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تعداد آیتم قابل مشاهده باقیمانده : 3 مورد
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Interferon alfa-2b (United States and Canada: Not available): Drug information

Interferon alfa-2b (United States and Canada: Not available): Drug information
(For additional information see "Interferon alfa-2b (United States and Canada: Not available): Patient drug information" and see "Interferon alfa-2b (United States and Canada: Not available): Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
ALERT: US Boxed Warning
Neuropsychiatric, autoimmune, ischemic, and infectious disorders:

Alpha interferons, including interferon alfa-2b, cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders. Patients should be monitored closely with periodic clinical and laboratory evaluations. Patients with persistently severe or worsening signs or symptoms of these conditions should be withdrawn from therapy. In many but not all cases, these disorders resolve after stopping interferon alfa-2b therapy.

Brand Names: US
  • Intron A [DSC]
Brand Names: Canada
  • Intron A (Hsa-Free) [DSC];
  • Intron A [DSC]
Pharmacologic Category
  • Antineoplastic Agent, Biological Response Modulator;
  • Biological Response Modulator;
  • Interferon
Dosing: Adult

Note: Consider premedication with acetaminophen prior to administration to reduce the incidence of some adverse reactions. Not all dosage forms and strengths are appropriate for all indications; refer to product labeling for details. Interferon alfa-2b at doses ≥10 million units/m2 is associated with a moderate emetic potential; antiemetics may be recommended to prevent nausea and vomiting.

Adult T-cell leukemia/lymphoma

Adult T-cell leukemia/lymphoma (off-label use): SubQ: 5 million units once daily (in combination with zidovudine); if interferon is tolerated, may escalate dose after 1 week to 10 million units once daily; continue until at least 4 weeks after achieving a complete remission or for 1 year in the absence of a complete remission (Gill 1995) or 3 to 5 million units once daily or once every other day (in combination with zidovudine), may escalate dose if well tolerated (Matutes 2001) or 5 million units once daily (in combination with zidovudine and arsenic trioxide) (Kchour 2009). Refer to protocol(s) for dosage adjustment recommendations.

AIDS-related Kaposi sarcoma

AIDS-related Kaposi sarcoma: IM, SubQ: 30 million units/m2 3 times a week; continue until disease progression or until maximal response has been achieved after 16 weeks.

O ff-label dosing: SubQ: 8 million units once daily in the evening (in combination with zidovudine) until disease progression or for a maximum of 1 year (Shepherd 1998). Refer to protocol for dosage adjustment recommendations.

Behçet syndrome

Behçet syndrome (mucocutaneous ulcers) (off-label use; based on limited data): SubQ: 5 million units 3 times/week for 6 weeks, followed by 5 million units once a week for 10 weeks (Hamuryudan 1994). The optimal dose, frequency, and duration of interferon alfa-2b therapy for management of Behçet syndrome is unclear; dosing from case reports and small studies is variable (ranging from ~2 to 5 million units/dose) (Kötter 2004).

Chronic hepatitis B

Chronic hepatitis B (alternative therapy [WHO 2015]): IM, SubQ: 5 million units once daily or 10 million units 3 times a week for 16 weeks.

Chronic myeloid leukemia

Chronic myeloid leukemia (alternate therapy in patients unable to take tyrosine kinase inhibitors) (off-label use; based on limited data): SubQ: 3 million units once daily; if needed (based on WBC counts), may increase to 6 million units once daily (Kuroiwa 1998) or 4 million units 5 days/week (Lipton 1996).

Condyloma acuminata

Condyloma acuminata: Intralesional: 1 million units/lesion (maximum: 5 lesions per treatment) 3 times a week (on alternate days) for 3 weeks. May administer a second course at 12 to 16 weeks.

Cutaneous T-cell lymphomas

Cutaneous T-cell lymphomas (mycosis fungoides/Sézary syndrome) (off-label use): Early stage disease (in combination with psoralen and ultraviolet A therapy [PUVA]): SubQ: 1.5 million units once daily during week 1, followed by 3 million units once daily during week 2, followed by 6 million units 3 times/week during week 3 (on the day prior to PUVA) until complete response or for a maximum of 2 months, then maintenance therapy of 3 million units 3 times/week for 2 months followed by 3 million units 2 times/week for 10 months (Rupoli 2005).

Desmoid tumors

Desmoid tumors (off-label use; based on limited data [dosing extrapolated from interferon alfa-2c]): SubQ: 3.5 million units 3 times/week (with or without tretinoin) until disease progression or unacceptable toxicity (Leithner 2000).

Essential thrombocythemia, advanced

Essential thrombocythemia, advanced (off-label use): SubQ: 3 million units 3 times a week for 2 years, followed by 5 million units twice a week (Huang 2014).

Hairy cell leukemia

Hairy cell leukemia: IM, SubQ: 2 million units/m2 3 times a week for up to 6 months (may continue treatment with sustained treatment response); discontinue for disease progression or failure to respond after 6 months.

Lymphoma

Lymphoma (follicular): SubQ: 5 million units 3 times a week for up to 18 months (initially in combination with an anthracycline-containing combination chemotherapy regimen, and then as monotherapy after completion of the chemotherapy regimen).

Melanoma, adjuvant therapy

Melanoma (malignant), adjuvant therapy (alternative therapy): Induction: 20 million units/m2 IV for 5 consecutive days per week for 4 weeks, followed by maintenance dosing of 10 million units/m2 SUBQ 3 times a week for 48 weeks. Note: High-dose interferon no longer has a defined role in the adjuvant treatment of cutaneous melanoma and is not recommended for routine adjuvant use (ASCO [Seth 2020]).

Myelofibrosis, early

Myelofibrosis, early (off-label use): SubQ: 0.5 to 1 million units 3 times a week, gradually increasing to 2 to 3 million units 3 times a week as tolerated (Silver 2017).

Neuroendocrine tumors, gastrointestinal carcinoid tumors

Neuroendocrine tumors, gastrointestinal carcinoid tumors (alternate therapy) (off-label use; based on limited data): SubQ: 3 to 5 million units 3 times a week (Oberg 2003; Pavel 2013) or 5 million units (median dose) every other day (range: 3 to 9 million units once daily or every other day), titrate to a dose that maintains leukocyte count <3,000/mm3 (Oberg 2003).

Peyronie disease

Peyronie disease (off-label use): Intralesional: 5 million units (in 10 mL NS) every other week for a total of 6 doses (Hellstrom 2006) or 2 million units (in 10 mL NS) every other week for a median of 12 injections (Stewart 2015).

Polycythemia vera, advanced

Polycythemia vera, advanced (off- label use): SubQ: 3 million units 3 times a week for 2 years, followed by 5 million units twice a week (Huang 2014).

