recommended. Data on genotypes 5 and 6 are insufficient for dosing recommendations. Consider treatment discontinuation if there is not at least a 2 log10 reduction in HCV RNA from baseline by 12 weeks or if the HCV RNA is detectable after 24 weeks.

Adults WITH HIV coinfection

180 mcg subcutaneously once weekly plus daily ribavirin for 48 weeks, regardless of genotype. Consider treatment discontinuation if there is not at least a 2 log10 reduction in HCV RNA from baseline by 12 weeks or if the HCV RNA is detectable after 24 weeks.

Children and Adolescents 5 years and older

180 mcg/1.73 m2 x BSA subcutaneously once weekly (max: 180 mcg/week) plus ribavirin. Duration of treatment is 24 weeks for genotype 2 and 3 and 48 weeks for all other genotypes. Consider treatment discontinuation if there is not at least a 2 log10 reduction in HCV RNA from baseline by 12 weeks or if the HCV RNA is detectable after 24 weeks. Patients who reach their 18th birthday while on therapy should remain on the pediatric dosing regimen.

For the treatment of chronic hepatitis C as part of combination therapy with ribavirin and HCV direct-acting antivirals (DAA). Subcutaneous dosage Adults

180 mcg subcutaneously once weekly plus daily ribavirin and an HCV direct-acting antiviral (DAA). The treatment duration of the entire regimen is dependent upon the specific DAA selected and the HCV genotype being treated.

For the treatment of chronic hepatitis B infection. Subcutaneous dosage Adults

180 mcg subcutaneously once weekly for 48 weeks. Peginterferon alfa-2a is FDA-approved for the treatment of adults with HBeAg-positive and HBeAg-negative chronic hepatitis B infection who have compensated liver disease with evidence of viral replication and liver inflammation.

Children and Adolescents 3 to 17 years

180 mcg/1.73 m2 x BSA (Max: 180 mcg/dose) subcutaneously once weekly for 48 weeks. Maintain the recommended pediatric dosage throughout the entire duration of therapy in children who turn 18 years during treatment. Peginterferon alfa-2a is FDA-approved for the treatment of HBeAg-positive chronic hepatitis B infection in non-cirrhotic children with evidence of viral replication and elevations in serum alanine aminotransferase.

Dosing Considerations
Hepatic Impairment

Patients with decompensated hepatic disease (e.g., Child-Pugh class B or C) should not be treated with peginterferon alfa-2a. Peginterferon alfa-2a is also contraindicated for use in patients with autoimmune hepatitis. If ALT increases are progressive despite dose reduction or are accompanied by increased bilirubin or evidence of hepatic decompensation, immediately discontinue therapy.
 
Adult patients with chronic hepatitis C: In patients with progressive ALT increases above baseline values, reduce the dose to 135 mcg SC once weekly and perform more frequent liver function monitoring. Peginterferon alfa-2a may be resumed after the ALT flare has subsided.
 
Adult patients with chronic hepatitis B: In patients with ALT values greater than 5 times the upper limit of normal, consider dose reduction to 135 mcg SC once weekly or temporary drug discontinuation and perform more frequent liver function monitoring. Peginterferon alfa-2a may be resumed after ALT flares subside. Therapy discontinuation may be appropriate for patients with persistent ALT elevations more than 10 times the upper limit of normal.
 
Children and Adolescents with chronic hepatitis C:
-For alanine transaminase (ALT) > 5 but < 10 x upper limit of normal (ULN) in children and adolescents: Reduce dose to 135 mcg/1.73 m2 x BSA SC once weekly. If necessary, further modify dose until stable or ALT concentrations decrease.
-For persistent alanine transaminase (ALT) > 10 x ULN in children and adolescents: Discontinue treatment.

Renal Impairment

NOTE: In all patients, estimate the creatinine clearance before peginterferon alfa-2a initiation. Due to a lack of data, dosage recommendations cannot be made for pediatric patients with renal impairment.
CrCl >= 30 ml/min: No dosage adjustment needed.
CrCl < 30 ml/min (Adults): Reduce dose to 135 mcg SC once weekly and closely monitor for signs and symptoms of interferon toxicity. If severe adverse reactions or laboratory abnormalities develop, the dose may be further reduced to 90 mcg SC once weekly until the adverse reactions abate. If intolerance persists after dose adjustment, discontinue peginterferon alfa-2a.
 
