Interferon Alfa

Class: Antineoplastic Agents
VA Class: AM800
Chemical Name: Interferon α2b (human leukocyte clone Hif-SN206 protein moiety reduced)
Molecular Formula: C860H1353N229O255S9C860H1353N227O255S9
CAS Number: 99210-65-8
Brands: Intron A, Infergen, Alferon N

Warning(s)

  • May cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders.2 4 Monitor patients closely with periodic clinical and laboratory evaluations.2 4 Discontinue therapy in patients with persistently severe or worsening signs or symptoms of these conditions.2 4 In many, but not all cases, these disorders resolve after the drug is discontinued.2 4

  • Concomitant use of ribavirin may cause birth defects and/or death of the fetus; avoid pregnancy in female patients and female partners of male patients.4 Ribavirin causes hemolytic anemia which may exacerbate cardiac disease.4 Ribavirin is a potential carcinogen.4

Introduction

Interferon alfa is a family of proteins and glycoproteins with antiviral, antineoplastic, and immunomodulating activities.2 4 8 47 70 255 259 261 456 648 714 717 740 906 1211 1240 1241 1339 1426 1464 Available in the US as interferon alfa-2b,2 interferon alfacon-1,4 and interferon alfa-n3.3 Also available covalently bound to monomethoxy polyethylene glycol (PEG) (i.e., peginterferon alfa).20 48

Uses for Interferon Alfa

Chronic HBV Infection

Interferon alfa-2b: Treatment of chronic HBV infection in adults, adolescents, and children ≥1 year of age with compensated liver disease.2 14 16 25 27 97

Goal of antiviral therapy is sustained suppression of HBV replication and remission of liver disease;97 long-term goal is prevention of cirrhosis, hepatic failure, and hepatocellular carcinoma.97 110

Currently available therapies (e.g., interferon alfa, peginterferon alfa, adefovir, entecavir, lamivudine, telbivudine, tenofovir) do not eradicate HBV and may have only limited long-term efficacy.97 When making decisions regarding treatment, consider patient’s age, severity of liver disease, likelihood of response, safety and efficacy of the drug, potential for selection of resistant HBV strains, potential for adverse reactions, costs, patient’s pregnancy potential, and patient and provider preferences.97

American Association for the Study of Liver Diseases (AASLD) states that drugs of choice for initial treatment of chronic HBV infection in patients with compensated liver disease are peginterferon alfa, entecavir, or tenofovir, unless contraindicated or ineffective.97 Efficacy of peginterferon alfa and nonconjugated interferon alfa are considered similar, but peginterferon alfa dosage schedule more convenient and generally preferred.97

Treatment of chronic HBV infection is complex and rapidly evolving and should be directed by clinicians familiar with the disease; consult specialist to obtain the most up-to-date information.97

Chronic HCV Infection

Interferon alfa-2b, interferon alfacon-1: Treatment of chronic HCV infection in adults with compensated liver disease; used alone or in conjunction with oral ribavirin.2 4

Interferon alfa-2b: Treatment of chronic HCV infection in treatment-naive children ≥3 years of age with compensated liver disease; used in conjunction with oral ribavirin.2

Goal of antiviral therapy is sustained suppression of HCV replication and prevention of HCV-related complications (e.g., necroinflammation, fibrosis, cirrhosis, hepatocellular carcinoma) and death.96 120 When making decisions regarding treatment, consider severity of liver disease, HCV genotype, treatment history, potential for serious adverse reactions, likelihood of treatment response, presence of coexisting conditions, and patient’s readiness for treatment.96 119 120 121

Interferon alfa in conjunction with oral ribavirin associated with lower response rates than peginterferon alfa in conjunction with oral ribavirin;39 96 peginterferon alfa now preferred instead of interferon alfa for treatment of chronic HCV infection.96

Interferon alfa monotherapy associated with lower response rates than interferon alfa in conjunction with oral ribavirin;35 36 37 38 90 interferon alfa monotherapy not recommended unless patient unable to take oral ribavirin.4

AASLD and other experts state peginterferon alfa in conjunction with oral ribavirin is the standard of care for treatment of HCV infection (genotypes 2, 3, 4, 5, 6) in treatment-naive patients (have not previously received interferon alfa therapy) and also is recommended for previously treated patients following failure of prior therapy (nonconjugated interferon alfa monotherapy, concomitant nonconjugated interferon alfa and oral ribavirin).96 119 120 121

Treatment of chronic HCV infection is complex and rapidly evolving; consult specialist to obtain the most up-to-date information regarding patient selection criteria and preferred regimens.96 119 120 121

Acute HCV Infection

Interferon alfa-2b: Has been used for treatment of acute HCV infection in an attempt to prevent progression to chronic HCV infection.56 57 58 59 60

Patients with acute HCV infection have higher treatment response rates than those with chronic HCV infection, and treatment of acute infection can reduce risk that the disease will evolve to chronic infection.96 120

Approximately 10–50% of patients with acute HCV have self-limited disease and spontaneous virus clearance without treatment;96 120 rate of spontaneous resolution depends on whether patient is asymptomatic or symptomatic, route of HCV transmission, and age at which infection acquired.96 120

AASLD and other experts recommend that treatment with peginterferon alfa (with or without oral ribavirin) be considered for acute HCV infection,96 120 121 but optimum regimen (including dosage and duration of therapy) and optimum time to initiate treatment not established.96 120 190 Some experts suggest delaying initiation of treatment (especially in symptomatic patients) for 8–12 weeks after acute onset of hepatitis, unless HCV RNA levels are high and not declining.96 120

Consult specialist to obtain most up-to-date information regarding treatment of acute HCV infection.96 120 121

Postexposure Prophylaxis Following Exposure to HCV

CDC and others state that postexposure prophylaxis with antivirals (e.g., peginterferon alfa or interferon alfa with or without oral ribavirin), immune globulin, or immunomodulators not recommended following occupational or other exposures known or likely to involve an HCV-positive source,33 120 192 193 including penetrating injuries or nonintact skin exposures in bombings or other mass casualty settings.193

Postexposure management in exposed individuals involves early identification of HCV infection and appropriate antiviral treatment if indicated.33 192 193 Some experts suggest evaluating ALT concentrations and anti-HCV at time of exposure (within 7–14 days) and 4–6 months later and testing for HCV RNA at 4–6 weeks or at 2-week intervals.33 192 193

Chronic HDV Infection

Interferon alfa: Has been used with some limited success for treatment of chronicHDV infection in adults and children coinfected with HBV.6 97 99 100 101 102 130 140 141 Although interferon alfa may suppress viral activity in some patients, sustained response not obtained and relapse generally occurs after drug discontinued.6 101 140 141

HDV infection only occurs in individuals with HBV infection since the virus depends on HBV for production of envelope proteins.97 140 Can be acquired as a coinfection with HBV or as a superinfection in HBV carriers.97 140 HDV superinfection in HBV carriers almost always results in chronic infection with both viruses and is associated with high risk of cirrhosis, hepatic decompensation, and hepatocellular carcinoma.97

Human Papillomavirus (HPV) Infections

Interferon alfa-2b, interferon alfa-n3: Intralesional treatment of external genital and perianal exophytic warts (condylomata acuminata) caused by HPV.2 3 17

CDC states that intralesional interferon alfa is an alternative (not preferred) option for treatment of external HPV warts because of higher frequency of adverse effects (including rare severe systemic adverse effects) and/or less efficacy data compared with other options.17

No currently available option has been shown to eradicate HPV infectivity.17

West Nile Virus Infection

Interferon alfa-2b, interferon alfa-n3: Have been investigated for treatment of serious West Nile virus (WNV) infection†.92 93 94 196 201

Despite initial case reports suggesting some clinical benefits in neuroinvasive disease,92 93 94 196 201 efficacy not proven in controlled clinical trials.68 201 Unlikely to inhibit WNV replication following establishment of infection.194 195 200 201