West Nile virus, neurologic symptoms

West Nile virus, neurologic symptoms (off-label use; based on limited data): SubQ: 3 million units once daily for 14 days (Kalil 2005; Sayao 2004).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

Renal impairment at treatment initiation: There are no dosage adjustments provided in the manufacturer's labeling.

Renal toxicity during treatment: Indication-specific adjustment: Lymphoma (follicular): Serum creatinine >2 mg/dL: Permanently discontinue.

Dosing: Hepatic Impairment: Adult

Hepatic impairment at treatment initiation: There are no dosage adjustments provided in the manufacturer's labeling. Contraindicated in patients with decompensated liver disease or autoimmune hepatitis.

Hepatotoxicity during treatment: Permanently discontinue for severe (grade 3) hepatic injury or hepatic decompensation (Child-Pugh class B and C [score >6]).

Indication-specific adjustments:

Lymphoma (follicular): AST >5 times ULN: Permanently discontinue.

Melanoma, malignant (induction and maintenance):

ALT/AST >5 to 10 times ULN: Temporarily withhold; resume with a 50% dose reduction when adverse reaction abates

ALT/AST >10 times ULN: Permanently discontinue.

Dosing: Adjustment for Toxicity: Adult

Hematologic toxicity (also refer to indication specified adjustments below): ANC <500/mm3 or platelets <25,000/mm3: Discontinue treatment.

Hypersensitivity reaction (acute, serious), ophthalmic disorders (new or worsening), thyroid abnormality development (which cannot be normalized with medication), signs or symptoms of liver failure: Discontinue treatment.

Liver function abnormality, pulmonary infiltrate development, evidence of pulmonary function impairment, or autoimmune disorder development, triglycerides >1,000 mg/dL: Monitor closely and discontinue if appropriate. Permanently discontinue for severe (grade 3) hepatic injury or hepatic decompensation (Child-Pugh class B and C [score >6]).

Neuropsychiatric disorders (during treatment):

Clinical depression or other psychiatric problem: Monitor closely during and for 6 months after treatment.

Severe depression or other psychiatric disorder: Discontinue treatment.

Persistent or worsening psychiatric symptoms, suicidal ideation, aggression towards others: Discontinue treatment and follow with appropriate psychiatric intervention.

Manufacturer-recommended adjustments, listed according to indication:

Lymphoma (follicular):

Neutrophils >1000/mm3 to <1,500/mm3: Reduce dose by 50%; may re-escalate to starting dose when neutrophils return to >1,500/mm3

Severe toxicity (neutrophils <1000/mm3 or platelets <50,000/mm3): Temporarily withhold.

AST >5 times ULN or serum creatinine >2 mg/dL: Permanently discontinue.

Hairy cell leukemia:

Platelet count <50,000/mm3: Do not administer intramuscularly (administer SubQ instead).

Severe toxicity: Reduce dose by 50% or temporarily withhold and resume with 50% dose reduction; permanently discontinue if persistent or recurrent severe toxicity is noted.

Chronic hepatitis B:

WBC <1,500/mm3, granulocytes <750/mm3, or platelet count <50,000/mm3, or other laboratory abnormality or severe adverse reaction: Reduce dose by 50%; may re-escalate to starting dose upon resolution of hematologic toxicity. Discontinue for persistent intolerance.

WBC <1,000/mm3, granulocytes <500/mm3, or platelet count <25,000/mm3: Permanently discontinue

AIDS-related Kaposi sarcoma: Severe toxicity: Reduce dose by 50% or temporarily withhold; may resume at reduced dose with toxicity resolution; permanently discontinue for persistent/recurrent toxicities.

Melanoma, malignant (induction and maintenance):

Severe toxicity including neutrophils >250/mm3 to <500/mm3 or ALT/AST >5 to 10 times ULN: Temporarily withhold; resume with a 50% dose reduction when adverse reaction abates.

Neutrophils <250/mm3, ALT/AST >10 times ULN, or severe/persistent adverse reactions: Permanently discontinue.

Dosing: Older Adult

Refer to adult dosing.

Dosing: Pediatric

(For additional information see "Interferon alfa-2b (United States and Canada: Not available): Pediatric drug information")

Note: Consider premedication with acetaminophen to reduce the incidence of some adverse reactions. Not all dosage forms and strengths are appropriate for all indications; refer to product labeling for details.

Chronic hepatitis B

Chronic hepatitis B: Children and Adolescents: SubQ: 3 million units/m2/dose 3 times per week for 1 week; then 6 million units/m2/dose 3 times per week; maximum dose: 10 million units/dose; total duration of therapy is 16 to 24 weeks. Note: In HIV-exposed/-infected patients, higher doses may be used for retreatment of failed lower-dose therapy: 10 million units/m2/dose 3 times per week for 6 months (HHS [OI pediatric 2016]).

Chronic hepatitis C

Chronic hepatitis C: Note: Interferon-free therapies are generally preferred in the treatment of hepatitis C (AASLD/IDSA 2017; WHO 2016): Children ≥3 years and Adolescents: IM, SubQ: 3 million units/m2/dose 3 times per week in combination with ribavirin

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosage adjustment for toxicity:

Hematologic toxicity (also refer to indication specified adjustments below): Children and Adolescents: ANC <500/mm3 or platelets <25,000/mm3: Discontinue treatment.

Hypersensitivity reaction (acute, serious), ophthalmic disorders (new or worsening), thyroid abnormality development (which cannot be normalized with medication), signs or symptoms of liver failure: Children and Adolescents: Discontinue treatment.

Liver function abnormality, pulmonary infiltrate development, evidence of pulmonary function impairment, or autoimmune disorder development, persistently elevated triglycerides (eg, >1,000 mg/dL in adults): Children and Adolescents: Monitor closely and discontinue if appropriate.

Neuropsychiatric disorders (during treatment): Children and Adolescents:

Clinical depression or other psychiatric problem: Monitor closely during and for 6 months after treatment.

Severe depression or other psychiatric disorder: Discontinue treatment.

Persistent or worsening psychiatric symptoms, suicidal ideation, aggression towards others: Discontinue treatment and follow with appropriate psychiatric intervention.

Indication-specific, manufacturer-recommended adjustments:

Chronic hepatitis B: Children and Adolescents:

WBC <1500/mm3, granulocytes <750/mm3, or platelet count <50,000/mm3, or other laboratory abnormality or severe adverse reaction: Reduce dose by 50%; may re-escalate to starting dose upon resolution of hematologic toxicity. Discontinue for persistent intolerance.

WBC <1000/mm3, granulocytes <500/mm3, or platelet count <25,000/mm3: Permanently discontinue.

