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  • CLASSES

    Interferons for Hepatitis B and C
    Interferons, Alpha

    BOXED WARNING

    Alcoholism, depression, driving or operating machinery, psychiatric event, seizure disorder, substance abuse, suicidal ideation

    Development or exacerbation of a fatal or life-threatening neuro-psychiatric event (e.g., depression, suicidal ideation, suicide attempts, completed suicides, homicidal ideation, and aggression towards others) has been observed in patients receiving alpha interferons. Patients with pre-existing history of depression or severe psychiatric disorder may be at increased risk; thus, interferon therapy must be administered with extreme caution to these patients. In addition, pediatric drug recipients (primarily adolescents) are more likely to experience suicidal ideation or attempts as compared to adults (2.4% vs. 1%). Caution is also advised for patients with history of substance abuse (e.g., alcoholism), as relapse and drug overdose may occur. Instruct all patients to immediately report any symptoms of depression or suicidal ideation to their health care provider. Closely monitor patients for depression and other psychiatric symptoms during treatment and for 6 months after the last alfa interferon dose. For patients who experience persistent or worsening psychiatric symptoms, immediately discontinue interferon alfa-2b treatment. Although, dose reduction or cessation of therapy may lead to resolution of the symptoms, depression may persist and suicides have occurred after withdrawing therapy. Full resolution of symptoms may take up to 3 weeks in severe cases. Any patient with a seizure disorder or compromised nervous system function should receive interferon alfa-2b with caution. Central nervous system toxicities have occurred. Patients should be warned against driving or operating machinery until they know how interferon alfa-2b therapy will affect them.

    Stroke, thrombophlebitis

    Development or exacerbation of fatal or life-threatening ischemic disorders has been observed in patients receiving alpha interferons. Ischemic and hemorrhagic cerebrovascular events have been observed in patients treated with interferon alfa-2b; some patients had few or no reported risk factors for stroke. Caution should be observed in patients with coagulation disorders (eg, thrombophlebitis, pulmonary embolism). Patients should be monitored closely with periodic clinical and laboratory evaluations. Interferon alfa-2b should be discontinued in patients with persistently severe or worsening signs or symptoms of ischemic conditions. In many but not all cases, these disorders resolve after stopping interferon alfa-2b.

    Anemia, angina, cardiac arrhythmias, cardiac disease, chronic obstructive pulmonary disease (COPD), heart failure, myocardial infarction, neoplastic disease, pulmonary disease, use with ribavirin

    Interferon alfa-2b should be used cautiously in patients with debilitating conditions such as those with a history of cardiac disease (e.g., angina or congestive heart failure) or pulmonary disease (e.g., chronic obstructive pulmonary disease (COPD)) because of fever and flu-like symptoms associated with interferon alfa-2b. Patients with a history of myocardial infarction and/or previous or current cardiac arrhythmias who require interferon alfa-2b therapy should be closely monitored. Supraventricular tachycardia appears to be correlated with preexisting conditions or previous treatment with cardiotoxic agents. Patients with preexisting cardiac abnormalities and/or advanced stage neoplastic disease should have electrocardiograms taken before and during the course of treatment. Patients who develop persistent or unexplained pulmonary infiltrates or pulmonary function impairment should be closely monitored; discontinue interferon alfa-2b, if appropriate. Use with ribavirin: Interferon alfa-2b may be used with ribavirin, and ribavirin causes hemolytic anemia. Hemoglobin < 10 g/dL was observed in approximately 10% of adult and pediatric patients in clinical trials. Anemia occurred within 1—2 weeks of ribavirin initiation. Anemia may worsen cardiac disease. Ribavirin is not recommended for patients with a history of significant or unstable cardiac disease, and do not administer combination treatment with interferon alfa-2b and ribavirin to patients with creatinine clearance < 50 mL/minute. Do not use ribavirin in pregnant patients, as the drug may also cause birth defects or fetal death.

    Autoimmune disease, psoriasis, rheumatoid arthritis, systemic lupus erythematosus (SLE), thrombocytopenia

    Interferon alfa-2b should be used with caution in patients with a history of autoimmune disease and only if the potential benefit justifies the risk; patients with chronic hepatitis B or C and a history of autoimmune disease should not be treated with interferon alfa-2b because of reports of worsening liver disease including jaundice, hepatic encephalopathy, hepatic failure, and death after interferon alfa-2b in such patients. Interferon alfa-2b is contraindicated for use in patients with autoimmune hepatitis. Development or exacerbation of fatal or life-threatening autoimmune diseases (e.g., thyroiditis, thrombocytopenia, rheumatoid arthritis, interstitial nephritis, systemic lupus erythematosus (SLE), sarcoidosis, or psoriasis) has been observed in patients receiving interferon alfa-2b. Patients should be monitored closely with periodic clinical and laboratory evaluations. Interferon 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 interferon alfa-2b.

    Infection, neutropenia

    Development or exacerbation of fatal or life-threatening infectious disorders has been observed in patients receiving alpha interferons. Serious and severe bacterial infections, some fatal and some not associated with neutropenia, have been observed in patients treated with alpha interferons. Patients should be monitored closely with baseline and periodic clinical and laboratory evaluations. Interferon alfa-2b should be discontinued in patients with persistently severe or worsening signs or symptoms of infectious processes. In many but not all cases, these disorders resolve after stopping interferon alfa-2b.

    DEA CLASS

    Rx

    DESCRIPTION

    Recombinant alpha interferon; represents only one specific subtype of alpha interferon; used in hairy cell leukemia, melanoma, NHL, genital warts, Kaposi's sarcoma, chronic hepatitis C and B.

    COMMON BRAND NAMES

    Intron A

    HOW SUPPLIED

    Intron A Intralesional Inj Pwd F/Sol: 10000000IU
    Intron A Intralesional Inj Sol: 0.5mL, 5000000IU
    Intron A Intramuscular Inj Pwd F/Sol: 10000000IU, 18000000IU, 50000000IU
    Intron A Intramuscular Inj Sol: 0.5mL, 3000000IU, 5000000IU
    Intron A Intravenous Inj Pwd F/Sol: 10000000IU, 18000000IU, 50000000IU
    Intron A Subcutaneous Inj Pwd F/Sol: 10000000IU, 18000000IU, 50000000IU
    Intron A Subcutaneous Inj Sol: 0.5mL, 3000000IU, 5000000IU

    DOSAGE & INDICATIONS

    For the treatment of hairy-cell leukemia.
    Subcutaneous or Intramuscular dosage

    NOTE: Administer interferon alfa-2b subcutaneously as opposed to intramuscularly if the patient's platelet counts is less than 50,000/mm3.

    Adults

    2 million International Units/m2 IM or subcutaneously 3 times a week for up to 6 months. Higher doses are not recommended. Therapeutic benefit may not be seen for 2 months. Responding patients may benefit from continued treatment. If severe adverse reactions occur, the dosage should be reduced by 50% or temporarily discontinued until symptoms resolve, and resume dose at 1 million International Units/m2 IM or subcutaneously 3 times a week. If persistent or recurrent intolerance develops following adequate dosage adjustment or disease progresses, treatment should be permanently discontinued. The minimum effective dose has not been established.

    For the adjuvant treatment of malignant melanoma in patients who are disease free and at high risk for systemic recurrence within 56 days of surgery.
    Intravenous or Subcutaneous dosage

    NOTE: Intron A Solution for Injection in vials is NOT recommended for intravenous administration and should not be used for the induction phase treatment of melanoma.

    Adults

    20 million international Units/m2 IV infusion for 5 consecutive days per week for 4 weeks as induction therapy followed by 10 million International Units/m2 subcutaneously 3 times per week for 48 weeks. Monitor white blood cell count and liver function tests weekly during induction and monthly during maintenance therapy. If the absolute neutrophil count (ANC) decreases to less than 500/mm3 or serum transaminases increase to 5 times the upper limit of normal, therapy should be held until values normalize. Therapy should be restarted at 50% of the previous dose. If toxicity does not abate after withholding interferon alfa-2b, if intolerance continues after dose adjustments, or if the ANC decreases to less than 250/mm3 or transaminases increase to more than 10 times the upper limit of normal, interferon alfa-2b therapy should be permanently discontinued.

    For the treatment of aggressive, follicular non-Hodgkin's lymphoma (NHL) in conjunction with an anthracycline-containing combination chemotherapy regimen.
    Subcutaneous dosage
    Adults

    5 million International Units subcutaneously 3 times per week for up to 18 months in combination with an anthracycline-containing combination chemotherapy regimen and following completion of the chemotherapy regimen. In published reports, the doses of myelosuppressive drugs were reduced 25% from those utilized in the full-dose CHOP regimen, and the cycle length was increased from 21 to 28 days when alfa interferon was added. The following dose adjustments are recommended: For absolute neutrophil count (ANC) less than 1500/mm3 or platelet count less than 75,000/mm3, the chemotherapy regimen was delayed. For an ANC less than 1000/mm3 or platelet count less than 50,000/mm3, interferon alfa-2b treatment was held. For ANC more than 1000/mm3 but less than 1500/mm3, reduce the dose by 50% to a dose of 2.5 million International Units subcutaneously 3 times per week. The initial dose may be restarted once the ANC is more than 1500/mm3. Interferon alfa-2b therapy should be permanently discontinued if the SGOT exceeds 5 times the upper limit of normal or if the serum creatinine is more than 2 mg/dL.

    For the treatment of condylomata acuminata (genital or venereal warts), due to the human papillomavirus (HPV) infection, involving the external surfaces of the genital and perianal areas.
    Intralesional dosage

    NOTE: Use only the 10 million International Unit vials of Intron A powder for injection or the 25 million International Unit strengths of Intron A solution for injection, each having a final concentration of 10 million International Units/mL. Other Intron A formulations should not be used because the concentrations or tonicity may be inappropriate.

    Adults

    Inject 1 million International Units (0.1 mL) into each lesion 3 times per week on alternating days for 3 weeks. A maximum of 5 warts should be treated per course. An additional course may be administered at 12 to 16 weeks. The HIV guidelines generally do not recommend due to cost, administration difficulties, and systemic side effects.

    For the treatment of AIDS-related Kaposi's sarcoma.
    NOTE: Interferon alfa-2b should not be used for the treatment of visceral AIDS-related Kaposi's sarcoma associated with rapidly progressive disease.
    NOTE: Interferon alfa-2b has been designated an orphan drug by the FDA for this indication.
    Subcutaneous or Intramuscular dosage

    NOTE: Intron A Solution for Injection in vials should NOT be used for the treatment of AIDS-related Kaposi's sarcoma.

    Adults

    The recommended dose is 30 million International Units/m2 IM or subcutaneously 3 times per week until disease progression or achievement of maximal response after 16 weeks of treatment. Dose reduction by 50% or drug suspension is needed for severe adverse reactions. If severe reactions abate with dosing interruption, resume interferon alfa-2b at a reduced dose. Permanently discontinue interferon alfa-2b if severe reactions persist or if they recur at a reduced dose. The average tolerated dose at the end of 12 weeks is 110 million International Unit/week and 75 million International Unit/week after 24 weeks. The likelihood of response to interferon alfa-2b therapy is greater in patients without systemic symptoms, who have limited lymphadenopathy, and who have a relatively intact immune system, as indicated by total CD4 count.