Hairy Cell Leukemia

Interferon alfa-2b: Treatment of hairy cell leukemia2 135 153 219 439 1620 1621 1623 1625 1627 1629 1635 (leukemic reticuloendotheliosis).171 1636

Complete response achieved in 10% of patients and overall response achieved in approximately 80% of patients.2 122 123 124 125 126 127 128 129 131 132 134 135 136 138 142 143 170 175 178 181 182 184 185 188 199 202 219 220 237 239 243 248 249 250 251 252 253 260 266 278 439 1620 1624 1635 1636

An alternative for hairy cell leukemia; cladribine or pentostatin preferred (achieve higher complete response rates than interferon alfa).439 1619 1620 1621 1622 1623 1624 1625 1627 1632 1637

AIDS-related Kaposi’s Sarcoma

Interferon alfa-2b: Palliative treatment of AIDS-related Kaposi’s sarcoma in selected adults2 152 153 204 206 210 378 440 1625 1647 1648 (designated an orphan drug by FDA for this indication).1546

Do not use in patients with rapidly progressive visceral or life-threatening disease;2 153 440 1549 response generally is slow88 156 440 1549 and poor.2 145 153 154 155 156 203 204 378 381 383 384 385 386 387 388 389 1549

Likelihood of response to interferon alfa is greater in patients without systemic symptoms who have limited lymphadenopathy and relatively intact immune systems as indicated by CD4+ T-cell counts.2

All patients with AIDS-related Kaposi's sarcoma should be receiving highly active antiretroviral therapy; in some patients, initiation of antiretroviral therapy alone may result in tumor regression and resolution of lesions.190 440

Non-Hodgkin’s and Cutaneous T-cell Lymphomas

Interferon alfa-2b: Although labeled by FDA for use in conjunction with an anthracycline for initial treatment of clinically aggressive follicular non-Hodgkin’s lymphoma in adults,2 other agents preferred.442 1625

Efficacy in patients with low-grade, low-tumor-burden follicular non-Hodgkin’s lymphoma not demonstrated.2

Interferon alfa: Has been used for treatment of cutaneous T-cell lymphomas.172 217 254 257 299 302 342 348 1109 1110 1111 1117 1118 1382 1385

Melanoma

Interferon alfa-2b: Used as an adjunct to surgery (within 56 days of surgery) in adults with malignant melanoma who are disease free but at high risk for systemic recurrence.2 450

Palliative treatment of metastatic melanoma in selected patients, alone and in conjunction with other therapies (e.g., radiation).450 1342 1343 1344 1345 1346 1347 1443 1444 1445 1446 1530 1531 1532

Basal Cell and Squamous Cell Skin Cancers

Interferon alfa: Has been used intralesionally for treatment of basal cell carcinoma272 1466 1467 1468 1469 1470 and squamous cell carcinoma.158

Chronic Myelogenous Leukemia

Interferon alfa-2b: Has been used for treatment of adult-type (Philadelphia chromosome-positive) chronic myelogenous (myelocytic, myeloid) leukemia (CML).259 260 261 299 300 301 302 303 305 306 307 308 309 310 311 312 441 1029 1420 1479 1533 1594 1625 1638 1639 1640 1641 1642 1643 1644

Renal Cell Carcinoma

Interferon alfa: Has been used for treatment of metastatic renal cell carcinoma in selected patients.443 715 1625 1694 1697

Bladder Cancer

Interferon alfa: Has been used intravesically for prophylaxis351 or treatment356 448 1552 of superficial bladder cancer.

Ovarian Cancer

Interferon alfa: Has been used intraperitoneally for treatment of minimal residual epithelial ovarian cancer in a limited number of patients.358 359 360

Interferon Alfa Dosage and Administration

General

  • Various interferon alfa subtypes (alfa-2b, alfacon-1, n3) and dosage forms (powder for injection, solution for injection, multiple-dose injection pens) are commercially available;2 3 4 preparation to be used and appropriate concentration depend on intended use.2 Ensure that correct preparation is used.2 3 4

Administration

Interferon alfa-2b (Intron A): Administer by IM, sub-Q, or intralesional injection or by IV infusion.2

Interferon alfacon-1 (Infergen): Administer by sub-Q injection.4

Interferon alfa-n3 (Alferon N): Administer by intralesional injection.3

Interferon alfa-2b and alfacon-1 may be self-administered if clinician determines that the patient and/or their caregiver are competent to prepare and safely administer the drug after appropriate training and with medical follow-up as necessary.2 4

Administration in the evening or at bedtime may prevent or ameliorate some adverse effects (e.g., flu-like syndrome).2 4

Administration of acetaminophen or other nonopiate analgesic at the time interferon alfa dose is given may reduce incidence of adverse effects.2 4

IV Administration

Interferon Alfa-2b (Intron A)

Use single-dose vial of interferon alfa-2b powder for injection containing 10, 18, or 50 million units to prepare IV solutions.2 Do not use solution for injection available in multiple-dose vials or multiple-dose injection pens for IV administration.2

Melanoma (induction therapy): Reconstitute single-dose vial of powder for injection containing 10, 18, or 50 million units by adding 1 mL of sterile water for injection provided by manufacturer; resultant solution contains 10, 18, or 50 million units/mL.2 Withdraw appropriate dose of reconstituted solution and add to 100 mL of 0.9% sodium chloride injection.2 Do not dilute to final concentration <10 million units/100 mL (<100,000 units/mL).2

Prepare IV solutions immediately before use.2

Administer by IV infusion over 20 minutes.2

IM Injection

Interferon Alfa-2b (Intron A)

Depending on indication and dosage, use single-dose vial of powder for injection or multiple-dose vial of solution.2 Multiple-dose injection pens are for sub-Q administration only; do not use for IM injection.2

When powder for injection is indicated for IM injection, reconstitute single-dose vial of powder for injection containing 10 or 50 million units by adding 1 mL of sterile water for injection provided by manufacturer; resultant solution contains 10 or 50 million units/mL, respectively.2 Withdraw appropriate dose and administer IM undiluted.2

When multiple-dose vial containing 6 or 10 million units/mL is indicated for IM injection, withdraw appropriate dose and administer IM undiluted.2

Administer IM into anterolateral thigh, upper arm, or outer area of the buttocks.2

Chronic HBV infection: Use single-dose vial of powder for injection containing 10 million units or multiple-dose vial containing 10 million units/mL.2

Chronic HCV infection: Use multiple-dose vial containing 6 million units/mL.2

Hairy cell leukemia: Use single-dose vial of powder for injection containing 10 million units or multiple-dose vial containing 6 or 10 million units/mL.2 Do not use IM injection if platelet count <50,000/mm3.2

AIDS-related Kaposi's sarcoma: Use single-dose vial of powder for injection containing 50 million units.2

Sub-Q Injection

Interferon Alfa-2b (Intron A)

Depending on indication and dosage, use single-dose vial of powder for injection, multiple-dose vial of solution, or multiple-dose injection pen.2

When powder for injection is indicated for sub-Q injection, reconstitute single-dose vial of powder for injection containing 10, 18, or 50 million units by adding 1 mL of sterile water for injection provided by manufacturer; resultant solution contains 10, 18, or 50 million units/mL, respectively.2 Withdraw appropriate dose and administer sub-Q undiluted.2

When multiple-dose vial containing 6 or 10 million units/mL is indicated for sub-Q injection, withdraw appropriate dose and administer sub-Q undiluted.2

When multiple-dose injection pen containing 15, 25, or 50 million units/mL is indicated, consult manufacturer information regarding proper administration technique.2 Injection pens are for sub-Q administration only; do not be use for IM injection.2 The pens are designed to deliver 3–12 doses (depending on the individual dose) using a dial mechanism.2 Needles are provided with the pens; use a new needle for each dose.2

Administer sub-Q into anterolateral thigh, upper arm, or abdomen (avoiding navel).115 Do not make sub-Q injections into areas where skin is irritated, red, bruised, infected, or has scars, stretch marks, or lumps.115

