PegIntron

Interferons for Hepatitis B and C
Interferons, Alpha

 
NOTE: Variations in dosage and adverse reactions exist among different subtypes of interferon alfa. Therefore, do not use different brands of interferon in a single treatment regimen.

exfoliative dermatitis / Delayed / 36.0-36.0
proteinuria / Delayed / 7.0-7.0
myocardial infarction / Delayed / 4.0-4.0
ventricular tachycardia / Early / 4.0-4.0
suicidal ideation / Delayed / 0-1.0
cranial nerve palsies / Delayed / 0-1.0
pericardial effusion / Delayed / 0-1.0
pleural effusion / Delayed / 0-1.0
vasculitis / Delayed / 0-1.0
retinal thrombosis / Delayed / 0-1.0
retinopathy / Delayed / 0-1.0
retinal hemorrhage / Delayed / 0-1.0
visual impairment / Early / 0-1.0
retinal detachment / Delayed / 0-1.0
seizures / Delayed / Incidence not known
coma / Early / Incidence not known
GI bleeding / Delayed / Incidence not known
pancreatitis / Delayed / Incidence not known
hepatic failure / Delayed / Incidence not known
erythema multiforme / Delayed / Incidence not known
anaphylactic shock / Rapid / Incidence not known
angioedema / Rapid / Incidence not known
thrombotic thrombocytopenic purpura (TTP) / Delayed / Incidence not known
toxic epidermal necrolysis / Delayed / Incidence not known
Stevens-Johnson syndrome / Delayed / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known
pulmonary hypertension / Delayed / Incidence not known
pericarditis / Delayed / Incidence not known
bronchiolitis obliterans / Delayed / Incidence not known
pulmonary fibrosis / Delayed / Incidence not known
cardiomyopathy / Delayed / Incidence not known
red cell aplasia / Delayed / Incidence not known
aplastic anemia / Delayed / Incidence not known
diabetic ketoacidosis / Delayed / Incidence not known
macular edema / Delayed / Incidence not known
papilledema / Delayed / Incidence not known
optic neuritis / Delayed / Incidence not known
lupus-like symptoms / Delayed / Incidence not known
interstitial nephritis / Delayed / Incidence not known
autoimmune disease / Delayed / Incidence not known
stroke / Early / Incidence not known
renal failure (unspecified) / Delayed / Incidence not known
rhabdomyolysis / Delayed / Incidence not known
hearing loss / Delayed / Incidence not known

elevated hepatic enzymes / Delayed / 10.0-77.0
depression / Delayed / 29.0-59.0
antibody formation / Delayed / 0-35.0
neutropenia / Delayed / 6.0-33.0
hyperbilirubinemia / Delayed / 7.0-14.0
anemia / Delayed / 6.0-11.0
impaired cognition / Early / 10.0-10.0
leukopenia / Delayed / 0-10.0
thrombocytopenia / Delayed / 7.0-7.0
hepatomegaly / Delayed / 6.0-6.0
chest pain (unspecified) / Early / 6.0-6.0
dyspnea / Early / 4.0-6.0
hypothyroidism / Delayed / 5.0-5.0
supraventricular tachycardia (SVT) / Early / 4.0-4.0
bundle-branch block / Early / 4.0-4.0
conjunctivitis / Delayed / 4.0-4.0
hyperthyroidism / Delayed / 3.0-3.0
blurred vision / Early / 0-2.0
constipation / Delayed / 1.0-1.0
encephalopathy / Delayed / Incidence not known
hallucinations / Early / Incidence not known
mania / Early / Incidence not known
confusion / Early / Incidence not known
psychosis / Early / Incidence not known
memory impairment / Delayed / Incidence not known
migraine / Early / Incidence not known
hypertriglyceridemia / Delayed / Incidence not known
stomatitis / Delayed / Incidence not known
colitis / Delayed / Incidence not known
hepatitis / Delayed / Incidence not known
pneumonitis / Delayed / Incidence not known
hypertension / Early / Incidence not known
hypotension / Rapid / Incidence not known
sinus tachycardia / Rapid / Incidence not known
palpitations / Early / Incidence not known
angina / Early / Incidence not known
diabetes mellitus / Delayed / Incidence not known
hyperglycemia / Delayed / Incidence not known
dehydration / Delayed / Incidence not known
psoriasis / Delayed / Incidence not known
growth inhibition / Delayed / Incidence not known
peripheral neuropathy / Delayed / Incidence not known

