CONTRAINDICATIONS / PRECAUTIONS
E. coli protein hypersensitivity, risk of serious hypersensitivity reactions or anaphylaxis, serious rash
Peginterferon alfa-2b is contraindicated in patients with known hypersensitivity reactions to alpha interferons, including peginterferon alfa-2b or any of its components. There is a risk of serious hypersensitivity reactions or anaphylaxis with peginterferon alfa-2b, including angioedema, acute bronchospasm, urticaria, or other allergic-type events. Such reactions have also been observed during alpha interferon and ribavirin therapy. Serious rash, including vesiculobullous eruptions, reactions in the spectrum of Stevens-Johnson Syndrome (erythema multiforme major) with varying degrees of skin and mucosal involvement, toxic epidermal necrolysis (TEN), and exfoliative dermatitis (erythroderma) have been reported in patients receiving peginterferon alfa-2b with and without ribavirin. Patients developing signs or symptoms of severe skin reactions or severe hypersensitivity must discontinue therapy. Institute appropriate medical treatment. Pegnterferon alfa-2b is produced using recombinant DNA technology using Escherichia coli; do not use in patients with E. coli protein hypersensitivity.
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-2b, 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-2b 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-2b 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 or performing other hazardous tasks until they know how peginterferon alfa-2b therapy will affect them. EEG abnormalities and seizures have been reported in post-market use and peginterferon alfa-2b 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-2b, 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-2b. Suppression of the bone marrow due to peginterferon alfa-2b 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-2b therapy should be considered.
Anemia, aplastic anemia, bleeding, bone marrow suppression, human immunodeficiency virus (HIV) infection, neutropenia, organ transplant, sickle cell disease, thalassemia, thrombocytopenia
Peginterferon alfa-2b suppresses bone marrow function and may result in severe cytopenias, including anemia, neutropenia, lymphopenia, and thrombocytopenia. Peginterferon alfa-2b is associated with decreases in white cell, neutrophil, and platelet counts during the first 2 weeks of therapy. Very rarely, alpha interferons may be associated with aplastic anemia. Complete blood counts (CBC) should be obtained pretreatment and monitored routinely during therapy. Peginterferon alfa-2b should be discontinued, at least temporarily, in patients who develop severe decreases in neutrophil and/or platelet counts. Bleeding or serious infectious disorders may occur due to bone marrow suppression. In many, but not all cases, these disorders resolve after stopping peginterferon alfa-2b. Anemia from peginterferon alfa-2b may complicate the management of other blood disorders, such as thalassemia or sickle cell disease. Patients who develop neutropenia or thrombocytopenia during treatment require dosage adjustment of peginterferon alfa-2b therapy; patients that develop severe decreases in neutrophil or platelet counts should discontinue peginterferon alfa-2b treatment, at least temporarily. Severe neutropenia and thrombocytopenia occur with a greater incidence in those with human immunodeficiency virus (HIV) infection and may place them at greater infectious and bleeding risk; use cautiously if the CD4 cell count is less than 350 cells/mcL. Safety and efficacy have not been established in patients with liver or other organ transplant. Patients receiving immunosuppressive therapy due to an organ transplant may have increased risk for bone marrow suppression. As with other alpha interferons, liver and renal graft rejections have been reported in patients receiving peginterferon alfa-2b. Certain medications may increase the risk for severe bone marrow suppression. Ribavirin co-therapy may potentiate the neutropenia and lymphopenia induced by alpha interferons. Peginterferon alfa-2b/ribavirin combination therapy should be used with caution in patients with baseline neutrophil counts less than 1500/mm3, platelet counts less than 90,000/mm3, or anemia (hemoglobin less than 10 grams/dL). Pancytopenia and bone marrow suppression have been reported in the literature to occur within 3 to 7 weeks after the concomitant administration of peginterferon/ribavirin combination treatment and azathioprine. Myelotoxicity was reversible within 4 to 6 weeks upon withdrawal of both peginterferon/ribavirin therapy and concomitant azathioprine and did not recur upon reintroduction of either treatment alone. Discontinue therapy for pancytopenia, and do not re-introduce peginterferon/ribavirin treatment with azathioprine.
Ethanol ingestion, hepatic decompensation, hepatic disease, hepatitis, hepatitis C and HIV coinfection, jaundice
Peginterferon alfa-2b, increases the risk of hepatic decompensation and death in patients with cirrhosis, including chronic hepatitis C (CHC) patients. Peginterferon alfa-2b is contraindicated for use by patients with autoimmune hepatitis and in patients with hepatic decompensation (Child-Pugh score greater than 6, class B and C) before treatment. Patients with non-compensated cirrhosis may experience worsening hepatic disease including, but not limited to, jaundice, hepatic failure, and death after peginterferon alfa-2b treatment. Monitor hepatic function with serum bilirubin, ALT, AST, alkaline phosphatase, and LDH at 2, 8, and 12 weeks after peginterferon alfa-2b initiation and then every 6 months. Any patient developing liver function test (LFT) abnormalities during peginterferon alfa-2b therapy should receive more frequent monitoring of liver function tests (LFTs); consider dose reduction. Patients who experience progressive ALT increases above baseline concentrations require dosage adjustment. If increases are progressive despite reduction of peginterferon alfa-2b dose or are accompanied by hyperbilirubinemia, immediately discontinue peginterferon alfa-2b. Permanently discontinue for evidence of severe (Grade 3) hepatic injury or hepatic decompensation (Child-Pugh score greater than 6, class B and C) during treatment. Also, patients with chronic hepatitis C and HIV coinfection with cirrhosis receiving highly active antiretroviral therapy (HAART) and alpha interferons with or without ribavirin appear to be at increased risk for the development of hepatic decompensation as compared with patients not receiving HAART. HIV treatment guidelines recommend hepatitis C and HIV coinfected patients be treated for both viral infections concurrently. For most patients, the benefits of concurrent therapy outweighs the potential risks (i.e., drug-induced hepatic injury, complex drug interactions, overlapping toxicities); therefore, it is recommended to initiate a fully suppressive antiretroviral (ARV) therapy and a hepatitis C regimen in all coinfected patients regardless of CD4 count. However, for antiretroviral naive patients with CD4 counts greater than 500 cells/mm3, consideration may be given to deferring ARV until the hepatitis C treatment regimen has been completed. Conversely, for patients with CD4 counts less than 200 cells/mm3, consider delaying initiation of the hepatitis C treatment regimen until the patient is stable on fully suppressive ARV regimen. Instruct coinfected patients to avoid ethanol ingestion, and offer vaccinations against hepatitis A and hepatitis B as appropriate.
Autoimmune disease, idiopathic thrombocytopenic purpura (ITP), psoriasis, rheumatoid arthritis, systemic lupus erythematosus (SLE), thrombotic thrombocytopenic purpura (TTP)
Peginterferon alfa-2b should be used with caution in patients with a history of autoimmune disease. Peginterferon alfa-2b 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-2b 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-2b.[29627] [43887]
Graves' disease, hyperthyroidism, hypothyroidism, thyroid disease
Patients with thyroid disease (e.g., hyperthyroidism or hypothyroidism) whose thyroid stimulating hormone (TSH) serum concentration cannot be maintained in the normal range by medication should not be treated with peginterferon alfa-2b. If the TSH concentration can be maintained within the normal range, TSH concentration assessment is recommended before treatment, at 3 and 6 months following initiation, then every 6 months thereafter while receiving the drug. If the TSH concentration cannot be controlled with medications, peginterferon alfa-2b should be discontinued. Also, the development or exacerbation of autoimmune thyroid diseases (e.g., Graves' disease, thyroiditis) has been observed in patients receiving peginterferon alfa-2b. Patients should be monitored closely with periodic clinical and laboratory evaluations. Peginterferon alfa-2b should be discontinued in patients with persistently severe or worsening signs or symptoms of autoimmune thyroid disease. In many, but not all cases, autoimmune disorders resolve after stopping peginterferon alfa-2b.
Diabetes mellitus, hyperglycemia, hypoglycemia
Hyperglycemia, hypoglycemia, and diabetes mellitus have been observed to develop in patients treated with peginterferon alfa-2b. Patients with these conditions at baseline who cannot be effectively treated by medication should not begin peginterferon alfa-2b therapy. Patients who develop these conditions during treatment and cannot be controlled with medication may require discontinuation of peginterferon alfa-2b therapy.
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-2b. 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-2b 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-2b. 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-2b 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-2b. 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.
Pneumonitis, pulmonary disease, pulmonary hypertension, respiratory insufficiency, sarcoidosis
Dyspnea, pulmonary infiltrates, pneumonia, bronchiolitis obliterans, interstitial pneumonitis, pulmonary hypertension, and sarcoidosis, some resulting in respiratory failure or patient deaths, may be induced or aggravated by peginterferon alfa-2b or alpha interferon therapy. Recurrence of respiratory insufficiency and failure has been observed with interferon rechallenge. Peginterferon alfa-2b combination treatment should be suspended in patients who develop pulmonary infiltrates or pulmonary function impairment. Patients who resume peginterferon treatment should be closely monitored. Use with caution in patients with known pulmonary disease.