Chronic HBV infection: Use single-dose vial of powder for injection containing 10 million units, multiple-dose vial containing 10 million units/mL, or multiple-dose injection pen containing 15, 25, or 50 million units/mL.2

Chronic HCV infection: Use multiple-dose vial containing 6 million units/mL or multiple-dose injection pen containing 15, 25, or 50 million units/mL.2

Hairy cell leukemia: Use single-dose vial of powder for injection containing 10 million units, multiple-dose vial containing 6 or 10 million units/mL, or multiple-dose injection pen containing 15 or 25 million units/mL.2

AIDS-related Kaposi's sarcoma: Use single-dose vial of powder for injection containing 50 million units.2 Do not use multiple-dose vials or multiple-dose injection pens containing solution for injection.2

Follicular non-Hodgkin's lymphoma: Use single-dose vial of powder for injection containing 10 million units, multiple-dose vial containing 6 or 10 million units/mL, or multiple-dose injection pen containing 25 or 50 million units/mL.2

Melanoma (maintenance therapy): Use single-dose vial of powder for injection containing 10 or 18 million units, multiple-dose vial containing 6 or 10 million units/mL, or multiple-dose injection pen containing 15, 25, or 50 million units/mL.2

Interferon Alfacon-1 (Infergen)

Chronic HCV infection: Administer sub-Q undiluted.4

Vials of interferon alfacon-1 are for single-use only; discard any unused portion.4

Intralesional Injection

Interferon Alfa-2b (Intron A)

Treatment of external genital and perianal warts (condylomata acuminata): Reconstitute single-dose vial of powder for injection containing 10 million units by adding 1 mL of sterile water for injection diluent provided by manufacturer; resultant solution contains 10 million units/mL.2 Withdraw appropriate dose and administer intralesionally undiluted.2 Alternatively, withdraw appropriate dose of solution for injection from multiple-dose vial containing 25 million units/mL and administer intralesionally undiluted.2

Use a tuberculin or similar syringe and a 25- to 30-gauge short (e.g., 0.25- to 0.5-inch) needle.2 Direct needle toward center of base of wart, at an angle nearly parallel to the plane of the skin.2 Maintain needle at this angle to deliver the drug to dermal core of the lesion, infiltrating lesion and causing formation of a small wheal.2

Do not use single-dose vials of powder for injection containing 18 or 50 million units or multiple-dose vials containing 6 million units/mL to prepare solutions for intralesional injection.2 Multiple-dose injection pens are for sub-Q administration only and should not be used for intralesional injection.2

Interferon Alfa-n3 (Alferon N)

Treatment of external genital and perianal warts (condylomata acuminata): Administer intralesionally undiluted.3

Use a 30-gauge needle.3 Direct needle toward base of wart.3

Dosage

Because of differences in potencies and recommended dosages and routes of administration among the various commercially available interferon alfa preparations, use the interferon alfa preparation selected for the patient throughout the treatment regimen.2 3 4 Caution patients not to change brands or alter dosage without consulting clinician.2 3

Pediatric Patients

Treatment of Chronic HBV Infection
Interferon Alfa-2b (Intron A)
Sub-Q

Children ≥1 year of age: 3 million units/m2 3 times weekly for first week, then 6 million units/m2 3 times weekly (maximum of 10 million units 3 times weekly).2

Manufacturer recommends treatment duration of 16–24 weeks.2 AASLD recommends 16–24 weeks in hepatitis B e antigen (HBeAg) -positive patients and ≥12 months in HBeAg-negative patients.97 Duration of 24 months may increase rate of sustained response in HBeAg-negative patients.97

Dosage modification for toxicity: Reduce dosage by 50% if leukocyte count <1500/mm3, granulocyte count <750/mm3, or platelet count <50,000/mm3.2 If leukocyte, granulocyte, and/or platelet counts return to normal or baseline values, resume at up to 100% of initial dosage.2 Permanently discontinue if leukocyte count <1000/mm3, granulocyte count <500/mm3, or platelet count <25,000/mm3.2

Treatment of Chronic HCV Infection
Concomitant Interferon Alfa-2b (Intron A) and Oral Ribavirin
IM or Sub-Q

Children ≥3 years of age (treatment-naive): 3 million units 3 times weekly in conjunction with oral ribavirin.2

Manufacturer of interferon alfa-2b recommends 18–24 months of concomitant therapy if well tolerated and serum ALT concentrations are normalized at 16 weeks; if ALT concentrations have not normalized or if high plasma HCV RNA levels persist after 16 weeks of treatment, consider discontinuance.2 Manufacturers of oral ribavirin recommend 24–48 weeks of concomitant therapy; consider discontinuance if plasma HCV RNA levels not below limits of detection at 24 weeks.90 91

Dosage modification of interferon alfa-2b for toxicity: Reduce dosage by 50%;2 discontinue if reduced dosage not tolerated.2 90 Reduce dosage if leukocyte count <1500/mm3, neutrophil count <750/mm3, or platelet count <50,000/mm3.90 Permanently discontinue if leukocyte count <1000/mm3, neutrophil count <500/mm3, platelet count <50,000/mm3, or hemoglobin <8.5 g/dL.90 If severe depression and/or suicidal ideation occurs, discontinue and initiate appropriate psychiatric care.2

Adults

Treatment of Chronic HBV Infection
Interferon Alfa-2b (Intron A)
IM or Sub-Q

30–35 million units per week (given as 5 million units once daily or 10 million units 3 times weekly).2

Manufacturer recommends treatment duration of 16 weeks.2 AASLD recommends 16–24 weeks in HBeAg-positive patients and ≥12 months in HBeAg-negative patients.97 Duration of 24 months may increase rate of sustained response in HBeAg-negative patients.97

Dosage modification for toxicity: Reduce dosage by 50% if leukocyte count <1500/mm3, granulocyte count <750/mm3, or platelet count <50,000/mm3.2 If leukocyte, granulocyte, and/or platelet counts return to normal or baseline values, resume at up to 100% of initial dosage.2 Permanently discontinue if leukocyte count <1000/mm3, granulocyte count <500/mm3, or platelet count <25,000/mm3.2

Treatment of Chronic HCV Infection
Concomitant Interferon Alfa-2b (Intron A) and Oral Ribavirin
IM or Sub-Q

3 million units 3 times weekly in conjunction with oral ribavirin.2

Manufacturer of interferon alfa-2b recommends 18–24 months of concomitant therapy if well tolerated and serum ALT concentrations are normalized at 16 weeks; if ALT concentrations have not normalized or if high plasma HCV RNA levels persist after 16 weeks of treatment, consider discontinuance.2 Manufacturers of oral ribavirin recommend 24–48 weeks of concomitant therapy; consider discontinuance if plasma HCV RNA levels not below limits of detection at 24 weeks.90 91

Dosage modification of interferon alfa-2b for toxicity: Reduce dosage by 50%;2 discontinue if reduced dosage not tolerated.2 90 Reduce dosage if leukocyte count <1500/mm3, neutrophil count <750/mm3, or platelet count <50,000/mm3.90 Permanently discontinue if leukocyte count <1000/mm3, neutrophil count <500/mm3, platelet count <25,000/mm3, or hemoglobin concentration <8.5 g/dL.90 If severe depression and/or suicidal ideation occurs, decrease dosage and initiate appropriate psychiatric care.2

Concomitant Interferon Alfacon-1 (Infergen) and Oral Ribavirin
Sub-Q

15 mcg once daily in conjunction with oral ribavirin.4

Manufacturer of interferon alfacon-1 recommends up to 48 weeks of concomitant therapy.4 If HCV RNA has not decreased ≥2 log10 at 12 weeks or if HCV RNA not undetectable at 24 weeks, consider discontinuance.4 Safety and efficacy data not available regarding treatment duration >1 year.4