    For the treatment of chronic hepatitis B infection in patients with compensated liver disease.
    NOTE: Patients who have been serum HBsAg positive for at least 6 months and have evidence of HBV replication (serum HBeAg positive) with elevated serum ALT are candidates for treatment.
    NOTE: Evaluate liver function tests, HBeAg, and HBsAg before treatment initiation, at therapy cessation, and at both 3 and 6 months after therapy cessation. In clinical studies, 15 of 38 responding adults lost HBeAg 1 to 6 months after interferon alfa-2b cessation. Further, 7 of 12 responding adults lost HBsAg 1 to 6 months after interferon alfa-2b cessation.
    Subcutaneous or Intramuscular dosage

    NOTE: Only the 25 million International Unit/dose Intron A Solution for Injection or the 10 million International Unit Powder for Injection should be used.

    Adults

    30 to 35 million International Units per week IM or subcutaneously for 16 weeks administered, either as 5 million International Units per day or as 10 million International Units 3 times per week. Dose reduction by 50% or drug suspension is needed for severe adverse reactions. If severe reactions abate with dosing interruption, resume interferon alfa-2b at a reduced dose. Discontinue interferon alfa-2b if severe reactions recur at a reduced dose. During therapy with interferon alfa-2b, if white blood cell counts, granulocyte counts, or platelet counts fall below 1500/mm3, 750/mm3, or 50,000/mm3, respectively, the dose should be reduced by 50%. If counts fall below 1000/mm3, 500/mm3, or 25,000/mm3, respectively, therapy should be permanently discontinued. Interferon alfa-2b may be restarted at up to 100% of initial dose when blood cell counts return to normal or baseline levels.

    Subcutaneous dosage

    NOTE: Only the 25 million International Unit/dose Intron A Solution for Injection or the 10 million International Unit Powder for Injection should be used.

    Children and Adolescents

    3 million International Units/m2 subcutaneously 3 times per week for the first week of therapy, then escalated to 6 million International Units/m2 (maximum 10 million International Units) subcutaneously 3 times per week for 16 to 24 weeks. Dose reduction by 50% or drug suspension is needed for severe adverse reactions. If severe reactions abate with dosing interruption, resume interferon alfa-2b at a reduced dose. Discontinue interferon alfa-2b if severe reactions recur at a reduced dose. During therapy with interferon alfa-2b, if white blood cell counts, granulocyte counts, or platelet counts fall below 1500/mm3, 750/mm3, or 50,000/mm3, respectively, the dose should be reduced by 50%. Interferon alfa-2b may be restarted at up to 100% of initial dose when blood counts return to normal or baseline levels. If the white blood cell count falls below 1000/mm3, the granulocyte count falls below 500/mm3, or the platelet count falls below 25,000/mm3, permanently discontinue interferon alfa-2b.

    For the treatment of hepatitis C infection in patients with compensated liver disease.
    In patients with a blood or blood-product exposure history or HCV antibody positivity.
    NOTE: Establish the diagnosis by liver biopsy.
    Subcutaneous or Intramuscular dosage

    NOTE: Only the 18 million International Unit/dose Intron A Solution for Injection should be used.

    Adults

    3 million International Units administered IM or subcutaneously 3 times per week should be continued for up to 18 to 24 months if a positive response (i.e., normalization of ALT values) is seen at 16 weeks of therapy. If no response is seen at 16 weeks of therapy, consider discontinuing therapy. If severe adverse reactions develop during therapy, the interferon alfa-2b dosage should be modified (50% reduction) or treatment held until symptoms resolve. If intolerance persists after dose adjustment, therapy should be discontinued.

    In combination with ribavirin in patients previously untreated with interferon alpha.
    Subcutaneous or Intramuscular dosage
    Adults

    3 million International Units IM or subcutaneously 3 times per week plus daily ribavirin. The recommended duration of treatment is 24 to 48 weeks for adults; consider treatment discontinuation if an HCV-RNA value below the level of detection has not been achieved at 24 weeks. There are no safety or efficacy data on treatment longer than 48 weeks.

    Children and Adolescents older than 3 years and weighing more than 61 kg

    3 million International Units IM or subcutaneously 3 times per week plus daily ribavirin. The duration of treatment for genotype 1 is 48 weeks; consider treatment discontinuation if an HCV-RNA value below the level of detection has not been achieved at 24 weeks. The duration of treatment for genotype 2 or 3 is 24 weeks. NOTE: Consider response prognostic factors, HCV genotype, viral load, and disease progression evidence such as hepatic inflammation and fibrosis when deciding to treat a pediatric patient. Weigh treatment benefits against safety findings from the clinical trials.

    Children and Adolescents older than 3 years and weighing 25 to 61 kg

    3 million International Units/m2 subcutaneously 3 times per week plus daily ribavirin. The duration of treatment for genotype 1 is 48 weeks; consider treatment discontinuation if an HCV-RNA value below the level of detection has not been achieved at 24 weeks. The duration of treatment for genotype 2 or 3 is 24 weeks. NOTE: Consider response prognostic factors, HCV genotype, viral load, and disease progression evidence such as hepatic inflammation and fibrosis when deciding to treat a pediatric patient. Weigh treatment benefits against safety findings from the clinical trials.

    In combination with ribavirin in patients who have relapsed following interferon alpha therapy.
    Subcutaneous or Intramuscular dosage
    Adults

    3 million International Units IM or subcutaneously 3 times per week plus daily ribavirin for 24 weeks in adults; consider treatment discontinuation if an HCV-RNA value below the level of detection has not been achieved at 24 weeks. There are no safety or efficacy data on treatment longer than 24 weeks.

    Children and Adolescents older than 3 years and weighing more than 61 kg

    3 million International Units IM or subcutaneously 3 times per week plus daily ribavirin. The duration of treatment for genotype 1 is 48 weeks; consider treatment discontinuation if an HCV-RNA value below the level of detection has not been achieved at 24 weeks. The duration of treatment for genotype 2 or 3 is 24 weeks. NOTE: Consider response prognostic factors, HCV genotype, viral load, and disease progression evidence such as hepatic inflammation and fibrosis when deciding to treat a pediatric patient. Weigh treatment benefits against safety findings from the clinical trials.

    Children and Adolescents older than 3 years and weighing 25 to 61 kg

    3 million International Units subcutaneously 3 times per week plus daily ribavirin. The duration of treatment for genotype 1 is 48 weeks; consider treatment discontinuation if an HCV-RNA value below the level of detection has not been achieved at 24 weeks. The duration of treatment for genotype 2 or 3 is 24 weeks. NOTE: Consider response prognostic factors, HCV genotype, viral load, and disease progression evidence such as hepatic inflammation and fibrosis when deciding to treat a pediatric patient. Weigh treatment benefits against safety findings from the clinical trials.

    For the treatment of West Nile virus infection† (i.e., symptomatic flavivirus infections).
    NOTE: Other than supportive care, there is no established treatment for symptomatic flavivirus infections. The use of interferon alfa-2b for the treatment of West Nile virus is suggested by in vitro data only.
    Subcutaneous dosage
    Adults

    In the US, a government-supported national trial has been initiated to study the use of alpha-interferon for West Nile infection (press-release, August 26, 2002); a regimen of interferon alfa-2b therapy for 2 weeks will be used for the treatment of infected hospitalized patients 50 years of age and older. In an in vitro study, interferon alfa-2b at low doses was protective and therapeutic against West Nile virus infection. In humans, daily doses of 3 million International units subcutaneously result in serum concentrations well above those required for in vitro efficacy against West Nile virus.

    For the treatment of St. Louis encephalitis† (i.e., symptomatic flavivirus infections).
    Subcutaneous dosage
    Adults

    For the treatment of St. Louis encephalitis, interferon alfa-2b 6 million International Units subcutaneously on day 1, then 3 million International Units subcutaneously once daily for a total 14 days was studied in 15 patients. The increase in mean neurologic score was significantly higher in treated patients from week 0 to 3 and 0 to 4 as compared to untreated controls. Among the 17 untreated patients, 3 developed quadriplegia and ventilator dependence after admission, while no patient treated with interferon alfa-2b developed these complications.

    For the first-line treatment of Philadelphia chromosome positive, chronic phase, chronic myelogenous leukemia (CML)†, in combination with cytarabine.
    Subcutaneous dosage
    Adults less than 72 years, Adolescents, and Children older than 7 years

    5 million International Units/m2/day subcutaneously as continuous therapy plus cytarabine 20 mg/m2/day subcutaneously for 10 days each month (median duration of therapy, 34 months) was evaluated in a large randomized trial. Cytarabine therapy was initiated 2 weeks after interferon therapy had begun. All patients also received hydroxyurea 50 mg/kg/day (or less depending on white blood cell count) until a complete hematologic remission was achieved.

    For the treatment of renal cell cancer† in combination with bevacizumab for previously untreated metastatic disease.
    NOTE: Bevacizumab is FDA-approved for this indication.
    Subcutaneous dosage
    Adults

    9 million International Units subcutaneously 3 times weekly in combination with bevacizumab (10 mg/kg IV every 2 weeks). In a phase III trial of 710 patients with previously untreated metastatic renal cell carcinoma, median progression-free survival was significantly longer with interferon alfa-2b plus bevacizumab versus interferon alfa-2b therapy alone (8.5 months vs. 5.2 months). Grade 3 toxicities that were significantly greater in the bevacizumab arm include hypertension, anorexia, fatigue, and proteinuria. Results for the primary endpoint, overall survival, have not yet been released for this trial.

    For the maintenance treatment for multiple myeloma†.
    Subcutaneous dosage
    Adults

    3 million International Units/dose or 3 million International Units/m2/dose subcutaneously 3 times weekly as maintenance therapy in patients who respond to standard therapy for multiple myeloma has been studied in randomized clinical studies.

    For the treatment of hypereosinophilic syndrome†.
    Subcutaneous dosage
    Adults

    Six patients with hypereosinophilic syndrome were given 1 to 6.25 million International Units/day subcutaneously in a phase I trial. A satisfactory response was noted in 5 patients.

    For the treatment of hemangioma† of infancy or pulmonary hemangiomatosis†.
    Subcutaneous dosage
    Infants and Children

    1 to 3 million International Units/m2/day subcutaneously once daily.

    For the treatment of adult T-cell leukemia/lymphoma† in combination with zidovudine in patients infected with human T-lymphotropic virus type I (HTLV-I).
    Subcutaneous dosage
    Adults

    In a small study, the combination of interferon alfa-2b 5 million International Units subcutaneously once daily for the first week with the dose escalated to 10 million International Units subcutaneously once daily after 1 week, if tolerated, with oral zidovudine produced major responses in 11 of 19 patients (58%), including complete remissions in 5 of 19 (26%). Doses were adjusted for hematologic toxicity. Treatment was continued for at least 4 weeks after the onset of complete remission, or, for up to 1 year in the absence of remission.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    20 million International Units/m2/day IV; 35 million International Units/m2 subcutaneous/IM as a single dose.

    Geriatric

    20 million International Units/m2/day IV; 35 million International Units/m2 subcutaneous/IM as a single dose.