Intermittent hemodialysis
Adults: 135 mcg SC once weekly. Monitor patients closely for the potential for reduced efficacy and for signs and symptoms of interferon toxicity. If severe adverse reactions or laboratory abnormalities develop, the dose may be reduced to 90 mcg SC once weekly until the adverse reactions abate. If intolerance persists after dose adjustment, discontinue peginterferon alfa-2a.

Drug Interactions

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.
Aldesleukin, IL-2: (Moderate) Myocardial injury, exacerbation or the initial presentation of autoimmune and inflammatory disorders, and hypersensitivity reactions appear to be increased in patients receiving aldesleukin, IL-2 and alpha interferons concurrently.
Alemtuzumab: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
Alteplase: (Moderate) An increased risk of bleeding may occur when thrombolytic agents are used following agents that cause clinically significant thrombocytopenia including antineoplastic agents.
Altretamine: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
Arsenic Trioxide: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
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.
Azathioprine: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
Bacillus Calmette-Guerin Vaccine, BCG: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient, including those receiving Interferon therapy. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Basiliximab: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
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.
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.
Estramustine: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
Filgrastim, G-CSF: (Major) Filgrastim induces the proliferation of neutrophil-progenitor cells, and, because antineoplastic agents exert toxic effects against rapidly growing cells, filgrastim is contraindicated for use during the 24 hours before or after cytotoxic chemotherapy.
Folate analogs: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
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.
Hydroxyurea: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
Ibritumomab Tiuxetan: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
Imatinib: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
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.
Intranasal Influenza Vaccine: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient, including those receiving Interferon therapy. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
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).
Live Vaccines: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient, including those receiving Interferon therapy. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Lomustine, CCNU: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
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.
Measles Virus; Mumps Virus; Rubella Virus; Varicella Virus Vaccine, Live: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient, including those receiving Interferon therapy. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Measles/Mumps/Rubella Vaccines, MMR: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient, including those receiving Interferon therapy. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Methadone: (Major) Addition of peginterferon alfa-2a 180 mcg SC once weekly to methadone maintenance therapy resulted in 10 to 15% higher mean methadone pharmacokinetic parameter values after 4 weeks of dual therapy as compared with baseline values. The pharmacokinetic parameter values of peginterferon alfa-2a were not altered by methadone. Patients received a median methadone dose of 95 mg (range, 30150 mg). If both drugs will be used concomitantly, the dosage of methadone may need to be lowered. Patients need to be cautioned to not drive or operate machinery until the effects of both drugs on them are known.
Methotrexate: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
Methoxsalen: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
Methylprednisolone: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
Mitoxantrone: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
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.
Pegfilgrastim: (Major) Pegfilgrastim induces the proliferation of neutrophil-progenitor cells, and because antineoplastic agents exert toxic effects against rapidly growing cells, pegfilgrastim should not be given 14 days before or for 24 hours after cytotoxic chemotherapy.
Pemetrexed: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
Pexidartinib: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with peginterferon alfa-2a. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
Pralatrexate: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
Prednisolone: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
Prednisone: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
Pretomanid: (Major) Avoid coadministration of pretomanid with peginterferon alfa-2a, 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.
Purine analogs: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
Reteplase, r-PA: (Moderate) An increased risk of bleeding may occur when thrombolytic agents are used following agents that cause clinically significant thrombocytopenia including antineoplastic agents.
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 alfa-2a. 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.
Rotavirus Vaccine: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient, including those receiving Interferon therapy. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
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.
Smallpox and Monkeypox Vaccine, Live, Nonreplicating: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient, including those receiving Interferon therapy. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Smallpox Vaccine, Vaccinia Vaccine: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient, including those receiving Interferon therapy. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
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).
Tbo-Filgrastim: (Major) Filgrastim induces the proliferation of neutrophil-progenitor cells, and, because antineoplastic agents exert toxic effects against rapidly growing cells, filgrastim is contraindicated for use during the 24 hours before or after cytotoxic chemotherapy.
Tenecteplase: (Moderate) An increased risk of bleeding may occur when thrombolytic agents are used following agents that cause clinically significant thrombocytopenia including antineoplastic agents.
Theophylline, Aminophylline: (Major) Alpha interferons, when administered systemically, may decrease the clearance of aminophylline resulting in increased plasma concentrations. Concomitant use may result in a significant increase in theophylline concentrations due to reduced aminophylline clearance. In studies, increases in theophylline levels of 25% up to 100% have occurred. Reductions in CYP1A2 activity have been noted with various alpha interferons, and likely provide a mechanism for the interaction. Monitor theophylline concentrations and for signs and symptoms of toxicity when interferons are used concomitantly; consider appropriate dose adjustments as clinically indicated. (Major) Alpha interferons, when administered systemically, may decrease the clearance of theophylline resulting in increased plasma concentrations. Concomitant use may result in a significant increase in theophylline concentrations due to reduced theophylline clearance. In studies, increases in theophylline levels of 25% up to 100% have occurred. Reductions in CYP1A2 activity have been noted with various alpha interferons, and likely provide a mechanism for the interaction. Monitor theophylline concentrations and for signs and symptoms of theophylline toxicity when interferons are used concomitantly; consider appropriate dose adjustments as clinically indicated.
Thrombolytic Agents: (Moderate) An increased risk of bleeding may occur when thrombolytic agents are used following agents that cause clinically significant thrombocytopenia including antineoplastic agents.
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.
Tositumomab: (Moderate) Use of alpha interferons are associated with myelosuppression; additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
Tretinoin, ATRA: (Moderate) Use of alpha interferons are associated with myelosuppression; additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
Typhoid Vaccine: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient, including those receiving Interferon therapy. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Varicella-Zoster Virus Vaccine, Live: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient, including those receiving Interferon therapy. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
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.
Yellow Fever Vaccine, Live: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient, including those receiving Interferon therapy. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
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.