Dosage modification of interferon alfacon-1 for toxicity: Reduce dosage from 15 to 9 mcg once daily and from 9 to 6 mcg once daily if moderate depression occurs, ANC <750/mm3, or platelet count <50,000/mm3.4 If ANC <500/mm3, withhold until ANC is >1000/mm3.4 Permanently discontinue if severe depression occurs, platelet count <25,000/mm3, or hemoglobin <8.5 g/dL.4

Interferon Alfa-2b (Intron A) Monotherapy
IM or Sub-Q

3 million units 3 times weekly.2

Manufacturer recommends treatment duration of 18–24 months if well tolerated and serum ALT concentrations are normalized at 16 weeks; if ALT concentrations have not normalized or if high plasma HCV RNA levels persist at 16 weeks, consider discontinuance.2

Dosage modification for toxicity: If severe adverse effects develop, reduce dosage by 50% or temporarily interrupt therapy until adverse events resolve.2 Discontinue if intolerance persists after dosage adjustment.2

Interferon Alfacon-1 (Infergen) Monotherapy
Sub-Q

9 mcg 3 times weekly for 24 weeks.4

Individuals who tolerated previous interferon therapy and did not respond to the initial regimen or relapsed after discontinuance may receive 15 mcg 3 times weekly for up to 48 weeks.4

Dosage modification for toxicity: If serious adverse reactions occur, reduce dosage to 7.5 mcg 3 times weekly.4 If reactions do not subside, interrupt or discontinue therapy.4 Efficacy of dosage <7.5 mcg 3 times weekly not established.4

Treatment of HPV Infections (External Genital and Perianal Warts)
Interferon Alfa-2b (Intron A)
Intralesional Injection

1 million units into each lesion (up to 5 lesions) 3 times weekly on alternate days for 3 weeks.2

Another course may be administered after 12–16 weeks.2

Interferon Alfa-n3 (Alferon N)
Intralesional Injection

250,000 units (0.05 mL) into each wart twice weekly for up to 8 weeks.3 Large warts may be injected at multiple locations around their periphery, using a total dose of 250,000 units per lesion.3 Maximum dose per treatment session is 2.5 million units.3

Dosage modification for toxicity: Regimen may need to be modified or discontinued if moderate to severe adverse effects occur.3

Delay administration of a second course or other therapy until 3 months after first course unless warts enlarge or new lesions develop; many patients do not exhibit complete resolution of lesions until 3 months following cessation of therapy.3

Safety and efficacy of a second course not determined.3

Hairy Cell Leukemia
Interferon Alfa-2b (Intron A)
IM or Sub-Q

2 million units/m2 3 times weekly.2 124 126 129 131 132 135 172 179 185 186 220 251 252 278 1152 1153 Administer sub-Q (not IM) if platelet count <50,000/mm3.2

Optimum treatment duration not established.141 188 202 219 220 1549 Manufacturer states continue for up to 6 months;2 patients not responding may benefit from continued treatment, but discontinue if disease progresses or fails to respond after 6 months of treatment.2 If no evidence of disease progression, some clinicians suggest continuing for at least 12 months before considering discontinuance for nonresponse.124 141 220 243 250 1549

Dosage modification for toxicity: If severe adverse effects develop, reduce dosage by 50% or temporarily interrupt therapy.2 If adverse effects abate, resume using reduced dosage (1 million units/m2 3 times weekly).2 Permanently discontinue if severe adverse effects persist or recur after dosage reduction.2

AIDS-Related Kaposi’s Sarcoma
Interferon Alfa-2b (Intron A)
IM or Sub-Q

FDA-labeled dosage is 30 million units/m2 3 times weekly.2

Response is slow; maximum effect occurs after ≥6 months of treatment.440 Continue until disease progresses or maximal response is achieved after 16 weeks of treatment.2

Dosage modification for toxicity: If severe adverse effects develop, reduce dosage by 50% or temporarily interrupt therapy.2 If adverse effects abate, may resume using reduced dosage.2 Permanently discontinue if severe adverse effects persist or recur after dosage reduction.2

Follicular non-Hodgkin’s Lymphoma
Interferon Alfa-2b (Intron A)
Sub-Q

5 million units 3 times weekly in conjunction with anthracycline-containing chemotherapy regimen.2 Continue interferon alfa-2b after completion of chemotherapy regimen;2 interferon alfa-2b is given for up to 18 months.2

Doses of myelosuppressive drugs were reduced by 25% from full dose and cycle length increased by 33% (e.g., from 21 to 28 days) when interferon alfa was added to the regimen.2 Delay chemotherapy cycle if neutrophil counts <1500/mm3 or platelet counts <75,000/mm3.2

Dosage modification of interferon alfa-2b for toxicity: Withhold if neutrophil count <1000/mm3 or platelet count <50,000/mm3.2 Reduce dosage by 50% (2.5 million units 3 times weekly) if neutrophil count >1000/mm3 but less than 1500/mm3.2 May reescalate to initial starting dosage (5 million units 3 times weekly) if hematologic toxicity resolves (ANC >1500/mm3).2 Permanently discontinue if AST >5 times ULN or Scr >2 mg/dL.2

Melanoma
Interferon Alfa-2b (Intron A)
IV

Induction therapy: 20 million units/m2 daily for 5 consecutive days per week for 4 weeks.2

Dosage modification for toxicity: Withhold for severe adverse effects (e.g., granulocyte count >250/mm3 but <500/mm3, ALT and/or AST >5 to 10 times ULN).2 When adverse effects abate, may reinitiate at 50% of previous dosage.2 Permanently discontinue if toxicity does not abate while drug withheld, serious adverse effects recur after reduced dosage, granulocyte count <250/mm3, or ALT and/or AST >10 times ULN.2

Sub-Q

Maintenance therapy: 10 million units/m2 3 times weekly for 48 weeks.2

Dosage modification for toxicity: Withhold for severe adverse effects (e.g., granulocyte count >250/mm3 but <500/mm3, ALT and/or AST >5 to 10 times ULN).2 When adverse effects abate, may reinitiate at 50% of previous dosage.2 Permanently discontinue if toxicity does not abate while drug withheld, serious adverse effects recur after reduced dosage, granulocyte count <250/mm3, or ALT and/or AST >10 times ULN.2

Prescribing Limits

Pediatric Patients

Treatment of Chronic HBV Infection
Interferon Alfa-2b (Intron A)
Sub-Q

Maximum dosage is 10 million units 3 times weekly.2

Adults

Treatment of HPV Infections (External Genital and Perianal Warts)
Interferon Alfa-2b (Intron A)
Intralesional Injection

Maximum 5 warts treated per course (total dose 5 million units).2

Interferon Alfa-n3 (Alferon N)
Intralesional Injection

Maximum recommended dose per treatment session is 2.5 million units.3

Special Populations

Renal Impairment

Treatment of Chronic HCV Infection
IM or Sub-Q

Concomitant interferon alfa-2b (Intron A) or interferon alfacon-1 (Infergen) and oral ribavirin therapy contraindicated in patients with Clcr <50 mL/minute.2 4 90

Cautions for Interferon Alfa

Contraindications

  • Interferon alfa-2a (Intron A), interferon alfacon-1 (Infergen): Known hypersensitivity (e.g., urticaria, angioedema, bronchoconstriction, anaphylaxis) to interferon alfa or any ingredient in the formulation.2 4

  • Interferon alfa-n3 (Alferon N): Known hypersensitivity to human interferon alfa proteins or any component in the formulation; history of anaphylactic reactions to murine (mouse) IgG, egg protein, or neomycin.3 (See Sensitivity Reactions under Cautions.)

  • Interferon alfa-2b, interferon alfacon-1: Autoimmune hepatitis2 4 or hepatic decompensation (Child-Pugh score >6, class B and C).2 4 (See Hepatic Effects under Cautions.)