Dialysis, renal failure, renal impairment
Patients with renal impairment or renal failure are at increased risk of toxicity and should be closely monitored while receiving peginterferon alfa-2b. The mean exposure (AUC) to peginterferon alfa-2b was increased in subjects with moderate and severe renal impairment or end-stage renal disease (ESRD) requiring dialysis, as compared to subjects with normal renal function. Reduced dosing for peginterferon alfa-2b monotherapy is recommended in patients with both moderate and severe renal impairment and peginterferon alfa-2b should be discontinued in patients whose renal function continues to decline during treatment. Permanent peginterferon alfa-2b discontinuation is advised for pediatric patients 3—17 years of age with a serum creatinine (SCr) greater than 2 mg/dL. When used in conjunction with ribavirin, peginterferon alfa-2b should not be used in patients with CrCl less than 50 mL/min. Renal transplant patients may have an increased risk for renal failure with combination therapy use. In a single-center, uncontrolled case experience, renal failure in 16 renal allograft recipients receiving interferon alpha and ribavirin was more frequent than expected from the center's previous experience with renal allograft recipients not receiving combination therapy. The relationship of the renal failure to renal allograft rejection is not clear. The safety and efficacy of peginterferon alfa-2b alone or in combination with ribavirin have not been studied in organ transplant recipients.
Colitis, ischemic colitis, ulcerative colitis
Fatal and nonfatal ulcerative colitis and hemorrhagic or ischemic colitis have been observed within 12 weeks of the start of alpha interferon treatment. Abdominal pain, bloody diarrhea, and fever are the typical manifestations. Peginterferon alfa-2b treatment should be discontinued immediately in patients who develop these signs and symptoms. The colitis usually resolves within 1 to 3 weeks of discontinuation of alpha interferon.
Hypertriglyceridemia, pancreatitis
Pancreatitis, sometimes fatal, has occurred during alpha interferon and ribavirin treatment. Peginterferon alfa-2b/ribavirin combination treatment should be suspended if symptoms or signs suggestive of pancreatitis are observed. Discontinue in patients who are diagnosed with pancreatitis. Triglyceride levels are commonly elevated in subjects receiving alpha interferon therapy and were elevated in the majority of subjects participating in clinical studies receiving either peginterferon alfa-2b alone or in combination with ribavirin. Hypertriglyceridemia may occur or worsen; monitor triglycerides during therapy and watch for pancreatitis symptoms in at-risk patients.
Diabetic retinopathy, ocular disease, optic neuritis, papilledema, retinal bleeding, retinal detachment, visual disturbance
Decrease or loss of vision, retinopathy including macular edema, retinal artery or vein thrombosis, retinal bleeding and cotton wool spots, optic neuritis, papilledema and serous retinal detachment are induced or aggravated by treatment with peginterferon alfa-2b or other alpha interferons. All patients should receive an eye examination at baseline. Patients with pre-existing ocular disease (e.g., hypertensive or diabetic retinopathy) should receive periodic ophthalmologic exams during interferon alpha treatment. Any patient who develops ocular symptoms or visual disturbance should receive a prompt and complete eye examination. Discontinue treatment in patients who develop new or worsening ophthalmologic disorders.
Geriatric
Younger adult patients typically have higher virologic response rates than older patients. Clinical studies of peginterferon alfa-2b alone or in combination with ribavirin did not include sufficient numbers of subjects 65 years of age or over to determine whether they respond differently from younger adults. Adverse reactions related to alpha interferons, such as CNS, cardiac, and systemic (e.g., flu-like) effects may be more severe in the geriatric patient. Also, peginterferon alfa-2b is excreted by the kidney, and the risk of toxic reactions may be greater in patients with impaired renal function, including geriatric patients. Use with caution and with appropriate dose adjustments for renal function.
Pregnancy, use with ribavirin
Data regarding use of peginterferon alfa-2b (as monotherapy) during human pregnancy are insufficient to assess the risk for major birth defects, miscarriages, or adverse maternal or fetal outcomes; however, in animal studies, administration of interferon to rhesus monkeys during organogenesis resulted in increased abortion and premature infant deaths. Before initiating peginterferon alfa-2b monotherapy, counsel pregnant women of the potential risks the fetus. Peginterferon alfa-2b use with ribavirin is contraindicated in women who are or may become pregnant and in men whose female partners are pregnant; as ribavirin has been associated with an increased risk for birth defects, intrauterine fetal death, and male-mediated teratogenicity. Females (or the female sexual partner of a treated male) who become pregnant while taking peginterferon alfa-2b and ribavirin or within 6 months after discontinuation of treatment should report the pregnancy to the Ribavirin Pregnancy Registry at 1-800-593-2214.[29627] [43887]
Contraception requirements, infertility, pregnancy testing, reproductive risk
Counsel patients about the reproductive risk and contraception requirements during peginterferon alfa-2b treatment. All females or reproductive potential should use effective contraception during therapy. If peginterferon alfa-2b is given with ribavirin for the treatment of chronic hepatitis C, females of reproductive potential must have a negative pregnancy test prior to therapy, use at least 2 forms of contraception during therapy, and undergo monthly pregnancy tests due to the risk of birth defects and fetal death with ribavirin. Pregnancy testing should be performed prior to initiating therapy in females of reproductive potential who are receiving peginterferon alfa-2b for the treatment of melanoma. These patients should use effective contraception during therapy and for at least 10 days after the final peginterferon alfa-2b dose. Peginterferon alfa-2b may cause infertility in female patients, based on data from animal studies. Menstrual cycle irregularities were observed in female cynomolgus monkeys following subcutaneous administration of peginterferon alfa-2b at doses that were much higher than the recommended weekly human dose (based on body surface area).[29627] [43887]
Breast-feeding
It is not known if peginterferon alfa-2b is secreted in human milk or if it has effects on the breast-fed infant or on milk production. Non-pegylated interferon alfa-2b is present in human milk at low concentrations. Consider the benefits of breast-feeding versus the risk to the fetus in breastfeeding women who are receiving peginterferon alfa-2b for the treatment of melanoma.[43887] Because of the potential for adverse reactions from the drug in a nursing infant, discontinue breast-feeding or discontinue peginterferon alfa-2b in breastfeeding women who are receiving peginterferon alfa-2b for the treatment of chronic hepatitis C infection.[29627] A case report involving 2 pregnant women receiving interferon alfa treatment has been published. In an analysis immediately postpartum, interferon concentrations in the breast milk (1.4 units/mL and 6 units/mL) were considerably lower than the maternal serum concentrations (20.8 units/mL and 58 units/mL, respectively).[48506]
Children, growth inhibition, infants, neonates
The safety and efficacy of peginterferon alfa-2b in neonates, infants and children less than 3 years of age with chronic hepatitis C have not been established. Use of peginterferon alfa-2a/ribavirin has been associated with growth inhibition in children and adolescents 3 years of age and older; monitor growth carefully in these patients. In general, the weight and height gain of pediatric drug recipients lags behind that predicted by normative population data for the entire length of treatment. Severe inhibition of growth velocity (less than the 3rd percentile) has been observed in 70% of pediatric patients while on treatment. In most cases, rebound growth and weight gains occur after treatment discontinuation. However, long-term follow-up data suggest combination therapy may induce growth inhibition that results in reduced adult height in some patients. The greatest risk appears to correlate with initiation of combination therapy during the years of expected peak growth velocity.
Dental disease, dental work
Dental disease and periodontal disorders have been reported in patients receiving peginterferon alfa-2b and ribavirin combination therapy. Dry mouth due to peginterferon alfa/ribavirin combination therapy can impact oral health. Patients should check with their healthcare provider before having any dental work completed. Myelosuppressive effects of peginterferon alfa-2b may increase the risk of infection and bleeding during dental procedures. However, it is important for treated patients to receive regular dental care and emergency treatment when necessary. Patients should report any signs of oral infection or unusual bleeding. Patients should be instructed in proper oral hygiene, including gentle brushing and flossing of teeth and receiving regular dental exams.
Hepatitis B exacerbation
Use of medications to treat hepatitis C virus (HCV) infections, such as peginterferon alfa-2b, in patients currently or previously infected with hepatitis B virus (HBV) has been associated with reactivation and exacerbation of the HBV infection. To decrease the risk of reactivating a HBV infection, consider screening potential drug recipients for evidence of current or prior HBV infection by measuring hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc). In addition, consider monitoring coinfected patients during and after treatment for clinical and laboratory signs of hepatitis B exacerbation (i.e., HBsAg, HBV DNA, hepatic enzymes, bilirubin). Instruct patients to immediately report any signs of liver toxicity (e.g., yellow eyes or skin, fatigue, weakness, loss of appetite, nausea, vomiting, or light-colored stools) to their health care provider. If signs of HBV reactivation develop, initiate appropriate treatment for HBV infection or consult a physician with expertise in the management of hepatitis infections.
Vaccination
Vaccination during peginterferon alfa-2b therapy should be avoided because the antibody response is suboptimal. The administration of live vaccines to immunocompromised patients should be avoided. Passive immunoprophylaxis with immune globulins may be indicated for immunocompromised persons instead of, or in addition to, vaccination. When exposed to a vaccine-preventable disease such as measles, severely immunocompromised children should be considered susceptible regardless of their vaccination history.
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.
Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) The effects of peginterferon alfa-2b on CYP1A2 were evaluated in drug interaction studies. Administration of peginterferon alfa-2b with caffeine, a CYP1A2 substrate, resulted in an 18% to 39% increase in the geographic mean exposure for caffeine, suggesting inhibition of CYP1A2. Monitor for adverse effects associated with increased exposure to caffeine if peginterferon alfa-2b is coadministered with caffeine.
