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PEG-Intron (Peginterferon Alfa-2B) - Side Effects and Adverse Reactions

 
 



ADVERSE REACTIONS

Nearly all study patients in clinical trials experienced one or more adverse events. In the PEG monotherapy trial the incidence of serious adverse events was similar (about 12%) in all treatment groups. In the PEG-Intron/REBETOL combination trial the incidence of serious adverse events was 17% in the PEG-Intron/REBETOL groups compared to 14% in the INTRON A/REBETOL group.

In many but not all cases, adverse events resolved after dose reduction or discontinuation of therapy. Some patients experienced ongoing or new serious adverse events during the 6-month follow-up period. In the PEG-Intron/REBETOL trial 13 patients experienced life-threatening psychiatric events (suicidal ideation or attempt) and one patient accomplished suicide.

There have been five patient deaths which occurred in clinical trials: one suicide in a patient receiving PEG-Intron monotherapy and one suicide in a patient receiving PEG-Intron/REBETOL combination therapy; two deaths among patients receiving INTRON A monotherapy (1 murder/suicide and 1 sudden death) and one patient death in the INTRON A/REBETOL group (motor vehicle accident).

Overall 10-14% of patients receiving PEG-Intron, alone or in combination with REBETOL, discontinued therapy compared with 6% treated with INTRON A alone and 13% treated with INTRON A in combination with REBETOL. The most common reasons for discontinuation of therapy were related to psychiatric, systemic (e.g. fatigue, headache), or gastrointestinal adverse events.

In the combination therapy trial, dose reductions due to adverse reactions occurred in 42% of patients receiving PEG-Intron (1.5 µg/kg)/REBETOL and in 34% of those receiving INTRON A/REBETOL. The majority of patients (57%) weighing 60 kg or less receiving PEG-Intron (1.5 µg/kg)/REBETOL required dose reduction. Reduction of interferon was dose related (PEG-Intron 1.5 µg/kg >PEG-Intron 0.5 µg/kg or INTRON A), 40%, 27%, 28%, respectively. Dose reduction for REBETOL was similar across all three groups, 33-35%. The most common reasons for dose modifications were neutropenia (18%), or anemia (9%). (see Laboratory Values). Other common reasons included depression, fatigue, nausea, and thrombocytopenia.

In the PEG-Intron/REBETOL combination trial the most common adverse events were psychiatric which occurred among 77% of patients and included most commonly depression, irritability, and insomnia, each reported by approximately 30-40% of subjects in all treatment groups. Suicidal behavior (ideation, attempts, and suicides) occurred in 2% of all patients during treatment or during follow-up after treatment cessation (see WARNINGS).

PEG-Intron induced fatigue or headache in approximately two-thirds of patients, and induced fever or rigors in approximately half of the patients. The severity of some of these systemic symptoms (e.g. fever and headache) tended to decrease as treatment continues. The incidence tends to be higher with PEG-Intron than with INTRON A therapy alone or in combination with REBETOL.

Application site inflammation and reaction (e.g. bruise, itchiness, irritation) occurred at approximately twice the incidence with PEG-Intron therapies (in up to 75% of patients) compared with INTRON A. However injection site pain was infrequent (2-3%) in all groups.

Other common adverse events in the PEG-Intron/REBETOL group included myalgia (56%), arthralgia (34%), nausea (43%), anorexia (32%), weight loss (29%), alopecia (36%), and pruritus (29%).

In the PEG-Intron monotherapy trial the incidence of severe adverse events was 13% in the INTRON A group and 17% in the PEG-Intron groups. In the PEG-Intron/REBETOL combination therapy trial the incidence of severe adverse events was 23% in the INTRON A/REBETOL group and 31-34% in the PEG-Intron/REBETOL groups. The incidence of life-threatening adverse events was </=1% across all groups in the monotherapy and combination therapy trials.

Adverse events that occurred in the clinical trial at >5% incidence are provided in Table 3 by treatment group. Due to potential differences in ascertainment procedures, adverse event rate comparisons across studies should not be made.