  • Interferon alfa-2b, interferon alfacon-1: Concomitant use of oral ribavirin contraindicated in women who are or may become pregnant, men whose female partners are pregnant, patients with known hypersensitivity to ribavirin or any ingredient in the formulation, patients with hemoglobinopathies (e.g., thalassemia major, sickle cell anemia), and patients with Clcr <50 mL/minute.2 4

Warnings/Precautions

Warnings

Serious Disorders

May cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders.2 4 Monitor closely with periodic clinical and laboratory evaluations; discontinue in those with persistently severe or worsening signs or symptoms of these disorders.2 4 In many, but not all cases, these disorders resolve after interferon alfa discontinued.2 4 (See Other Warnings/Precautions under Cautions.)

Concomitant Oral Ribavirin

Observe usual cautions, precautions, and contraindications associated with oral ribavirin when the drug is used concomitantly with interferon alfa-2b or interferon alfacon-1 for treatment of chronic HCV infection.90 91

Ribavirin is genotoxic and mutagenic and should be considered a potential carcinogen.4

Ribavirin may cause birth defects and/or fetal death.2 4 90 91 If oral ribavirin is used in conjunction with interferon alfa, extreme care must be taken to avoid pregnancy in female patients and female partners of male patients.2 4 90 91 (See Pregnancy under Cautions.)

Ribavirin causes hemolytic anemia, which may exacerbate cardiac disease.4 90

Sensitivity Reactions

Serious, acute hypersensitivity reactions (e.g., urticaria, angioedema, bronchoconstriction, anaphylaxis) reported rarely in patients receiving interferon alfa.2

If serious hypersensitivity reaction occurs, immediately discontinue interferon alfa and provide appropriate supportive care.2 4

Transient rash reported; has not necessitated interruption of interferon alfa treatment.2

Interferon alfa-n3: May contain trace amounts of murine (mouse) protein which can stimulate antibody formation in some patients.3 Although egg protein (ovalbumin) not detected in final product, manufacturing process includes propagation in chick embryo tissue culture and possibility exists that patients receiving the drug could develop hypersensitivity to egg protein.3 (See Contraindications under Cautions.)

Other Warnings/Precautions

Neuropsychiatric Effects

Depression, psychoses, suicidal ideation or suicidal attempts (including some fatalities), hallucinations, aggressive or violent behavior, and rare cases of homicidal ideation reported with interferon alfa (alone or in conjunction with oral ribavirin) in patients with and without preexisting psychiatric disorders.2 4 Anxiety, abnormal thinking, agitation, nervousness, emotional lability, apathy, and relapse of drug addiction may occur.4

Exacerbated symptoms of psychiatric disorders may occur in patients with both psychiatric and substance use disorders.2 If initiated in patient with history of psychiatric conditions or substance use disorders, consider need for drug screening and periodic clinical evaluation, including psychiatric symptom monitoring.2 Early intervention for new or re-emergent neuropsychiatric symptoms or substance use recommended.2

Obtundation, coma, and encephalopathy reported, primarily in geriatric patients treated with high interferon alfa dosage.2

Use with caution in patients with history of preexisting psychiatric disorders, especially those with history of depression.2 4 Closely monitor all patients for evidence of depression and other psychiatric symptoms and advise patients to immediately report any sign or symptom of depression or suicidal ideation to their clinician.2 4

If severe depression and/or other psychiatric condition develops, immediately discontinue interferon alfa and provide appropriate psychiatric intervention.2 4

Cardiovascular Effects

Hypotension,2 4 3 148 206 208 257 260 261 376 470 angina pectoris,4 arrhythmia,2 4 260 300 374 376 461 465 469 470 475 tachycardia2 4 (≥150 bpm),2 cardiomyopathy,2 4 155 204 469 470 1340 1362 and MI2 4 11 235 259 261 341 376 461 465 470 471 473 474 490 963 reported in patients with or without history of cardiovascular disease.2 4

Hypotension may occur during administration or up to 2 days posttherapy and may require supportive therapy, including fluid replacement to maintain intravascular volume.2 Supraventricular arrhythmias have occurred rarely and appeared to correlate with preexisting cardiovascular conditions and prior therapy with cardiotoxic agents.2 These adverse experiences were controlled by modifying dosage or discontinuing the drug, but may require additional specialized care.2

Perform ECG prior to and periodically during interferon alfa therapy in patients with preexisting cardiac abnormalities and/or advanced stages of cancer.2 4

Use with caution and close monitoring in those with cardiovascular disease or history of any cardiac condition, including MI or arrhythmia.2 4 Do not use concomitant interferon alfa and oral ribavirin in patients with history of substantial or unstable cardiac disease.4 90 91

Cerebrovascular Effects

Ischemic and hemorrhagic cerebrovascular events, including hemorrhagic stroke, reported in patients receiving interferon alfa.2 4 Such events have occurred in patients with few or no risk factors for stroke, including patients <45 years of age.2 4

Causal relationship not established.2

Myelosuppression

Suppresses bone marrow function and may cause severe cytopenias and anemia, including aplastic anemia.2 4

Concomitant oral ribavirin may potentiate neutropenia associated with interferon alfa.4 Use concomitant oral ribavirin with caution in patients with low baseline neutrophil counts (i.e., <1500 cells/mm3); may need to discontinue if a severe decrease in neutrophil count occurs;4 do not use in patients with hemoglobinopathies (e.g., thalassemia, sickle cell anemia).2 4

Perform CBCs prior to and routinely during interferon alfa therapy.2 4 Adjust dosage or discontinue drug if necessary.2 4 (See Dosage under Dosage and Administration.)

Because mild to moderate leukopenia has been reported in patients receiving intralesional interferon alfa, also consider hematologic monitoring in these patients.2

Use with caution in patients with coagulation disorders (e.g., pulmonary embolism, thrombophlebitis, hemophilia).2 3 Also use with caution in patients with myelosuppression or receiving drugs that may be myelosuppressive (e.g., zidovudine).2 3 4 (See Specific Drugs under Interactions.)

Flu-like Syndrome

Most frequent adverse effect of interferon alfa is flu-like syndrome,2 4 generally characterized by fever,2 4 headache,2 4 chills,2 myalgia/arthralgia,2 4 fatigue,2 4 increased sweating,2 4 asthenia,2 rigors,2 4 dizziness,2 influenza-like symptoms,2 back pain,2 dry mouth,2 chest pain,2 malaise,2 and pain (unspecified).2 Consider other possible causes if persistent high fever occurs.2 4

Use with caution in patients with debilitating diseases such as cardiac disease (e.g., unstable angina, uncontrolled CHF), severe pulmonary disease (e.g., COPD), or diabetes mellitus (prone to ketoacidosis).2 3

Ophthalmologic Effects

Decrease or loss of vision and retinopathy, including macular edema, optic neuritis, papilledema, retinal hemorrhages, cotton-wool spots, serous retinal detachment, and retinal artery or vein thrombosis, may be induced or aggravated by interferon alfa therapy.2 4

Perform baseline ophthalmologic examinations in all patients prior to initiation of interferon alfa.2 4 Perform ophthalmologic examinations periodically during interferon alfa therapy in those with preexisting ophthalmologic disorders (e.g. diabetic or hypertensive retinopathy).2 4

Perform prompt and complete eye examination in any patient who develops ocular symptoms.2 4

Discontinue in patients who develop new or worsening ophthalmologic disorders.2 4

Endocrine and Metabolic Effects

May cause or aggravate thyroid dysfunction (hypothyroidism2 4 376 507 508 510 1361 1533 1565 or hyperthyroidism).2 376 507 509 510 1361 1362 1533 1565

Evaluate TSH prior to initiation of interferon alfa.2 4 Use with caution in those with preexisting thyroid disorders.4 If symptoms consistent with possible thyroid dysfunction occur during interferon alfa therapy, evaluate thyroid function and initiate treatment if needed.2

Interferon alfa can be continued in patients with hypothyroidism or hyperthyroidism if thyroid function can be normalized with antithyroid therapy or hormone replacement therapy.2 Discontinue interferon alfa if thyroid dysfunction cannot be controlled with medication.4