Acetaminophen; Caffeine: (Moderate) The effects of peginterferon alfa-2b on CYP1A2 were evaluated in drug interaction studies. Administration of peginterferon alfa-2b with caffeine, a CYP1A2 substrate, resulted in an 18% to 39% increase in the geographic mean exposure for caffeine, suggesting inhibition of CYP1A2. Monitor for adverse effects associated with increased exposure to caffeine if peginterferon alfa-2b is coadministered with caffeine.
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of dihydrocodeine with peginterferon alfa-2b may increase dihydrocodeine plasma concentrations, but decrease the plasma concentration of the active metabolite, dihydromorphine, resulting in reduced efficacy or symptoms of opioid withdrawal. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of dihydrocodeine until stable drug effects are achieved. Discontinuation of peginterferon alfa-2b could decrease dihydrocodeine plasma concentrations and increase dihydromorphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If peginterferon alfa-2b is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Dihydrocodeine is primarily metabolized by CYP2D6 to dihydromorphine, and by CYP3A4. Peginterferon alfa-2b is a weak inhibitor of CYP2D6. (Moderate) The effects of peginterferon alfa-2b on CYP1A2 were evaluated in drug interaction studies. Administration of peginterferon alfa-2b with caffeine, a CYP1A2 substrate, resulted in an 18% to 39% increase in the geographic mean exposure for caffeine, suggesting inhibition of CYP1A2. Monitor for adverse effects associated with increased exposure to caffeine if peginterferon alfa-2b is coadministered with caffeine.
Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine: (Moderate) The effects of peginterferon alfa-2b on CYP1A2 were evaluated in drug interaction studies. Administration of peginterferon alfa-2b with caffeine, a CYP1A2 substrate, resulted in an 18% to 39% increase in the geographic mean exposure for caffeine, suggesting inhibition of CYP1A2. Monitor for adverse effects associated with increased exposure to caffeine if peginterferon alfa-2b is coadministered with caffeine.
Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide: (Moderate) The effects of peginterferon alfa-2b on CYP1A2 were evaluated in drug interaction studies. Administration of peginterferon alfa-2b with caffeine, a CYP1A2 substrate, resulted in an 18% to 39% increase in the geographic mean exposure for caffeine, suggesting inhibition of CYP1A2. Monitor for adverse effects associated with increased exposure to caffeine if peginterferon alfa-2b is coadministered with caffeine.
Acetaminophen; Chlorpheniramine: (Moderate) Monitor for adverse effects associated with increased exposure to chlorpheniramine if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while chlorpheniramine is a CYP2D6 substrate.
Acetaminophen; Chlorpheniramine; Dextromethorphan: (Moderate) Monitor for adverse effects associated with increased exposure to chlorpheniramine if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while chlorpheniramine is a CYP2D6 substrate. (Minor) Monitor for adverse effects associated with increased exposure to dextromethorphan if peginterferon alfa-2b is coadministered. Peginterferon alfa -2b is a CYP2D6 inhibitor, while dextromethorphan is a CYP2D6 substrate.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Monitor for adverse effects associated with increased exposure to chlorpheniramine if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while chlorpheniramine is a CYP2D6 substrate. (Minor) Monitor for adverse effects associated with increased exposure to dextromethorphan if peginterferon alfa-2b is coadministered. Peginterferon alfa -2b is a CYP2D6 inhibitor, while dextromethorphan is a CYP2D6 substrate.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Monitor for adverse effects associated with increased exposure to chlorpheniramine if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while chlorpheniramine is a CYP2D6 substrate. (Minor) Monitor for adverse effects associated with increased exposure to dextromethorphan if peginterferon alfa-2b is coadministered. Peginterferon alfa -2b is a CYP2D6 inhibitor, while dextromethorphan is a CYP2D6 substrate.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Monitor for adverse effects associated with increased exposure to chlorpheniramine if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while chlorpheniramine is a CYP2D6 substrate.
Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine: (Moderate) Monitor for adverse effects associated with increased exposure to chlorpheniramine if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while chlorpheniramine is a CYP2D6 substrate.
Acetaminophen; Codeine: (Moderate) Peginterferon alfa-2b inhibits CYP2D6. Exposure of drugs metabolized by CYP2D6 such as codeine may be increased when co-administered with peginterferon alfa-2b. The pharmacological activity of codeine is due to its conversion to morphine via the cytochrome CYP2D6 hepatic isoenzyme. Codeine has a low affinity for CYP2D6; therefore, its analgesic activity may vary greatly when it is combined with drugs that inhibit CYP2D6. Therefore, appropriate monitoring and dose adjustment may be necessary.
Acetaminophen; Dextromethorphan: (Minor) Monitor for adverse effects associated with increased exposure to dextromethorphan if peginterferon alfa-2b is coadministered. Peginterferon alfa -2b is a CYP2D6 inhibitor, while dextromethorphan is a CYP2D6 substrate.
Acetaminophen; Dextromethorphan; Doxylamine: (Minor) Monitor for adverse effects associated with increased exposure to dextromethorphan if peginterferon alfa-2b is coadministered. Peginterferon alfa -2b is a CYP2D6 inhibitor, while dextromethorphan is a CYP2D6 substrate.
Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Minor) Monitor for adverse effects associated with increased exposure to dextromethorphan if peginterferon alfa-2b is coadministered. Peginterferon alfa -2b is a CYP2D6 inhibitor, while dextromethorphan is a CYP2D6 substrate.
Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Minor) Monitor for adverse effects associated with increased exposure to dextromethorphan if peginterferon alfa-2b is coadministered. Peginterferon alfa -2b is a CYP2D6 inhibitor, while dextromethorphan is a CYP2D6 substrate.
Acetaminophen; Dextromethorphan; Phenylephrine: (Minor) Monitor for adverse effects associated with increased exposure to dextromethorphan if peginterferon alfa-2b is coadministered. Peginterferon alfa -2b is a CYP2D6 inhibitor, while dextromethorphan is a CYP2D6 substrate.
Acetaminophen; Dextromethorphan; Pseudoephedrine: (Minor) Monitor for adverse effects associated with increased exposure to dextromethorphan if peginterferon alfa-2b is coadministered. Peginterferon alfa -2b is a CYP2D6 inhibitor, while dextromethorphan is a CYP2D6 substrate.
Acetaminophen; Diphenhydramine: (Moderate) Monitor for adverse effects associated with increased exposure to diphenhydramine if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP1A2 and CYP2D6 inhibitor, while diphenhydramine is a CYP1A2 and CYP2D6 substrate.
Acetaminophen; Hydrocodone: (Minor) The metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as peginterferon alfa-2b, may result in a reduction in the analgesic effect of hydrocodone.
Acetaminophen; Propoxyphene: (Minor) Two drug interaction studies have evaluated the effects of peginterferon alfa-2b on CYP2D6, with differing results. In the first study, administration of two 3 mcg/kg SC doses of peginterferon alfa-2b with desipramine, a CYP2D6 substrate, resulted in a 30% increase in the geographic mean exposure for desipramine; thereby suggesting inhibition of CYP2D6. However in the other study, receipt of peginterferon alfa-2b 1.5 mcg/kg once weekly for 4 weeks by patients with chronic hepatitis C led to a mean increase of 66% in a measure of CYP2D6 activity, but the effect was variable: 13 patients had an increase, 5 patients had a decrease, and 4 patients had no significant change in CYP2D6 activity. Caution is recommended if peginterferon alfa-2b is used with CYP2D6 substrates such as propoxyphene. The pharmacologic effects of CYP2D6 substrates may be increased or decreased when administered with peginterferon alfa-2b.
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.
Alosetron: (Major) Monitor for adverse effects, such as constipation, associated with increased exposure to alosetron if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP1A2 inhibitor, while alosetron is a CYP1A2 substrate.
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.
Amitriptyline: (Moderate) Monitor for adverse effects associated with increased exposure to amitriptyline if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while amitriptyline is a CYP2D6 substrate.
Amprenavir: (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.
Anagrelide: (Moderate) Monitor for adverse effects, such as bleeding, associated with increased exposure to anagrelide if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP1A2 inhibitor, while anagrelide is a CYP1A2 substrate.
Aripiprazole: (Moderate) Monitor for adverse effects associated with increased exposure to aripiprazole if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor and aripiprazole is a partial CYP2D6 substrate. Because aripiprazole is also metabolized by CYP3A4, patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter (25%) of the usual dose with subsequent adjustments based upon clinical response. Adults receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their Abilify Maintena dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively. There are no dosing recommendations for Aristada or Aristada Initio during use of a mild to moderate CYP2D6 inhibitor.
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.
Asenapine: (Moderate) Peginterferon alfa-2b is an inhibitor of CYP2D6 and CYP1A2 and may decrease the clearance of atypical antipsychotics that are CYP2D6 and CYP1A2 substrates including asenapine. Decreased metabolism of asenapine may lead to adverse reactions such as extrapyramidal symptoms. In addition, asenapine is associated with a risk for QT prolongation and TdP and should be used cautiously with CYP2D6 and CYP1A2 inhibitors.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) The effects of peginterferon alfa-2b on CYP1A2 were evaluated in drug interaction studies. Administration of peginterferon alfa-2b with caffeine, a CYP1A2 substrate, resulted in an 18% to 39% increase in the geographic mean exposure for caffeine, suggesting inhibition of CYP1A2. Monitor for adverse effects associated with increased exposure to caffeine if peginterferon alfa-2b is coadministered with caffeine.