    Adolescents

    10 million International Units/day subcutaneously.

    Children

    10 million International Units/day subcutaneously.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Avoid use in patients with severe hepatic injury (Grade 3) or hepatic decompensation (Child-Pugh score > 6; Class B and C). Interferon alfa-2b has not been studied in patients with decompensated hepatic disease.

    Renal Impairment

    Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed. However, close monitoring of patients with impaired renal function is warranted, as interferon alfa-2b is substantially excreted by the kidney. Alfa interferons are not cleared by hemodialysis.

    ADMINISTRATION

     
    NOTE: Variations in dosage, routes of administration, and adverse reactions exist among different brands of interferon. Therefore, do not use different brands of interferon in any single treatment regimen.

    Injectable Administration

    Interferon alfa-2b may be administered intramuscularly, subcutaneously, intralesionally, or by intravenous infusion.
    IMPORTANT: Interferon Alfa-2b (Intron A) is packaged as 1) powder for reconstitution/injection; 2) solution for injection in vials.
    Not all dosage forms and strengths are appropriate for some indications (see below NOTES under each administration route). CAREFULLY read the instructions for the indication treated to ensure selection of an appropriate dosage form, strength, and route of administration.
    Premedication with acetaminophen may decrease the incidence of administration-related reactions (i.e., fever). Bedtime administration may increase patient tolerance of therapy.
    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
     
    Solution for injection in vials:
    Clear and colorless solution that does not require reconstitution before administration.
    NOT recommended for intravenous administration.
    Discard any unused solution for injection remaining in the multidose vial after 1 month.
     
    Reconstitution of powder for injection:
    Reconstitute Intron A powder vials, regardless of vial strength, with 1 mL sterile water for injection, USP (provided). The sterile water for injection, USP vial contains an excess amount of diluent (5 mL); the remaining diluent must be discarded. Do NOT use any diluent besides the one that is supplied, and do NOT add other medications to the reconstituted solution.
    Swirl gently to aid in dissolution of the powder; do not shake.
    Reconstituted interferon alfa-2b solution does not contain a preservative, and is intended for a single dose. Do not re-enter the vial after withdrawing the dose. Once the dose has been withdrawn from the vial, sterility can no longer be guaranteed. Discard the vial and unused portion after withdrawing the dose.
    After reconstitution, the interferon alfa-2b solution is clear and colorless to light yellow and should be used immediately but may be stored at 2 to 8 degrees C (36 to 46 degrees F) for up to 24 hours.
    For hairy cell leukemia: Reconstitute the 10 million international unit vials for a concentration of 10 million international unit/mL.
    For condylomata acuminata: Reconstitute the 10 million international unit vials for a concentration of 10 million international unit/mL.
    For AIDS-related Kaposi's Sarcoma: Reconstitute the 50 million international unit vials for a concentration of 50 million international unit/mL.
    For malignant melanoma: Reconstitute the 10, 18, or 50 million international unit vials for concentrations of 10, 18, or 50 million international unit/mL, respectively.
    For follicular lymphoma: Reconstitute the 10 million international unit vials for a concentration of 10 million international unit/mL.
    For chronic hepatitis B: Reconstitute the 10 million international unit vials for a concentration of 10 million international unit/mL.

    Intravenous Administration

    Intravenous (IV) infusion:
    For the induction phase of the adjuvant treatment of malignant melanoma: Use only the 10 million, 18 million, or 50 million international unit vials of Intron A powder for injection.
    The appropriate dose of the reconstituted solution should be further diluted with 100 mL 0.9% Sodium Chloride injection.
    The final concentration should not be less than 10 million international unit/100 mL.
    The prepared solution should be infused over 20 minutes. The interferon alfa-2b infusion solution should be prepared immediately prior to use.

    Intramuscular Administration

    For Hairy Cell Leukemia: Use the 10 million international unit vials of Intron A powder for injection or the 18 or 25 million international unit vials of intron A solution for injection.
    For AIDS-related Kaposi's sarcoma: Use the 50 million international unit vials of Intron A powder for injection.
    For chronic hepatitis C: Use the 18 million international unit vials of Intron A solution for injection.
    For chronic hepatitis B in adults: Use the 10 million international unit vials of Intron A powder for injection or the 25 million international unit vials of Intron A solution for injection.
    Inject interferon alfa-2b deeply into a large muscle. Aspirate prior to injection to avoid injection into a blood vessel.

    Subcutaneous Administration

    For the maintenance phase of the adjuvant treatment of malignant melanoma: Use the 10 or 18 million international unit vials of Intron A powder for injection; the 18 or 25 million international unit vials of Intron A solution for injection. The 10 million international unit vials of Intron A powder for injection is only for patients who get a 50% reduced dose, and the 18 million international unit vials of Intron A powder for injection are only for patients who get the full dose.
    For Hairy Cell Leukemia: Use the 10 million international unit vials of Intron A powder for injection or the 18 or 25 million international unit vials of intron A solution for injection.
    For follicular lymphoma: Use the 10 million international unit vials of Intron A powder for injection or the 18 or 25 million international unit vials of Intron A solution for injection.
    For AIDS-related Kaposi's sarcoma: Use only the 50 million international unit vials of Intron A powder for injection.
    For chronic hepatitis C: Use the 18 million international unit vials of Intron A solution for injection.
    For chronic hepatitis B in adults: Use the 10 million international unit vials of Intron A powder for injection or the 25 million international unit vials of Intron A solution for injection.
    For chronic hepatitis B in children: Use the 10 million international unit vials of Intron A powder for injection or the 25 million international unit vials of Intron A solution for injection.
    Inject interferon alfa-2b subcutaneously taking care not to inject intradermally.

    Other Injectable Administration

    Intralesional Administration
    For condylomata acuminata: Use only the 10 million international unit vials of Intron A powder for injection or the 25 million international unit vials of Intron A solution for injection, each having a final concentration of 10 million international unit/ml.
    Use a Tuberculin or similar syringe and a 25- to 30-gauge needle.
    The needle should be directed at the center base of the wart and at an angle almost parallel to the plane of the skin. This will deliver the interferon to the dermal core of the lesion, infiltrating the lesion and causing a small wheal.
    Do not go beneath the lesion too deeply; avoid subcutaneous injection. Do not inject too superficially because infiltration of only the keratinized layer and not the dermal core will occur and leakage may occur.

    STORAGE

    Intron A:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Discard unused portion. Do not store for later use.
    - Reconstituted product should be refrigerated and used within 24 hours if not used immediately
    - Refrigerate (between 36 and 46 degrees F)
    Intron A Multidose Pen:
    - Avoid exposure to heat
    - Do not freeze
    - Refrigerate (between 36 and 46 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    Acute bronchospasm, albumin hypersensitivity, E. coli protein hypersensitivity, urticaria

    Interferon alfa-2b is contraindicated in persons with known hypersensitivity to alfa interferon or to any component of the product including E. coli protein hypersensitivity. The powder formulations of interferon alfa-2b contain albumin and may be inappropriate for patients with albumin hypersensitivity. Serious acute hypersensitivity reactions (e.g., anaphylaxis, angioedema, acute bronchospasm, and urticaria) have been rarely observed during alfa interferon therapy. If such a reaction develops during treatment with interferon alfa-2b, discontinue treatment and begin appropriate medical therapy immediately.

    Alcoholism, depression, driving or operating machinery, psychiatric event, seizure disorder, substance abuse, suicidal ideation

    Development or exacerbation of a fatal or life-threatening neuro-psychiatric event (e.g., depression, suicidal ideation, suicide attempts, completed suicides, homicidal ideation, and aggression towards others) has been observed in patients receiving alpha interferons. Patients with pre-existing history of depression or severe psychiatric disorder may be at increased risk; thus, interferon therapy must be administered with extreme caution to these patients. In addition, pediatric drug recipients (primarily adolescents) are more likely to experience suicidal ideation or attempts as compared to adults (2.4% vs. 1%). Caution is also advised for patients with history of substance abuse (e.g., alcoholism), as relapse and drug overdose may occur. Instruct all patients to immediately report any symptoms of depression or suicidal ideation to their health care provider. Closely monitor patients for depression and other psychiatric symptoms during treatment and for 6 months after the last alfa interferon dose. For patients who experience persistent or worsening psychiatric symptoms, immediately discontinue interferon alfa-2b treatment. Although, dose reduction or cessation of therapy may lead to resolution of the symptoms, depression may persist and suicides have occurred after withdrawing therapy. Full resolution of symptoms may take up to 3 weeks in severe cases. Any patient with a seizure disorder or compromised nervous system function should receive interferon alfa-2b with caution. Central nervous system toxicities have occurred. Patients should be warned against driving or operating machinery until they know how interferon alfa-2b therapy will affect them.

    Stroke, thrombophlebitis

    Development or exacerbation of fatal or life-threatening ischemic disorders has been observed in patients receiving alpha interferons. Ischemic and hemorrhagic cerebrovascular events have been observed in patients treated with interferon alfa-2b; some patients had few or no reported risk factors for stroke. Caution should be observed in patients with coagulation disorders (eg, thrombophlebitis, pulmonary embolism). Patients should be monitored closely with periodic clinical and laboratory evaluations. Interferon alfa-2b should be discontinued in patients with persistently severe or worsening signs or symptoms of ischemic conditions. In many but not all cases, these disorders resolve after stopping interferon alfa-2b.

    Anemia, angina, cardiac arrhythmias, cardiac disease, chronic obstructive pulmonary disease (COPD), heart failure, myocardial infarction, neoplastic disease, pulmonary disease, use with ribavirin

    Interferon alfa-2b should be used cautiously in patients with debilitating conditions such as those with a history of cardiac disease (e.g., angina or congestive heart failure) or pulmonary disease (e.g., chronic obstructive pulmonary disease (COPD)) because of fever and flu-like symptoms associated with interferon alfa-2b. Patients with a history of myocardial infarction and/or previous or current cardiac arrhythmias who require interferon alfa-2b therapy should be closely monitored. Supraventricular tachycardia appears to be correlated with preexisting conditions or previous treatment with cardiotoxic agents. Patients with preexisting cardiac abnormalities and/or advanced stage neoplastic disease should have electrocardiograms taken before and during the course of treatment. Patients who develop persistent or unexplained pulmonary infiltrates or pulmonary function impairment should be closely monitored; discontinue interferon alfa-2b, if appropriate. Use with ribavirin: Interferon alfa-2b may be used with ribavirin, and ribavirin causes hemolytic anemia. Hemoglobin < 10 g/dL was observed in approximately 10% of adult and pediatric patients in clinical trials. Anemia occurred within 1—2 weeks of ribavirin initiation. Anemia may worsen cardiac disease. Ribavirin is not recommended for patients with a history of significant or unstable cardiac disease, and do not administer combination treatment with interferon alfa-2b and ribavirin to patients with creatinine clearance < 50 mL/minute. Do not use ribavirin in pregnant patients, as the drug may also cause birth defects or fetal death.

    Diabetes mellitus, diabetic ketoacidosis

    Interferon alfa-2b should be used cautiously in patients with diabetes mellitus including patients with a history of diabetic ketoacidosis. Do not initiate interferon alfa-2b in a patient with diabetes mellitus that cannot be effectively treated by medication. Patients with diabetes mellitus may require adjustment of their antidiabetic medications. Discontinue interferon alfa-2b in a patient who develop diabetes mellitus that cannot be controlled with medication.