Development of diabetes mellitus and hyperglycemia reported rarely in patients receiving interferon alfa.2 4 Use with caution in those with preexisting diabetes mellitus.4 Interferon alfa can be continued in patients with diabetes mellitus as long as their diabetes can be controlled with drug therapy.2 4 Discontinue interferon alfa if diabetes cannot be controlled.4

Hepatic Effects

Patients with chronic HBV infection may experience transient increase (>2 times baseline) in serum ALT (“flare”), usually 8–12 weeks following initiation of therapy.2 Interferon alfa generally can be continued, unless there are signs and symptoms of liver failure.2 Monitor symptomatology, liver function tests (serum ALT, alkaline phosphatase, albumin, bilirubin), and PT at approximately 2-week intervals during these occurrences.2 Patients with chronic HBV infection and evidence of decreasing hepatic synthetic function (e.g., decreasing serum albumin, prolonged PT) may be at increased risk of clinical decompensation if an increase in serum ALT occurs during interferon alfa therapy; use the drug with caution and close monitoring of symptoms and liver function tests if serum ALT increases.2

Patients with chronic HCV infection with cirrhosis may be at risk of hepatic decompensation when treated with interferon alfa.4 Closely monitor clinical status and hepatic function;4 immediately discontinue if manifestations of hepatic decompensation (e.g., jaundice, ascites, coagulopathy, decreased serum albumin concentrations) occur.2 4 Contraindicated in patients with hepatic decompensation.2 4 (See Contraindications under Cautions.)

Closely monitor patients who develop liver function abnormalities (e.g., increase in serum ALT) during interferon alfa therapy and discontinue the drug as needed.2

Worsening liver disease, including jaundice, hepatic encephalopathy, hepatic failure, and death, reported in patients with decompensated liver disease, autoimmune hepatitis, history of autoimmune disease, or immunosuppression (e.g., organ transplant recipients) treated with interferon alfa; do not use the drug in these patients.2

Respiratory Effects

Dyspnea, pulmonary infiltrates, pneumonia, bronchiolitis obliterans, interstitial pneumonitis, pulmonary hypertension, and sarcoidosis reported; respiratory failure and/or death has occurred,2 4 principally in those receiving the drug for treatment of chronic HCV infection.2 Etiologic explanation for these findings not established.2

One manufacturer suggests baseline chest radiographs in all patients before initiating interferon alfa and whenever clinically indicated in patients who develop fever, cough, dyspnea, or other respiratory symptoms during therapy.2

Discontinue interferon alfa in patients who develop persistent or unexplained pulmonary infiltrates or pulmonary function impairment.4 Recurrence of respiratory failure has occurred with interferon rechallenge; closely monitor patients if interferon alfa resumed.2 4

Autoimmune Disease

Development or exacerbation of autoimmune disease (e.g., autoimmune thrombocytopenia, idiopathic thrombocytopenic purpura, vasculitis, Raynaud’s phenomenon, rheumatoid arthritis, psoriasis, interstitial nephritis, thyroiditis, lupus erythematosus, hepatitis, rhabdomyolysis) reported in patients receiving interferon alfa.2 4 Fatalities reported rarely.2

Do not use in patients with autoimmune hepatitis; use with caution in patients with other autoimmune disorders.4

If autoimmune disease develops, closely monitor and discontinue the drug if necessary.2

Risk of Transmissible Infectious Agents from Plasma-derived Preparations

Interferon alfa-2b contains albumin (a derivative of human blood);2 interferon alfa-n3 is produced using human leukocytes.3 Because of effective donor screening and product manufacturing processes, these preparations are associated with an extremely remote risk for transmission of viral diseases and a theoretical risk for transmission of Creutzfeldt-Jakob disease (CJD).2 3

Colitis

Hemorrhagic/ischemic colitis (sometimes fatal) observed within 12 weeks after initiation of interferon alfa.4

Discontinue immediately in patients who develop signs and symptoms of colitis.4

Pancreatitis

Pancreatitis (sometimes fatal) reported in patients receiving interferon alfa.2 4

Suspend interferon alfa in patients with signs and symptoms of pancreatitis (e.g., abdominal pain, nausea, vomiting); discontinue the drug if a diagnosis of pancreatitis is established.2 4

Peripheral Neuropathy

Peripheral neuropathy reported in patients receiving telbivudine concomitantly with an interferon alfa.2 4 (See Specific Drugs under Interactions.)

Triglycerides

Increased serum triglycerides reported in patients receiving interferon alfa alone or in conjunction with oral ribavirin; severe hypertriglyceridemia may result in pancreatitis.2 (See Pancreatitis under Cautions.)

Consider discontinuing interferon alfa in patients with persistently elevated triglycerides (>1000 mg/dL) accompanied by symptoms suggestive of pancreatitis (abdominal pain, nausea, vomiting).2

Renal Effects

Increased Scr, including renal failure, reported in patients with HCV infection receiving interferon alfacon-1.4 (See Renal Impairment under Cautions.)

Evaluate electrolytes prior to and periodically during therapy.2

Dental and Periodontal Disorders

Dental and periodontal disorders reported in patients receiving interferon alfa and oral ribavirin;2 dry mouth may contribute to damage of teeth and oral mucous membranes during long-term treatment.2

Advise patients to have regular dental examinations during treatment, brush their teeth thoroughly twice daily, and rinse their mouth thoroughly after vomiting.2

Antibody Formation

Serum anti-interferon neutralizing antibodies may develop in patients receiving interferon alfa.2

Clinical importance of development of serum neutralizing antibodies unknown.4 No apparent correlation of antibody development to clinical response or adverse events.2 4

Organ Transplant Recipients

Safety and efficacy of interferon alfa alone or in conjunction with oral ribavirin not established for treatment of chronic HCV infection in patients with liver or other transplants.2 4

Specific Populations

Pregnancy

Interferon alfa (alfa-2b, alfacon-1, alfa-n3) monotherapy: Category C.2 3 4

Concomitant interferon alfa (alfa-2b, alfacon-1) and oral ribavirin: Category X.2 4

Lactation

Not known whether interferon alfa is distributed into milk;2 3 4 murine interferons distribute into milk in mice.2 3 Discontinue nursing or the drug.2 3 4

Pediatric Use

Interferon alfa-2b: Safety and efficacy established for treatment of chronic HBV infection in children 1–17 years of age and for the treatment of chronic HCV infection in treatment-naive children 3–16 years of age.2 Safety and efficacy not established for any other indications in pediatric patients.2

Interferon alfacon-1: Safety and efficacy not established in children <18 years of age.4

Interferon alfa-n3: Safety and efficacy not established in children <18 years of age.3

Suicidal ideation or attempted suicide reported more frequently in pediatric patients (principally adolescents) receiving interferon alfa than in adults receiving the drug; these events occurred during treatment and following discontinuance.2

Delay in weight and height increases compared with baseline reported in pediatric patients receiving interferon alfa for treatment of chronic HBV or HCV infection.2 12 52

Geriatric Use

Insufficient experience in those ≥65 years of age to determine whether they respond differently than younger adults.2 4

Use with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.2 4

Hepatic Impairment

Patients with chronic HBV infection may be at risk for transient acute exacerbations (flares) of HBV infection.2 (See Hepatic Effects under Cautions.)

Patients with chronic HCV infection with cirrhosis may be at risk of hepatic decompensation.4 Closely monitor clinical status and hepatic function; immediately discontinue interferon alfa if decompensation occurs.2 4 (See Hepatic Effects under Cautions.)