TABLE 3. Adverse Events Occurring in >5% of Patients
Percentage of Patients Reporting Adverse Events *
Study 1 Study 2
Adverse Events PEG-Intron
1.0 µg/kg (n=297)
INTRON A
3 MIU (n=303)
PEG-Intron
1.5 µg/kg/
REBETOL (n=511)
INTRON A/
REBETOL (n=505)
Application Site
   Injection Site                  
   Inflammation/Reaction 47 20 75 49
Autonomic Nervous Sys.
   Mouth Dry   6   7 12   8
   Sweating Increased   6   7 11   7
   Flushing   6   3   4   3
Body as a Whole
   Fatigue/Asthenia 52 54 66 63
   Headache 56 52 62 58
   Rigors 23 19 48 41
   Fever 22 12 46 33
   Weight Decrease 11 13 29 20
   RUQ Pain   8   8 12   6
   Chest Pain   6   4   8   7
   Malaise   7   6   4   6
Central/Periph. Nerv. Sys.
   Dizziness 12 10 21 17
Endocrine Disorders
   Hypothyroidism   5   3   5   4
Gastrointestinal
   Nausea 26 20 43 33
   Anorexia 20 17 32 27
   Diarrhea 18 16 22 17
   Vomiting   7   6 14 12
   Abdominal Pain 15 11 13 13
   Dyspepsia   6   7   9   8
   Constipation   1   3   5   5
Hematologic Disorders
   Neutropenia   6   2 26 14
   Anemia   0   0 12 17
   Leukopenia <1   0   6   5
   Thrombocytopenia   7 <1   5   2
Liver and Biliary System
   Hepatomegaly   6   5   4   4
Musculoskeletal
   Myalgia 54 53 56 50
   Arthralgia 23 27 34 28
   Musculoskeletal Pain 28 22 21 19
Psychiatric
   Insomnia 23 23 40 41
   Depression 29 25 31 34
   Anxiety/Emotional Lability/Irritability 28 34 47 47
   Concentration Impaired 10   8 17 21
   Agitation   2   2   8   5
   Nervousness   4   3   6   6
Reproductive, Female
   Menstrual Disorder   4   3   7   6
Resistance Mechanism
   Infection Viral 11 10 12 12
   Infection Fungal <1   3   6   1
Respiratory System
   Dyspnea   4   2 26 24
   Coughing   8   5 23 16
   Pharyngitis 10   7 12 13
   Rhinitis   2   2   8   6
   Sinusitis   7   7   6   5
Skin and Appendages
   Alopecia 22 22 36 32
   Pruritus 12   8 29 28
   Rash   6   7 24 23
   Skin Dry 11   9 24 23
Special Senses Other,
   Taste Perversion <1   2   9   4
Vision Disorders
   Vision blurred   2   3   5   6
   Conjunctivitis   4   2   4   5
* Patients reporting one or more adverse events. A patient may have reported more than one adverse event within a body system/organ class category.

Many patients continued to experience adverse events several months after discontinuation of therapy. By the end of the 6-month follow-up period the incidence of ongoing adverse events by body class in the PEG-Intron 1.5/REBETOL group was 33% (psychiatric), 20% (musculoskeletal), and 10% (for endocrine and for GI). In approximately 10-15% of patients weight loss, fatigue and headache had not resolved.

Individual serious adverse events occurred at a frequency </=1% and included suicide attempt, suicidal ideation, severe depression; psychosis, aggressive reaction, relapse of drug addiction/overdose; nerve palsy (facial, oculomotor); cardiomyopathy, myocardial infarction, angina, pericardial effusion, retinal ischemia, retinal artery or vein thrombosis, blindness, decreased visual acuity, optic neuritis, transient ischemic attack, supraventricular arrhythmias, loss of consciousness; neutropenia, infection (sepsis, pneumonia, abscess, cellulitis); emphysema, bronchiolitis obliterans, pleural effusion, gastroenteritis, pancreatitis, gout, hyperglycemia, hyperthyroidism and hypothyroidism, autoimmune thrombocytopenia with or without purpura, rheumatoid arthritis, interstitial nephritis, lupus-like syndrome, sarcoidosis, aggravated psoriasis; urticaria, injection-site necrosis, vasculitis, phototoxicity.