Aspirin, ASA; Butalbital; Caffeine; Codeine: (Moderate) Peginterferon alfa-2b inhibits CYP2D6. Exposure of drugs metabolized by CYP2D6 such as codeine may be increased when co-administered with peginterferon alfa-2b. The pharmacological activity of codeine is due to its conversion to morphine via the cytochrome CYP2D6 hepatic isoenzyme. Codeine has a low affinity for CYP2D6; therefore, its analgesic activity may vary greatly when it is combined with drugs that inhibit CYP2D6. Therefore, appropriate monitoring and dose adjustment may be necessary. (Moderate) The effects of peginterferon alfa-2b on CYP1A2 were evaluated in drug interaction studies. Administration of peginterferon alfa-2b with caffeine, a CYP1A2 substrate, resulted in an 18% to 39% increase in the geographic mean exposure for caffeine, suggesting inhibition of CYP1A2. Monitor for adverse effects associated with increased exposure to caffeine if peginterferon alfa-2b is coadministered with caffeine.
Aspirin, ASA; Caffeine: (Moderate) The effects of peginterferon alfa-2b on CYP1A2 were evaluated in drug interaction studies. Administration of peginterferon alfa-2b with caffeine, a CYP1A2 substrate, resulted in an 18% to 39% increase in the geographic mean exposure for caffeine, suggesting inhibition of CYP1A2. Monitor for adverse effects associated with increased exposure to caffeine if peginterferon alfa-2b is coadministered with caffeine.
Aspirin, ASA; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of dihydrocodeine with peginterferon alfa-2b may increase dihydrocodeine plasma concentrations, but decrease the plasma concentration of the active metabolite, dihydromorphine, resulting in reduced efficacy or symptoms of opioid withdrawal. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of dihydrocodeine until stable drug effects are achieved. Discontinuation of peginterferon alfa-2b could decrease dihydrocodeine plasma concentrations and increase dihydromorphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If peginterferon alfa-2b is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Dihydrocodeine is primarily metabolized by CYP2D6 to dihydromorphine, and by CYP3A4. Peginterferon alfa-2b is a weak inhibitor of CYP2D6. (Moderate) The effects of peginterferon alfa-2b on CYP1A2 were evaluated in drug interaction studies. Administration of peginterferon alfa-2b with caffeine, a CYP1A2 substrate, resulted in an 18% to 39% increase in the geographic mean exposure for caffeine, suggesting inhibition of CYP1A2. Monitor for adverse effects associated with increased exposure to caffeine if peginterferon alfa-2b is coadministered with caffeine.
Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) The effects of peginterferon alfa-2b on CYP1A2 were evaluated in drug interaction studies. Administration of peginterferon alfa-2b with caffeine, a CYP1A2 substrate, resulted in an 18% to 39% increase in the geographic mean exposure for caffeine, suggesting inhibition of CYP1A2. Monitor for adverse effects associated with increased exposure to caffeine if peginterferon alfa-2b is coadministered with caffeine.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Peginterferon alfa-2b inhibits CYP2D6. Exposure of drugs metabolized by CYP2D6 such as codeine may be increased when co-administered with peginterferon alfa-2b. The pharmacological activity of codeine is due to its conversion to morphine via the cytochrome CYP2D6 hepatic isoenzyme. Codeine has a low affinity for CYP2D6; therefore, its analgesic activity may vary greatly when it is combined with drugs that inhibit CYP2D6. Therefore, appropriate monitoring and dose adjustment may be necessary.
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.
Atomoxetine: (Moderate) Monitor for adverse effects associated with increased exposure to atomoxetine if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while atomoxetine is a CYP2D6 substrate.
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.
Bendamustine: (Major) Consider the use of an alternative therapy if peginterferon alfa-2b treatment is needed in patients receiving bendamustine. Peginterferon alfa-2b may increase bendamustine exposure, which may increase the risk of adverse reactions (e.g., myelosuppression, infection, hepatotoxicity). Bendamustine is a CYP1A2 substrate and peginterferon alfa-2b is a CYP1A2 inhibitor.
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.
Brexpiprazole: (Moderate) Because brexpiprazole is primarily metabolized by CYP3A4 and CYP2D6, use caution when co-administering moderate inhibitors of CYP2D6 such as peginterferon Alfa-2b. The manufacturer recommends that the brexpiprazole dose be reduced to one-quarter (25%) of the usual dose in patients receiving a moderate to strong inhibitor of CYP3A4 in combination with a moderate to strong inhibitor of CYP2D6. If peginterferon alfa-2b is used in combination with brexpiprazole and a moderate to strong CYP3A4 inhibitor, the brexpiprazole dose should be reduced and the patient should be carefully monitored for brexpiprazole-related adverse reactions.
Brimonidine; Timolol: (Moderate) Monitor for adverse effects associated with increased exposure to timolol if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while timolol is a CYP2D6 substrate.
Brompheniramine; Dextromethorphan; Guaifenesin: (Minor) Monitor for adverse effects associated with increased exposure to dextromethorphan if peginterferon alfa-2b is coadministered. Peginterferon alfa -2b is a CYP2D6 inhibitor, while dextromethorphan is a CYP2D6 substrate.
Brompheniramine; Dextromethorphan; Phenylephrine: (Minor) Monitor for adverse effects associated with increased exposure to dextromethorphan if peginterferon alfa-2b is coadministered. Peginterferon alfa -2b is a CYP2D6 inhibitor, while dextromethorphan is a CYP2D6 substrate.
Brompheniramine; Guaifenesin; Hydrocodone: (Minor) The metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as peginterferon alfa-2b, may result in a reduction in the analgesic effect of hydrocodone.
Brompheniramine; Hydrocodone; Pseudoephedrine: (Minor) The metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as peginterferon alfa-2b, may result in a reduction in the analgesic effect of hydrocodone.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Minor) Monitor for adverse effects associated with increased exposure to dextromethorphan if peginterferon alfa-2b is coadministered. Peginterferon alfa -2b is a CYP2D6 inhibitor, while dextromethorphan is a CYP2D6 substrate.
Bupivacaine; Lidocaine: (Major) Monitor for adverse effects associated with increased exposure to systemic lidocaine if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP1A2 inhibitor, while lidocaine is a CYP1A2 substrate.
Butalbital; Acetaminophen; Caffeine: (Moderate) The effects of peginterferon alfa-2b on CYP1A2 were evaluated in drug interaction studies. Administration of peginterferon alfa-2b with caffeine, a CYP1A2 substrate, resulted in an 18% to 39% increase in the geographic mean exposure for caffeine, suggesting inhibition of CYP1A2. Monitor for adverse effects associated with increased exposure to caffeine if peginterferon alfa-2b is coadministered with caffeine.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Peginterferon alfa-2b inhibits CYP2D6. Exposure of drugs metabolized by CYP2D6 such as codeine may be increased when co-administered with peginterferon alfa-2b. The pharmacological activity of codeine is due to its conversion to morphine via the cytochrome CYP2D6 hepatic isoenzyme. Codeine has a low affinity for CYP2D6; therefore, its analgesic activity may vary greatly when it is combined with drugs that inhibit CYP2D6. Therefore, appropriate monitoring and dose adjustment may be necessary. (Moderate) The effects of peginterferon alfa-2b on CYP1A2 were evaluated in drug interaction studies. Administration of peginterferon alfa-2b with caffeine, a CYP1A2 substrate, resulted in an 18% to 39% increase in the geographic mean exposure for caffeine, suggesting inhibition of CYP1A2. Monitor for adverse effects associated with increased exposure to caffeine if peginterferon alfa-2b is coadministered with caffeine.
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.
Caffeine: (Moderate) The effects of peginterferon alfa-2b on CYP1A2 were evaluated in drug interaction studies. Administration of peginterferon alfa-2b with caffeine, a CYP1A2 substrate, resulted in an 18% to 39% increase in the geographic mean exposure for caffeine, suggesting inhibition of CYP1A2. Monitor for adverse effects associated with increased exposure to caffeine if peginterferon alfa-2b is coadministered with caffeine.
Caffeine; Sodium Benzoate: (Moderate) The effects of peginterferon alfa-2b on CYP1A2 were evaluated in drug interaction studies. Administration of peginterferon alfa-2b with caffeine, a CYP1A2 substrate, resulted in an 18% to 39% increase in the geographic mean exposure for caffeine, suggesting inhibition of CYP1A2. Monitor for adverse effects associated with increased exposure to caffeine if peginterferon alfa-2b is coadministered with caffeine.
Carbetapentane; Chlorpheniramine: (Moderate) Monitor for adverse effects associated with increased exposure to chlorpheniramine if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while chlorpheniramine is a CYP2D6 substrate.
Carbetapentane; Chlorpheniramine; Phenylephrine: (Moderate) Monitor for adverse effects associated with increased exposure to chlorpheniramine if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while chlorpheniramine is a CYP2D6 substrate.
Carbetapentane; Diphenhydramine; Phenylephrine: (Moderate) Monitor for adverse effects associated with increased exposure to diphenhydramine if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP1A2 and CYP2D6 inhibitor, while diphenhydramine is a CYP1A2 and CYP2D6 substrate.
Carbinoxamine; Dextromethorphan; Pseudoephedrine: (Minor) Monitor for adverse effects associated with increased exposure to dextromethorphan if peginterferon alfa-2b is coadministered. Peginterferon alfa -2b is a CYP2D6 inhibitor, while dextromethorphan is a CYP2D6 substrate.
Carbinoxamine; Hydrocodone; Phenylephrine: (Minor) The metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as peginterferon alfa-2b, may result in a reduction in the analgesic effect of hydrocodone.
Carbinoxamine; Hydrocodone; Pseudoephedrine: (Minor) The metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as peginterferon alfa-2b, may result in a reduction in the analgesic effect of hydrocodone.
