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Interferon Alfa-2b

Medically reviewed on September 10, 2018

Pronunciation

See also: Mavyret

(in ter FEER on AL fa too bee)

Index Terms

  • INF-alpha 2
  • Interferon Alpha-2b
  • rLFN-α2
  • α-2-interferon

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Injection:

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

Solution Reconstituted, Injection [preservative free]:

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

Brand Names: U.S.

  • Intron A

Pharmacologic Category

  • Antineoplastic Agent, Biological Response Modulator
  • Biological Response Modulator
  • Immunomodulator, Systemic
  • Interferon

Pharmacology

Binds to a specific receptor on the cell membrane to initiate intracellular activity; multiple effects can be detected including induction of gene transcription. 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

Distribution

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

Metabolism

Primarily renal, filtered and absorbed at the renal tubule

Time to Peak

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

Half-Life Elimination

IV: ~2 hours; IM, SubQ: ~2 to 3 hours

Use: Labeled Indications

AIDS-related Kaposi sarcoma: Treatment of patients 18 years and older with AIDS-related Kaposi sarcoma

Chronic hepatitis B: Treatment of chronic hepatitis B in patients 1 year and older with compensated liver disease

Chronic hepatitis C: Treatment of chronic hepatitis C in patients 18 years and older with compensated liver disease who have a history of blood or blood-product exposure and/or are hepatitis C virus (HCV) antibody-positive; in combination with ribavirin for treatment of chronic hepatitis C in patients 3 years and older with compensated liver disease previously untreated with alpha interferon therapy and in patients 18 years and older who have relapsed following alpha interferon therapy. Note: Interferon-containing regimens are no longer recommended in the HCV treatment guidelines (AASLD/IDSA 2017).

Condylomata acuminata: Treatment of patients 18 years and older with condylomata acuminata involving external surfaces of the genital and perianal areas

Follicular lymphoma: Initial treatment of clinically aggressive follicular non-Hodgkin lymphoma in conjunction with anthracycline-containing combination chemotherapy in patients 18 years and older

Hairy cell leukemia: Treatment of patients 18 years and older with hairy cell leukemia

Melanoma (malignant): Adjuvant to surgical treatment in patients 18 years and older with malignant melanoma who are free of disease but at high risk for systemic recurrence, within 56 days of surgery

Off Label Uses

Polycythemia vera

Pegylated or conventional interferon alfa has been recommended as first- or second-line treatment for younger patients (younger than 75 years) with polycythemia vera in multiple guidelines. It may also be considered as the drug of choice in pregnant women who are at high risk of polycythemia vera complications. Patients prescribed interferon alfa should be monitored for signs and symptoms of depression, suicidal ideation, and infection.

Additional Off-Label Uses

Chronic myelogenous leukemia (CML); Cutaneous T-cell lymphoma; Cutaneous ulcerations of Behçet's disease; Desmoid tumor; Hepatitis D; Multiple myeloma; Neuroendocrine tumors (including carcinoid syndrome and islet cell tumor); Non-Hodgkin lymphomas (other than follicular lymphoma, see approved use); Renal cell carcinoma; West Nile virus

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 women who are pregnant, in males with pregnant partners; in patients with hemoglobinopathies (eg, thalassemia major, sickle-cell anemia); creatinine clearance <50 mL/minute; or hypersensitivity to ribavirin or any component of the formulation

Documentation of allergenic cross-reactivity for interferons is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

Dosing: Adult

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.

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

Lymphoma (follicular): SubQ: 5 million units 3 times weekly for up to 18 months

Malignant melanoma: 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 weekly for 48 weeks

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

Chronic hepatitis B: IM, SubQ: 5 million units daily or 10 million units 3 times weekly for 16 weeks

Chronic hepatitis C: IM, SubQ: 3 million units 3 times weekly. In patients with normalization of ALT at 16 weeks, continue treatment (if tolerated) for 18 to 24 months; consider discontinuation if normalization does not occur at 16 weeks. Note: Interferon-containing regimens are no longer recommended in the HCV treatment guidelines (AASLD/IDSA 2017).

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

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

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.

Chronic hepatitis B (including HIV coinfection): SubQ: Children and Adolescents 1 to 17 years: 3 million units/m2/dose 3 times weekly for 1 week, followed by 6 million units/m2/dose 3 times weekly (maximum: 10 million units per dose); total duration of therapy 16 to 24 weeks. Note: In HIV-exposed/-positive patients, higher doses (off-label dose) may be used for retreatment of failed lower-dose therapy: 10 million units/m2/dose 3 times weekly for 6 months (HHS [OI pediatric 2016]).

Chronic hepatitis C with HIV coinfection: Note: Interferon-free therapies are generally preferred in the treatment of hepatitis C (AASLD/IDSA 2017; WHO 2016). IM, SubQ: Children and Adolescents 3 to 17 years: 3 million units/m2/dose 3 times weekly with ribavirin

Dosing: Renal Impairment

Renal impairment at treatment initiation: 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.

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

Dosing: Hepatic Impairment

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.

Malignant melanoma (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

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

Chronic hepatitis C: Severe toxicity: Reduce dose by 50% or temporarily withhold until subsides; permanently discontinue for persistent toxicities after dosage reduction.