Hepatitis C, chronic: Children and Adolescents: Severe toxicity: Reduce dose by 50% or temporarily withhold until subsides; permanently discontinue for persistent toxicities after dosage reduction.

In other oncology uses, the following have been used in adult patients:

Lymphoma (follicular): Adults:

Neutrophils >1,000/mm3 to <1,500/mm3: Reduce dose by 50%; may re-escalate to starting dose when neutrophils return to >1,500/mm3

Severe toxicity (neutrophils <1,000/mm3 or platelets <50,000/mm3): Temporarily withhold.

AST >5 times ULN or serum creatinine >2 mg/dL: Permanently discontinue.

Hairy cell leukemia: Adults:

Platelet count <50,000/mm3: Do not administer intramuscularly (administer SubQ instead).

Severe toxicity: Reduce dose by 50% or temporarily withhold and resume with 50% dose reduction; permanently discontinue if persistent or recurrent severe toxicity is noted.

AIDS-related Kaposi sarcoma: Adults: Severe toxicity: Reduce dose by 50% or temporarily withhold; may resume at reduced dose with toxicity resolution; permanently discontinue for persistent/recurrent toxicities.

Malignant melanoma (induction and maintenance): Adults:

Severe toxicity, including neutrophils >250/mm3 to <500/mm3 or ALT/AST >5 to 10 times ULN: Temporarily withhold; resume with a 50% dose reduction when adverse reaction abates.

Neutrophils <250/mm3, ALT/AST >10 times ULN, or severe/persistent adverse reactions: Permanently discontinue.

Dosing: Kidney Impairment: Pediatric

Baseline renal impairment: Children and Adolescents: Combination therapy with ribavirin (hepatitis C) is contraindicated in patients with CrCl <50 mL/minute; use combination therapy with ribavirin (hepatitis C) with caution in patients with impaired renal function and CrCl ≥50 mL/minute.

Nephrotoxicity during therapy: There are no pediatric specific recommendations; based on experience in adult patients, dosage adjustment suggested.

Dosing: Hepatic Impairment: Pediatric

Baseline hepatic impairment: There are no dosage adjustments provided in the manufacturer's labeling. Contraindicated in patients with decompensated liver disease or autoimmune hepatitis.

Hepatotoxicity during treatment: Children and Adolescents: Permanently discontinue for severe (grade 3) hepatic injury or hepatic decompensation (Child-Pugh class B and C [score >6]).

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%:

Central nervous system: Fatigue (8% to 96%), headache (21% to 62%), chills (45% to 54%), rigors (2% to 42%), depression (3% to 40%), drowsiness (1% to 33%), dizziness (≤23%), vertigo (≤23%), irritability (≤22%), pain (3% to 18%), right upper quadrant pain (≤15%), malaise (3% to 14%), paresthesia (≤13%), confusion (≤12%), insomnia (≤12%)

Dermatologic: Alopecia (8% to 38%), skin rash (1% to 25%), diaphoresis (1% to 13%), pruritus (1% to 11%)

Endocrine & metabolic: Weight loss (≤13%), amenorrhea (≤12%)

Gastrointestinal: Anorexia (1% to 69%), nausea and vomiting (66%; children: 40%), nausea (17% to 66%), gastrointestinal disease (≤7%; children: 46%), diarrhea (2% to 35%), vomiting (2% to 40%), dysgeusia (≤24%), xerostomia (1% to 22%), abdominal pain (≤20%), constipation (≤14%)

Hematologic & oncologic: Neutropenia (≤92%; grades 3/4: 26%; children: 13% to 14%), granulocytopenia (31% to 92%), decreased white blood cell count (9% to 68%), leukopenia (<5%; malignant melanoma, grades 3/4: ≤26%), anemia (≤22%), decreased platelet count (1% to 15%), thrombocytopenia (≤10%; children: 3%)

Hepatic: Increased serum aspartate aminotransferase (4% to 63%), increased serum alkaline phosphatase (4% to 13%), increased serum alanine aminotransferase (2% to 13%)

Local: Injection site reaction (≤20%; children: 5%)

Neuromuscular & skeletal: Myalgia (16% to 75%), asthenia (≤63%), musculoskeletal pain (1% to 21%), arthralgia (3% to 19%), back pain (1% to 19%)

Renal: Increased blood urea nitrogen (2% to 12%)

Respiratory: Flu-like symptoms (≤45%; children: 100%), dyspnea (≤15%), cough (≤13%)

Miscellaneous: Fever (34% to 94%)

1% to 10%:

Cardiovascular: Hypertension (≤9%), chest pain (≤8%; includes substernal), peripheral edema (≤6%), edema (≤5%), peripheral vascular insufficiency (≤5%), angina pectoris (<5%), arteritis (<5%), atrial fibrillation (<5%), bradycardia (<5%), cardiac arrhythmia (<5%), cardiac failure (<5%), cardiomegaly (<5%), cardiomyopathy (<5%), cerebrovascular accident (<5%), coronary artery disease (<5%), extrasystoles (<5%), flushing (<5%), heart valve disease (<5%), hypotension (<5%), orthostatic hypotension (<5%), palpitations (<5%), polyarteritis nodosa (<5%), peripheral ischemia (<5%), phlebitis (<5%), pulmonary embolism (<5%), Raynaud disease (<5%), syncope (<5%), tachycardia (<5%), thrombosis (<5%), varicose veins (<5%), facial edema (≤3%)

Central nervous system: Anxiety (≤9%), lack of concentration (≤8), agitation (≤7%), hypothermia (≤5%), abnormal dreams (<5%), abnormal gait (<5%), abnormality in thinking (<5%), aggressive behavior (<5%), altered sense of smell (<5%), amnesia (<5%), apathy (<5%), aphasia (<5%), ataxia (<5%), Bell palsy (<5%), carpal tunnel syndrome (<5%), central nervous system dysfunction (<5%), coma (<5%), delirium (<5%), dysphasia (<5%), emotional lability (<5%), exacerbation of depression (<5%), extrapyramidal reaction (<5%), hyperesthesia (<5%), hyperthermia (<5%), hypertonia (<5%), hypoesthesia (<5%), hyporeflexia (<5%), intoxicated feeling (<5%), loss of consciousness (<5%), manic depressive reaction (<5%), manic reaction (<5%), migraine (<5%), myasthenia (<5%), neuralgia (<5%), neuritis (<5%), neuropathy (<5%), nightmares (<5%), paresis (<5%), personality disorder (<5%), polyneuropathy (<5%), psychoneurosis (<5%), psychosis (<5%), seizure (<5%), speech disturbance (<5%), twitching (<5%), voice disorder (<5%), nervousness (1% to 3%), attempted suicide (≤2%), suicidal ideation (≤2%),