How Supplied

Pegasys/Peginterferon Alfa-2a Subcutaneous Inj Sol: 0.5mL, 1mL, 180mcg

Maximum Dosage
Adults

180 mcg/week subcutaneously.

Geriatric

180 mcg/week subcutaneously.

Adolescents

180 mcg/1.73 m2 x BSA subcutaneously once weekly, up to a maximum of 180 mcg weekly.

Children

5 years and older: 180 mcg/1.73 m2 x BSA subcutaneously once weekly, up to a maximum of 180 mcg weekly.
3 to 4 years: 180 mcg/1.73 m2 x BSA subcutaneously once weekly, up to a maximum of 180 mcg weekly for chronic hepatitis B; safety and efficacy for hepatitis C have not been established.
Younger than 3 years: Safety and efficacy have not been established.

Infants

Use not recommended.

Neonates

Use not recommended.

Mechanism Of Action

Mechanism of Action: The active component of peginterferon alfa-2a is the interferon alfa-2a moiety. Interferon alfa-2a acts similarly to native interferon alpha. Endogenous alpha-interferons (IFNs) are secreted by leukocytes (e.g., macrophages, B lymphocytes, and non-B non-T lymphocytes) in response to viral infection or various synthetic and biological inducers. All alpha-IFNs share common biologic activities generated by the binding of interferon to the cell-surface receptor. Although the exact mechanism of action is not fully understood, interferon binding to the cell surface receptor is followed by activation of tyrosine kinases, which leads to the production of several IFN-stimulated enzymes such as 2'-5'-oligoadenylate synthetase (2'-5'-OAS) and beta2-microglobulin. These and possibly other IFN-stimulated enzymes are thought to be responsible for the pleiotropic biologic effects of alpha-IFNs, which include antiviral, antiproliferative and immunomodulatory effects, cellular differentiation, regulation of cell surface major histocompatibility antigen expression (HLA class I), and cytokine induction.•Antiviral effects: Interferon exerts antiviral effects by augmenting the production and/or release of specific enzymes. Interferon-induced intracellular enzymes such as 2'5'-OAS and protein kinase contribute to inhibition of viral replication by activating endoribonucleases that cleave single-stranded viral RNA. Thus, translation of viral proteins is inhibited. The activity of IFN-induced enzymes depends on the presence of double-stranded RNA (dsRNA) formed during viral replication. It has been suggested that the antiviral activity of IFNs may be related, in part, to an effect on dsRNA. Interferon-induced enzymes may also inhibit viral penetration and uncoating, and/or viral assembly and release. Expression of major histocompatibility antigens by IFNs may also contribute to antiviral activity by enhancing the lytic effects of cytotoxic T lymphocytes.A wide range of viruses, particularly RNA viruses, are sensitive to the antiviral actions of IFN. Alpha interferons are generally active against the following viruses in vitro: adenovirus; coronavirus; encephalomyocarditis virus; hepatitis B virus; hepatitis C virus (HCV); hepatitis D virus; herpes simplex virus type 1; herpes simplex virus type 2; human immunodeficiency virus (HIV); papillomavirus; poliovirus; rhinovirus; vaccinia virus; varicella-zoster virus; vesicular stomatitis virus; human T-lymphotropic virus type I (HTLV-I). In chronic hepatitis C, INF treatment is associated with normalization of ALT and reduction of serum HCV RNA, as well as improvement in liver histopathology, in responding patients. The HCV genotype 1 is more resistant to interferon alfa treatment than other viral genotypes; 75% of persons in the United States infected with HCV carry this genotype. Many patients with a biochemical and virologic response relapse 1—2 months after stopping IFN therapy.•Effect on hepatic microsomal enzymes: Alpha interferons may inhibit microsomal enzymes involved in the hepatic cytochrome P-450 system. The effect of interferon on the CYP450 system may be related to increased enzyme degradation, suppressed enzyme synthesis, or inhibition of cytochrome P-450. Implications of this effect have not been fully evaluated, but the metabolism of certain drugs may be affected (see Drug Interactions).