LABORATORY VALUES

Changes in selected laboratory values during treatment with PEG-Intron alone or in combination with REBETOL treatment are described below. Decreases in hemoglobin, neutrophils, and platelets may require dose reduction or permanent discontinuation from therapy. (See DOSAGE AND ADMINISTRATION - Dose Reduction)

Hemoglobin.    REBETOL induced a decrease in hemoglobin levels in approximately two thirds of patients. Hemoglobin levels decreased to <11 g/dL in about 30% of patients. Severe anemia (<8 g/dL) occurred in <1% of patients. Dose modification was required in 9 and 13% of patients in the PEG-Intron/REBETOL and INTRON A/REBETOL groups. Hemoglobin levels become stable by treatment week 4-6 on average. Hemoglobin levels return to baseline between 4 and 12 weeks posttreatment. In the PEG-Intron monotherapy trial hemoglobin decreases were generally mild and dose modifications were rarely necessary. (See DOSAGE AND ADMINISTRATION: Dose Reduction).

Neutrophils.    Decreases in neutrophil counts were observed in a majority of patients treated with PEG-Intron alone (70%) or as combination therapy with REBETOL (85%) and INTRON A/REBETOL (60%). Severe potentially life-threatening neutropenia (<0.5 × 109/L) occurred in 1% of patients treated with PEG-Intron monotherapy, 2% of patients treated with INTRON A/REBETOL and in 4% of patients treated with PEG-Intron/REBETOL. Two percent of patients receiving PEG-Intron monotherapy and 18% of patients receiving PEG-Intron/REBETOL required modification of interferon dosage. Few patients (</=1%) required permanent discontinuation of treatment. Neutrophil counts generally return to pre-treatment levels within 4 weeks of cessation of therapy. (See DOSAGE AND ADMINISTRATION: Dose Reduction).

Platelets.    Platelet counts decrease in approximately 20% of patients treated with PEG-Intron alone or with REBETOL and in 6% of patients treated with INTRON A/REBETOL. Severe decreases in platelet counts (<50,000/mm3) occur in <1% of patients. Patients may require discontinuation or dose modification as a result of platelet decreases. (See DOSAGE AND ADMINISTRATION: Dose Reduction). In the PEG-Intron/REBETOL combination therapy trial 1% or 3% of patients required dose modification of INTRON A or PEG-Intron respectively. Platelet counts generally returned to pretreatment levels within 4 weeks of the cessation of therapy.

Thyroid Function.    Development of TSH abnormalities, with and without clinical manifestations, are associated with interferon therapies. Clinically apparent thyroid disorders occur among patients treated with either INTRON A or PEG-Intron (with or without REBETOL) at a similar incidence (5% for hypothyroidism and 3% for hyperthyroidism). Subjects developed new onset TSH abnormalities while on treatment and during the follow-up period. At the end of the follow-up period 7% of subjects still had abnormal TSH values.

Bilirubin and uric acid.    In the PEG-Intron/REBETOL trial 10-14% of patients developed hyperbilirubinemia and 33-38% developed hyperuricemia in association with hemolysis. Six patients developed mild to moderate gout.

POSTMARKETING EXPERIENCE

The following adverse reactions have been identified and reported during post-approval use of PEG-Intron therapy: seizures, hearing impairment, hearing loss, and peripheral neuropathy, cardiac ischemia, rhabdomyolysis, stomatitis, vertigo, renal insufficiency, renal failure, Stevens Johnson Syndrome, toxic epidermal necrolysis, and erythema multiforme. Because the reports of these reactions are voluntary and the population of uncertain size, it is not always possible to reliably estimate the frequency of the reaction or establish a causal relationship to drug exposure.