Carvedilol: (Moderate) Monitor for adverse effects associated with increased exposure to carvedilol if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while carvedilol is a CYP2D6 substrate.
Celecoxib; Tramadol: (Moderate) Monitor for adverse effects associated with increased exposure to tramadol if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while tramadol is a CYP2D6 substrate.
Chlordiazepoxide; Amitriptyline: (Moderate) Monitor for adverse effects associated with increased exposure to amitriptyline if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while amitriptyline is a CYP2D6 substrate.
Chloroquine: (Moderate) Concurrent use of chloroquine and interferons is not recommended as there is an increased risk of retinal toxicity.
Chlorpheniramine: (Moderate) Monitor for adverse effects associated with increased exposure to chlorpheniramine if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while chlorpheniramine is a CYP2D6 substrate.
Chlorpheniramine; Codeine: (Moderate) Monitor for adverse effects associated with increased exposure to chlorpheniramine if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while chlorpheniramine is a CYP2D6 substrate. (Moderate) Peginterferon alfa-2b inhibits CYP2D6. Exposure of drugs metabolized by CYP2D6 such as codeine may be increased when co-administered with peginterferon alfa-2b. The pharmacological activity of codeine is due to its conversion to morphine via the cytochrome CYP2D6 hepatic isoenzyme. Codeine has a low affinity for CYP2D6; therefore, its analgesic activity may vary greatly when it is combined with drugs that inhibit CYP2D6. Therefore, appropriate monitoring and dose adjustment may be necessary.
Chlorpheniramine; Dextromethorphan: (Moderate) Monitor for adverse effects associated with increased exposure to chlorpheniramine if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while chlorpheniramine is a CYP2D6 substrate. (Minor) Monitor for adverse effects associated with increased exposure to dextromethorphan if peginterferon alfa-2b is coadministered. Peginterferon alfa -2b is a CYP2D6 inhibitor, while dextromethorphan is a CYP2D6 substrate.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Monitor for adverse effects associated with increased exposure to chlorpheniramine if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while chlorpheniramine is a CYP2D6 substrate. (Minor) Monitor for adverse effects associated with increased exposure to dextromethorphan if peginterferon alfa-2b is coadministered. Peginterferon alfa -2b is a CYP2D6 inhibitor, while dextromethorphan is a CYP2D6 substrate.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Monitor for adverse effects associated with increased exposure to chlorpheniramine if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while chlorpheniramine is a CYP2D6 substrate. (Minor) Monitor for adverse effects associated with increased exposure to dextromethorphan if peginterferon alfa-2b is coadministered. Peginterferon alfa -2b is a CYP2D6 inhibitor, while dextromethorphan is a CYP2D6 substrate.
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Concomitant use of dihydrocodeine with peginterferon alfa-2b may increase dihydrocodeine plasma concentrations, but decrease the plasma concentration of the active metabolite, dihydromorphine, resulting in reduced efficacy or symptoms of opioid withdrawal. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of dihydrocodeine until stable drug effects are achieved. Discontinuation of peginterferon alfa-2b could decrease dihydrocodeine plasma concentrations and increase dihydromorphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If peginterferon alfa-2b is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Dihydrocodeine is primarily metabolized by CYP2D6 to dihydromorphine, and by CYP3A4. Peginterferon alfa-2b is a weak inhibitor of CYP2D6. (Moderate) Monitor for adverse effects associated with increased exposure to chlorpheniramine if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while chlorpheniramine is a CYP2D6 substrate.
Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (Moderate) Concomitant use of dihydrocodeine with peginterferon alfa-2b may increase dihydrocodeine plasma concentrations, but decrease the plasma concentration of the active metabolite, dihydromorphine, resulting in reduced efficacy or symptoms of opioid withdrawal. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of dihydrocodeine until stable drug effects are achieved. Discontinuation of peginterferon alfa-2b could decrease dihydrocodeine plasma concentrations and increase dihydromorphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If peginterferon alfa-2b is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Dihydrocodeine is primarily metabolized by CYP2D6 to dihydromorphine, and by CYP3A4. Peginterferon alfa-2b is a weak inhibitor of CYP2D6. (Moderate) Monitor for adverse effects associated with increased exposure to chlorpheniramine if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while chlorpheniramine is a CYP2D6 substrate.
Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Monitor for adverse effects associated with increased exposure to chlorpheniramine if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while chlorpheniramine is a CYP2D6 substrate. (Minor) The metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as peginterferon alfa-2b, may result in a reduction in the analgesic effect of hydrocodone.
Chlorpheniramine; Hydrocodone: (Moderate) Monitor for adverse effects associated with increased exposure to chlorpheniramine if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while chlorpheniramine is a CYP2D6 substrate. (Minor) The metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as peginterferon alfa-2b, may result in a reduction in the analgesic effect of hydrocodone.
Chlorpheniramine; Hydrocodone; Phenylephrine: (Moderate) Monitor for adverse effects associated with increased exposure to chlorpheniramine if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while chlorpheniramine is a CYP2D6 substrate. (Minor) The metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as peginterferon alfa-2b, may result in a reduction in the analgesic effect of hydrocodone.
Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Monitor for adverse effects associated with increased exposure to chlorpheniramine if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while chlorpheniramine is a CYP2D6 substrate. (Minor) The metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as peginterferon alfa-2b, may result in a reduction in the analgesic effect of hydrocodone.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Monitor for adverse effects associated with increased exposure to chlorpheniramine if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while chlorpheniramine is a CYP2D6 substrate.
Chlorpheniramine; Phenylephrine: (Moderate) Monitor for adverse effects associated with increased exposure to chlorpheniramine if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while chlorpheniramine is a CYP2D6 substrate.
Chlorpheniramine; Pseudoephedrine: (Moderate) Monitor for adverse effects associated with increased exposure to chlorpheniramine if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while chlorpheniramine is a CYP2D6 substrate.
Chlorpromazine: (Moderate) Monitor for adverse effects associated with increased exposure to chlorpromazine if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while chlorpromazine is a CYP2D6 substrate.
Cinacalcet: (Moderate) Monitor for adverse effects associated with increased exposure to cinacalcet if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP1A2 and CYP2D6 inhibitor, while cinacalcet is a CYP1A2 and CYP2D6 substrate.
Clomipramine: (Moderate) Monitor for adverse effects associated with increased exposure to clomipramine if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while clomipramine is a CYP2D6 substrate.
Clozapine: (Major) Peginterferon alfa-2b is a CYP1A2 and CYP2D6 inhibitor and clozapine is a substrate of these enzymes; therefore, coadministration may lead to increased clozapine concentrations. According to the manufacturer of clozapine, patients receiving clozapine in combination with a CYP1A2 and CYP2D6 inhibitor should be monitored for adverse reactions. Consideration should be given to reducing the clozapine dose if necessary. In addition, 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.
Codeine: (Moderate) Peginterferon alfa-2b inhibits CYP2D6. Exposure of drugs metabolized by CYP2D6 such as codeine may be increased when co-administered with peginterferon alfa-2b. The pharmacological activity of codeine is due to its conversion to morphine via the cytochrome CYP2D6 hepatic isoenzyme. Codeine has a low affinity for CYP2D6; therefore, its analgesic activity may vary greatly when it is combined with drugs that inhibit CYP2D6. Therefore, appropriate monitoring and dose adjustment may be necessary.
Codeine; Guaifenesin: (Moderate) Peginterferon alfa-2b inhibits CYP2D6. Exposure of drugs metabolized by CYP2D6 such as codeine may be increased when co-administered with peginterferon alfa-2b. The pharmacological activity of codeine is due to its conversion to morphine via the cytochrome CYP2D6 hepatic isoenzyme. Codeine has a low affinity for CYP2D6; therefore, its analgesic activity may vary greatly when it is combined with drugs that inhibit CYP2D6. Therefore, appropriate monitoring and dose adjustment may be necessary.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Peginterferon alfa-2b inhibits CYP2D6. Exposure of drugs metabolized by CYP2D6 such as codeine may be increased when co-administered with peginterferon alfa-2b. The pharmacological activity of codeine is due to its conversion to morphine via the cytochrome CYP2D6 hepatic isoenzyme. Codeine has a low affinity for CYP2D6; therefore, its analgesic activity may vary greatly when it is combined with drugs that inhibit CYP2D6. Therefore, appropriate monitoring and dose adjustment may be necessary.
Codeine; Phenylephrine; Promethazine: (Moderate) Monitor for adverse effects associated with increased exposure to promethazine if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while promethazine is a CYP2D6 substrate. (Moderate) Peginterferon alfa-2b inhibits CYP2D6. Exposure of drugs metabolized by CYP2D6 such as codeine may be increased when co-administered with peginterferon alfa-2b. The pharmacological activity of codeine is due to its conversion to morphine via the cytochrome CYP2D6 hepatic isoenzyme. Codeine has a low affinity for CYP2D6; therefore, its analgesic activity may vary greatly when it is combined with drugs that inhibit CYP2D6. Therefore, appropriate monitoring and dose adjustment may be necessary.
Codeine; Promethazine: (Moderate) Monitor for adverse effects associated with increased exposure to promethazine if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while promethazine is a CYP2D6 substrate. (Moderate) Peginterferon alfa-2b inhibits CYP2D6. Exposure of drugs metabolized by CYP2D6 such as codeine may be increased when co-administered with peginterferon alfa-2b. The pharmacological activity of codeine is due to its conversion to morphine via the cytochrome CYP2D6 hepatic isoenzyme. Codeine has a low affinity for CYP2D6; therefore, its analgesic activity may vary greatly when it is combined with drugs that inhibit CYP2D6. Therefore, appropriate monitoring and dose adjustment may be necessary.