Dermatologic: Xeroderma (≤9%), dermatitis (1% to 8%), injection site pruritus (≤5%), abnormal hair texture (<5%), acne vulgaris (<5%), cellulitis (<5%), cold and clammy skin (<5%), eczema (<5%), epidermal cyst of skin (<5%), erythema (<5%), erythema nodosum (<5%), erythematous rash (<5%), exacerbation of psoriasis (<5%), folliculitis (<5%), furunculosis (<5%), genital pruritus (<5%), lichenoid dermatitis (<5%), maculopapular rash (<5%), nail disease (<5%), pallor (<5%), psoriasis (<5%), skin depigmentation (<5%), skin discoloration (<5%), skin photosensitivity (<5%), toxic epidermal necrolysis (<5%), urticaria (<5%), vitiligo (<5%)

Endocrine & metabolic: Cachexia (≤5%), decreased libido (≤5%), dehydration (≤5%), hypercalcemia (≤5%), hyperglycemia (≤5%), increased thirst (≤5%), weight gain (≤5%), albuminuria (<5%), cutaneous nodule (<5%), exacerbation of diabetes mellitus (<5%), goiter (<5%), gynecomastia (<5%), heavy menstrual bleeding (<5%), hypertrichosis (<5%), hot flash (<5%), hyperthyroidism (<5%), hypertriglyceridemia (<5%), hypothyroidism (<5%), menstrual disease (<5%), increased lactate dehydrogenase (≤1%)

Gastrointestinal: Dyspepsia (2% to 8%), gingivitis (1% to 7%), hernia of abdominal cavity (≤5%), abdominal distention (<5%), ageusia (<5%), aphthous stomatitis (<5%; including non-herpetic cold sore), biliary colic (<5%), cholelithiasis (<5%), colitis (<5%), dental disease (<5%), dysphagia (<5%), eructation (<5%), esophagitis (<5%), flatulence (<5%), gastric ulcer (<5%), gastritis (<5%), gastroenteritis (<5%), gastrointestinal hemorrhage (<5%), gingival hemorrhage (<5%), gingival hyperplasia (<5%), halitosis (<5%), hemorrhoids (<5%), increased appetite (<5%), melanosis (<5%), melena (<5%), mucositis (<5%), oral leukoplakia (<5%), oral mucosa ulcer (<5%), sialorrhea (<5%), stomatitis (<5%), tongue disease (<5%), loose stools (≤2%)

Genitourinary: Mastitis (≤5%), penile swelling (≤5%), scrotal edema (≤5%), urinary tract infection (≤5%), herpes genitalis (1% to 5%), cystitis (<5%), dysmenorrhea (<5%), dysuria (<5%), hematuria (<5%), impotence (<5%), leukorrhea (<5%), nocturia (<5%), pelvic pain (<5%), penile disease (<5%), proteinuria (<5%), sexual disorder (<5%), urinary frequency (<5%), urinary incontinence (<5%), urination disorder (<5%), uterine hemorrhage (<5%), vaginal dryness (<5%), virilization (<5%), genital candidiasis (≤1%)

Hematologic & oncologic: Lymphadenitis (≤5%), lymphadenopathy (≤5%), purpuric rash (≤5%), hematoma (<5%), hemolytic anemia (<5%), hypochromic anemia (<5%), lipoma (<5%), lymphocytosis (<5%), oral hemorrhage (<5%), rectal hemorrhage (<5%), thrombotic thrombocytopenic purpura (<5%)

Hepatic: Abnormal hepatic function tests (<5%), ascites (<5%), hepatic encephalopathy (<5%), hepatic failure (<5%), hepatitis (<5%), hyperbilirubinemia (<5%), jaundice (<5%)

Hypersensitivity: Hypersensitivity reaction (≤5%; includes acute reaction)

Infection: Infection (≤7%; including hemophilus), viral infection (7%), abscess (<5%), bacterial infection (<5%), fungal infection (<5%), herpes zoster infection (<5%), parasitic infection (including trichomonas), sepsis (<5%)

Local: Bleeding at injection site (≤5%), burning sensation at injection site (≤5%), local pain (pleural: ≤5%), pain at injection site (≤5%), inflammation at injection site (1% to 5%), local discoloration (gastrointestinal mucosa: <5%)

Neuromuscular & skeletal: Amyotrophy (<5%), arthritis (<5%), bone disease (<5%), exacerbation of arthritis (<5%), hyperkinesia (<5%), hypokinesia (<5%), lower limb cramp (<5%), ostealgia (<5%), osteoarthritis (<5%), rheumatoid arthritis (<5%), spondylitis (<5%), tendinopathy (<5%), tremor (<5%)

Ophthalmic: Periorbital edema (≤5%), blurred vision (<5%), conjunctivitis (<5%), diplopia (<5%), eye pain (<5%), hordeolum (<5%), lacrimation (<5%), nystagmus (<5%), photophobia (<5%), visual disturbance (<5%), xerophthalmia (<5%)

Otic: Otalgia (≤5%), auditory impairment (<5%), labyrinth disease (<5%), otitis media (<5%), tinnitus (<5%)

Renal: Polyuria (≤10%), increased serum creatinine (2% to 6%), renal insufficiency (<5%)

Respiratory: Bronchitis (≤10%), pharyngitis (≤8%), epistaxis (≤7%), nasal congestion (≤7%), asthma (≤5%), bronchospasm (≤5%), cyanosis (≤5%), hemoptysis (≤5%), hypoventilation (≤5%), laryngitis (≤5%), orthopnea (≤5%), pleural effusion (≤5%), pneumonia (≤5%), pneumonitis (≤5%), pneumothorax (≤5%), pulmonary fibrosis (≤5%), rales (≤5%), respiratory insufficiency (≤5%), respiratory tract disease (≤5%), sneezing (≤5%), tonsillitis (≤5%), tracheitis (≤5%), wheezing (≤5%), rhinitis (<5%), rhinorrhea (<5%), upper respiratory tract infection (<5%), sinusitis (1% to 4%)

Miscellaneous: Inflammation (≤5%), alcohol intolerance (<5%)

<1%, postmarketing, and/or case reports: Anaphylaxis, angioedema, aplastic anemia, autoimmune disease, bronchoconstriction, encephalopathy, erythema multiforme, exacerbation of sarcoidosis, hallucination, hepatotoxicity, homicidal ideation, immune thrombocytopenia, ischemic changes (cerebrovascular events), leukemia (intralesional administration), macular edema, myocardial infarction, myositis, nephrotic syndrome, optic neuritis, pancreatitis, pancytopenia, pericarditis, peripheral neuropathy, pituitary insufficiency, pulmonary hypertension, pulmonary infiltrates, pure red cell aplasia, reactivation of HBV, reduced ejection fraction, renal failure syndrome, retinal detachment (serous), rhabdomyolysis, sarcoidosis, Stevens-Johnson syndrome, suicidal tendencies, supraventricular cardiac arrhythmia, systemic lupus erythematosus, tissue necrosis at injection site, tongue discoloration, vasculitis, Vogt-Koyanagi-Harada syndrome

Contraindications

Hypersensitivity to interferon alfa or any component of the formulation; decompensated liver disease; autoimmune hepatitis.

