Medical Editor: John P. Cunha, DO, FACOEP
Intron A (Interferon alfa-2b) is an alpha interferon made from human proteins used to treat hairy cell leukemia, malignant melanoma, follicular lymphoma, Kaposi's sarcoma caused by AIDS, certain types of genital warts, and chronic hepatitis B or C. Intron A is often used in combination with another drug called ribavirin (Rebetol). Common side effects of Intron A include injection site reactions (pain, swelling, redness, burning, bleeding, itching, or skin changes), diarrhea, upset stomach, loss of appetite, back pain, dizziness, spinning sensation, dry mouth, dry cough, sore throat, taste changes, nausea, vomiting, hair loss, tiredness, or itching or skin rash. Flu-like symptoms such as headache, tiredness, fever, chills, and muscle aches and pains may occur, especially when you first start Intron A. These side effects usually last about 1 day after the Intron A injection and improve or go away after a few weeks of continued use.
Intron A is given intramuscularly or subcutaneously under physician supervision. Dose is determined by the condition being treated, the patient's weight, and other factors. Intron A may interact with zidovudine, theophylline, or medicines used to prevent organ transplant rejection. Tell your doctor all medications you use. Intron A is not recommended for use during pregnancy due to possible harm to a fetus and the risk of serious side effects for the pregnant woman. Both males and females using this drug must use birth control (e.g., condoms, birth control pills) during treatment. Consult your doctor about birth control. It is unknown if this drug passes into breast milk. Consult your doctor before breastfeeding.
Our Intron A (Interferon alfa-2b) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.
Stop using interferon alfa-2b and call your doctor at once if you have a serious side effect such as:
- severe depression, aggressive behavior, or thoughts of hurting yourself or others;
- fast, slow, or uneven heart rate, feeling like you might pass out;
- fever, chills, body aches, flu symptoms, pale skin, easy bruising or bleeding, unusual weakness;
- vision or hearing problems;
- urinating less than usual or not at all;
- severe stomach pain, jaundice (yellowing of the skin or eyes);
- cough with yellow or green mucus, feeling short of breath;
- chest pain, pain spreading to the arm or shoulder, nausea, sweating, general ill feeling;
- sudden numbness or weakness, headache, confusion, or problems with speech or balance; or
- a severe blistering, peeling, and red skin rash.
Less serious side effects may include:
- dizziness, spinning sensation;
- muscle pain, tired feeling;
- nausea, vomiting, diarrhea, loss of appetite;
- dry mouth, dry cough, sore throat, hair loss;
- mild itching or skin rash; or
- burning, bleeding, pain, itching, or skin changes where the medicine was injected.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
Read the entire detailed patient monograph for Intron A (Interferon alfa-2b, Recombinant for Injection)
The adverse experiences listed below were reported to be possibly or probably related to INTRON® A therapy during clinical trials. Most of these adverse reactions were mild to moderate in severity and were manageable. Some were transient and most diminished with continued therapy.
The most frequently reported adverse reactions were “flu-like” symptoms, particularly fever, headache, chills, myalgia, and fatigue. More severe toxicities are observed generally at higher doses and may be difficult for patients to tolerate.