Cyclosporine: (Moderate) Concomitant use of immunosuppressive agents, such as cyclosporine, with peginterferon alfa-2b warrants the therapeutic monitoring of the immunosuppressant in appropriate populations as the effect on immunosuppressant concentrations is unknown.
Darifenacin: (Moderate) The plasma concentrations of darifenacin may be elevated when administered concurrently with peginterferon alfa-2b. Clinical monitoring for adverse effects, such as anticholinergic effects, is recommended during coadministration. Peginterferon alfa-2b is a CYP2D6 inhibitor, while darifenacin is a CYP2D6substrate.
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.
Dasabuvir; Ombitasvir; Paritaprevir; 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.
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. In addition, monitor for adverse effects associated with increased exposure to delavirdine if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while delavirdine is partially metabolized by CYP2D6.
Desipramine: (Moderate) Drug interaction studies have evaluated the effects of peginterferon alfa-2b on CYP2D6. Administration of peginterferon alfa-2b with desipramine, a CYP2D6 substrate, resulted in a 30% increase in the geographic mean exposure for desipramine; thereby suggesting inhibition of CYP2D6. Monitor for adverse effects associated with increased exposure to desipramine if peginterferon alfa-2b is coadministered.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Minor) Monitor for adverse effects associated with increased exposure to dextromethorphan if peginterferon alfa-2b is coadministered. Peginterferon alfa -2b is a CYP2D6 inhibitor, while dextromethorphan is a CYP2D6 substrate.
Dextromethorphan: (Minor) Monitor for adverse effects associated with increased exposure to dextromethorphan if peginterferon alfa-2b is coadministered. Peginterferon alfa -2b is a CYP2D6 inhibitor, while dextromethorphan is a CYP2D6 substrate.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Monitor for adverse effects associated with increased exposure to diphenhydramine if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP1A2 and CYP2D6 inhibitor, while diphenhydramine is a CYP1A2 and CYP2D6 substrate. (Minor) Monitor for adverse effects associated with increased exposure to dextromethorphan if peginterferon alfa-2b is coadministered. Peginterferon alfa -2b is a CYP2D6 inhibitor, while dextromethorphan is a CYP2D6 substrate.
Dextromethorphan; Guaifenesin: (Minor) Monitor for adverse effects associated with increased exposure to dextromethorphan if peginterferon alfa-2b is coadministered. Peginterferon alfa -2b is a CYP2D6 inhibitor, while dextromethorphan is a CYP2D6 substrate.
Dextromethorphan; Guaifenesin; Phenylephrine: (Minor) Monitor for adverse effects associated with increased exposure to dextromethorphan if peginterferon alfa-2b is coadministered. Peginterferon alfa -2b is a CYP2D6 inhibitor, while dextromethorphan is a CYP2D6 substrate.
Dextromethorphan; Guaifenesin; Potassium Guaiacolsulfonate: (Minor) Monitor for adverse effects associated with increased exposure to dextromethorphan if peginterferon alfa-2b is coadministered. Peginterferon alfa -2b is a CYP2D6 inhibitor, while dextromethorphan is a CYP2D6 substrate.
Dextromethorphan; Guaifenesin; Pseudoephedrine: (Minor) Monitor for adverse effects associated with increased exposure to dextromethorphan if peginterferon alfa-2b is coadministered. Peginterferon alfa -2b is a CYP2D6 inhibitor, while dextromethorphan is a CYP2D6 substrate.
Dextromethorphan; Quinidine: (Minor) Monitor for adverse effects associated with increased exposure to dextromethorphan if peginterferon alfa-2b is coadministered. Peginterferon alfa -2b is a CYP2D6 inhibitor, while dextromethorphan is a CYP2D6 substrate.
Dihydrocodeine; Guaifenesin; Pseudoephedrine: (Moderate) Concomitant use of dihydrocodeine with peginterferon alfa-2b may increase dihydrocodeine plasma concentrations, but decrease the plasma concentration of the active metabolite, dihydromorphine, resulting in reduced efficacy or symptoms of opioid withdrawal. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of dihydrocodeine until stable drug effects are achieved. Discontinuation of peginterferon alfa-2b could decrease dihydrocodeine plasma concentrations and increase dihydromorphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If peginterferon alfa-2b is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Dihydrocodeine is primarily metabolized by CYP2D6 to dihydromorphine, and by CYP3A4. Peginterferon alfa-2b is a weak inhibitor of CYP2D6.
Diphenhydramine: (Moderate) Monitor for adverse effects associated with increased exposure to diphenhydramine if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP1A2 and CYP2D6 inhibitor, while diphenhydramine is a CYP1A2 and CYP2D6 substrate.
Diphenhydramine; Hydrocodone; Phenylephrine: (Moderate) Monitor for adverse effects associated with increased exposure to diphenhydramine if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP1A2 and CYP2D6 inhibitor, while diphenhydramine is a CYP1A2 and CYP2D6 substrate. (Minor) The metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as peginterferon alfa-2b, may result in a reduction in the analgesic effect of hydrocodone.
Diphenhydramine; Ibuprofen: (Moderate) Monitor for adverse effects associated with increased exposure to diphenhydramine if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP1A2 and CYP2D6 inhibitor, while diphenhydramine is a CYP1A2 and CYP2D6 substrate.
Diphenhydramine; Naproxen: (Moderate) Monitor for adverse effects associated with increased exposure to diphenhydramine if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP1A2 and CYP2D6 inhibitor, while diphenhydramine is a CYP1A2 and CYP2D6 substrate.
Diphenhydramine; Phenylephrine: (Moderate) Monitor for adverse effects associated with increased exposure to diphenhydramine if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP1A2 and CYP2D6 inhibitor, while diphenhydramine is a CYP1A2 and CYP2D6 substrate.
Dolasetron: (Moderate) Monitor for adverse effects associated with increased exposure to dolasetron if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while dolasetron is a CYP2D6 substrate.
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).
Dorzolamide; Timolol: (Moderate) Monitor for adverse effects associated with increased exposure to timolol if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while timolol is a CYP2D6 substrate.
Doxepin: (Moderate) Caution is warranted with the use of doxepin and peginterferon alfa-2b. Doxepin is a substrate of CYP2D6 and CYP1A2, while peginterferon alfa-2b inhibits these enzymes. The pharmacologic effects of CYP2D6 and CYP1A2 substrates may be increased when administered with peginterferon alfa-2b.
Doxorubicin Liposomal: (Major) Monitor for adverse effects associated with increased exposure to doxorubicin if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while doxorubicin is a CYP2D6 substrate.
Doxorubicin: (Major) Monitor for adverse effects associated with increased exposure to doxorubicin if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while doxorubicin is a CYP2D6 substrate.
Duloxetine: (Moderate) Monitor for adverse effects associated with increased exposure to duloxetine if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP1A2 and CYP2D6 inhibitor, while duloxetine is a CYP1A2 and CYP2D6 substrate.
Dutasteride; Tamsulosin: (Minor) Use caution when administering tamsulosin with a moderate CYP2D6 inhibitor such as peginterferon alfa-2b. Tamsulosin is extensively metabolized by CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP2D6 inhibitor resulted in increases in tamsulosin exposure; interactions with moderate CYP2D6 inhibitors have not been evaluated. If concomitant use in necessary, monitor patient closely for increased side effects.
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: (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.
Eliglustat: (Moderate) In extensive or intermediate CYP2D6 metabolizers (EMs or IMs), coadministration of peginterferon alfa-2b and eliglustat requires dosage reduction of eliglustat to 84 mg PO once daily; however, coadministration of eliglustat with both peginterferon alfa-2b and a strong or moderate CYP3A inhibitor is contraindicated. Peginterferon alfa-2b is a moderate CYP2D6 inhibitor; eliglustat is a CYP2D6 and CYP3A substrate. Coadministration with CYP2D6 inhibitors, may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias). Physiology-based pharmacokinetic (PBPK) models suggest that peginterferon alfa-2b may increase the Cmax and AUC of eliglustat 3.8- and 4.5-fold, respectively, in EMs and 1.6-fold (both Cmax and AUC) in IMs. In addition, PBPK modeling suggests concomitant use of eliglustat (84 mg PO twice daily) with a moderate 2D6 inhibitor and a moderate 3A4 inhibitor may increase the Cmax and AUC of eliglustat 10.2- and 13.6-fold, respectively, in EMs and 4.2- and 5-fold, respectively, in IMs.
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.
Encainide: (Moderate) Monitor for adverse effects associated with increased exposure to encainide if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while encainide is a CYP2D6 substrate.
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.
Ergotamine; Caffeine: (Moderate) The effects of peginterferon alfa-2b on CYP1A2 were evaluated in drug interaction studies. Administration of peginterferon alfa-2b with caffeine, a CYP1A2 substrate, resulted in an 18% to 39% increase in the geographic mean exposure for caffeine, suggesting inhibition of CYP1A2. Monitor for adverse effects associated with increased exposure to caffeine if peginterferon alfa-2b is coadministered with caffeine.
Estramustine: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
Ethanol: (Major) As with other interferon therapies, patients should be advised to avoid drinking alcohol to reduce the chance of injury to the liver during peginterferon alfa-2b treatment. Alcohol may also potentiate drowsiness, dizziness, and dehydration. Patients who develop dizziness, confusion, somnolence, and fatigue with peginterferon alfa-2b treatment should be cautioned to avoid driving or operating machinery.
