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Intron A (Interferon Alfa-2B (Recombinant)) - Side Effects and Adverse Reactions

 
 



ADVERSE REACTIONS

General

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 PatientsDash (- -) indicates not reported
MALIGNANT MELANOMAFOLLICULAR LYMPHOMAHAIRY CELL LEUKEMIACONDYLOMATA ACUMINATAAIDS-RELATED KAPOSI'S SARCOMACHRONIC HEPATITIS CPercentages based upon a summary of all adverse events during 18 to 24 months of treatmentCHRONIC HEPATITIS B
AdultsPediatrics
20 MIU/m2 Induction (IV)
10 MIU/m2 Maintenance (SC)
5 MIU TIW/SC2 MIU/m2 TIW/SC1 MIU/lesion30 MIU/m2 TIW/SC35 MIU QD/SC3 MIU TIW5 MIU QD10 MIU TIW6 MIU/m2 TIW
ADVERSE EXPERIENCEN=143N=135N=145N=352N=74N=29N=183N=101N=78N=116
Application-Site Disorders20
  injection site   inflammation- -1- -- -- -- -53- -- -
  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
  facial edema- -1- -<1- -10<131<1
  weight   decrease313<1<15310253
  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
Flu-like Symptoms
  fever81566856475534668694
  headache62213947362143614457
  chills54- -4645- -- -- -- -- -- -
  myalgia75163944342843594027
  fatigue9686118844823756971
  increased sweating613824214113
  asthenia- -637- -11- -405155
  rigors27- -- -301416384230
  arthralgia6889- -31619815
  dizziness23- -129724913108
  influenza-like symptoms101837- -4579265- -<1
  back pain- -1519613- -- -- -- -
  dry mouth1219- -2228565- -
  chest pain28<1<112844- -- -
  malaise6- -- -145- -13963
  pain (unspecified)15918333- -- -- -- -
  other (<5%)chest pain substernal, hyperthermia, rhinitis, rhinorrhea
Gastrointestinal System Disorders
  diarrhea351918218451319812
  anorexia6921191384114435343
  nausea66242117282119503318
  taste alteration24213<157210- -- -
  abdominal pain220<51521165423
  loose stools- -1- -<1- -1022- -2
  vomitingVomiting was reported with nausea as a single term32621114871027
  constipation114<1- -11045- -2
  gingivitis2 1 7- -- -- -14- -1- -- -
  dyspepsia- -2- -24- -7383
  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
  musculoskeletal pain- -18- -- -- -- -219110
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
  depression40963928191764
  paresthesia131361321563<1
  impaired concentration- -1- -<13143853
  amnesiaAmnesia was reported with confusion as a single term1<5- -- -14- -- -- -- -
  confusion82<5412101- -- -2
  hypoesthesia- -1<51- -10- -- -- -- -
  irritability11- -- -- -- -13161222
  somnolence12<533- -33Predominantly lethargy1495
  anxiety195<11352- -3
  insomnia54- -<133121168
  nervousness11- -1- -323- -3
  decreased libido11<5- -- -- -151- -
  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
  moniliasis- -1- -<1- -17- -- -- -- -
  herpes simplex12- -1- -315- -- -
  other (<5%)abscess, conjunctivitis, fungal infection, hemophilus, herpes zoster, infection, infection bacterial, infection nonspecific (7% follicular lymphoma), infection parasitic, otitis media, sepsis, stye, trichomonas, upper respiratory tract infection, viral infection (7% in chronic hepatitis C)
Respiratory System Disorders
  dyspnea1514<1- -13435- -- -
  coughing613<1- -- -3114- -5
  pharyngitis28<511313717
  sinusitis14- -- -- -212- -- -- -
  nonproductive coughing27- -- -- -1401- -- -
  nasal congestion17- -1- -10<14- -- -
  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
  dermatitis1- -8- -- -- -21- -- -
  alopecia29238- -123128263817
  pruritus- -101117- -9643
  rash191325- -9105815
  dry skin139- -91043- -<1
  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

1 Includes stomatitis/mucositis

Hairy Cell Leukemia

The adverse reactions most frequently reported during clinical trials in 145 patients with hairy cell leukemia were the "flu-like" symptoms of fever (68%), fatigue (61%), and chills (46%).

Malignant Melanoma

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 >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 >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).

Follicular Lymphoma

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 >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 vs 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 4 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.

Condylomata Acuminata

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 retreated 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 to 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 package insert for additional information.

Chronic Hepatitis B

Adults

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 "flu-like" 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.

Pediatrics

In pediatric patients, 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 were life-threatening. The majority were moderate to severe and resolved upon dose reduction or drug discontinuation.