TREATMENT-RELATED ADVERSE EXPERIENCES BY INDICATION
Dosing Regimens Percentage (%) of Patients*
|Dosing Regimens Percentage (%) of Patients*|
|MALIGNANT MELANOMA||FOLLICULAR LYMPHOMA||HAIRY CELL LEUKEMIA||CONDYLOMATA ACUMINATA||AIDS- RELATED KAPOSI'S SARCOMA||CHRONIC HEPATITIS C||||CHRONIC HEPATITIS B|
|20 MIU/m² Induction (IV) 10 MIU/m² Maintenance (SC)||5 MIU TIW/SC||2 MIU/m² TIW/SC||1 MIU/lesion||30 MIU/m 2 TIW/S C||35 MIU QD/S C||3 MIU TIW||5 MIU QD||10 MIU TIW||6 MIU/m² TIW|
|ADVERSE EXPERIENCE||N=143||N=135||N=145||N=352||N=74||N=29||N= 183||N=101||N=78||N=116|
|injection site inflammation||--||1||--||--||--||--||5||3||--||--|
|other (≤5%)||burning, injection site bleeding, injection site pain, injection site reaction (5% in chronic hepatitis B pediatrics), itching|
|Blood Disorders (<5%)||anemia, anemia hypochromic, granulocytopenia, hemolytic anemia, leukopenia, lymphocytosis, neutropenia (9% in chronic hepatitis C, 14% in chronic hepatitis B pediatrics), thrombocytopenia (10% in chronic hepatitis C) (bleeding 8% in malignant melanoma), thrombocytopenia purpura|
|Body as a Whole|
|other (≤5%)||allergic reaction, cachexia, dehydration, earache, hernia, edema, hypercalcemia, hyperglycemia, hypothermia, inflammation
nonspecific, lymphadenitis, lymphadenopathy, mastitis, periorbital edema, poor peripheral circulation, peripheral edema (6% in follicular lymphoma), phlebitis superficial, scrotal/penile edema, thirst, weakness, weight increase
|Cardiovascular System Disorders (<5%)||angina, arrhythmia, atrial fibrillation, bradycardia, cardiac failure, cardiomegaly, cardiomyopathy, coronary artery disorder, extrasystoles, heart valve disorder, hematoma, hypertension (9% in chronic hepatitis C), hypotension, palpitations, phlebitis, postural hypotension, pulmonary embolism, Raynaud's disease, tachycardia, thrombosis, varicose vein|
|Endocrine System Disorders (<5%)||aggravation of diabetes mellitus, goiter, gynecomastia, hyperglycemia, hyperthyroidism, hypertriglyceridemia, hypothyroidism, virilism|
|other (<5%)||chest pain substernal, hyperthermia, rhinitis, rhinorrhea|
|Gastrointestinal System Disorders|
|other (<5%)||abdominal ascites, abdominal distension, colitis, dysphagia, eructation, esophagitis, flatulence, gallstones, gastric ulcer, gastritis,
gastroenteritis, gastrointestinal disorder (7% in follicular lymphoma), gastrointestinal hemorrhage, gastrointestinal mucosal discoloration, gingival bleeding, gum hyperplasia, halitosis, hemorrhoids, increased appetite, increased saliva, intestinal disorder, melena, mouth ulceration, mucositis, oral hemorrhage, oral leukoplakia, rectal bleeding after stool, rectal hemorrhage, stomatitis, stomatitis ulcerative, taste loss, tongue disorder, tooth disorder
|Liver and Biliary System Disorders (<5%)||abnormal hepatic function tests, biliary pain, bilirubinemia, hepatitis, increased lactate dehydrogenase, increased transaminases (SGOT/SGPT) (elevated SGOT 63% in malignant melanoma and 24% in follicular lymphoma), jaundice, right upper quadrant pain (15% in chronic hepatitis C), and very rarely, hepatic encephalopathy, hepatic failure, and death|
|Musculoskeletal System Disorders|
|other (<5%)||arteritis, arthritis, arthritis aggravated, arthrosis, bone disorder, bone pain, carpal tunnel syndrome, hyporeflexia, leg cramps, muscle atrophy, muscle weakness, polyarteritis nodosa, tendinitis, rheumatoid arthritis, spondylitis|
|Nervous System and Psychiatric Disorders|
|other (<5%)||abnormal coordination, abnormal dreaming, abnormal gait, abnormal thinking, aggravated depression, aggressive reaction, agitation (7% in chronic hepatitis B pediatrics), alcohol intolerance, apathy, aphasia, ataxia, Bell's palsy, CNS dysfunction, coma, convulsions, delirium, dysphonia, emotional lability, extrapyramidal disorder, feeling of ebriety, flushing, hearing disorder, hearing impairment, hot flashes, hyperesthesia, hyperkinesia, hypertonia, hypokinesia, impaired consciousness, labyrinthine disorder, loss of consciousness, manic depression, manic reaction, migraine, neuralgia, neuritis, neuropathy, neurosis, paresis, paroniria, parosmia, personality disorder, polyneuropathy, psychosis, speech disorder, stroke, suicidal ideation, suicide attempt, syncope, tinnitus, tremor, twitching, vertigo (8% in follicular lymphoma)|
|Reproduction System Disorders (<5%)||amenorrhea (12% in follicular lymphoma), dysmenorrhea, impotence, leukorrhea, menorrhagia, menstrual irregularity, pelvic pain, penis disorder, sexual dysfunction, uterine bleeding, vaginal dryness|