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.
Flecainide: (Moderate) Monitor for adverse effects associated with increased exposure to flecainide if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while flecainide is a CYP2D6 substrate with a narrow therapeutic range.
Fluoxetine: (Moderate) Caution is warranted with the use of fluoxetine and peginterferon alfa-2b. Fluoxetine is a substrate of CYP2D6, while peginterferon alfa-2b inhibits this enzyme. The pharmacologic effects of CYP2D6 substrates may be increased when administered with peginterferon alfa-2b.
Fluphenazine: (Moderate) Monitor for adverse effects associated with increased exposure to fluphenazine if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while fluphenazine is a CYP2D6 substrate.
Flutamide: (Moderate) Monitor for adverse effects associated with increased exposure to flutamide if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP1A2 inhibitor, while flutamide is a CYP1A2 substrate.
Fluticasone; Umeclidinium; Vilanterol: (Moderate) Monitor for adverse effects associated with increased exposure to umeclidinium if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while umeclidinium is a CYP2D6 substrate.
Fluvoxamine: (Moderate) Monitor for adverse effects associated with increased exposure to fluvoxamine if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while fluvoxamine is a CYP2D6 substrate.
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.
Guaifenesin; Hydrocodone: (Minor) The metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as peginterferon alfa-2b, may result in a reduction in the analgesic effect of hydrocodone.
Guaifenesin; Hydrocodone; Pseudoephedrine: (Minor) The metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as peginterferon alfa-2b, may result in a reduction in the analgesic effect of hydrocodone.
Haloperidol: (Moderate) Monitor for adverse effects associated with increased exposure to haloperidol if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while haloperidol is a CYP2D6 substrate.
Homatropine; Hydrocodone: (Minor) The metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as peginterferon alfa-2b, may result in a reduction in the analgesic effect of hydrocodone.
Hydrocodone: (Minor) The metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as peginterferon alfa-2b, may result in a reduction in the analgesic effect of hydrocodone.
Hydrocodone; Ibuprofen: (Minor) The metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as peginterferon alfa-2b, may result in a reduction in the analgesic effect of hydrocodone.
Hydrocodone; Phenylephrine: (Minor) The metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as peginterferon alfa-2b, may result in a reduction in the analgesic effect of hydrocodone.
Hydrocodone; Potassium Guaiacolsulfonate: (Minor) The metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as peginterferon alfa-2b, may result in a reduction in the analgesic effect of hydrocodone.
Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (Minor) The metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as peginterferon alfa-2b, may result in a reduction in the analgesic effect of hydrocodone.
Hydrocodone; Pseudoephedrine: (Minor) The metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as peginterferon alfa-2b, may result in a reduction in the analgesic effect of hydrocodone.
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.
Iloperidone: (Moderate) Peginterferon alfa-2b is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as iloperidone may be increased when co-administered with peginterferon alfa-2b. Coadministration with potent CYP2D6 inhibitors results in a 2.3 fold increase in iloperidone plasma exposure and dosage adjustments are required. Appropriate monitoring may be necessary.
Imatinib: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
Imipramine: (Moderate) Monitor for adverse effects associated with increased exposure to imipramine if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while imipramine is a CYP2D6 substrate.
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).
Lidocaine: (Major) Monitor for adverse effects associated with increased exposure to systemic lidocaine if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP1A2 inhibitor, while lidocaine is a CYP1A2 substrate.
Lidocaine; Epinephrine: (Major) Monitor for adverse effects associated with increased exposure to systemic lidocaine if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP1A2 inhibitor, while lidocaine is a CYP1A2 substrate.
Lidocaine; Prilocaine: (Major) Monitor for adverse effects associated with increased exposure to systemic lidocaine if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP1A2 inhibitor, while lidocaine is a CYP1A2 substrate.
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.
Maprotiline: (Moderate) Monitor for adverse effects associated with increased exposure to maprotiline if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while maprotiline is a CYP2D6 substrate.
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.
Meclizine: (Moderate) Monitor for adverse effects associated with increased exposure to meclizine if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while meclizine is a CYP2D6 substrate in vitro.
Melatonin: (Moderate) Monitor for adverse effects associated with increased exposure to melatonin if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP1A2 inhibitor, while melatonin is a CYP1A2 substrate.
Meperidine; Promethazine: (Moderate) Monitor for adverse effects associated with increased exposure to promethazine if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while promethazine is a CYP2D6 substrate.
Methadone: (Major) The administration of weekly peginterferon alfa-2b 1.5 mcg/kg to patients on methadone treatment may be associated with increases in methadone AUC. After 4 weeks of peginterferon alfa-2b, a mean increase of 16% in methadone AUC occurred; 2 of the 18 patients experienced an approximate doubling in methadone AUC. All patients were on stable methadone maintenance therapy of at least 40 mg daily. The methadone dose may need to be reduced in patients who also take peginterferon alfa-2b. As too much methadone can be fatal, use with peginterferon alfa-2b should be with extreme caution. If the drugs are used together, carefully monitor patients for an increased narcotic effect.
Methamphetamine: (Moderate) Monitor for adverse effects associated with increased exposure to methamphetamine if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while methamphetamine is a CYP2D6 substrate.
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.
Metoclopramide: (Moderate) Monitor for adverse effects associated with increased exposure to metoclopramide if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while metoclopramide is a CYP2D6 substrate.
Mexiletine: (Moderate) Monitor for adverse effects associated with increased exposure to mexiletine if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while mexiletine is a CYP2D6 substrate.
Mirtazapine: (Moderate) Monitor for adverse effects associated with increased exposure to mirtazapine if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP1A2 and CYP2D6 inhibitor, while mirtazapine is a CYP1A2 and CYP2D6 substrate.
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.
Netupitant, Fosnetupitant; Palonosetron: (Moderate) Monitor for adverse effects associated with increased exposure to palonosetron if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while palonosetron is a CYP2D6 substrate.
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.
Nortriptyline: (Moderate) Monitor for adverse effects associated with increased exposure to nortriptyline if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while nortriptyline is a CYP2D6 substrate.
Olanzapine: (Minor) Monitor for adverse effects associated with increased exposure to olanzapine, such as extrapyramidal symptoms, sedation, and orthostatic hypotension, if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP1A2 inhibitor, while olanzapine is a CYP1A2 substrate.
Olanzapine; Fluoxetine: (Moderate) Caution is warranted with the use of fluoxetine and peginterferon alfa-2b. Fluoxetine is a substrate of CYP2D6, while peginterferon alfa-2b inhibits this enzyme. The pharmacologic effects of CYP2D6 substrates may be increased when administered with peginterferon alfa-2b. (Minor) Monitor for adverse effects associated with increased exposure to olanzapine, such as extrapyramidal symptoms, sedation, and orthostatic hypotension, if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP1A2 inhibitor, while olanzapine is a CYP1A2 substrate.
Olanzapine; Samidorphan: (Minor) Monitor for adverse effects associated with increased exposure to olanzapine, such as extrapyramidal symptoms, sedation, and orthostatic hypotension, if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP1A2 inhibitor, while olanzapine is a CYP1A2 substrate.
Ombitasvir; Paritaprevir; 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.
Palonosetron: (Moderate) Monitor for adverse effects associated with increased exposure to palonosetron if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while palonosetron is a CYP2D6 substrate.
Paroxetine: (Moderate) Monitor for adverse effects associated with increased exposure to paroxetine if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while paroxetine is a CYP2D6 substrate.
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.
Pentamidine: (Moderate) Monitor for adverse effects associated with increased exposure to pentamidine if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while pentamidine is partially metabolized by the CYP2D6 isoenzyme.
Perphenazine: (Moderate) Caution is warranted with the use of perphenazine and peginterferon alfa-2b. Perphenazine is a substrate of CYP2D6, while peginterferon alfa-2b inhibits this enzyme. The pharmacologic effects of CYP2D6 substrates may be increased when administered with peginterferon alfa-2b.
Perphenazine; Amitriptyline: (Moderate) Caution is warranted with the use of perphenazine and peginterferon alfa-2b. Perphenazine is a substrate of CYP2D6, while peginterferon alfa-2b inhibits this enzyme. The pharmacologic effects of CYP2D6 substrates may be increased when administered with peginterferon alfa-2b. (Moderate) Monitor for adverse effects associated with increased exposure to amitriptyline if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while amitriptyline is a CYP2D6 substrate.
Pexidartinib: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with peginterferon alfa-2b. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
Pirfenidone: (Moderate) Monitor for adverse effects associated with increased exposure to pirfenidone if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP1A2 and CYP2D6 inhibitor, while pirfenidone is a substrate of both these enzymes.
Pralatrexate: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
Promethazine: (Moderate) Monitor for adverse effects associated with increased exposure to promethazine if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while promethazine is a CYP2D6 substrate.
Promethazine; Dextromethorphan: (Moderate) Monitor for adverse effects associated with increased exposure to promethazine if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while promethazine is a CYP2D6 substrate. (Minor) Monitor for adverse effects associated with increased exposure to dextromethorphan if peginterferon alfa-2b is coadministered. Peginterferon alfa -2b is a CYP2D6 inhibitor, while dextromethorphan is a CYP2D6 substrate.
Promethazine; Phenylephrine: (Moderate) Monitor for adverse effects associated with increased exposure to promethazine if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while promethazine is a CYP2D6 substrate.
Propafenone: (Moderate) Monitor for adverse effects associated with increased exposure to propafenone if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while propafenone is a CYP2D6 substrate.