    Geriatric

    Geriatric patients may have difficulty tolerating the adverse reactions of interferon alfa-2b therapy. Obtundation and coma have been observed in some patients treated with high doses. Older patients may require lower doses because of decreased renal function. Carefully monitor patients during treatment, and make dose adjustments based on symptoms and/or laboratory abnormalities.

    Ascites, bleeding, hepatic disease, hepatic encephalopathy, hepatitis, immunosuppression, jaundice, organ transplant

    A liver biopsy to establish the presence of chronic hepatitis and the extent of liver damage is advised for patients with hepatitis B or C before interferon alfa-2b initiation. Patients with causes of chronic hepatitis other than chronic hepatitis B or chronic hepatitis C (e.g., autoimmune hepatitis) should not be treated with interferon alfa-2b. Patients with chronic hepatitis B or C need to have compensated hepatic disease before interferon alfa-2b initiation; use of the drug in patients with decompensated hepatic disease is contraindicated. For patients with chronic hepatitis C, the manufacturer recommends considering the following inclusion criteria prior to initiating interferon alfa-2b: no history of hepatic encephalopathy, variceal bleeding, ascites, or other signs of decompensation; bilirubin <= 2 mg/dL; albumin within normal limit and stable; prothrombin time < 3 seconds prolonged; WBC >= 3000/mm3; platelets >= 70,000/mm3; and normal or near normal serum creatinine. For patients with chronic hepatitis B, the manufacturer recommends considering the following inclusion criteria prior to initiating interferon alfa-2b: no history of hepatic encephalopathy, variceal bleeding, ascites, or other signs of clinical decompensation; normal bilirubin; albumin within normal limit and stable; prothrombin time < 3 seconds prolonged for adults and <= 2 seconds prolonged for pediatric patients; WBC >= 4000/mm3; and platelets >= 100,000/mm3 for adults and 150,000/mm3 for pediatric patients. Laboratory monitoring recommendations for patients with hepatitis C include complete blood count (CBC) and platelets at baseline, weeks 1 and 2, and monthly thereafter as well as ALT at approximately 3-month intervals. Laboratory monitoring recommendations for patients with hepatitis B include: CBC and platelets at baseline and weeks 1, 2, 4, 8, 12, and 16; ALT, albumin, and bilirubin at weeks 1, 2, 4, 8, 12, and 16; and HBeAg, HBsAg, and ALT at end of therapy, 3-month and 6-month post-therapy. Any patient developing liver function abnormalities during interferon alfa-2b therapy should be monitored closely because of the possibility of severe hepatotoxicity; fatal hepatotoxicities have been observed in recipients of interferon alfa-2b. Chronic hepatitis B patients with evidence of decreasing hepatic synthetic function, who nevertheless meet the criteria to start interferon alfa-2b therapy, may be at increased risk of clinical decompensation if a flare of aminotransferases occurs during interferon alfa-2b treatment. If increases in ALT occur during interferon alfa-2b therapy, closely monitor clinical symptoms and liver function tests including ALT, prothrombin time, alkaline phosphatase, albumin, and bilirubin at approximately 2-week intervals; evaluate the potential risks and benefits of interferon alfa-2b treatment for chronic hepatitis B. In general, interferon alfa-2b should be continued unless signs and symptoms of liver failure are observed. Organ transplant recipients with chronic hepatitis B or C and immunosuppression should not be treated with interferon alfa-2b. There are reports of worsening liver disease including jaundice, hepatic encephalopathy, hepatic failure, and death after interferon alfa-2b use in such patients. In addition, use of interferon alfa-2b in patients with cirrhosis may increase the risk for fatal hepatic decompensation. Discontinue treatment in any patient who develops signs and symptoms of liver failure.

    Children, growth inhibition, infants, neonates

    The safe and effective use of interferon alfa-2b in children aged 1 to 17 years with chronic hepatitis B has been established. Safety and effectiveness in children 3 to 16 years of age have been established based upon clinical studies in 118 patients with chronic hepatitis C; however, suicidal ideation or suicide attempts occurred more frequently among pediatric patients (2.4%) compared to adult patients (1%) during treatment and off-therapy follow-up. Monitor for the potential for growth inhibition in children and adolescents receiving interferon alfa-2b and ribavirin. A decrease in the rate of linear growth (mean percentile assignment decrease of 7%) and a decrease in the rate of weight gain (mean percentile assignment decrease of 9%) also occurred during the 48-week treatment period. Most children gain weight after therapy cessation; however, long-term follow-up data suggest that treatment with combination therapy may induce a growth inhibition resulting in decreased adult height in some patients. Safe and effective use of interferon alfa-2b for other uses besides chronic hepatitis B or C has not been established in children. The safety and effectiveness of interferon alfa-2b in infants or neonates have not been established.

    Colitis, pancreatitis, ulcerative colitis

    Patients who develop signs and symptoms of colitis or pancreatitis during interferon alfa-2b therapy should discontinue therapy. Use cautiously in those with a history of colitis, pancreatitis, or ulcerative colitis, as these conditions may be exacerbated by alpha interferon therapy.

    Kaposi's sarcoma

    Interferon alfa-2b should not be used in patients with AIDS-related Kaposi's sarcoma with rapidly progressive visceral disease. Interferon alfa-2b may also interact with zidovudine and other anti-retroviral agents (see Drug Interactions).

    Autoimmune disease, psoriasis, rheumatoid arthritis, systemic lupus erythematosus (SLE), thrombocytopenia

    Interferon alfa-2b should be used with caution in patients with a history of autoimmune disease and only if the potential benefit justifies the risk; patients with chronic hepatitis B or C and a history of autoimmune disease should not be treated with interferon alfa-2b because of reports of worsening liver disease including jaundice, hepatic encephalopathy, hepatic failure, and death after interferon alfa-2b in such patients. Interferon alfa-2b is contraindicated for use in patients with autoimmune hepatitis. Development or exacerbation of fatal or life-threatening autoimmune diseases (e.g., thyroiditis, thrombocytopenia, rheumatoid arthritis, interstitial nephritis, systemic lupus erythematosus (SLE), sarcoidosis, or psoriasis) has been observed in patients receiving interferon alfa-2b. Patients should be monitored closely with periodic clinical and laboratory evaluations. Interferon 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 interferon alfa-2b.

    Infection, neutropenia

    Development or exacerbation of fatal or life-threatening infectious disorders has been observed in patients receiving alpha interferons. Serious and severe bacterial infections, some fatal and some not associated with neutropenia, have been observed in patients treated with alpha interferons. Patients should be monitored closely with baseline and periodic clinical and laboratory evaluations. Interferon alfa-2b should be discontinued in patients with persistently severe or worsening signs or symptoms of infectious processes. In many but not all cases, these disorders resolve after stopping interferon alfa-2b.

    Bone marrow suppression, radiation therapy

    Caution should be exercised when administering interferon alfa-2b to patients with bone marrow suppression or in combination with other myelosuppressive therapy including radiation therapy. Complete blood counts (CBC) should be obtained pretreatment and monitored routinely during therapy. Patients who develop neutropenia (neutrophil count < 500/mm3) or thrombocytopenia (platelet count < 25,000/mm3) should discontinue interferon alfa-2b therapy. Closely monitor patients with anemia (hemoglobin < 10g/dl) while receiving interferon alfa-2b.

    Renal failure, renal impairment

    Closely monitor patients with renal impairment/renal failure (i.e., serum creatinine > 1.5 mg/dL) while receiving interferon alfa-2b. Interferon alfa-2b is substantially excreted by the kidney, and the risk of adverse reactions from interferon alfa-2b may be greater in patients with impaired renal function. Use with ribavirin: Do not administer combination treatment with interferon alfa-2b and ribavirin to patients with creatinine clearance < 50 mL/min.

    Intramuscular injections

    Intramuscular injections should be avoided in patients with platelet counts < 50,000/mm3 who are receiving interferon alfa-2b. Intramuscular injections can cause bleeding, bruising, or hematomas in patients with thrombocytopenia. Interferon alfa-2b should be withheld if the platelet count is < 50,000/mm3 unless the drug is being used for the treatment of hairy cell leukemia; subcutaneous administration is recommended instead of intramuscular administration of interferon alfa-2b for these patients.

    Dental disease, dental work

    Interferon alfa-2b should be used with caution in patients with dental disease. Myelosuppressive effects of interferon alfa-2b increase the risk of infection and bleeding. Dental work should be performed prior to initiating interferon alfa-2b therapy or deferred until blood counts return to normal. Patients should be instructed in proper oral hygiene including caution in use of regular toothbrushes, dental floss, and toothpicks.

    Hyperthyroidism, hypothyroidism, thyroid disease

    Patients with thyroid disease (e.g., hyperthyroidism or hypothyroidism) whose thyroid function cannot be maintained in the normal range by medication should not be treated with interferon alfa-2b. Ascertainment of TSH is recommended for all patients at baseline and every 3 months following initiation of interferon alfa-2b therapy. If hypothyroidism or hyperthyroidism develops, institute appropriate therapy. If thyroid function cannot be normalized by medication, discontinue interferon alfa-2b. Discontinuation of interferon alfa-2b has not always reversed thyroid dysfunction occurring during treatment.

    Pregnancy

    Use interferon alfa-2b during pregnancy only if the potential benefit justifies the potential risk to the fetus. There are no adequate and well controlled studies of interferon alfa-2b in pregnant women. Interferon alfa-2b has shown abortifacient effects in rhesus monkeys. Interferon alfa-2b may be used with ribavirin, and ribavirin is contraindicated in women who are pregnant and in the male partners of women who are pregnant. Significant teratogenic and/or embryocidal effects have been demonstrated in animals exposed to ribavirin. If pregnancy occurs in a patient or partner of a patient during treatment with interferon alfa-2b and ribavirin or in the 6 months after treatment cessation, physicians and patients are encouraged to report such cases by calling 1-800-593-2214.

    Breast-feeding

    It is not known if interferon alfa-2b is excreted in breast milk. Because of the potential for serious adverse reactions from interferon alfa-2b in a nursing infant, FDA-approved product labeling recommends discontinuing breast-feeding or interferon alfa-2b therapy, taking into consideration the importance of the drug to the mother. However, previous American Academy of Pediatrics (AAP) recommendations considered interferon alfa to be compatible with breast-feeding. In a case report of 2 pregnant women receiving interferon alfa treatment, interferon concentrations in the breast milk (1.4 units/mL and 6 units/mL) were found to be considerably lower than the maternal serum concentrations (20.8 units/mL and 58 units/mL, respectively) immediately postpartum.

    Contraception requirements, infertility, reproductive risk

    Interferon alfa-2b may be associated with reproductive risk. Interferon may impair fertility leading to infertility. Serum estradiol and progesterone concentration decreases have been observed in women treated with human leukocyte interferon, and in nonhuman primates, menstrual cycle abnormalities have been noted. When using interferon alfa-2b with ribavirin, negative pregnancy testing is required immediately prior to start of therapy followed by monthly pregnancy testing. Women of childbearing potential should not receive interferon alfa-2b unless they are using effective contraception during treatment. Use interferon alfa-2b with caution in fertile men. Discuss contraception requirements with the patient. When used concurrently with ribavirin, effective contraception is defined as at least 2 forms of contraception for females of childbearing potential as well as male patients, due to risk for male-mediated teratogenicity.