|Resistance Mechanism Disorders|
|other (<5%)||abscess, conjunctivitis, fungal infection, hemophilus, herpes zoster, infection, infection bacterial, infection nonspecific (7% in follicular
lymphoma), infection parasitic, otitis media, sepsis, stye, trichomonas, upper respiratory tract infection, viral infection (7% in chronic hepatitis C)
|Respiratory System Disorders|
|other (<5%)||asthma, bronchitis (10% in follicular lymphoma), bronchospasm, cyanosis, epistaxis (7% in chronic hepatitis B pediatrics), hemoptysis, hypoventilation, laryngitis, lung fibrosis, pleural effusion, orthopnea, pleural pain, pneumonia, pneumonitis, pneumothorax, rales, respiratory disorder, respiratory insufficiency, sneezing, tonsillitis, tracheitis, wheezing|
|Skin and Appendages Disorders|
|other (<5%)||abnormal hair texture, acne, cellulitis, cyanosis of the hand, cold and clammy skin, dermatitis lichenoides, eczema, epidermal necrolysis, erythema, erythema nodosum, folliculitis, furunculosis, increased hair growth, lacrimal gland disorder, lacrimation, lipoma, maculopapular rash, melanosis, nail disorders, nonherpetic cold sores, pallor, peripheral ischemia, photosensitivity, pruritus genital, psoriasis, psoriasis aggravated, purpura (5% in chronic hepatitis C), rash erythematous, sebaceous cyst, skin depigmentation, skin discoloration, skin nodule, urticaria, vitiligo|
|Urinary System Disorders (<5%)||albumin/protein in urine, cystitis, dysuria, hematuria, incontinence, increased BUN, micturition disorder, micturition frequency, nocturia, polyuria (10% in follicular lymphoma), renal insufficiency, urinary tract infection (5% in chronic hepatitis C)|
|Vision Disorders (<5%)||abnormal vision, blurred vision, diplopia, dry eyes, eye pain, nystagmus, photophobia|
|* Dash (--) indicates not
† Vomiting was reported with nausea as a single term
‡ Includes stomatitis/mucositis
§ Amnesia was reported with confusion as a single term
|| Percentages based upon a summary of all adverse events during 18 to 24 months of treatment
¶ Predominantly lethargy
Hairy Cell Leukemia
The INTRON A dose was modified because of adverse events in 65% (n=93) of the patients. INTRON A therapy was discontinued because of adverse events in 8% of the patients during induction and 18% of the patients during maintenance. The most frequently reported adverse reaction was fatigue, which was observed in 96% of patients. Other adverse reactions that were recorded in greater than 20% of INTRON A-treated patients included neutropenia (92%), fever (81%), myalgia (75%), anorexia (69%), vomiting/nausea (66%), increased SGOT (63%), headache (62%), chills (54%), depression (40%), diarrhea (35%), alopecia (29%), altered taste sensation (24%), dizziness/vertigo (23%), and anemia (22%).
Adverse reactions classified as severe or life threatening (ECOG Toxicity Criteria grade 3 or 4) were recorded in 66% and 14% of INTRON A-treated patients, respectively. Severe adverse reactions recorded in greater than 10% of INTRON A-treated patients included neutropenia/leukopenia (26%), fatigue (23%), fever (18%), myalgia (17%), headache (17%), chills (16%), and increased SGOT (14%). Grade 4 fatigue was recorded in 4% and grade 4 depression was recorded in 2% of INTRON A-treated patients. No other grade 4 AE was reported in more than 2 INTRON A-treated patients. Lethal hepatotoxicity occurred in 2 INTRON A-treated patients early in the clinical trial. No subsequent lethal hepatotoxicities were observed with adequate monitoring of liver function tests (see PRECAUTIONS, Laboratory Tests).
Ninety-six percent of patients treated with CHVP plus INTRON A therapy and 91% of patients treated with CHVP alone reported an adverse event of any severity. Asthenia, fever, neutropenia, increased hepatic enzymes, alopecia, headache, anorexia, “flu-like” symptoms, myalgia, dyspnea, thrombocytopenia, paresthesia, and polyuria occurred more frequently in the CHVP plus INTRON A-treated patients than in patients treated with CHVP alone. Adverse reactions classified as severe or life threatening (World Health Organization grade 3 or 4) recorded in greater than 5% of CHVP plus INTRON A-treated patients included neutropenia (34%), asthenia (10%), and vomiting (10%). The incidence of neutropenic infection was 6% in CHVP plus INTRON A versus 2% in CHVP alone. One patient in each treatment group required hospitalization.