Combination therapy with interferon alfa-2b and ribavirin is also contraindicated in females who are pregnant, in males whose female partners are pregnant; in patients with hemoglobinopathies (eg, thalassemia major, sickle-cell anemia); CrCl <50 mL/minute; or hypersensitivity to ribavirin or any ribavirin component.

Warnings/Precautions

Concerns related to adverse effects:

• Bone marrow suppression: Interferon alfa-2b causes bone marrow suppression, including potentially severe cytopenias, and, very rarely, aplastic anemia. Discontinue treatment for severe neutropenia (ANC <500/mm3) or thrombocytopenia (platelets <25,000/mm3). Hemolytic anemia (hemoglobin <10 g/dL) was observed in ~10% of treated patients in clinical trials when combined with ribavirin; anemia occurred within 1 to 2 weeks of initiation of therapy. Use caution in patients with preexisting myelosuppression and in patients with concomitant medications which cause myelosuppression.

• Cerebrovascular events: Hemorrhagic and ischemic cerebrovascular events have been observed.

• Dental and periodontal disorders: In patients receiving combination interferon and ribavirin therapy, dental and periodontal disorders have been reported; additionally, dry mouth can damage teeth and mouth mucous membranes during chronic therapy.

• Flu-like symptoms: Interferon alfa-2b is commonly associated with fever and flu-like symptoms; rule out other causes/infections with persistent fever. Use with caution in patients with debilitating conditions.

• GI toxicity: Antiemetics may be recommended to prevent nausea and vomiting; interferon alfa-2b doses of 15 to 30 million units/m2/day IV are associated with a moderate emetic potential in pediatrics (POGO [Paw Cho Sing 2019]), and doses ≥10 million units/m2 are associated with a moderate emetic potential in adults.

• Hepatic effects: Interferon alfa-2b may cause hepatotoxicity (including fatality); monitor closely if abnormal LFTs develop. A transient increase in ALT (≥2 times baseline) may occur in patients treated with interferon alfa-2b for chronic hepatitis B. Therapy generally may continue, however, functional indicators (eg, albumin, prothrombin time, bilirubin) should be monitored frequently. Worsening and potentially fatal liver disease, including jaundice, hepatic encephalopathy, and hepatic failure, have been reported in patients receiving interferon alfa for chronic hepatitis B and C with decompensated liver disease, autoimmune hepatitis, history of autoimmune disease, and immunosuppressed transplant recipients; avoid interferon treatment (if appropriate) in these patients (use is contraindicated in decompensated liver disease). Patients with cirrhosis are at increased risk of hepatic decompensation. Therapy should be discontinued for any patient developing signs and symptoms of liver failure. Permanently discontinue for severe (grade 3) hepatic injury or hepatic decompensation (Child-Pugh class B and C [score >6]).

• Hepatitis B virus reactivation: The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), total Ig or IgG, and antibody to hepatitis B surface antigen (anti-HBs) prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.

• Hypersensitivity: Acute hypersensitivity reactions (eg, urticaria, angioedema, bronchoconstriction, anaphylaxis) have been reported (rarely) with alfa interferons. If an acute reaction develops, discontinue therapy immediately; transient rashes have occurred in some patients following injection, but have not necessitated treatment interruption.

• Hypertriglyceridemia: Elevated triglycerides have been reported (discontinue if persistent and severe, particularly if combined with symptoms of pancreatitis).

• Neuropsychiatric disorders: [US Boxed Warning]: May cause or aggravate severe neuropsychiatric adverse events; monitor closely with clinical evaluations (periodic); discontinue treatment for severe persistent or worsening symptoms; some cases may resolve with discontinuation. Psychiatric events may include depression psychosis, mania, suicidal ideation, suicide attempts, completed suicides, and homicidal ideation; may occur in patients with or without previous psychiatric symptoms. Effects are usually rapidly reversible upon therapy discontinuation, but have persisted up to 3 weeks. If psychiatric symptoms persist or worsen, or suicidal or homicidal ideation or aggressive behavior towards others is identified, discontinue treatment and follow the patient closely. Careful neuropsychiatric monitoring is recommended during and for 6 months after treatment in patients who develop psychiatric disorders (including clinical depression). New or exacerbated neuropsychiatric or substance abuse disorders are best managed with early intervention. Use with caution in patients with a history of psychiatric disorders. Drug screening and periodic health evaluation (including monitoring of psychiatric symptoms) is recommended if initiating treatment in patients with coexisting psychiatric condition or substance abuse disorders. Suicidal ideation or attempts may occur more frequently in pediatric patients (eg, adolescents) when compared to adults. Higher doses, usually in patients ≥65 years of age, may result in increased CNS toxicity (eg, obtundation and coma).

• Ocular effects: Decreased or loss of vision, macular edema, optic neuritis, retinal hemorrhages, cotton wool spots, papilledema, retinal detachment (serous), and retinal artery or vein thrombosis have occurred (or been aggravated) in patients receiving alfa interferons. Use caution in patients with preexisting eye disorders; monitor closely; a complete eye exam should be done promptly in patients who develop ocular symptoms; discontinue with new or worsening ophthalmic disorders.

• Pulmonary effects: Dyspnea, pulmonary infiltrates, pulmonary hypertension, interstitial pneumonitis, pneumonia, bronchiolitis obliterans, and sarcoidosis may be induced or aggravated by treatment, sometimes resulting in respiratory failure or fatality. Has been reported more in patients who were treated for chronic hepatitis C, although has also occurred with use for oncology indications. Patients with fever, cough, dyspnea or other respiratory symptoms should be evaluated with a chest x-ray; monitor closely and consider discontinuing treatment with evidence of impaired pulmonary function. Use with caution in patients with a history of pulmonary disease.

Disease-related concerns:

• AIDS-related Kaposi sarcoma: Do not treat patients with visceral AIDS-related Kaposi sarcoma associated with rapidly-progressing or life-threatening disease.

• Autoimmune disease: [US Boxed Warning]: May cause or aggravate fatal or life-threatening autoimmune disorders; monitor closely with clinical and laboratory evaluations (periodic); discontinue treatment for severe persistent or worsening symptoms; some cases may resolve with discontinuation. Autoimmune disorders (thrombocytopenia, vasculitis, Raynaud disease, rheumatoid arthritis, lupus erythematosus and rhabdomyolysis) have been associated with alfa interferons. Worsening of psoriasis and sarcoidosis (and the development of new sarcoidosis) have been reported; use caution in patients with these conditions.