    Coronary artery disease, diabetic retinopathy, hyperlipidemia, hypertension, non-arteritic anterior ischemic optic neuropathy, ocular disease, visual disturbance

    Conduct an ophthalmic exam in all patients prior to beginning therapy with interferon alfa-2b and follow with periodic ophthalmic exams for patients with ocular disease, including hypertensive or diabetic retinopathy, during interferon alfa-2b use. Decreased vision or loss of vision has been associated with interferon alfa therapy. Conduct a prompt, complete eye exam in any patient who experiences changes in vision or other visual disturbance during interferon alfa therapy. Discontinue interferon alfa-2b therapy in any patient who develops new or worsening ophthalmologic disorders. Limited data from case reports indicate that there may be an association between interferon alfa therapy and the development of non-arteritic anterior ischemic optic neuropathy (NAION). Use interferon alfa-2b with caution in patients with a history of NAION or other risk factors for development of the disease, such as low cup to disc ratio (crowded disc), age older than 50 years, diabetes, hypertension, coronary artery disease, and hyperlipidemia.

    Hepatitis B exacerbation

    Interferon alfa-2b is indicated for the treatment of chronic hepatitis C virus (HCV) infections; however, use of the drug in patients coinfected with HCV and hepatitis B virus (HBV) has not been established. Administering medications to treat HCV infections, such as interferon alfa-2b, in patients currently or previously infected with HBV has been associated with reactivation and exacerbation of the HBV infection. To decrease the risk of reactivating a HBV infection, consider screening potential drug recipients for evidence of current or prior HBV infection by measuring hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc). In addition, consider monitoring all drug recipients for clinical and laboratory signs of hepatitis B exacerbation (i.e., HBsAg, HBV DNA, hepatic enzymes, bilirubin). Instruct patients to immediately report any signs of liver toxicity (e.g., yellow eyes or skin, fatigue, weakness, loss of appetite, nausea, vomiting, or light-colored stools) to their health care provider. If signs of HBV reactivation develop, initiate appropriate treatment for HBV infection or consult a physician with expertise in the management of hepatitis infections.

    Vaccination

    Vaccination with live vaccines should be avoided due to the risk of neutropenia during interferon alfa-2b therapy.

    ADVERSE REACTIONS

    Severe

    bronchospasm / Rapid / 0-5.0
    hemolytic anemia / Delayed / 0-5.0
    suicidal ideation / Delayed / 1.0-3.0
    seizures / Delayed / 2.0
    cardiomyopathy / Delayed / 2.0
    coma / Early / Incidence not known
    GI bleeding / Delayed / Incidence not known
    pancreatitis / Delayed / Incidence not known
    hepatic failure / Delayed / Incidence not known
    myocardial infarction / Delayed / Incidence not known
    pericarditis / Delayed / Incidence not known
    pulmonary fibrosis / Delayed / Incidence not known
    pulmonary hypertension / Delayed / Incidence not known
    stroke / Early / Incidence not known
    aplastic anemia / Delayed / Incidence not known
    red cell aplasia / Delayed / Incidence not known
    vasculitis / Delayed / Incidence not known
    autoimmune disease / Delayed / Incidence not known
    lupus-like symptoms / Delayed / Incidence not known
    rhabdomyolysis / Delayed / Incidence not known
    non-arteritic anterior ischemic optic neuropathy / Delayed / Incidence not known
    retinopathy / Delayed / Incidence not known
    visual impairment / Early / Incidence not known
    retinal hemorrhage / Delayed / Incidence not known
    optic neuritis / Delayed / Incidence not known
    papilledema / Delayed / Incidence not known
    retinal thrombosis / Delayed / Incidence not known
    macular edema / Delayed / Incidence not known

    Moderate

    depression / Delayed / 3.0-40.0
    dyspnea / Early / 0-34.0
    neutropenia / Delayed / 0-34.0
    anemia / Delayed / 0-27.0
    thrombocytopenia / Delayed / 0-10.0
    confusion / Early / 1.0-8.0
    psychosis / Early / 0-5.0
    hot flashes / Early / 0-5.0
    leukopenia / Delayed / 0-5.0
    hallucinations / Early / Incidence not known
    hostility / Early / Incidence not known
    encephalopathy / Delayed / Incidence not known
    ascites / Delayed / Incidence not known
    hyperbilirubinemia / Delayed / Incidence not known
    growth inhibition / Delayed / Incidence not known
    hypertriglyceridemia / Delayed / Incidence not known
    elevated hepatic enzymes / Delayed / Incidence not known
    colitis / Delayed / Incidence not known
    supraventricular tachycardia (SVT) / Early / Incidence not known
    hypertension / Early / Incidence not known
    angina / Early / Incidence not known
    sinus tachycardia / Rapid / Incidence not known
    chest pain (unspecified) / Early / Incidence not known
    hypotension / Rapid / Incidence not known
    pneumonitis / Delayed / Incidence not known
    psoriasis / Delayed / Incidence not known

    Mild

    fatigue / Early / 8.0-96.0
    fever / Early / 34.0-94.0
    myalgia / Early / 16.0-75.0
    anorexia / Delayed / 1.0-69.0
    nausea / Early / 18.0-66.0
    asthenia / Delayed / 5.0-63.0
    headache / Early / 21.0-62.0
    chills / Rapid / 45.0-54.0
    dizziness / Early / 7.0-50.0
    musculoskeletal pain / Early / 1.0-50.0
    diarrhea / Early / 2.0-50.0
    abdominal pain / Early / 1.0-50.0
    dysgeusia / Early / 0-50.0
    weight loss / Delayed / 0-50.0
    vomiting / Early / 2.0-50.0
    alopecia / Delayed / 0-50.0
    pharyngitis / Delayed / 1.0-50.0
    xerostomia / Early / 1.0-28.0
    paresthesias / Delayed / 0-21.0
    diaphoresis / Early / 1.0-21.0
    sinusitis / Delayed / 1.0-21.0
    arthralgia / Delayed / 3.0-19.0
    malaise / Early / 3.0-14.0
    cough / Delayed / 0-13.0
    insomnia / Early / 0-12.0
    nasal congestion / Early / 0-10.0
    anxiety / Delayed / 0-9.0
    emotional lability / Early / 0-5.0
    tongue discoloration / Delayed / Incidence not known
    injection site reaction / Rapid / Incidence not known
    pruritus / Rapid / Incidence not known
    back pain / Delayed / Incidence not known
    xerosis / Delayed / Incidence not known
    purpura / Delayed / Incidence not known
    infection / Delayed / Incidence not known