Twenty-eight percent of CHVP plus INTRON A-treated patients had a temporary modification/interruption of their INTRON A therapy, but only 13 patients (10%) permanently stopped INTRON A therapy because of toxicity. There were four deaths on study; two patients committed suicide in the CHVP plus INTRON A arm and two patients in the CHVP arm had unwitnessed sudden death. Three patients with hepatitis B (one of whom also had alcoholic cirrhosis) developed hepatotoxicity leading to discontinuation of INTRON A. Other reasons for discontinuation included intolerable asthenia (5/135), severe flu symptoms (2/135), and one patient each with exacerbation of ankylosing spondylitis, psychosis, and decreased ejection fraction.
Eighty-eight percent (311/352) of patients treated with INTRON A for condylomata acuminata who were evaluable for safety reported an adverse reaction during treatment. The incidence of the adverse reactions reported increased when the number of treated lesions increased from one to five. All 40 patients who had five warts treated reported some type of adverse reaction during treatment.
Adverse reactions and abnormal laboratory test values reported by patients who were re-treated were qualitatively and quantitatively similar to those reported during the initial INTRON A treatment period.
AIDS-Related Kaposi's Sarcoma
In patients with AIDS-Related Kaposi's Sarcoma, some type of adverse reaction occurred in 100% of the 74 patients treated with 30 million IU/m² three times a week and in 97% of the 29 patients treated with 35 million IU per day.
Of these adverse reactions, those classified as severe (World Health Organization grade 3 or 4) were reported in 27% to 55% of patients. Severe adverse reactions in the 30 million IU/m² TIW study included: fatigue (20%), influenza-like symptoms (15%), anorexia (12%), dry mouth (4%), headache (4%), confusion (3%), fever (3%), myalgia (3%), and nausea and vomiting (1% each). Severe adverse reactions for patients who received the 35 million IU QD included: fever (24%), fatigue (17%), influenza-like symptoms (14%), dyspnea (14%), headache (10%), pharyngitis (7%), and ataxia, confusion, dysphagia, GI hemorrhage, abnormal hepatic function, increased SGOT, myalgia, cardiomyopathy, face edema, depression, emotional lability, suicide attempt, chest pain, and coughing (1 patient each). Overall, the incidence of severe toxicity was higher among patients who received the 35 million IU per day dose.
Chronic Hepatitis C
Two studies of extended treatment (18-24 months) with INTRON A show that approximately 95% of all patients treated experience some type of adverse event and that patients treated for extended duration continue to experience adverse events throughout treatment. Most adverse events reported are mild to moderate in severity. However, 29/152 (19%) of patients treated for 18 to 24 months experienced a serious adverse event compared to 11/163 (7%) of those treated for 6 months. Adverse events which occur or persist during extended treatment are similar in type and severity to those occurring during short-course therapy.
Of the patients achieving a complete response after 6 months of therapy, 12/79 (15%) subsequently discontinued INTRON A treatment during extended therapy because of adverse events, and 23/79 (29%) experienced severe adverse events (WHO grade 3 or 4) during extended therapy.
In patients using combination treatment with INTRON A and REBETOL, the primary toxicity observed was hemolytic anemia. Reductions in hemoglobin levels occurred within the first 1 to 2 weeks of therapy. Cardiac and pulmonary events associated with anemia occurred in approximately 10% of patients treated with INTRON A/REBETOL therapy. See REBETOL prescribing information for additional information.
Chronic Hepatitis C
In pediatric patients with chronic hepatitis C treated with INTRON A 3 MIU/m² three times weekly and REBETOL 15 mg/kg per day, all subjects (n=118) had at least one adverse event during 24-48 weeks of treatment, of which 80% were considered to be mild or moderate in severity. Six percent discontinued therapy due to adverse reactions and dose modifications were required in 30% of subjects, most commonly for anemia and neutropenia. Adverse events occurring in more than 50% of subjects included headache, fever, fatigue and anorexia. Adverse events occurring in 20-50% of subjects included influenza-like symptoms, abdominal pain, vomiting, nausea, myalgia, pharyngitis, diarrhea, viral infection, rigors, weight decrease, musculoskeletal pain, alopecia and dizziness. The most common laboratory test abnormalities were neutropenia (34%) and anemia (27%). Depression was reported in 13% (n=15) of children. Three of these subjects had suicidal ideation, and one attempted suicide. Weight loss and slowed growth are common in pediatric patients during combination therapy with INTRON A and REBETOL. Following treatment, rebound growth and weight gain occurred in most subjects. Long-term follow-up data in pediatric subjects, however, indicates that INTRON A in combination with REBETOL may induce a growth inhibition that results in reduced adult height in some patients (see PRECAUTIONS, Pediatric Use).