• Cardiovascular disease: Use with caution in patients with a history of cardiovascular disease; monitor closely in patients with cardiovascular disease (ischemic or thromboembolic), arrhythmias, hypertension, and in patients with a history of MI and/or prior therapy with cardiotoxic drugs. Patients with preexisting cardiac disease and/or advanced cancer should have baseline and periodic ECGs. May cause hypotension (during administration or delayed up to 2 days), arrhythmia, tachycardia (≥150 bpm), cardiomyopathy (~2% in patients with AIDS-related Kaposi sarcoma), and/or myocardial infarction (MI); some experiencing cardiovascular adverse effects had no prior history of cardiac disease. Supraventricular arrhythmias occur rarely and are associated with preexisting cardiac disease or prior therapy with cardiotoxic agents. Dose modification, discontinuation and/or additional therapies may be necessary. In a scientific statement from the American Heart Association, interferon has been determined to be an agent that may either cause reversible direct myocardial toxicity or exacerbate underlying myocardial dysfunction (magnitude: moderate/major) (AHA [Page 2016]).

• Chronic hepatitis: Patients being treated for chronic hepatitis B or C with a history of autoimmune disease or who are immunosuppressed transplant recipients should not receive interferon alfa-2b.

• Coagulation disorders: Use with caution and monitor closely in patients with coagulation disorders (eg, thrombophlebitis, pulmonary embolism).

• Diabetes: Diabetes mellitus has been reported; discontinue if diabetes cannot be effectively managed with medication. Use with caution in patients with a history of diabetes mellitus, particularly if prone to DKA.

• Infectious disorders: [US Boxed Warning]: May cause or aggravate fatal or life-threatening infectious disorders; monitor closely with clinical and laboratory evaluations (periodic); discontinue treatment for severe persistent or worsening symptoms; some cases may resolve with discontinuation.

• Ischemic disorders: [US Boxed Warning]: May cause or aggravate fatal or life-threatening ischemic disorders; monitor closely with clinical and laboratory evaluations (periodic); discontinue treatment for severe persistent or worsening symptoms; some cases may resolve with discontinuation.

• Pulmonary disorders: Use with caution and monitor closely in patients with pulmonary disorders (eg, chronic obstructive pulmonary disease).

• Thyroid disorders: Use with caution in patients with preexisting thyroid disease; thyroid disorders (hyper- or hypothyroidism) have been reported. Thyroid-stimulating hormone levels should be within normal limits prior to initiating interferon; treatment should not be initiated in patients with preexisting thyroid disease who cannot be maintained in normal ranges by medication. Discontinue interferon use in patients who develop thyroid abnormalities during treatment and in patients with thyroid disease who subsequently cannot maintain normal ranges with thyroid medication. Discontinuation of interferon therapy may or may not reverse thyroid dysfunction.

Concurrent drug therapy issues:

• Combination therapy with ribavirin: Combination therapy with ribavirin is associated with birth defects and/or fetal mortality and hemolytic anemia.

Dosage form specific issues:

• Albumin: Some formulations contain albumin, which may carry a remote risk of viral transmission, including a theoretical risk of Creutzfeldt-Jakob disease transmission.

• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.

• Product variability: Due to differences in dosage, patients should not change brands of interferons without the concurrence of their health care provider.

Product Availability

The manufacturer of Intron A, Merck, has made the decision to voluntarily discontinue the supply of all strengths of Intron A. Supplies of Intron A solution for injection are expected to be depleted around July 2021 and supplies of Intron A powder for reconstitution are expected to be depleted around March 2022.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Injection:

Intron A: 6,000,000 units/mL (3.8 mL [DSC]); 10,000,000 units/mL (3.2 mL [DSC]) [contains edetate (edta) disodium, metacresol, polysorbate 80]

Solution Reconstituted, Injection [preservative free]:

Intron A: 10,000,000 units (1 ea [DSC]); 18,000,000 units (1 ea [DSC]); 50,000,000 units (1 ea [DSC]) [contains albumin human]

Generic Equivalent Available: US

No

Pricing: US

Solution (reconstituted) (Intron A Injection)

10000000 unit (per each): $368.76

50000000 unit (per each): $1,843.80

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Injection:

Intron A (Hsa-Free): 6,000,000 units/mL ([DSC]); 10,000,000 units/mL ([DSC]) [contains edetate (edta) disodium, metacresol, polysorbate 80]

Solution Reconstituted, Injection:

Intron A: 10,000,000 units ([DSC])

Administration: Adult

Administer dose in the evening (if possible) to enhance tolerability. Not all dosage forms are recommended for all administration routes; refer to manufacturer's labeling. Interferon alfa-2b at doses ≥10 million units/m2 is associated with a moderate emetic potential; antiemetics may be recommended to prevent nausea and vomiting.

IM: Rotate injection sites; preferred sites for injection are anterior thigh, deltoid, and superolateral buttock. Some patients may be appropriate for self-administration with appropriate training. Allow to reach room temperature prior to injection. In hairy cell leukemia treatment, if platelets are <50,000/mm3, do not administer intramuscularly (administer SubQ instead).

IV: Infuse over ~20 minutes

SubQ: Suggested for those who are at risk for bleeding or are thrombocytopenic. Rotate SubQ injection site; preferred sites for injection are abdomen (except around the navel), anterior thigh, and outer upper arm. Patient should be well hydrated. Some patients may be appropriate for self-administration with appropriate training. Allow to reach room temperature prior to injection.

Intralesional: Inject at an angle nearly parallel to the plane of the skin, directing the needle to center of the base of the wart to infiltrate the lesion core and cause a small wheal. Only infiltrate the keratinized layer; avoid administration which is too deep or shallow. Allow to reach room temperature prior to injection.

Administration: Pediatric

Parenteral: Not all dosage forms are recommended for all administration routes; refer to manufacturer's labeling. Allow product to reach room temperature prior to injection.

IM: Administer dose in the evening (if possible) to enhance tolerability. Rotate injection sites; preferred sites for injection are anterior thigh, deltoid, and superolateral buttock. Some patients may be appropriate for self-administration with appropriate training. In hairy cell leukemia treatment, if platelets are <50,000/mm3, do not administer intramuscularly (administer SubQ instead).

SubQ: Suggested for those who are at risk for bleeding or are thrombocytopenic. Rotate SubQ injection site; preferred sites for injection are abdomen (except around the navel), anterior thigh, and outer upper arm. Administer dose in the evening (if possible) to enhance tolerability. Patient should be well hydrated. Some patients may be appropriate for self-administration with appropriate training.

Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/103132s5196lbl.pdf#page=40, must be dispensed with this medication.

Use: Labeled Indications

AIDS-related Kaposi sarcoma: Treatment of AIDS-related Kaposi sarcoma in select patients ≥18 years of age.

Chronic hepatitis B: Treatment of chronic hepatitis B in patients ≥1 year of age with compensated liver disease.

Condylomata acuminata: Treatment of condylomata acuminata involving external surfaces of the genital and perianal areas in patients ≥18 years of age.

Follicular lymphoma: Initial treatment of clinically aggressive follicular non-Hodgkin lymphoma in conjunction with anthracycline-containing combination chemotherapy in patients ≥18 years of age. Note: Indications in the manufacturer's labeling may not reflect current clinical practices.

Hairy cell leukemia: Treatment of hairy cell leukemia in patients ≥18 years of age.

Melanoma (malignant): Adjuvant to surgical treatment of malignant melanoma in patients ≥18 years of age who are free of disease but at high risk for systemic recurrence within 56 days of surgery. Note: High-dose interferon no longer has a defined role in the adjuvant treatment of cutaneous melanoma and is not recommended for routine adjuvant use (ASCO [Seth 2020]).

Use: Off-Label: Adult

Adult T-cell leukemia/lymphoma; Behçet syndrome (mucocutaneous ulcers); Chronic myeloid leukemia (alternate therapy in patients unable to take tyrosine kinase inhibitors); Cutaneous T-cell lymphomas (mycosis fungoides/Sézary syndrome); Desmoid tumors; Essential thrombocythemia (advanced); Myelofibrosis, early; Neuroendocrine tumors, GI carcinoid tumors (alternate therapy); Peyronie disease; Polycythemia vera (advanced); West Nile virus, neurologic symptoms

Medication Safety Issues
Sound-alike/look-alike issues:

Interferon alfa-2b may be confused with interferon alfa-2a, interferon alfa-n3, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon beta-1a.

Intron A may be confused with PEG-Intron.

International issues:

Interferon alfa-2b may be confused with interferon alpha multi-subtype which is available in international markets.

Metabolism/Transport Effects

Inhibits CYP1A2 (weak)

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy

Aldesleukin: Interferons (Alfa) may enhance the adverse/toxic effect of Aldesleukin. In particular, risks of myocardial and renal toxicity may be increased by this combination. Management: Consider using lower doses to minimize toxicity of this combination. Only coadminister aldesleukin and interferons (alfa) in patients in whom potential benefits outweigh the risk of severe toxicity. Monitor renal and cardiac function closely if combined. Risk D: Consider therapy modification

BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination

Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy

Chloramphenicol (Systemic): Myelosuppressive Agents may enhance the myelosuppressive effect of Chloramphenicol (Systemic). Risk X: Avoid combination

Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination

CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy

CloZAPine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of CloZAPine. Risk C: Monitor therapy

Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider therapy modification

Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination

Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination

Fezolinetant: CYP1A2 Inhibitors (Weak) may increase the serum concentration of Fezolinetant. Risk X: Avoid combination

Fluorouracil Products: Interferons (Alfa) may increase the serum concentration of Fluorouracil Products. Risk C: Monitor therapy

Methadone: Interferons (Alfa) may increase the serum concentration of Methadone. Risk C: Monitor therapy

Olaparib: Myelosuppressive Agents may enhance the myelosuppressive effect of Olaparib. Risk C: Monitor therapy

Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy

Ribavirin (Oral Inhalation): Interferons (Alfa) may enhance the adverse/toxic effect of Ribavirin (Oral Inhalation). Hemolytic anemia has been observed. Risk C: Monitor therapy

Ribavirin (Systemic): Interferons (Alfa) may enhance the adverse/toxic effect of Ribavirin (Systemic). Hemolytic anemia has been observed. Risk C: Monitor therapy

Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider therapy modification

Telbivudine: Interferons (Alfa) may enhance the adverse/toxic effect of Telbivudine. Specifically, the risk of peripheral neuropathy may be increased. Risk C: Monitor therapy

Theophylline Derivatives: CYP1A2 Inhibitors (Weak) may increase the serum concentration of Theophylline Derivatives. Risk C: Monitor therapy

TiZANidine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of TiZANidine. Management: Avoid these combinations when possible. If combined use is necessary, initiate tizanidine at an adult dose of 2 mg and increase in 2 to 4 mg increments based on patient response. Monitor for increased effects of tizanidine, including adverse reactions. Risk D: Consider therapy modification

Vitamin K Antagonists (eg, warfarin): Interferons (Alfa) may enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Zidovudine: Interferons may enhance the adverse/toxic effect of Zidovudine. Interferons may decrease the metabolism of Zidovudine. Risk C: Monitor therapy

Reproductive Considerations

Verify pregnancy status prior to administration in females of reproductive potential. Disruption of the normal menstrual cycle may occur. Female patients of reproductive potential should use effective contraception during treatment.

If used in combination with ribavirin, all warnings related to the use of ribavirin and contraception should be followed. Refer to the Ribavirin monograph for additional information.

Pregnancy Considerations

Alfa interferon is endogenous to normal amniotic fluid (Lebon 1982); however, placenta perfusion studies note exogenous interferon alfa does not cross the placenta (Waysbort 1993).

Essential thrombocythemia is associated with an increased risk of thrombosis, bleeding and, when untreated, may increase the risk of pregnancy loss. Maternal use of interferon alfas may improve pregnancy outcomes; use of interferon alfa-2b may be considered in pregnant women when other agents are not appropriate (Lapoirie 2020; Maze 2019; Sakai 2018; Tefferi 2019; Yazdani Brojeni 2012; Yoshida 2017).

The European Society for Medical Oncology (ESMO) has published guidelines for diagnosis, treatment, and follow-up of cancer during pregnancy. The guidelines suggest that interferon-alfa may be used for the treatment of chronic myeloid leukemia (CML) during pregnancy and recommend referral to a facility with expertise in cancer during pregnancy; a multidisciplinary team (obstetrician, neonatologist, oncology team) is encouraged (ESMO [Peccatori 2013]). An international consensus panel suggests use of interferon-alfa in pregnant patients once WBC and platelet counts have risen to a level associated with CML symptom onset (Lishner 2016).

Interferon alfa-2b in combination with ribavirin is contraindicated in pregnant females and males whose female partners are pregnant. Combination therapy with ribavirin may cause birth defects and death in an unborn child. If used in combination with ribavirin, all warnings related to the use of ribavirin and pregnancy should be followed. Refer to the Ribavirin monograph for additional information.