Pharmacokinetics

Peginterferon alfa-2a is given subcutaneously (SC). In patients with hepatitis C infection, the mean elimination half-life of peginterferon alfa-2a (i.e., Pegasys) is 80 hours (range 50—140 hours) as compared with 5.1 hours (range 3.7—8.5 hours) for interferon alfa-2a (i.e., Roferon-A). When compared to interferon alfa-2a in healthy patients, the mean systemic clearance of peginterferon alfa-2a is approximately 100-fold lower, allowing for a reduced dosing frequency.

Subcutaneous Route

Following a single SC dose, the mean absorption half-life is 4.6 hours. Maximal concentrations occur between 72 and 96 hours post dose and are sustained for 168 hours. With multiple dosing there is an increase in peginterferon alfa-2a bioavailability. Steady-state serum concentrations are reached within 5—8 weeks of once weekly dosing. Mean trough concentrations (16 ng/ml) at week 48 of treatment are roughly 2-fold higher than the trough concentrations (8 ng/ml) at week 1 of treatment.

Pregnancy And Lactation
Pregnancy

There are no adequate and well-controlled studies evaluating use of peginterferon alfa-2a in pregnant women. Peginterferon alfa-2a should be assumed to have abortifacient potential based on studies in pregnant Rhesus monkeys, which showed a statistically significant increase in abortions. No teratogenic effects were seen in the offspring delivered at term. Peginterferon alfa-2a monotherapy may be administered to women of childbearing potential only after a confirmed negative pregnancy test. Advise female patients to use effective contraception requirements during therapy. Ribavirin use with peginterferon alfa-2a poses additional risks during pregnancy, and clinicians should be fully aware of the contraindications, as well as the proper use and monitoring for ribavirin therapy. Peginterferon alfa-2a use with ribavirin is contraindicated in women who are pregnant and men whose female partners are pregnant. Ribavirin may cause birth defects and death of the unborn child (intrauterine fetal death), and is genotoxic and mutagenic. Extreme care must be taken to avoid pregnancy in female patients and in female partners of male patients if ribavirin is prescribed. Females drug recipients and female partners of male drug recipients must undergo pregnancy testing before starting peginterferon alfa-2a and ribavirin combination therapy, every month while being treated, and every month for the 6 months after treatment is discontinued. Contraceptive requirements exist for both males and females of childbearing potential in whom both ribavirin and peginterferon alfa-2a are prescribed. Both men and women of childbearing potential must use 2 forms of effective contraception during treatment and for 6 months after combination treatment discontinuation. If a female or the female sexual partner of a treated male becomes pregnant while taking peginterferon alfa-2a and ribavirin or within 6 months after discontinuation of treatment, the healthcare provider should be informed right away. The Ribavirin Pregnancy Registry (1-800-593-2214) should be contacted.