    DRUG INTERACTIONS

    Abacavir: (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) can both cause hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART.
    Abacavir; Dolutegravir; Lamivudine: (Moderate) Monitor for treatment-associated toxicities, especially hepatic decompensation, during coadministration of interferons (with or without ribavirin) and lamivudine. Dose reduction or discontinuation of interferon, ribavirin, or both should be considered if worsening clinical toxicities are observed, including hepatic decompensation (e.g., Child-Pugh score greater than 6). (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) can both cause hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART.
    Abacavir; Lamivudine, 3TC: (Moderate) Monitor for treatment-associated toxicities, especially hepatic decompensation, during coadministration of interferons (with or without ribavirin) and lamivudine. Dose reduction or discontinuation of interferon, ribavirin, or both should be considered if worsening clinical toxicities are observed, including hepatic decompensation (e.g., Child-Pugh score greater than 6). (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) can both cause hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART.
    Abacavir; Lamivudine, 3TC; Zidovudine, ZDV: (Major) Use interferons and zidovudine together with caution. Closely monitor patients for treatment-associated toxicities, especially hematologic effects and hepatic decompensation, and manage as recommended for the individual therapies. Coadministration of alpha interferons may increase the hematologic toxicity of zidovudine. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) are also associated with hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. Interferon therapy may also reduce zidovudine clearance. (Moderate) Monitor for treatment-associated toxicities, especially hepatic decompensation, during coadministration of interferons (with or without ribavirin) and lamivudine. Dose reduction or discontinuation of interferon, ribavirin, or both should be considered if worsening clinical toxicities are observed, including hepatic decompensation (e.g., Child-Pugh score greater than 6). (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) can both cause hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART.
    Aldesleukin, IL-2: (Moderate) Myocardial injury, exacerbation or the initial presentation of autoimmune and inflammatory disorders, and hypersensitivity reactions appear to be increased in patients receiving aldesleukin, IL-2 and alpha interferons concurrently.
    Alemtuzumab: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
    Alteplase: (Moderate) An increased risk of bleeding may occur when thrombolytic agents are used following agents that cause clinically significant thrombocytopenia including antineoplastic agents.
    Altretamine: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
    Amprenavir: (Moderate) The concomitant use of interferons and anti-retroviral protease inhibitors should be done with caution as both can cause hepatotoxicity. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation. Most protease inhibitors have been associated with episodes of liver toxicity. Cirrhotic chronic HCV infected patients co-infected with HIV receiving HAART and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. The HCV-HIV International Panel recommends the management of hepatotoxicity should be based on the knowledge of the mechanisms involved for each drug. Furthermore, they state that there are lower rates of liver-related mortality in coinfected patients taking HAART, even in those with end-stage liver disease, compared with patients not receiving HAART.
    Anticoagulants: (Moderate) An additive risk of bleeding may be seen in thrombocytopenic patients receiving antineoplastic agents in combination with anticoagulants.
    Antithrombin III: (Moderate) An additive risk of bleeding may be seen in thrombocytopenic patients receiving antineoplastic agents in combination with anticoagulants.
    Antithymocyte Globulin: (Moderate) Because antithymocyte globulin is an immunosuppressant, additive affects may be seen with other immunosuppressives or antineoplastic agents. While therapy is designed to take advantage of this effect, patients may be predisposed to over-immunosuppression resulting in an increased risk of infection or other side effects.
    Antitumor antibiotics: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
    Apixaban: (Moderate) An additive risk of bleeding may be seen in thrombocytopenic patients receiving antineoplastic agents in combination with anticoagulants.
    Argatroban: (Moderate) An additive risk of bleeding may be seen in thrombocytopenic patients receiving antineoplastic agents in combination with anticoagulants.
    Arsenic Trioxide: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
    Atazanavir: (Moderate) The concomitant use of interferons and anti-retroviral protease inhibitors should be done with caution as both can cause hepatotoxicity. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation. Most protease inhibitors have been associated with episodes of liver toxicity. Cirrhotic chronic HCV infected patients co-infected with HIV receiving HAART and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. The HCV-HIV International Panel recommends the management of hepatotoxicity should be based on the knowledge of the mechanisms involved for each drug. Furthermore, they state that there are lower rates of liver-related mortality in coinfected patients taking HAART, even in those with end-stage liver disease, compared with patients not receiving HAART.
    Atazanavir; Cobicistat: (Moderate) The concomitant use of interferons and anti-retroviral protease inhibitors should be done with caution as both can cause hepatotoxicity. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation. Most protease inhibitors have been associated with episodes of liver toxicity. Cirrhotic chronic HCV infected patients co-infected with HIV receiving HAART and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. The HCV-HIV International Panel recommends the management of hepatotoxicity should be based on the knowledge of the mechanisms involved for each drug. Furthermore, they state that there are lower rates of liver-related mortality in coinfected patients taking HAART, even in those with end-stage liver disease, compared with patients not receiving HAART.
    Azathioprine: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
    Bacillus Calmette-Guerin Vaccine, BCG: (Severe) 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.
    Betrixaban: (Moderate) An additive risk of bleeding may be seen in thrombocytopenic patients receiving antineoplastic agents in combination with anticoagulants.
    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.
    Bivalirudin: (Moderate) An additive risk of bleeding may be seen in thrombocytopenic patients receiving antineoplastic agents in combination with anticoagulants.
    Carbamazepine: (Moderate) Myelosuppressive antineoplastic agents and radiation therapy possess hematologic toxicities similar to carbamazepine, and should be used concomitantly with caution. Dosage adjustments may be necessary. Monitor patient closely.
    Chloroquine: (Moderate) Concurrent use of chloroquine and interferons is not recommended as there is an increased risk of retinal toxicity.
    Clozapine: (Major) It is unclear if concurrent use of other drugs known to cause neutropenia (e.g., certain antineoplastic agents) increases the risk or severity of clozapine-induced neutropenia. Because there is no strong rationale for avoiding clozapine in patients treated with these drugs, consider increased absolute neutrophil count (ANC) monitoring and consult the treating oncologist.
    Corticosteroids: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Dabigatran: (Moderate) An additive risk of bleeding may be seen in thrombocytopenic patients receiving antineoplastic agents in combination with anticoagulants.
    Dalteparin: (Moderate) An additive risk of bleeding may be seen in thrombocytopenic patients receiving antineoplastic agents in combination with anticoagulants.
    Danaparoid: (Moderate) An additive risk of bleeding may be seen in thrombocytopenic patients receiving antineoplastic agents in combination with anticoagulants.
    Darunavir: (Moderate) The concomitant use of interferons and anti-retroviral protease inhibitors should be done with caution as both can cause hepatotoxicity. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation. Most protease inhibitors have been associated with episodes of liver toxicity. Cirrhotic chronic HCV infected patients co-infected with HIV receiving HAART and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. The HCV-HIV International Panel recommends the management of hepatotoxicity should be based on the knowledge of the mechanisms involved for each drug. Furthermore, they state that there are lower rates of liver-related mortality in coinfected patients taking HAART, even in those with end-stage liver disease, compared with patients not receiving HAART.
    Darunavir; Cobicistat: (Moderate) The concomitant use of interferons and anti-retroviral protease inhibitors should be done with caution as both can cause hepatotoxicity. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation. Most protease inhibitors have been associated with episodes of liver toxicity. Cirrhotic chronic HCV infected patients co-infected with HIV receiving HAART and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. The HCV-HIV International Panel recommends the management of hepatotoxicity should be based on the knowledge of the mechanisms involved for each drug. Furthermore, they state that there are lower rates of liver-related mortality in coinfected patients taking HAART, even in those with end-stage liver disease, compared with patients not receiving HAART.
    Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) The concomitant use of interferons and anti-retroviral protease inhibitors should be done with caution as both can cause hepatotoxicity. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation. Most protease inhibitors have been associated with episodes of liver toxicity. Cirrhotic chronic HCV infected patients co-infected with HIV receiving HAART and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. The HCV-HIV International Panel recommends the management of hepatotoxicity should be based on the knowledge of the mechanisms involved for each drug. Furthermore, they state that there are lower rates of liver-related mortality in coinfected patients taking HAART, even in those with end-stage liver disease, compared with patients not receiving HAART. (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) can both cause hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Moderate) The concomitant use of interferons and anti-retroviral protease inhibitors should be done with caution as both can cause hepatotoxicity. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation. Most protease inhibitors have been associated with episodes of liver toxicity. Cirrhotic chronic HCV infected patients co-infected with HIV receiving HAART and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. The HCV-HIV International Panel recommends the management of hepatotoxicity should be based on the knowledge of the mechanisms involved for each drug. Furthermore, they state that there are lower rates of liver-related mortality in coinfected patients taking HAART, even in those with end-stage liver disease, compared with patients not receiving HAART.
    Delavirdine: (Major) The concomitant use of interferons and anti-retroviral non-nucleoside reverse transcriptase inhibitors (NNRTIs) should be done with caution as both can cause hepatic damage. NNRTIs may cause liver damage in the context of hypersensitivity reactions or by direct toxic effects. Many studies demonstrate that nevirapine is more hepatotoxic than efavirenz. Underlying chronic HCV infection enhances the risk of developing liver enzyme elevations in patients receiving nevirapine. Overall, the HCV-HIV International Panel recommends the management of hepatotoxicity should be based on the knowledge of the mechanisms involved for each drug. Furthermore, they state that there are lower rates of liver-related mortality in coinfected patients taking HAART, even in those with end-stage liver disease, compared with patients not receiving HAART. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation.
    Desirudin: (Moderate) An additive risk of bleeding may be seen in thrombocytopenic patients receiving antineoplastic agents in combination with anticoagulants.
    Diclofenac: (Minor) An increased risk of bleeding may occur when NSAIDs, such as diclofenac, are used with agents that cause clinically significant thrombocytopenia, such as myelosuppressive antineoplastic agents. Monitor closely for bleeding.
    Diclofenac; Misoprostol: (Minor) An increased risk of bleeding may occur when NSAIDs, such as diclofenac, are used with agents that cause clinically significant thrombocytopenia, such as myelosuppressive antineoplastic agents. Monitor closely for bleeding.
    Digoxin: (Moderate) Some antineoplastic agents have been reported to decrease the absorption of digoxin tablets due to their adverse effects on the GI mucosa; the effect on digoxin liquid is not known. The reduction in digoxin tablet absorption has resulted in plasma concentrations that are 50% of pretreatment levels and has been clinically significant in some patients. It is prudent to closely monitor patients for loss of clinical efficacy of digoxin while receiving antineoplastic therapy.
    Diphenhydramine; Ibuprofen: (Major) An increased risk of bleeding may occur when NSAIDs, such as ibuprofen, are used with agents that cause clinically significant thrombocytopenia, such as myelosuppressive antineoplastic agents. Monitor closely for bleeding.
    Diphenhydramine; Naproxen: (Minor) An increased risk of bleeding may occur when NSAIDs, such as naproxen, are used with agents that cause clinically significant thrombocytopenia, such as myelosuppressive antineoplastic agents. Monitor closely for bleeding.
    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).
    Edoxaban: (Moderate) An additive risk of bleeding may be seen in thrombocytopenic patients receiving antineoplastic agents in combination with anticoagulants.
    Efalizumab: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
    Efavirenz: (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and efavirenz can both cause hepatotoxicity. Cirrhotic chronic HCV infected patients co-infected with HIV receiving HAART and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART.
    Efavirenz; Emtricitabine; Tenofovir: (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) can both cause hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and efavirenz can both cause hepatotoxicity. Cirrhotic chronic HCV infected patients co-infected with HIV receiving HAART and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART.
    Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Monitor for treatment-associated toxicities, especially hepatic decompensation, during coadministration of interferons (with or without ribavirin) and lamivudine. Dose reduction or discontinuation of interferon, ribavirin, or both should be considered if worsening clinical toxicities are observed, including hepatic decompensation (e.g., Child-Pugh score greater than 6). (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and efavirenz can both cause hepatotoxicity. Cirrhotic chronic HCV infected patients co-infected with HIV receiving HAART and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART.
    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.
    Enoxaparin: (Moderate) An additive risk of bleeding may be seen in thrombocytopenic patients receiving antineoplastic agents in combination with anticoagulants.
    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.
    Esomeprazole; Naproxen: (Minor) An increased risk of bleeding may occur when NSAIDs, such as naproxen, are used with agents that cause clinically significant thrombocytopenia, such as myelosuppressive antineoplastic agents. Monitor closely for bleeding.
    Estramustine: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
    Ethanol: (Major) Consider the potential risk of interferon alfa products used in combination with known hepatotoxic drugs or other products (e.g., alcohol) prior to use. Monitor hepatic function during interferon beta treatment. Patients should be advised to avoid drinking alcohol to reduce the chance of injury to the liver during inteferon alfa treatment. Alcohol may also potentiate drowsiness and dizziness. Patients who develop dizziness, confusion, somnolence, and fatigue with interferon alfa treatment should be cautioned to avoid driving or operating machinery.
    Etodolac: (Minor) An increased risk of bleeding may occur when NSAIDs, such as etodolac, are used with agents that cause clinically significant thrombocytopenia, such as myelosuppressive antineoplastic agents. Monitor closely for bleeding.
    Famotidine; Ibuprofen: (Major) An increased risk of bleeding may occur when NSAIDs, such as ibuprofen, are used with agents that cause clinically significant thrombocytopenia, such as myelosuppressive antineoplastic agents. Monitor closely for bleeding.
    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.
    Fluorouracil, 5-FU: (Minor) Interferon alfa-2b has been studied extensively in clinical trials with systemic fluorouracil, 5-FU. It has been shown in vitro that the addition of alfa interferon to 5-FU increases single-strand and double-strand DNA breaks and increases natural killer cell-mediated cytotoxicity. However, in clinical trials the addition of alfa interferons to 5-FU therapy resulted in an increased incidence of adverse effects with no increase in response rate versus 5-FU alone.
    Flurbiprofen: (Minor) An increased risk of bleeding may occur when NSAIDs, such as flurbiprofen, are used with agents that cause clinically significant thrombocytopenia, such as myelosuppressive antineoplastic agents. Monitor closely for bleeding.
    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.
    Fondaparinux: (Moderate) An additive risk of bleeding may be seen in thrombocytopenic patients receiving antineoplastic agents in combination with anticoagulants.
    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.
    Heparin: (Moderate) An additive risk of bleeding may be seen in thrombocytopenic patients receiving antineoplastic agents in combination with anticoagulants.
    Hydrocodone; Ibuprofen: (Major) An increased risk of bleeding may occur when NSAIDs, such as ibuprofen, are used with agents that cause clinically significant thrombocytopenia, such as myelosuppressive antineoplastic agents. Monitor closely for bleeding.
    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.
    Ibuprofen: (Major) An increased risk of bleeding may occur when NSAIDs, such as ibuprofen, are used with agents that cause clinically significant thrombocytopenia, such as myelosuppressive antineoplastic agents. Monitor closely for bleeding.
    Ibuprofen; Oxycodone: (Major) An increased risk of bleeding may occur when NSAIDs, such as ibuprofen, are used with agents that cause clinically significant thrombocytopenia, such as myelosuppressive antineoplastic agents. Monitor closely for bleeding.