fatigue / Early / 30.0-94.0
fever / Early / 22.0-80.0
headache / Early / 56.0-70.0
anorexia / Delayed / 20.0-69.0
myalgia / Early / 17.0-68.0
nausea / Early / 18.0-64.0
chills / Rapid / 21.0-63.0
injection site reaction / Rapid / 29.0-62.0
asthenia / Delayed / 15.0-52.0
arthralgia / Delayed / 17.0-51.0
dysgeusia / Early / 0-38.0
diarrhea / Early / 18.0-37.0
dizziness / Early / 12.0-35.0
alopecia / Delayed / 17.0-34.0
anxiety / Delayed / 28.0-28.0
irritability / Delayed / 14.0-28.0
emotional lability / Early / 28.0-28.0
vomiting / Early / 7.0-27.0
insomnia / Early / 23.0-23.0
paresthesias / Delayed / 21.0-21.0
abdominal pain / Early / 8.0-21.0
weight loss / Delayed / 11.0-19.0
pruritus / Rapid / 12.0-12.0
xerosis / Delayed / 11.0-11.0
infection / Delayed / 0-11.0
pharyngitis / Delayed / 10.0-10.0
cough / Delayed / 5.0-8.0
malaise / Early / 7.0-7.0
sinusitis / Delayed / 7.0-7.0
diaphoresis / Early / 6.0-6.0
xerostomia / Early / 6.0-6.0
dyspepsia / Early / 6.0-6.0
rash / Early / 6.0-6.0
flushing / Rapid / 6.0-6.0
menstrual irregularity / Delayed / 4.0-4.0
agitation / Early / 2.0-2.0
rhinitis / Early / 2.0-2.0
photosensitivity / Delayed / 0-1.0
tongue discoloration / Delayed / Incidence not known
urticaria / Rapid / Incidence not known
musculoskeletal pain / Early / Incidence not known
vertigo / Early / Incidence not known

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.

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.

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]

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.

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]

PegIntron, PegIntron Redipen, PegIntron Redipen Pak, SYLATRON

Rx

Covalent conjugate of recombinant interferon alfa-2b with PEG
Used as monotherapy or in combination with other antivirals to treat chronic hepatitis C virus infection; used as adjuvant treatment of melanoma with microscopic or gross nodal involvement within 84 days of definitive surgical resection including complete lymphadenectomy
May cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders

†Indicates off-label use

Mild impairment (Child-Pugh class A, total score of 5 or 6): No dose adjustment needed.
Moderate to severe impairment (Child-Pugh class B or C, total score >= 7): Discontinue PegIntron, as PegIntron is only indicated for patients with compensated hepatic disease defined as a Child-Pugh < 6. Sylatron is contraindicated for use.

NOTE: If renal function decreases during PegIntron treatment, discontinue PegIntron. Also, permanent PegIntron discontinuation is advised for children or adolescents with a serum creatinine of > 2 mg/dl.
CrCl > 50 ml/min: No dosage adjustment is needed.
CrCl 30—50 ml/min: Reduce dose by 25%.
CrCl 10—29 ml/min: Reduce dose by 50%.
 
Intermittent hemodialysis
Reduce dose by 50%.

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; Aspirin; 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; 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; Pyrilamine: (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; 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.
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.
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 aripiprazole-related adverse reactions during concomitant use of peginterferon alfa-2b. Patients receiving both a CYP3A inhibitor plus peginterferon alfa-2b may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form and CYP3A inhibitor strength. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP2D6 and CYP3A substrate; peginterferon alfa-2b is a weak 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; 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; 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; 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; 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.
Butalbital; Aspirin; 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.
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; 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; 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.
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.
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; Bupropion: (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.
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; 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 Disoproxil Fumarate: (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) can both cause hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and efavirenz can both cause hepatotoxicity. Cirrhotic chronic HCV infected patients co-infected with HIV receiving HAART and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Monitor for treatment-associated toxicities, especially hepatic decompensation, during coadministration of interferons (with or without ribavirin) and lamivudine. Dose reduction or discontinuation of interferon, ribavirin, or both should be considered if worsening clinical toxicities are observed, including hepatic decompensation (e.g., Child-Pugh score greater than 6). (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and efavirenz can both cause hepatotoxicity. Cirrhotic chronic HCV infected patients co-infected with HIV receiving HAART and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART.
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.
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.
Fezolinetant: (Contraindicated) Concomitant use of fezolinetant and peginterferon alfa-2b is contraindicated due to the risk of increased fezolinetant exposure which may increase the risk of fezolinetant-related adverse effects. Fezolinetant is a CYP1A2 substrate; peginterferon alfa-2b is a weak CYP1A2 inhibitor. Concomitant use with another weak CYP1A2 inhibitor increased fezolinetant overall exposure by 100%.
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.
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 h ydrocodone.
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; 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.
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.
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 an increase in paroxetine-related adverse reactions, including serotonin syndrome, if concomitant use with peginterferon alfa-2b is necessary. Concomitant use may increase paroxetine exposure. Paroxetine is a CYP2D6 substrate and peginterferon alfa-2b is a weak CYP2D6 inhibitor.
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.
Pretomanid: (Major) Avoid coadministration of pretomanid with peginterferon alfa-2b, especially in patients with impaired hepatic function, due to increased risk for hepatotoxicity. Monitor for evidence of hepatotoxicity if coadministration is necessary. If new or worsening hepatic dysfunction occurs, discontinue hepatotoxic medications.
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.
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.
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).
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.
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.
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.
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.
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.