Propoxyphene: (Minor) Two drug interaction studies have evaluated the effects of peginterferon alfa-2b on CYP2D6, with differing results. In the first study, administration of two 3 mcg/kg SC doses of peginterferon alfa-2b with desipramine, a CYP2D6 substrate, resulted in a 30% increase in the geographic mean exposure for desipramine; thereby suggesting inhibition of CYP2D6. However in the other study, receipt of peginterferon alfa-2b 1.5 mcg/kg once weekly for 4 weeks by patients with chronic hepatitis C led to a mean increase of 66% in a measure of CYP2D6 activity, but the effect was variable: 13 patients had an increase, 5 patients had a decrease, and 4 patients had no significant change in CYP2D6 activity. Caution is recommended if peginterferon alfa-2b is used with CYP2D6 substrates such as propoxyphene. The pharmacologic effects of CYP2D6 substrates may be increased or decreased when administered with peginterferon alfa-2b.
Propranolol: (Moderate) Monitor for adverse effects associated with increased exposure to propranolol if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while propranolol is a CYP2D6 substrate.
Propranolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for adverse effects associated with increased exposure to propranolol if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while propranolol is a CYP2D6 substrate.
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.
Protriptyline: (Moderate) Monitor for adverse effects associated with increased exposure to protriptyline if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while protriptyline is a CYP2D6 substrate.
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.
Quinine: (Major) Monitor for adverse effects associated with increased exposure to quinine if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP1A2 and CYP2D6 inhibitor, while quinine is a substrate of both these enzymes.
Ranolazine: (Moderate) Monitor for adverse effects associated with increased exposure to ranolazine if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while ranolazine is partially metabolized by the CYP2D6 isoenzyme.
Rasagiline: (Moderate) Monitor for dopaminergic adverse effects during concurrent use of rasagiline and peginterferon Alfa-2b. Coadministration may result in increased rasagiline concentrations. A dose reduction of rasagiline may be necessary. Rasagiline is primarily metabolized by CYP1A2; peginterferon Alfa-2b is a weak CYP1A2 inhibitor. When administered with a strong CYP1A2 inhibitor, the AUC of rasagiline was increased by 83%.
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-2b. 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.
Ropinirole: (Moderate) If peginterferon alfa-2b and ropinirole are coadministered, a downward adjustment of ropinirole dose may be required. Peginterferon alfa-2b is a CYP1A2 inhibitor, while ropinirole is a CYP1A2 substrate. Drug interaction studies have shown that coadministration of a potent inhibitor of CYP1A2 increases the ropinirole AUC (exposure) by an average of 84% and maximal concentration (Cmax) by an average of 60%. Monitor for excessive side effects of ropinirole, such as sedation, difficulty staying alert, nausea, vomiting, dizziness or feeling faint, hallucinations, or problems with impulse control. Consider a decrease in ropinirole drug dosage if such side effects occur.
Ropivacaine: (Moderate) Monitor for adverse effects, such as hypotension, bradycardia or GI effects, associated with increased exposure to ropivacaine if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP1A2 inhibitor and ropivacaine is metabolized to a 3-OH metabolite primarily by CYP1A2 and to a lesser extent to the pipecoloxylidide (PPX) metabolite by CYP3A4.
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.
Rubella 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.
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.
Sertraline: (Moderate) Monitor for adverse effects associated with increased exposure to sertraline if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while sertraline is partially metabolized by the CYP2D6 isoenzyme.
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).
Streptokinase: (Moderate) An increased risk of bleeding may occur when thrombolytic agents are used following agents that cause clinically significant thrombocytopenia including antineoplastic agents.
Tamsulosin: (Minor) Use caution when administering tamsulosin with a moderate CYP2D6 inhibitor such as peginterferon alfa-2b. Tamsulosin is extensively metabolized by CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP2D6 inhibitor resulted in increases in tamsulosin exposure; interactions with moderate CYP2D6 inhibitors have not been evaluated. If concomitant use in necessary, monitor patient closely for increased side effects.
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.
Telbivudine: (Major) An increased risk and severity of peripheral neuropathy has been reported with telbivudine alone or in combination with pegylated interferon alfa-2a and other interferons. Patients should be advised to report any numbness, tingling, and/or burning sensations in the arms and/or legs, with or without gait disturbance. Interrupt telbivudine if peripheral neuropathy is suspected, and discontinue the drug if peripheral neuropathy is confirmed. Since both interferons and telbivudine may cause hepatotoxicity, hepatic function should also be closely monitored.
Tenecteplase: (Moderate) An increased risk of bleeding may occur when thrombolytic agents are used following agents that cause clinically significant thrombocytopenia including antineoplastic agents.
Terbinafine: (Moderate) Caution is advised when administering terbinafine with peginterferon alfa-2b. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of systemic terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, including CYP1A2, which is inhibited by peginterferon alfa-2b. Monitor patients for adverse reactions if these drugs are coadministered.
Tetrabenazine: (Moderate) Peginterferon alfa-2b is a CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as tetrabenazine may be increased when co-administered with peginterferon alfa-2b. Two of the primary metabolites of tetrabenazine, alpha-dihydrotetrabenzaine (alpha-HTBZ) and beta-dihydrotetrabenazine (beta-HTBZ), are substrates for CYP2D6. Therefore, appropriate monitoring may be necessary.
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.
Thioridazine: (Contraindicated) Peginterferon Alfa-2b is a mild inhibitor of CYP2D6 and the use of thioridazine concomitantly with CYP2D6 inhibitors is contraindicated due to the possible risk of QT prolongation and subsequent arrhythmias, or other serious side effects, occurring from elevated serum concentrations of thioridazine.
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.
Timolol: (Moderate) Monitor for adverse effects associated with increased exposure to timolol if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while timolol is a CYP2D6 substrate.
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.
Tizanidine: (Major) Tizanidine is primarily metabolized by CYP1A2. The presystemic availability of tizanidine has been shown to be substantially increased by coadministration with CYP1A2 inhibitors, such as peginterferon alfa-2b. Average increases in tizanidine AUC of 10-fold and 33-fold have been reported following administration of strong CYP1A2 inhibitors. These increases in tizanidine concentrations have been associated with significant hypotensive and sedative effects. The use of potent CYP1A2 inhibitors with tizanidine is contraindicated. If possible, avoid the concurrent use of tizanidine with other CYP1A2 inhibitors, as concurrent use could lead to substantial increases in tizanidine blood concentrations. Discontinue tizanidine if hypotension, bradycardia, or excessive drowsiness occur.
Tolterodine: (Moderate) Monitor for adverse effects associated with increased exposure to tolterodine if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while tolterodine is a CYP2D6 substrate.
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.
Tramadol: (Moderate) Monitor for adverse effects associated with increased exposure to tramadol if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while tramadol is a CYP2D6 substrate.
Tramadol; Acetaminophen: (Moderate) Monitor for adverse effects associated with increased exposure to tramadol if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while tramadol is a CYP2D6 substrate.
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.
Triamterene: (Minor) Monitor for adverse effects associated with increased exposure to triamterene if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP1A2 inhibitor, while triamterene is a CYP1A2 substrate.
Triamterene; Hydrochlorothiazide, HCTZ: (Minor) Monitor for adverse effects associated with increased exposure to triamterene if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP1A2 inhibitor, while triamterene is a CYP1A2 substrate.
Trimipramine: (Moderate) Monitor for adverse effects associated with increased exposure to trimipramine if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while trimipramine is a CYP2D6 substrate.
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.
Umeclidinium: (Moderate) Monitor for adverse effects associated with increased exposure to umeclidinium if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while umeclidinium is a CYP2D6 substrate.
Umeclidinium; Vilanterol: (Moderate) Monitor for adverse effects associated with increased exposure to umeclidinium if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while umeclidinium is a CYP2D6 substrate.
Urokinase: (Moderate) An increased risk of bleeding may occur when thrombolytic agents are used following agents that cause clinically significant thrombocytopenia including antineoplastic agents.
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.
Venlafaxine: (Moderate) Monitor for adverse effects associated with increased exposure to venlafaxine if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while venlafaxine is a CYP2D6 substrate.
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.
Warfarin: (Moderate) Closely monitor the INR if coadministration of warfarin with peginterferon alfa-2b is necessary as concurrent use may increase the exposure of warfarin leading to increased bleeding risk. Peginterferon alfa-2b is a CYP1A2 inhibitor and the R-enantiomer of warfarin is a CYP1A2 substrate. The S-enantiomer of warfarin exhibits 2 to 5 times more anticoagulant activity than the R-enantiomer, but the R-enantiomer generally has a slower clearance.
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.
Yohimbine: (Moderate) Caution is warranted with the use of peginterferon alfa-2b and yohimbine. Peginterferon alfa-2b is a CYP2D6 inhibitor and the active metabolite of yohimbine, 11-hydroxy-yohimbine is preferentially formed via CYP2D6.
Zalcitabine, ddC: (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.
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.
Zileuton: (Moderate) Caution is warranted with the use of peginterferon alfa-2b and zileuton. Peginterferon alfa-2b is a CYP2D6 inhibitor and zileuton and its N-dehydroxylated metabolite can be oxidatively metabolized by the cytochrome P450 isoenzymes 1A2, 2C9, and 3A4.
Zolmitriptan: (Moderate) Monitor for adverse effects associated with increased exposure to zolmitriptan if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP1A2 inhibitor, while zolmitriptan is partially metabolized by the CYP1A2 isoenzyme.