Chronic Hepatitis B
In patients with chronic hepatitis B, some type of adverse reaction occurred in 98% of the 101 patients treated at 5 million IU QD and 90% of the 78 patients treated at 10 million IU TIW. Most of these adverse reactions were mild to moderate in severity, were manageable, and were reversible following the end of therapy.
Adverse reactions classified as severe (causing a significant interference with normal daily activities or clinical state) were reported in 21% to 44% of patients. The severe adverse reactions reported most frequently were the “flu-like” symptoms of fever (28%), fatigue (15%), headache (5%), myalgia (4%), rigors (4%), and other severe “flulike” symptoms, which occurred in 1% to 3% of patients. Other severe adverse reactions occurring in more than one patient were alopecia (8%), anorexia (6%), depression (3%), nausea (3%), and vomiting (2%).
To manage side effects, the dose was reduced, or INTRON A therapy was interrupted in 25% to 38% of patients. Five percent of patients discontinued treatment due to adverse experiences.
Chronic Hepatitis B
In pediatric patients with chronic hepatitis B (n=72) during 16-24 weeks of treatment, the most frequently reported adverse events were those commonly associated with interferon treatment: flu-like symptoms (100%), gastrointestinal system disorders (46%), and nausea and vomiting (40%). Neutropenia (13%) and thrombocytopenia (3%) were also reported. None of the adverse events was life threatening and most were moderate to severe and resolved upon dose reduction or drug discontinuation.
ABNORMAL LABORATORY TEST VALUES BY INDICATION Dosing
Regimens Percentage (%) of Patients
|MALIGNANT MELANOMA||FOLLICULAR LYMPHOMA||HAIRY CELL LEUKEMIA||CONDYLOMATA ACUMINATA||AIDS-RELATED KAPOSI'S SARCOMA||CHRONIC HEPATITIS C||CHRONIC HEPATITIS B|
|20 MIU/m² Induction (IV) 10 MIU/m² Maintenance (SC)||5 MIU TIW/SC||2 MIU/m² TIW/SC||1 MIU/lesion||30 MIU/m² TIW/SC||35MIU QD/SC||3MIU TIW||5 MIU QD||10 MIU TIW||6 MIU/m² TIW|
|White Blood Cell Count||||||-||NA||17||10||22||26†||68†||34†||†|
|Serum Urea Nitrogen||12||4||0||-||-||-||-||2||0||2|
|NA - Not Applicable - Patients'
initial hematologic laboratory test values were abnormal due to their
* Decrease of ≥2 g/dL
** Decrease of ≥2 g/dL; 14% 2-<3 g/dL; 3% ≥3 g/dL
† Decrease to <3000/mm³
‡ Decrease to <70,000/mm³
§ Neutrophils plus bands
║ White Blood Cell Count was reported as neutropenia
¶Decrease of ≥2 g/dL; 20% 2-<3 g/dL; 6% ≥3 g/dL
The following adverse reactions have been identified during postapproval use of INTRON A alone or in combination with REBETOL. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Blood and Lymphatic System Disorders
pancytopenia (concurrent anemia, leukopenia, thrombocytopenia), aplastic anemia, pure red cell aplasia, thrombotic thrombocytopenic purpura, idiopathic thrombocytopenic purpura
Ear and Labyrinth Disorders
Vogt-Koyanagi-Harada syndrome, serous retinal detachment
General Disorders and Administration Site Conditions
asthenic conditions (including asthenia, malaise, fatigue)
Immune System Disorders
Infections and Infestations
Musculoskeletal and Connective Tissue Disorders
Nervous System Disorders
homicidal ideation, psychosis including hallucinations
Renal and Urinary Disorders
renal failure, renal insufficiency, nephrotic syndrome
Respiratory, Thoracic, and Mediastinal Disorders
Skin and Subcutaneous Tissue Disorders
Read the entire FDA prescribing information for Intron A (Interferon alfa-2b, Recombinant for Injection)
© Intron A Patient Information is supplied by Cerner Multum, Inc. and Intron A Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.