Interferon alfa-2b and interferon alfacon-1 contraindicated in patients with autoimmune hepatitis or hepatic decompensation (Child-Pugh score >6, class B and C).2 4

Interferon alfacon-1: Safety and efficacy alone or in conjunction with oral ribavirin not evaluated for treatment of HCV infection in patients with hepatic impairment.4

Renal Impairment

Concomitant interferon alfa-2b or interferon alfacon-1 and oral ribavirin contraindicated if Clcr <50 mL/minute.2 4 90 91

Interferon alfacon-1 alone or in conjunction with oral ribavirin not evaluated for treatment of HCV infection in patients with renal impairment.4 Monitor patients with impaired renal function closely for signs and symptoms of interferon toxicity, including increased Scr.4

Common Adverse Effects

Flu-like symptoms (e.g., fever, headache, chills, myalgia/arthralgia, fatigue, increased sweating, asthenia, rigors, dizziness),2 3 4 abdominal pain,4 alopecia,2 4 anorexia,4 anxiety/emotional lability/irritability,4 back pain,3 4 depression,2 3 4 diarrhea,4 dyspnea,4 injection site erythema,4 insomnia,4 nausea,3 4 nervousness,4 pharyngitis,4 somnolence.2

Interactions for Interferon Alfa

Drugs Metabolized by Hepatic Microsomal System

Interferons may inhibit hepatic CYP enzyme system.8 31 41 44 104 105 106 107 108 109 164 950 951 952 953 954 1544

Specific Drugs

Drug

Interaction

Comments

Aldesleukin

Hypersensitivity reactions, development or exacerbation of autoimmune disease and inflammatory disorders, and increased incidence of myocardial injury (e.g., MI, myocarditis, ventricular hypokinesia, severe rhabdomyolysis) reported1747

Antineoplastic agents

Additive or synergistic antineoplastic activity with certain cytotoxic agents (e.g., cisplatin, cyclophosphamide, doxorubicin, eflornithine, fluorouracil, mechlorethamine, melphalan, mitomycin, nitrosoureas, vinblastine, vincristine)996 1042 1143 1159 1434 1435 1436 1437 1438 1439 1440

Myelosuppressive agents

Increased risk of myelosuppression2 3 149 211 265 398

Use concomitantly with caution;2 3 4 149 211 265 398 monitor WBC count2

Phenobarbital

Possible increased phenobarbital concentrations and toxicity (e.g., lethargy, fatigue)863

Radiation therapy

May result in severe toxicity235 522 523 936 937 938 939

Close monitoring advised523

Ribavirin

Possible additive hematologic toxicity (anemia)2

Concomitant use with oral ribavirin contraindicated if Clcr <50 mL/minute2 4

Telbivudine

Increased risk and severity of peripheral neuropathy2 4

Safety and efficacy of concomitant telbivudine and any interferon for treatment of chronic HBV infection not established2 4

Theophylline

Increased theophylline concentrations2 106 107 108 950

Vinca alkaloids (vinblastine, vincristine)

Possible increased toxicity of interferon alfa 156 207 227 260 299 331 332 333 336 376 385 386 394 459 931 932 1700 1732

Increased incidence of neurotoxicity376 487

Zidovudine

Increased risk of hematologic (e.g., neutropenia,2 149 1051 thrombocytopenia)149 and hepatic toxicity149

Use concomitantly with caution;2 monitor WBC count2

Interferon Alfa Pharmacokinetics

Absorption

Bioavailability

Interferon alfa is well absorbed following IM or sub-Q injection;9 21 29 409 mean serum concentrations following IM injection comparable to those following sub-Q injection.2

Following IV administration (interferon alfa-2b), peak serum concentrations achieved in 30 minutes.2

Following IM or sub-Q injection (interferon alfa-2b), peak serum concentrations achieved in 3–12 hours.2

Following intralesional injection (interferon alfa-2b dosage of 3 million units weekly per wart for 4 weeks), serum concentrations of the drug ranged from 5–40 units/mL.163 Peak serum concentrations reported to occur in 6 hours.1108

Following intralesional injection into anogenital warts (interferon alfa-n3), plasma concentrations of interferon were undetectable (detection limit 3 units/mL);3 some systemic absorption apparently occurs because adverse systemic effects were reported in these patients.3

Distribution

Extent

Interferons are widely and rapidly distributed into body tissues after systemic administration; highest concentrations occur in spleen, kidney, liver, and lung.8 15

Does not readily distribute into CSF following systemic administration of mixtures of naturally occurring human or recombinant interferons;5 8 9 18 21 23 30 34 42 165 409 413 414 421 low concentrations detected in CSF following administration of large systemic doses.9 30 34 42 414 434

Not known whether interferon crosses the placenta in humans.88

Distributed into milk in mice;2 3 975 not known whether interferon distributed into human milk.2 3

Elimination

Metabolism

Interferon alfa appears to be metabolized principally in the kidney.2 9 13 28 29 32 43 45 46 215 436 444 446 447 Hepatic metabolism and subsequent biliary excretion may be a minor pathway.46 402 984

Elimination Route

Interferon alfa generally undetectable or present only in trace quantities in urine.2 5 9 13 18 21 43 45 165 436 983

Half-life

Following IV infusion (interferon alfa-2b): 2 hours (range: 0.5–2.9 hours).2 13 144 215

Following IM or sub-Q injection (interferon alfa-2b): 2–3 hours.2

Special Populations

Limited data indicate that serum concentrations and clearance of interferon not substantially altered in those with chronic renal failure.9 150 May accumulate in body fluids of patients with markedly depressed GFR and Clcr.45

Stability

Storage

Parenteral

Solution for Injection

Interferon alfa-2b (Intron A) multiple-dose vials and multiple-dose injection pens: 2–8°C; do not freeze or expose to heat.2 After initial dose is given, discard any solution remaining in vial or injection pen after 4 weeks.2

Interferon alfacon-1 (Infergen): 2–8°C; protect from light and freezing.4

Interferon alfa-n3 (Alferon N): 2–8°C; protect from freezing.3

Powder for Injection

Interferon alfa-2b (Intron A): 2–8°C.2 Use immediately after reconstitution; may be stored at 2–8°C for up to 24 hours.2

Actions and Spectrum

  • Interferon alfa is a naturally occurring protein with antiviral, antineoplastic, and immunomodulating activity.8 47 70 255 259 261 456 648 714 717 719 740 906 1211 1240 1241 1426 Commercially available in US as interferon alfa-2b,2 interferon alfacon-1,4 and interferon alfa-n3.3

  • Interferon alfa-2b (Intron A): Single interferon subtype; recombinant preparation obtained from bacterial fermentation of Escherichia coli containing a genetically engineered plasmid with a human interferon alfa-2b gene.2

  • Interferon alfacon-1 (Infergen): Genetically modified interferon protein derived from several naturally occurring human interferon alfa proteins; recombinant preparation produced in E. coli cells genetically altered by insertion of a synthetically constructed sequence that codes for interferon alfacon-1.4

  • Interferon alfa-n3 (Alferon N): Mixture of naturally occurring human interferon alfa proteins; precise subtype composition not determined; manufactured from pooled units of human leukocytes induced by incomplete infection with a murine virus (Sendai virus) to produce interferon alfa-n3.3

  • Mechanisms of action of interferon alfa not fully elucidated.256 259 261 262 1174 1175 1176 1461

  • Interferons bind to specific membrane receptors on cell surfaces2 78 113 114 177 215 236 282 989 1190 1197 1426 1463 1464 and initiate a complex sequence of intracellular events, including induction of certain enzymes, suppression of cell proliferation, various immunomodulating activities, and inhibition of viral replication in virus-infected cells.2 55 63 71 78 177 214 533 534 1177

Advice to Patients

  • Advise patients receiving interferon alfa about appropriate use of the drug and the expected benefits and risks.2 4

  • Importance of reading the manufacturer's patient information and medication guide.2 4 112

  • If patient and/or their caregiver is to administer IM or sub-Q interferon alfa, provide careful instructions on proper administration methods, disposal procedures, and the importance of not reusing needles and syringes; provide patient with manufacturer's instructions for use.2 4 115

  • Caution patients not to change brands of interferon alfa without consulting their clinician.2 4

  • Importance of remaining well hydrated, especially during initial treatment.2

  • Advise patients with HCV infection that it is not known whether interferon alfa (alone or in conjunction with oral ribavirin) will prevent transmission of HCV infection to others or prevent long-term HCV-associated complications (cirrhosis, liver failure, liver cancer).2 Importance of taking precautions to prevent transmission of HCV.2 4