Abnormal Laboratory Test Values by Indication
Dosing Regimens
Percentage (%) of Patients
MALIGNANT MELANOMAFOLLICULAR LYMPHOMAHAIRY CELL LEUKEMIACONDYLOMATA ACUMINATAAIDS-RELATED KAPOSI'S SARCOMACHRONIC HEPATITIS CCHRONIC HEPATITIS B
AdultsPediatrics
20 MIU/m2 Induction (IV)
10 MIU/m2 Maintenance (SC)
5 MIU
TIW/SC
2 MIU/m2
TIW/SC
1 MIU/lesion30 MIU/m2
TIW/SC
35 MIU
QD/SC
3 MIU
TIW
5 MIU
QD
10 MIU
TIW
6 MIU/m2
TIW
LABORATORY TESTSN=143N=135N=145N=352N=69–73N=26–28N=140–171N=96–101N=75–103N=113–115
NA - Not Applicable- Patients' initial hematologic laboratory test values were abnormal due to their condition.
Hemoglobin228NA- -11526Decrease of ≥2 g/dL; 20% 2–<3 g/dL; 6% ≥3 g/dL32 1 2317Decrease of ≥2 g/dL; 14% 2–<3 g/dL; 3% ≥3 g/dL
White Blood Cell CountWhite Blood Cell Count was reported as neutropenia- -NA17102226 2 68349
Platelet Count1513NA- -0815 3 1251
Serum Creatinine320- -- -- -6303
Alkaline Phosphatase13- -4- -- -- -- -840
Lactate Dehydrogenase1- -0- -- -- -- -- -- -- -
Serum Urea Nitrogen1240- -- -- -- -202
SGOT63244121141- -- -- -- -
SGPT2- -13- -1015- -- -- -- -
Granulocyte Count
  • Total
9236NA- -313945 4 756170
  • 1000–<1500/mm3
66- -- -- -- -- -32303243
  • 750–<1000/mm3
- -21- -- -- -- -10241818
  • 500–<750/mm3
25- -- -- -- -- -11797
  • <500/mm3
113- -- -- -- -2422

1 Decrease of ≥2 g/dL
2 Decrease to <3000/mm3
3 Decrease to <70,000/mm3
4 Neutrophils plus bands

Postmarketing Experience

The following adverse reactions have been identified during postapproval use of INTRON A: nephrotic syndrome, renal failure, renal insufficiency, pancreatitis, psychosis including hallucinations, Stevens Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, injection site necrosis, myositis, and hearing loss. A wide variety of autoimmune and immune-mediated disorders have been reported with alpha interferons including idiopathic thrombocytopenic purpura and thrombotic thrombocytopenic purpura. Additionally, the following adverse reactions have been identified during postapproval use of INTRON A alone or in combination with REBETOL: aplastic anemia and pure red cell aplasia. Sarcoidosis or exacerbation of sarcoidosis has been reported. 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.



REPORTS OF SUSPECTED INTRON A SIDE EFFECTS / ADVERSE REACTIONS

Below is a sample of reports where side effects / adverse reactions may be related to Intron A. The information is not vetted and should not be considered as verified clinical evidence.

Possible Intron A side effects / adverse reactions in 51 year old female

Reported by a health professional (non-physician/pharmacist) from United States on 2011-10-04

Patient: 51 year old female

Reactions: Pancreatitis Acute, Chills, Hyperhidrosis, Pallor, Pancreatitis Necrotising, Glomerulonephritis, Obesity, Chest Pain, Gastrooesophageal Reflux Disease, Renal Failure Acute, Refusal of Treatment by Patient, Type 2 Diabetes Mellitus, Blood Triglycerides Decreased, Hyponatraemia, Haemodialysis, Heart Rate Decreased, Skin Neoplasm Excision, Hypertension, Sleep Apnoea Syndrome, Influenza Like Illness

Adverse event resulted in: hospitalization, disablity

Suspect drug(s):
Intron A
    Dosage: iv; iv
    Indication: Malignant Melanoma Stage III
    Start date: 2011-03-28
    End date: 2011-04-01

Intron A
    Dosage: iv; iv
    Indication: Malignant Melanoma Stage III
    Start date: 2011-03-21
    End date: 2011-03-25

Decadron

Other drugs received by patient: Compazine; Hydrochlorothiazide; Aspirin; Percocet; Norvasc



Possible Intron A side effects / adverse reactions in 43 year old female

Reported by a individual with unspecified qualification from United States on 2011-10-05

Patient: 43 year old female

Reactions: Procedural Pain, Renal Disorder, Cardiac Murmur, Impaired Work Ability, Ascites, Haematuria Traumatic, Anxiety, Malaise, Mental Disorder, Depression, Thrombocytopenia, Chronic Hepatic Failure, Fluid Retention

Adverse event resulted in: hospitalization

Suspect drug(s):
Intron A
    Dosage: 10 mg;qw;
    Indication: Hepatitis C
    Start date: 2006-01-01
    End date: 2006-01-01

Pegasys
    Indication: Product Used FOR Unknown Indication

Other drugs received by patient: Ambien; Tylenol-500; Quinine; Spironolactone; Ursodiol; Fluoxetine; Ciprofloxacin



Possible Intron A side effects / adverse reactions in 47 year old female

Reported by a physician from Sweden on 2011-10-24

Patient: 47 year old female

Reactions: Paraparesis

Suspect drug(s):
Intron A



See index of all Intron A side effect reports >>

Drug label data at the top of this Page last updated: 2008-05-22

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