Breastfeeding Considerations

Interferon alfa is endogenous to breast milk. Breast milk samples obtained from a lactating mother prior to and after administration of interferon alfa-2b showed that interferon alfa is present in breast milk and administration of the medication did not significantly affect endogenous levels (Kumar 2000).

According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.

If used in combination with ribavirin, all warnings related to the use of ribavirin and breastfeeding should be followed. Refer to the Ribavirin monograph for additional information.

Monitoring Parameters

General monitoring parameters for all indications:

At baseline (repeat during therapy if clinically indicated): Chest x-ray, serum creatinine, albumin, prothrombin time, triglycerides.

At baseline and periodically thereafter: CBC with differential, platelets and hemoglobin, liver function tests, electrolytes and TSH; ophthalmic exam (or with new ocular symptoms); ECG (in patients with pre-existing cardiac abnormalities or in advanced stages of cancer). Monitor serum bilirubin, ALT, AST, alkaline phosphatase and LDH at 2, 8 and 12 weeks following initiation, then every 6 months during treatment. Permanently discontinue for severe (grade 3) hepatic injury or hepatic decompensation (Child-Pugh class B and C [score >6]).

During therapy: Weight; neuropsychiatric changes during and for 6 months after therapy.

Additional indication-specific monitoring parameters:

Chronic hepatitis B: CBC with differential and platelets and liver function tests: Baseline, weeks 1, 2, 4, 8, 12, and 16, at the end of treatment, and then 3 and 6 months post treatment.

Condyloma acuminate (intralesional administration): Monitor CBC with differential, liver function tests (elevations have been reported).

Melanoma, malignant: CBC with differential and platelets and liver function tests: Weekly during induction phase, then monthly during maintenance.

Oncology uses: Thyroid function monitoring (Hamnvik 2011): TSH and anti-TPO antibodies at baseline; if TPO antibody positive, monitor TSH every 2 months; if TPO antibody negative, monitor TSH every 6 months. Hepatitis B virus screening with hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), total Ig or IgG, and antibody to hepatitis B surface antigen (anti-HBs) prior to beginning systemic anticancer therapy (ASCO [Hwang 2020]).

Mechanism of Action

Interferon alfas bind to a specific receptor on the cell membrane to initiate intracellular activity; multiple effects can be detected including induction of gene transcription. It inhibits cellular growth, alters the state of cellular differentiation, interferes with oncogene expression, alters cell surface antigen expression, increases phagocytic activity of macrophages, and augments cytotoxicity of lymphocytes for target cells

Pharmacokinetics (Adult Data Unless Noted)

Distribution: Vd: 31 L; but has been noted to be much greater (370 to 720 L) in patients with leukemia receiving continuous infusion IFN; IFN does not penetrate the CSF.

Metabolism: Primarily renal, filtered and absorbed at the renal tubule.

Bioavailability: IM: 83%; SubQ: 90%.

Half-life elimination: IV: ~2 hours; IM, SubQ: ~2 to 3 hours.

Time to peak, serum: IM, SubQ: ~3 to 12 hours; IV: By the end of a 30-minute infusion.

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AE) United Arab Emirates: Intron a;
  • (AR) Argentina: Bioferon | Inf | Inmutag | Interferon alfa 2b | Interimmun;
  • (AT) Austria: Introna;
  • (AU) Australia: Intron a;
  • (BE) Belgium: Intron a;
  • (BG) Bulgaria: Intron a | Realdiron;
  • (BR) Brazil: Alfainterferona 2b | Alfainterferona 2b (recombinante) | Blauferon b - interferon alfa-2b | Interferon | Intron a;
  • (CL) Chile: Intron a;
  • (CN) China: An da fen | Anferon | Anterferon | Interferon | Intron a | Kai yin yi sheng | Leferon | Long hua nuo | Reaferonum | Recombinant Human Interferon alfa 2b | Wan fu yin | Ying te long;
  • (CO) Colombia: Heberon alfa R | Intron a | Introna;
  • (CZ) Czech Republic: Alphaferon | Heberon alfa | Intron a;
  • (DE) Germany: Introna;
  • (DO) Dominican Republic: Heberon alfa R | Introna;
  • (EC) Ecuador: Heberon alfa R | Intron a;
  • (EG) Egypt: Egyferon | Intron a;
  • (ES) Spain: Introna;
  • (FI) Finland: Introna;
  • (FR) France: Introna | Viraferon;
  • (GB) United Kingdom: Intron a | Viraferon;
  • (GR) Greece: Intron a | Introna;
  • (HU) Hungary: Intron a;
  • (IE) Ireland: Intron a;
  • (IL) Israel: Intron a;
  • (IN) India: Inarif-3 | Intron a | Realfa 2b | Zavinex;
  • (IT) Italy: Intron a | Introna;
  • (JP) Japan: Intron a;
  • (KR) Korea, Republic of: Alphaferon | Intron a;
  • (KW) Kuwait: Intron a;
  • (LB) Lebanon: Bioferon | Intron a;
  • (LT) Lithuania: Intron a | Realdiron;
  • (LU) Luxembourg: Intron a;
  • (LV) Latvia: Intron a | Realdiron;
  • (MA) Morocco: Viraferon;
  • (MX) Mexico: Intron a | Lemeron | Urifron alfa 2-b;
  • (NL) Netherlands: Introna;
  • (NO) Norway: Introna;
  • (NZ) New Zealand: Intron a;
  • (PE) Peru: Bioferon | Intron a;
  • (PH) Philippines: Intron a | Uniferon;
  • (PK) Pakistan: Anferon | Bioferon | Blauferon B | Ceron Alpha | Heberon-alpha r | Inf | Intron a | Laifulong | Leveron | Uniferon;
  • (PL) Poland: Intron a;
  • (PR) Puerto Rico: Intron a;
  • (PT) Portugal: Introna;
  • (PY) Paraguay: Bioferon | Inf | Interferon alfa 2b fusa;
  • (RO) Romania: Intron a;
  • (RU) Russian Federation: Alfarona | Alpharona | Heberon alfa R | Interal p | Interferal | Interferon alfa 2b | Introna | Laferobion | Lifferon | Reaferon es | Realdiron | Recolin;
  • (SE) Sweden: Introna;
  • (SG) Singapore: Intron a;
  • (SI) Slovenia: Introna;
  • (SK) Slovakia: Intron a;
  • (TH) Thailand: Bioferon;
  • (TR) Turkey: Intron a | Introna;
  • (TW) Taiwan: Intron a;
  • (UA) Ukraine: Alfarekin | Alfiron | Bioferon | Introbion | Introna | Laferobion | Laferon | Realdiron;
  • (UY) Uruguay: Bioferon | Blauferon B | Interferon alfa 2b;
  • (VE) Venezuela, Bolivarian Republic of: Intron a;
  • (ZA) South Africa: Intron a
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