PegIntron/PegIntron Redipen/PegIntron Redipen Pak/SYLATRON Subcutaneous Inj Pwd F/Sol: 50mcg, 80mcg, 120mcg, 150mcg, 296mcg, 444mcg, 888mcg

For PegIntron, 1 mcg/kg/week SC for monotherapy or 1.5 mcg/kg/week SC for combination therapy. For Sylatron, 6 mcg/kg/week SC.

For PegIntron, 1 mcg/kg/week SC for monotherapy or 1.5 mcg/kg/week SC for combination therapy. For Sylatron, 6 mcg/kg/week SC.

For PegIntron, 60 mcg/m2/week SC in combination with ribavirin for chronic hepatitis C. For Sylatron, safety and efficacy have not been established.

>= 3 years: For PegIntron, 60 mcg/m2/week SC in combination with ribavirin for chronic hepatitis C. For Sylatron, safety and efficacy have not been established.
< 3 years: Safety and efficacy have not been established.

Peginterferon alfa-2b is indicated for the treatment of chronic hepatitis C virus infections and for the adjuvant treatment of melanoma. The active component of peginterferon alfa-2b is the interferon alfa-2b moiety. Interferon alfa-2b acts similarly to endogenous alfa interferons, which are cytokines with immunomodulatory, antiviral, antiangiogenic, antiproliferative, and antitumor activities. Interferons produce these therapeutic effects by directly binding to cell surface receptors (i.e., type I or type II interferon receptors) and by indirect inducting host antitumor responses. Of the 2 receptors, interferon alfa selectively binds to the type 1 interferon receptor. By binding to this receptor, interferon alfa causes autophosphorylation of tyrosine kinase 2 (Tyk2) and Janus kinase 1 (Jak1), which leads to activation of the following signal pathways: (1) phosphorylation and activation of the signal transducer and activator transcription (Stat) proteins (i.e., Jak-Stat pathway); (2) activation of CrkL, resulting in downstream activation of small GTPase Rap1 (Crk-pathway); (3) phosphorylation of insulin receptor substrates (IRS-1 and IRS-2), resulting in downstream activation of phosphatidylinositol and serine kinase activities of the phosphatidylinositol 3'kinase (IRS/PI3'-kinase pathway); (4) activation of p38 mitogen-activated protein (MAP) kinase which is involved in many signal transduction pathways in mammalian cells; (5) activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NFkB) which produces anti-inflammatory effects by inhibiting expression of proinflammatory genes and manipulating activity of anti-inflammatory cytokines. In addition to receptor-mediated effects, data suggest interferons may induce apoptosis in certain malignant cells. This effect appears to be cell type-dependent and interferon species-specific. [64460]

Peginterferon alfa-2b is given subcutaneously. The mean elimination half-life is 40 hours (range, 22 to 60 hours) in patients with hepatitis C infection. Renal elimination accounts for about 30% of the clearance. When compared to interferon alfa-2b (Intron A), peginterferon alfa-2b has approximately a 7-fold lower mean apparent clearance and a 5-fold greater mean half-life allowing for a reduced dosing frequency. At effective therapeutic doses, peginterferon alfa-2b has about a 10-fold greater Cmax and 50-fold greater AUC than interferon alfa-2b.
 
Affected cytochrome P450 isoenzymes: CYP1A2, CYP2D6
Peginterferon alfa-2b inhibits the activity of CYP1A2 and CYP2D6.

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]