Immunogenicity:    Approximately 2% of patients receiving PEG-Intron (32/1759) or INTRON A (11/728) with or without REBETOL developed low-titer (</=160) neutralizing antibodies to PEG-Intron or INTRON A. The clinical and pathological significance of the appearance of serum neutralizing antibodies is unknown. No apparent correlation of antibody development to clinical response or adverse events was observed. The incidence of post-treatment binding antibody ranged from 8 to 15 percent. The data reflect the percentage of patients whose test results were considered positive for antibodies to PEG-Intron in a Biacore assay that is used to measure binding antibodies, and in an antiviral neutralization assay, which measures serum-neutralizing antibodies. The percentage of patients whose test results were considered positive for antibodies is highly dependent on the sensitivity and specificity of the assays. Additionally the observed incidence of antibody positivity in these assays may be influenced by several factors including sample timing and handling, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to PEG-Intron with the incidence of antibodies to other products may be misleading.



REPORTS OF SUSPECTED PEG-INTRON SIDE EFFECTS / ADVERSE REACTIONS

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

Possible PEG-Intron side effects / adverse reactions in 62 year old female

Reported by a consumer/non-health professional from United States on 2011-10-03

Patient: 62 year old female

Reactions: LIP Swelling, Pruritus, Wrong Technique in Drug Usage Process, Skin Exfoliation, Tongue Haemorrhage, Loss of Consciousness, Pharyngeal Haemorrhage, Dizziness, Blister, Dyspnoea, Stomatitis, Gingival Bleeding, Mouth Haemorrhage, Tongue DRY, Anxiety, Syncope, Oral Pain, Eye Swelling

Suspect drug(s):
PEG-Intron
    Indication: Product Used FOR Unknown Indication

Rebetol
    Indication: Product Used FOR Unknown Indication

Victrelis
    Dosage: 800 mg;tid;po
    Administration route: Oral
    Indication: Hepatitis C
    Start date: 2011-09-01

Other drugs received by patient: Neurontin; Maxalt; Carisoprodol; Zantac; Ambien; Boniva; Synthroid; Protonix; Zoloft; Naproxen



Possible PEG-Intron side effects / adverse reactions in 65 year old female

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

Patient: 65 year old female

Reactions: Weight Decreased, White Blood Cell Count Decreased, Dyspnoea, Fatigue, Cystitis, Fall

Adverse event resulted in: hospitalization

Suspect drug(s):
Ribavirin
    Indication: Hepatitis C
    Start date: 2011-08-01

PEG-Intron
    Indication: Hepatitis C
    Start date: 2011-08-01



Possible PEG-Intron side effects / adverse reactions in 56 year old male

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

Patient: 56 year old male weighing 88.0 kg (193.6 pounds)

Reactions: Drug Interaction, DRY Skin, Sinus Bradycardia, Cardiac Disorder, Long QT Syndrome, Palpitations, International Normalised Ratio Decreased, Chest Pain, Hypertension, Skin Warm, Oxygen Saturation Decreased, Influenza Like Illness

Adverse event resulted in: hospitalization

Suspect drug(s):
PEG-Intron
    Dosage: 150 mg;qw
    Indication: Product Used FOR Unknown Indication
    Start date: 2011-08-10

Amitriptyline HCL
    Indication: Product Used FOR Unknown Indication
    End date: 2011-08-10

Ribavirin
    Dosage: 600 mg;bid;po
    Administration route: Oral
    Indication: Product Used FOR Unknown Indication
    Start date: 2011-08-09

PEG-Intron
    Indication: Product Used FOR Unknown Indication
    Start date: 2011-08-09
    End date: 2011-08-09

Trazodone Hydrochloride
    Indication: Product Used FOR Unknown Indication
    End date: 2011-08-10

Other drugs received by patient: Colace; Metoprolol Tartrate; Lovenox; Oxycontin; Nexium



See index of all PEG-Intron side effect reports >>

Drug label data at the top of this Page last updated: 2006-08-16

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