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.

Malignant melanoma (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.

Reconstitution

Powder for injection: The manufacturer recommends reconstituting vial with the diluent provided (SWFI). When reconstituted with SWFI 1 mL, the 10 million unit vial concentration is 10 million units/mL, the 18 million unit vial concentration is 18 million units/mL, and the 50 million unit vial concentration is 50 million units/mL. Swirl gently. To prepare solution for infusion, further dilute appropriate dose in NS 100 mL. Final concentration should be ≥10 million units/100 mL.

Administration

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.

Storage

Store intact vials under refrigeration at 2°C to 8°C (36°F to 46°F); do not freeze. After reconstitution of powder for injection, product should be used immediately, but may be stored under refrigeration for ≤24 hours.

Drug Interactions

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. Consider therapy modification

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

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

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

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

Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Avoid combination

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

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

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

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

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

Telbivudine: Interferon Alfa-2b may enhance the adverse/toxic effect of Telbivudine. Specifically, the risk for peripheral neuropathy may be increased. Avoid combination

Theophylline Derivatives: Interferons may decrease the metabolism of Theophylline Derivatives. Exceptions: Dyphylline. 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. Consider therapy modification

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

Adverse Reactions

>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%), tendonitis (<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

ALERT: U.S. Boxed Warning

Neuropsychiatric disorders:

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

Autoimmune disorders:

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

Ischemic disorders:

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

Infectious disorders:

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

Warnings/Precautions

Concerns related to adverse effects:

• Bone marrow suppression: 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: Commonly associated with fever and flu-like symptoms; rule out other causes/infections with persistent fever. Use with caution in patients with debilitating conditions.

• Gastrointestinal toxicity: 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.

• Hepatic effects: May cause hepatotoxicity (including fatality); monitor closely if abnormal liver function tests 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]).

• 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: Has 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 elderly patients, 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 being 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 AIDS-related Kaposi sarcoma patients), and/or 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: 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, COPD).

• Thyroid disorders: Use with caution in patients with preexisting thyroid disease; thyroid disorders (hyper- or hypothyroidism) have been reported. TSH 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. Do not use combination therapy with ribavirin in patients with creatinine clearance <50 mL/minute.

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

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.

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

Chronic hepatitis C:

CBC with differential and platelets: Baseline, weeks 1 and 2, then monthly

Liver function: Every 3 months

TSH: Baseline and periodically during treatment; in patients with pre-existing thyroid disorders also repeat at 3 months and 6 months

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

Malignant melanoma: CBC with differential and platelets and liver function tests: Weekly during induction phase, then monthly during maintenance

Oncology patients: 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

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). The Health and Human Services (HHS) Perinatal HIV Guidelines recommend against the use of interferon-alfa during pregnancy because of its antigrowth and antiproliferative effects (HHS [perinatal] 2017).

Treatment of hepatitis C is not currently recommended to treat maternal infection or to decrease the risk of mother-to-child transmission during pregnancy (Tran 2016). HCV-infected females of childbearing potential should consider postponing pregnancy until therapy is complete to reduce the risk of HCV transmission (AASLD/IDSA 2017).

Animal reproduction studies have demonstrated abortifacient effects. Disruption of the normal menstrual cycle was also observed in animal studies; therefore, the manufacturer recommends that reliable contraception is used in females of childbearing potential.

Use in combination with ribavirin is contraindicated in pregnant females or males whose female partners are pregnant. All warnings related to the use of ribavirin and pregnancy and/or contraception should be followed. Refer to the ribavirin monograph for additional information.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience weight loss, fatigue, nausea, vomiting, injection site irritation, dry mouth, diarrhea, lack of appetite, hair loss, insomnia, change in taste, constipation, or flu-like symptoms. Have patient report immediately to prescriber signs of a severe pulmonary disorder (lung or breathing problems like difficulty breathing, shortness of breath, or a cough that is new or worse), signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or jaundice), signs of high blood sugar (confusion, fatigue, increased thirst, increased hunger, polyuria, flushing, fast breathing, or breath that smells like fruit), signs of depression (suicidal ideation, anxiety, emotional instability, confusion), hallucination, psychosis, forceful actions, signs of infection, signs of pancreatitis (severe abdominal pain, severe back pain, severe nausea, or vomiting), signs of thyroid problems (change in weight without trying, anxiety, agitation, feeling very weak, hair thinning, depression, neck swelling, difficulty focusing, inability handling heat or cold, menstrual changes, tremors, or sweating), signs of severe cerebrovascular disease (change in strength on one side is greater than the other, difficulty speaking or thinking, change in balance, or vision changes), signs of bleeding (vomiting blood or vomit that looks like coffee grounds; coughing up blood; hematuria; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any severe or persistent bleeding), severe loss of strength and energy, severe dizziness, passing out, abnormal heartbeat, confusion, angina, tachycardia, shortness of breath, excessive weight gain, swelling of arms of legs, severe headache, severe abdominal pain, burning or numbness feeling, memory impairment, abnormal gait, urinary retention, change in amount of urine passed, anxiety, teeth or gingival changes, vision changes, or blindness (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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