    Ibuprofen; Pseudoephedrine: (Major) An increased risk of bleeding may occur when NSAIDs, such as ibuprofen, are used with agents that cause clinically significant thrombocytopenia, such as myelosuppressive antineoplastic agents. Monitor closely for bleeding.
    Imatinib: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
    Indinavir: (Moderate) The concomitant use of interferons and anti-retroviral protease inhibitors should be done with caution as both can cause hepatotoxicity. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation. Most protease inhibitors have been associated with episodes of liver toxicity. Cirrhotic chronic HCV infected patients co-infected with HIV receiving HAART and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. The HCV-HIV International Panel recommends the management of hepatotoxicity should be based on the knowledge of the mechanisms involved for each drug. Furthermore, they state that there are lower rates of liver-related mortality in coinfected patients taking HAART, even in those with end-stage liver disease, compared with patients not receiving HAART.
    Intranasal Influenza Vaccine: (Severe) 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.
    Ketoprofen: (Major) An increased risk of bleeding may occur when NSAIDs, such as ketoprofen, are used with agents that cause clinically significant thrombocytopenia, such as myelosuppressive antineoplastic agents. Monitor closely for bleeding.
    Ketorolac: (Major) An increased risk of bleeding may occur when NSAIDs, such as ketorolac, are used with agents that cause clinically significant thrombocytopenia, such as myelosuppressive antineoplastic agents. Monitor closely for bleeding.
    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).
    Lansoprazole; Naproxen: (Minor) An increased risk of bleeding may occur when NSAIDs, such as naproxen, are used with agents that cause clinically significant thrombocytopenia, such as myelosuppressive antineoplastic agents. Monitor closely for bleeding.
    Lepirudin: (Moderate) An additive risk of bleeding may be seen in thrombocytopenic patients receiving antineoplastic agents in combination with anticoagulants.
    Live Vaccines: (Severe) Live virus vaccines should generally not be administered to an immunosuppressed patient, including those receiving Interferon therapy. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
    Lomustine, CCNU: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
    Lopinavir; Ritonavir: (Moderate) The concomitant use of interferons and anti-retroviral protease inhibitors should be done with caution as both can cause hepatotoxicity. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation. Most protease inhibitors have been associated with episodes of liver toxicity. Cirrhotic chronic HCV infected patients co-infected with HIV receiving HAART and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. The HCV-HIV International Panel recommends the management of hepatotoxicity should be based on the knowledge of the mechanisms involved for each drug. Furthermore, they state that there are lower rates of liver-related mortality in coinfected patients taking HAART, even in those with end-stage liver disease, compared with patients not receiving HAART.
    Measles Virus; Mumps Virus; Rubella Virus; Varicella Virus Vaccine, Live: (Severe) 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: (Severe) 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.
    Meclofenamate Sodium: (Major) An increased risk of bleeding may occur when NSAIDs, such as meclofenamate sodium, are used with agents that cause clinically significant thrombocytopenia, such as myelosuppressive antineoplastic agents. Monitor closely for bleeding.
    Mefenamic Acid: (Major) An increased risk of bleeding may occur when NSAIDs, such as mefenamic acid, are used with agents that cause clinically significant thrombocytopenia, such as myelosuppressive antineoplastic agents. Monitor closely for bleeding.
    Meloxicam: (Minor) An increased risk of bleeding may occur when NSAIDs are used with agents that cause clinically significant thrombocytopenia, such as myelosuppressive antineoplastic agents. However, meloxicam may be associated with less risk than other NSAIDs due to its relative minimal platelet inhibitory effects and gastric ulceration or hemorrhagic potential. Monitor closely for bleeding.
    Melphalan: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
    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.
    Mitoxantrone: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
    Nabumetone: (Minor) An increased risk of bleeding may occur when NSAIDs are used with agents that cause clinically significant thrombocytopenia, such as myelosuppressive antineoplastic agents. However, nabumetone may be associated with less risk than other NSAIDs due to its relative minimal platelet inhibitory effects and gastric ulceration or hemorrhagic potential. Monitor closely for bleeding.
    Naproxen: (Minor) An increased risk of bleeding may occur when NSAIDs, such as naproxen, are used with agents that cause clinically significant thrombocytopenia, such as myelosuppressive antineoplastic agents. Monitor closely for bleeding.
    Naproxen; Pseudoephedrine: (Minor) An increased risk of bleeding may occur when NSAIDs, such as naproxen, are used with agents that cause clinically significant thrombocytopenia, such as myelosuppressive antineoplastic agents. Monitor closely for bleeding.
    Naproxen; Sumatriptan: (Minor) An increased risk of bleeding may occur when NSAIDs, such as naproxen, are used with agents that cause clinically significant thrombocytopenia, such as myelosuppressive antineoplastic agents. Monitor closely for bleeding.
    Natural Antineoplastics: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
    Nelfinavir: (Moderate) The concomitant use of interferons and anti-retroviral protease inhibitors should be done with caution as both can cause hepatotoxicity. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation. Most protease inhibitors have been associated with episodes of liver toxicity. Cirrhotic chronic HCV infected patients co-infected with HIV receiving HAART and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. The HCV-HIV International Panel recommends the management of hepatotoxicity should be based on the knowledge of the mechanisms involved for each drug. Furthermore, they state that there are lower rates of liver-related mortality in coinfected patients taking HAART, even in those with end-stage liver disease, compared with patients not receiving HAART.
    Nevirapine: (Major) The concomitant use of interferons and nevirapine should be done with caution as both can cause hepatotoxicity. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation. Nevirapine may cause liver damage in the context of hypersensitivity reactions or by direct toxic effects. Cirrhotic chronic HCV infected patients co-infected with HIV receiving HAART and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. Patients with signs or symptoms of hepatitis, or with increased transaminases combined with rash or other systemic symptoms, must discontinue nevirapine and seek medical evaluation immediately.
    Ombitasvir; Paritaprevir; Ritonavir: (Moderate) The concomitant use of interferons and anti-retroviral protease inhibitors should be done with caution as both can cause hepatotoxicity. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation. Most protease inhibitors have been associated with episodes of liver toxicity. Cirrhotic chronic HCV infected patients co-infected with HIV receiving HAART and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. The HCV-HIV International Panel recommends the management of hepatotoxicity should be based on the knowledge of the mechanisms involved for each drug. Furthermore, they state that there are lower rates of liver-related mortality in coinfected patients taking HAART, even in those with end-stage liver disease, compared with patients not receiving HAART.
    Oxaprozin: (Minor) An increased risk of bleeding may occur when NSAIDs, such as oxaprozin, are used with agents that cause clinically significant thrombocytopenia, such as myelosuppressive antineoplastic agents. Monitor closely for bleeding.
    Palifermin: (Moderate) Palifermin should not be administered within 24 hours before, during infusion of, or within 24 hours after administration of antineoplastic agents.
    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.
    Penicillamine: (Major) Do not use penicillamine with antineoplastic agents due to the increased risk of developing severe hematologic and renal toxicity.
    Pentosan: (Moderate) An additive risk of bleeding may be seen in thrombocytopenic patients receiving antineoplastic agents in combination with anticoagulants.
    Pexidartinib: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with interferon alfa. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
    Piroxicam: (Minor) An increased risk of bleeding may occur when NSAIDs, such as piroxicam, are used with agents that cause clinically significant thrombocytopenia, such as myelosuppressive antineoplastic agents. Monitor closely for bleeding.
    Pralatrexate: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
    Protease inhibitors: (Moderate) The concomitant use of interferons and anti-retroviral protease inhibitors should be done with caution as both can cause hepatotoxicity. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation. Most protease inhibitors have been associated with episodes of liver toxicity. Cirrhotic chronic HCV infected patients co-infected with HIV receiving HAART and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. The HCV-HIV International Panel recommends the management of hepatotoxicity should be based on the knowledge of the mechanisms involved for each drug. Furthermore, they state that there are lower rates of liver-related mortality in coinfected patients taking HAART, even in those with end-stage liver disease, compared with patients not receiving HAART.
    Purine analogs: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
    Reteplase, r-PA: (Moderate) An increased risk of bleeding may occur when thrombolytic agents are used following agents that cause clinically significant thrombocytopenia including antineoplastic agents.
    Rilpivirine: (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and rilpivirine can both cause hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving antiretroviral agents and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART.
    Riluzole: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and interferon alfa. 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.
    Rivaroxaban: (Moderate) An additive risk of bleeding may be seen in thrombocytopenic patients receiving antineoplastic agents in combination with anticoagulants.
    Rotavirus Vaccine: (Severe) Live virus vaccines should generally not be administered to an immunosuppressed patient, including those receiving Interferon therapy. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
    Rubella Virus Vaccine Live: (Severe) Live virus vaccines should generally not be administered to an immunosuppressed patient, including those receiving Interferon therapy. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
    Saquinavir: (Moderate) The concomitant use of interferons and anti-retroviral protease inhibitors should be done with caution as both can cause hepatotoxicity. Closely monitor patients for treatment-associated toxicities, especially hepatic decompensation. Most protease inhibitors have been associated with episodes of liver toxicity. Cirrhotic chronic HCV infected patients co-infected with HIV receiving HAART and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. The HCV-HIV International Panel recommends the management of hepatotoxicity should be based on the knowledge of the mechanisms involved for each drug. Furthermore, they state that there are lower rates of liver-related mortality in coinfected patients taking HAART, even in those with end-stage liver disease, compared with patients not receiving HAART.
    Smallpox and Monkeypox Vaccine, Live, Nonreplicating: (Severe) 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: (Severe) Live virus vaccines should generally not be administered to an immunosuppressed patient, including those receiving Interferon therapy. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
    Stavudine, d4T: (Major) Patients receiving stavudine with interferons (with or without ribavirin) should be closely monitored for treatment-associated toxicities, especially hepatic decompensation. Cirrhotic chronic HCV infected patients co-infected with HIV receiving HAART and alpha interferons appear to be at increased risk for hepatic decompensation compared to patients not receiving HAART. Additionally, stavudine has been associated with fatal and nonfatal lactic acidosis and hepatomegaly with or without steatosis and should be used cautiously in patients with hepatic disease. Discontinuation of stavudine should be considered as medically appropriate. Dose reduction or discontinuation of interferon, ribavirin, or both should also be considered if worsening clinical toxicities are observed, including hepatic decompensation (e.g., Child-Pugh score greater than 6).
    Streptokinase: (Moderate) An increased risk of bleeding may occur when thrombolytic agents are used following agents that cause clinically significant thrombocytopenia including antineoplastic agents.
    Sulindac: (Minor) An increased risk of bleeding may occur when NSAIDs, such as sulindac, are used with agents that cause clinically significant thrombocytopenia, such as myelosuppressive antineoplastic agents. Monitor closely for bleeding.
    Tbo-Filgrastim: (Major) Filgrastim induces the proliferation of neutrophil-progenitor cells, and, because antineoplastic agents exert toxic effects against rapidly growing cells, filgrastim is contraindicated for use during the 24 hours before or after cytotoxic chemotherapy.
    Telbivudine: (Major) An increased risk and severity of peripheral neuropathy has been reported with telbivudine alone or in combination with pegylated interferon alfa-2a and other interferons. Patients should be advised to report any numbness, tingling, and/or burning sensations in the arms and/or legs, with or without gait disturbance. Interrupt telbivudine if peripheral neuropathy is suspected, and discontinue the drug if peripheral neuropathy is confirmed. Since both interferons and telbivudine may cause hepatotoxicity, hepatic function should also be closely monitored.
    Tenecteplase: (Moderate) An increased risk of bleeding may occur when thrombolytic agents are used following agents that cause clinically significant thrombocytopenia including antineoplastic agents.
    Theophylline, Aminophylline: (Major) Alpha interferons, when administered systemically, may decrease the clearance of aminophylline resulting in increased plasma concentrations. Concomitant use may result in a significant increase in theophylline concentrations due to reduced aminophylline clearance. In studies, increases in theophylline levels of 25% up to 100% have occurred. Reductions in CYP1A2 activity have been noted with various alpha interferons, and likely provide a mechanism for the interaction. Monitor theophylline concentrations and for signs and symptoms of toxicity when interferons are used concomitantly; consider appropriate dose adjustments as clinically indicated. (Major) Alpha interferons, when administered systemically, may decrease the clearance of theophylline resulting in increased plasma concentrations. Concomitant use may result in a significant increase in theophylline concentrations due to reduced theophylline clearance. In studies, increases in theophylline levels of 25% up to 100% have occurred. Reductions in CYP1A2 activity have been noted with various alpha interferons, and likely provide a mechanism for the interaction. Monitor theophylline concentrations and for signs and symptoms of theophylline toxicity when interferons are used concomitantly; consider appropriate dose adjustments as clinically indicated.
    Thrombolytic Agents: (Moderate) An increased risk of bleeding may occur when thrombolytic agents are used following agents that cause clinically significant thrombocytopenia including antineoplastic agents.
    Tinzaparin: (Moderate) An additive risk of bleeding may be seen in thrombocytopenic patients receiving antineoplastic agents in combination with anticoagulants.
    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.
    Tolmetin: (Minor) An increased risk of bleeding may occur when NSAIDs, such as tolmetin, are used with agents that cause clinically significant thrombocytopenia, such as myelosuppressive antineoplastic agents. Monitor closely for bleeding.
    Tositumomab: (Moderate) Use of alpha interferons are associated with myelosuppression; additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
    Tretinoin, ATRA: (Moderate) Use of alpha interferons are associated with myelosuppression; additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
    Tuberculin Purified Protein Derivative, PPD: (Moderate) Immunosuppressives may decrease the immunological response to tuberculin purified protein derivative, PPD. This suppressed reactivity can persist for up to 6 weeks after treatment discontinuation. Consider deferring the skin test until completion of the immunosuppressive therapy.
    Typhoid Vaccine: (Severe) 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.
    Urokinase: (Moderate) An increased risk of bleeding may occur when thrombolytic agents are used following agents that cause clinically significant thrombocytopenia including antineoplastic agents.
    Varicella-Zoster Virus Vaccine, Live: (Severe) Live virus vaccines should generally not be administered to an immunosuppressed patient, including those receiving Interferon therapy. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
    Vigabatrin: (Major) Vigabatrin is associated with vision loss. The drug should not be used with interferons, which are associated with a potential for serious ophthalmic effects (e.g., retinopathy, optic neuritis, visual impairment), unless the benefit of treatment clearly outweighs the risks.
    Warfarin: (Moderate) An additive risk of bleeding may be seen in thrombocytopenic patients receiving antineoplastic agents in combination with anticoagulants.
    Yellow Fever Vaccine, Live: (Severe) 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.
    Zalcitabine, ddC: (Moderate) Use together with caution and monitor for hepatic decompensation. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) can both cause hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART.
    Zidovudine, ZDV: (Major) Use interferons and zidovudine together with caution. Closely monitor patients for treatment-associated toxicities, especially hematologic effects and hepatic decompensation, and manage as recommended for the individual therapies. Coadministration of alpha interferons may increase the hematologic toxicity of zidovudine. Interferons and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) are also associated with hepatotoxicity. Patients with chronic, cirrhotic HCV co-infected with HIV receiving NRTIs and alpha interferons appear to be at increased risk for hepatic decompensation (e.g., Childs-Pugh score 6 or more) compared to patients not receiving HAART. Interferon therapy may also reduce zidovudine clearance.