  • Advise patients that laboratory evaluations are required before starting and periodically during treatment.2 4

  • Advise patients that hives, generalized urticaria, chest tightness, wheezing, and hypotension may be early signs of hypersensitivity reactions and that they should notify their clinician if any of these conditions occur.3

  • Importance of reporting any sign or symptom of depression or suicidal ideation to clinician.2 4 Advise patients that the drug may need to be immediately discontinued and psychiatric intervention instituted in severe cases.2 4

  • Advise patients to maintain good oral hygiene, including brushing their teeth twice daily and rinsing their mouth after vomiting.2

  • Advise patients that some adverse effects (e.g., fatigue, impaired concentration) may impair ability to perform certain tasks.2

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.2 3 4

  • Advise patients of the teratogenic/embryocidal risks associated with concomitant oral ribavirin and the necessity for females of childbearing potential and male patients with female partners of childbearing age to practice effective contraception during and for 6 months after ribavirin therapy.2 4

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.2 3 4

  • Importance of advising patients of other important precautionary information.2 3 4 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Interferon Alfa-2b (Recombinant DNA Origin)

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection

10 million units

Intron A (with sterile water for injection diluent)

Schering

18 million units

Intron A (with sterile water for injection diluent)

Schering

50 million units

Intron A (with sterile water for injection diluent)

Schering

Injection

6 million units/mL (18 million units)

Intron A (available as multiple-dose vials)

Schering

10 million units/mL (25 million units)

Intron A (available as multiple-dose vials)

Schering

15 million units/mL (22.5 million units)

Intron A (available as multiple-dose pen, 6 disposable needles, and swabs)

Schering

25 million units/mL (37.5 million units)

Intron A (available as multiple-dose pen, 6 disposable needles, and swabs)

Schering

50 million units/mL (75 million units)

Intron A (available as multiple-dose pen, 6 disposable needles, and swabs)

Schering

Interferon Alfacon-1 (Recombinant DNA Origin)

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection, for subcutaneous use

9 mcg/0.3 mL

Infergen (available as single-dose vials)

Kadmon

15 mcg/0.5 mL

Infergen (available as single-dose vials)

Kadmon

Interferon Alfa-n3 (Human Leukocyte Origin)

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection

5 million units/mL

Alferon N (with albumin human and phenol)

Hemispherx

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions February 15, 2013. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

2. Schering Corporation. Intron A (interferon alfa-2b, recombinant) for injection prescribing information. Whitehouse Station, NJ; 2012 Aug.

3. Hemispherx Biopharma. Alferon N injection (interferon alfa-n3 [human leukocyte derived]) prescribing information. Philadelphia, PA; 2004 Jul.

4. Kadmon. Infergen (interferon alfacon-1) injection for subcutaneous use prescribing information. Warrendale, PA; 2010 Jul.

5. Houglum JE. Interferon: mechanisms of action and clinical value. Clin Pharm. 1983; 2:20-8. [IDIS 163575] [PubMed 6192965]

6. Farci P, Mandas A, Coiana A et al. Treatment of chronic hepatitis D with interferon alfa-2a. N Engl J Med. 1994; 330:88-94. [IDIS 323826] [PubMed 8259188]

8. Borden EC, Edwards BS, Hawkins MJ et al. Interferons: biological response modification and pharmacology. In: Mihich E, ed. Biological response in cancer: progress toward potential applications. New York: Plenum Press; 1982:169-218.

9. Balmer CM. The new alpha interferons. Drug Intell Clin Pharm. 1985; 19:887-93. [IDIS 207966] [PubMed 3910384]

11. Foon KA, Sherwin SA, Abrams PG et al. Treatment of advanced non-Hodgkin’s lymphoma with recombinant leukocyte A interferon. N Engl J Med. 1984; 311:1148-52. [IDIS 191909] [PubMed 6482933]

12. Lok AS, Heathcote EJ, Hoofnagle JH. Management of hepatitis B: 2000-Summary of a workshop. Gastroenterology. 2001; 120:1828-53. [IDIS 466664] [PubMed 11375963]

13. Schering-Plough Corporation. Interferon backgrounder. Kenilworth, NJ; 1988 May.

14. Perrillo RP, Schiffer, Davis GL et al and the Hepatitis Interventional Therapy Group. A randomized, control trial of interferon alfa-2b alone and after prednisone withdrawal for the treatment of chronic hepatitis B. N Engl J Med. 1990; 323:295-301. [IDIS 269488] [PubMed 2195346]

15. Hanley DF, Wiranowska-Stewart M, Stewart WE. Pharmacology of interferons: I. Pharmacologic distinctions between human leukocyte and fibroblast interferons. Int J Immunopharmacol. 1979; 1:219-26. [PubMed 95249]

16. Wong DKH, Cheung AM, O’apos;Rourke K et al. Effect of alfa-interferon treatment in patients with hepatitis B e antigen-positive chronic hepatitis B: a meta-analysis. Ann Intern Med. 1993; 119:312-23. [IDIS 318588] [PubMed 8328741]

17. Centers for Disease Control and Prevention (CDC). Sexually transmitted diseases treatment guidelines, 2010. MMWR Recomm Rep. 2010; 59(RR-12):1-110.

18. Larsson A, Forsgren M, Hard af Segerstad S et al. Administration of interferon to an infant with congenital rubella syndrome involving persistent viremia and cutaneous vasculitis. Acta Paediatr Scand. 1976; 65:105-10. [PubMed 1251716]

20. Genentech. Pegasys (peginterferon alfa-2a) injection for subcutaneous use prescribing information. South San Francisco, CA; 2011 Sep.

21. Emodi G, Just M, Hernandez R et al. Circulating interferon in man after administration of exogenous human leukocyte interferon. J Natl Cancer Inst. 1975; 54:1045- 9. [PubMed 1127735]

23. De Clercq E, Edy VG, De Vlieger H et al. Intrathecal administration of interferon in neonatal herpes. J Pediatr. 1975; 86:736-9. [PubMed 166151]

25. Perez V, Tanno H, Villamil F et al. Recombinant interferon alfa-2b following prednisone withdrawal in the treatment of chronic type B hepatitis. J Hepatol. 1990; 11:S113-5. [PubMed 2079567]

27. Sokal EM, Conjeevaram HS, Roberts EA et al. Interferon alfa therapy for chronic hepatitis B in children: a multinational randomized controlled trial. Gastroenterology. 1998; 114:988-95. [IDIS 405615] [PubMed 9558288]

28. Greischel A, Tanswell P, Busch U et al. Pharmacokinetics and biodistribution of recombinant human interferon-α2C in rat and marmoset. Arzneim Forsch. 1988; 38:1539-43.

29. Wills RJ, Dennis S, Spiegel H et al. Interferon kinetics and adverse reactions after intravenous, intramuscular, and subcutaneous injection. Clin Pharmacol Ther. 1984; 35:722-7. [IDIS 185263] [PubMed 6713784]

30. Smith RA, Norris F, Palmer D et al. Distribution of alpha interferon in serum and cerebrospinal fluid after systemic circulation. Clin Pharmacol Ther. 1985; 37:85-8. [IDIS 195525] [PubMed 3965239]

31. Williams SJ, Farrell GC. Inhibition of antipyrine metabolism by interferon. Br J Clin Pharmacol. 1986; 22:610-2. [IDIS 225049] [PubMed 3790409]

32. Wills RJ, Soike KF. Pharmacokinetics of human recombinant interferon-αI after IV infusion and im injection in African green monkeys. J Interferon Res. 1988; 8:427-32. [PubMed 3171243]

33. Henderson DK. Managing occupational risks for hepatitis C transmission in the health care setting. Clin Microbiol Rev. 2003; 16:546-68. [PubMed 12857782]

34. Billiau A. Interferon therapy: pharmacokinetic and pharmacological aspects. Arch Virol. 1981; 67:121-33. [PubMed 6163417]

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