    PREGNANCY AND LACTATION

    Pregnancy

    Use interferon alfa-2b during pregnancy only if the potential benefit justifies the potential risk to the fetus. There are no adequate and well controlled studies of interferon alfa-2b in pregnant women. Interferon alfa-2b has shown abortifacient effects in rhesus monkeys. Interferon alfa-2b may be used with ribavirin, and ribavirin is contraindicated in women who are pregnant and in the male partners of women who are pregnant. Significant teratogenic and/or embryocidal effects have been demonstrated in animals exposed to ribavirin. If pregnancy occurs in a patient or partner of a patient during treatment with interferon alfa-2b and ribavirin or in the 6 months after treatment cessation, physicians and patients are encouraged to report such cases by calling 1-800-593-2214.

    It is not known if interferon alfa-2b is excreted in breast milk. Because of the potential for serious adverse reactions from interferon alfa-2b in a nursing infant, FDA-approved product labeling recommends discontinuing breast-feeding or interferon alfa-2b therapy, taking into consideration the importance of the drug to the mother. However, previous American Academy of Pediatrics (AAP) recommendations considered interferon alfa to be compatible with breast-feeding. In a case report of 2 pregnant women receiving interferon alfa treatment, interferon concentrations in the breast milk (1.4 units/mL and 6 units/mL) were found to be considerably lower than the maternal serum concentrations (20.8 units/mL and 58 units/mL, respectively) immediately postpartum.

    MECHANISM OF ACTION

    Interferon alfa-2b acts similarly to native interferon alpha. Endogenous alpha-interferons (IFNs) are secreted by leukocytes (e.g., macrophages, B lymphocytes, and non-B non-T lymphocytes) in response to viral infection or various synthetic and biological inducers. All alpha-IFNs share common biologic activities generated by the binding of interferon to the cell-surface receptor. Although the exact mechanism of action is not fully understood, interferon binding to the cell surface receptor is followed by activation of tyrosine kinases, which leads to the production of several IFN-stimulated enzymes such as 2'-5'-oligoadenylate synthetase (2'-5'-OAS) and beta2-microglobulin. These and possibly other IFN-stimulated enzymes are thought to be responsible for the pleiotropic biologic effects of alpha-IFNs, which include antiviral, antiproliferative and immunomodulatory effects, cellular differentiation, regulation of cell surface major histocompatibility antigen expression (HLA class I), and cytokine induction.
     
    •Antiviral effects: Interferon exerts antiviral effects by augmenting the production and/or release of specific enzymes. Interferon-induced intracellular enzymes such as 2'5'-OAS and protein kinase contribute to inhibition of viral replication by activating endoribonucleases that cleave single-stranded viral RNA. Thus, translation of viral proteins is inhibited. The activity of IFN-induced enzymes depends on the presence of double-stranded RNA (dsRNA) formed during viral replication. It has been suggested that the antiviral activity of IFNs may be related, in part, to an effect on dsRNA. Interferon-induced enzymes may also inhibit viral penetration and uncoating, and/or viral assembly and release. Expression of major histocompatibility antigens by IFNs may also contribute to antiviral activity by enhancing the lytic effects of cytotoxic T lymphocytes.
     
    A wide range of viruses, particularly RNA viruses, are sensitive to the antiviral actions of IFN. Alpha interferons are generally active against the following viruses in vitro: adenovirus; coronavirus; encephalomyocarditis virus; hepatitis B virus; hepatitis C virus (HCV); hepatitis D virus; herpes simplex virus type 1; herpes simplex virus type 2; human immunodeficiency virus (HIV); papillomavirus; poliovirus; rhinovirus; vaccinia virus; varicella-zoster virus; vesicular stomatitis virus; human T-lymphotropic virus type I (HTLV-I). In chronic hepatitis C, INF treatment is associated with normalization of ALT and serum HCV RNA, as well as improvement in liver histopathology, in responding patients. The HCV genotype 1 is more resistant to interferon alfa treatment than other viral genotypes; 75% of persons in US infected with HCV carry this genotype. Many patients with a biochemical and virologic relapse 1—2 months after stopping IFN therapy.
     
    •Antineoplastic effects: The antineoplastic activity of interferons may result from a direct antiproliferative effect on the tumor cell and/or the ability of IFN to induce a host response to the tumor (e.g., immunomodulatory effects). Alpha IFNs exert a cytostatic effect on tumor cells, slowing the rate of cell proliferation until cell survival is threatened. The mechanism(s) of antiproliferative activity has not been fully elucidated; several effects may be involved, including the ability of interferons to enhance or inhibit the synthesis of specific proteins, modify cell surface antigen expression, and/or modulate the immune system. Interferon has been shown to prolong all phases of the cell cycle and induce cellular differentiation by promoting cells to enter the nonproliferative G0 (resting) phase. This differentiation effect is thought to be a key mechanism in the treatment of hairy cell leukemia. Inhibition of tumor cell proliferation may also be related to decreased transcription and expression of several oncogenes. Immunomodulatory effects that may contribute to the antitumor activity of interferons include activation of cytotoxic T cells and/or activation of natural killer (NK) cells. Natural killer cells are lymphocytes that recognize cell surface antigens and lyse certain types of tumor cells. The cytotoxic activity of NK cells against tumor cells can be increased following exposure to interferon, although this effect is highly variable. Interferons may increase the proportion of NK cells that become cytotoxic and/or decrease the time needed for NK cells to reach their maximum cytotoxic effect. In addition, interferons activate macrophages and monocytes, resulting in increased phagocytic activity and enhanced cytotoxicity against tumor cells and other target cells. Alpha interferons have been shown to stimulate production of cytokines such as interleukin (IL)-1beta and IL-1ra (an IL-1 receptor antagonist); thus, alpha-IFNs may affect the inflammatory response.
     
    •Effect on hepatic microsomal enzymes: Alpha interferons may inhibit microsomal enzymes involved in the hepatic cytochrome P-450 system. The effect of interferon on the CYP450 system may be related to increased enzyme degradation, suppressed enzyme synthesis, or inhibition of cytochrome P-450. Implications of this effect have not been fully evaluated, but the metabolism of certain drugs may be affected.

    PHARMACOKINETICS

    Interferon alfa-2b is administered parenterally via intravenous, intramuscular, or subcutaneous routes. The pharmacokinetics of interferon alfa-2b were studied in 12 healthy male volunteers. Mean serum concentrations following intramuscular or subcutaneous administration are similar. The main site for alfa interferon catabolism is the kidney. There is no pharmacokinetic information regarding intralesional administration.

    Intravenous Route

    Following a single intravenous infusion of 5 million International Units of interferon alfa-2b, the half-life of interferon alfa-2b is about 2 hours with serum levels becoming undetectable in about 4 hours.

    Intramuscular Route

    The Cmax following 5 million International Units given IM is 18—116 International Units/mL and occurred 3—12 hours after administration of interferon alfa-2b. The elimination half-life following IM injections is 2—3 hours.

    Subcutaneous Route

    The Cmax following 5 million International Units given subcutaneously is 18—116 International Units/mL and occurred 3—12 hours after administration of interferon alfa-2b. The elimination half-life following subcutaneous injections is 2—3 hours.