ADVERSE REACTIONS
Except where indicated, the data described below reflect exposure to ERBITUX in 774 patients with advanced metastatic colorectal cancer. ERBITUX was studied in combination with irinotecan (n=354) or as monotherapy (n=420). Patients receiving ERBITUX plus irinotecan received a median of 12 doses (with 88/354 [25%] treated for over 6 months), and patients receiving ERBITUX monotherapy received a median of 7 doses (with 36/420 [9%] treated for over 6 months). The population had a median age of 59 and was 59% male and 91% Caucasian. The range of dosing for patients receiving ERBITUX plus irinotecan was 1-84 infusions, and the range of dosing for patients receiving ERBITUX monotherapy was 1-63 infusions.
The most serious adverse reactions associated with ERBITUX were:
-
Infusion reaction (3%) (see BOX WARNING, WARNINGS, and DOSAGE AND ADMINISTRATION: Dose Modifications);
-
Dermatologic toxicity (1%) (see WARNINGS and DOSAGE AND ADMINISTRATION: Dose Modifications);
-
Interstitial lung disease (0.4%) (see WARNINGS);
-
Fever (5%);
-
Sepsis (3%);
-
Kidney failure (2%);
-
Pulmonary embolus (1%);
-
Dehydration (5%) in patients receiving ERBITUX plus irinotecan, 0.2% in patients receiving ERBITUX monotherapy;
-
Diarrhea (6%) in patients receiving ERBITUX plus irinotecan, 0.2% in patients receiving ERBITUX monotherapy.
Thirty-seven (10%) patients receiving ERBITUX plus irinotecan and 17 (4%) patients receiving ERBITUX monotherapy discontinued treatment primarily because of adverse events.
The most common adverse events seen in 354 patients receiving ERBITUX plus irinotecan were acneform rash (88%), asthenia/malaise (73%), diarrhea (72%), nausea (55%), abdominal pain (45%), and vomiting (41%).
The most common adverse events seen in 420 patients receiving ERBITUX monotherapy were acneform rash (90%), asthenia/malaise (48%), nausea (29%), fever (27%), constipation (26%), abdominal pain (26%), headache (26%), and diarrhea (25%).
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The adverse reaction information from clinical trials does, however, provide a basis for identifying the adverse events that appear to be related to drug use and for approximating rates.
Data in patients with advanced colorectal carcinoma in Table 3 are based on the experience of 354 patients treated with ERBITUX plus irinotecan and 420 patients treated with ERBITUX monotherapy.
Table 3: Incidence of Adverse Events (>/=10%) in Patients with Advanced Colorectal Carcinoma
|
|
ERBITUX plus Irinotecan (n=354) |
ERBITUX Monotherapy (n=420) |
| Body System |
Grades 1 - 4
|
Grades 3 and 4
|
Grades 1 - 4
|
Grades 3 and 4
|
|
Preferred Term 1 |
% of Patients
|
| Body as a Whole |
|
|
|
|
|
Asthenia/Malaise 2 |
73
|
16
|
48
|
10
|
|
Abdominal Pain
|
45
|
8
|
26
|
9
|
|
Fever 3 |
34
|
4
|
26
|
<1
|
|
Pain
|
23
|
6
|
17
|
5
|
|
Infusion Reaction 4 |
19
|
3
|
21
|
2
|
|
Infection
|
16
|
1
|
14
|
1
|
|
Back Pain
|
16
|
3
|
10
|
2
|
|
Headache
|
14
|
2
|
16
|
2
|
| Digestive |
|
|
|
|
|
Diarrhea
|
72
|
22
|
25
|
2
|
|
Nausea
|
55
|
6
|
29
|
2
|
|
Vomiting
|
41
|
7
|
25
|
3
|
|
Anorexia
|
36
|
4
|
23
|
2
|
|
Constipation
|
30
|
2
|
26
|
2
|
|
Stomatitis
|
26
|
2
|
10
|
<1
|
|
Dyspepsia
|
14
|
0
|
6
|
0
|
| Hematic/Lymphatic |
|
|
|
|
|
Leukopenia
|
25
|
17
|
<1
|
0
|
|
Anemia
|
16
|
5
|
9
|
3
|
| Metabolic/Nutritional |
|
|
|
|
|
Weight Loss
|
21
|
0
|
7
|
1
|
|
Peripheral Edema
|
16
|
1
|
10
|
1
|
|
Dehydration
|
15
|
6
|
10
|
3
|
| Nervous |
|
|
|
|
|
Insomnia
|
12
|
0
|
10
|
<1
|
|
Depression
|
10
|
0
|
7
|
0
|
| Respiratory |
|
|
|
|
|
Dyspnea 3 |
23
|
2
|
17
|
7
|
|
Cough Increased
|
20
|
0
|
11
|
1
|
| Skin/Appendages |
|
|
|
|
|
Acneform Rash 5 |
88
|
14
|
90
|
8
|
|
Alopecia
|
21
|
0
|
4
|
0
|
|
Skin Disorder
|
15
|
1
|
4
|
0
|
|
Nail Disorder
|
12
|
<1
|
16
|
<1
|
|
Pruritus
|
10
|
1
|
11
|
<1
|
|
Conjunctivitis
|
14
|
1
|
7
|
<1
|
| 1 Adverse events that occurred (toxicity Grades 1 through 4) in >/=10% of patients with refractory colorectal carcinoma treated with ERBITUX plus irinotecan or in >/=10% of patients with refractory colorectal carcinoma treated with ERBITUX monotherapy. |
| 2 Asthenia/malaise is defined as any event described as "asthenia", "malaise", or "somnolence".
|
| 3 Includes cases reported as infusion reaction.
|
| 4 Infusion reaction is defined as any event described at any time during the clinical study as "allergic reaction" or "anaphylactoid reaction", or any event occurring on the first day of dosing described as "allergic reaction", "anaphylactoid reaction", "fever", "chills", "chills and fever", or "dyspnea".
|
| 5 Acneform rash is defined as any event described as "acne", "rash", "maculopapular rash", "pustular rash", "dry skin", or "exfoliative dermatitis".
|
|
INFUSION REACTIONS (SEE BOX WARNING: INFUSION REACTIONS.)
In clinical trials, severe, potentially fatal infusion reactions were reported. These events include the rapid onset of airway obstruction (bronchospasm, stridor, hoarseness), urticaria, and/or hypotension. In studies in advanced colorectal cancer, severe infusion reactions were observed in 3% of patients receiving ERBITUX plus irinotecan and 2% of patients receiving ERBITUX monotherapy. Grade 1 and 2 infusion reactions, including chills, fever, and dyspnea usually occurring on the first day of initial dosing, were observed in 16% of patients receiving ERBITUX plus irinotecan and 19% of patients receiving ERBITUX monotherapy. (See WARNINGS: Infusion Reactions and DOSAGE AND ADMINISTRATION: Dose Modifications.)
In the clinical studies described above, a 20-mg test dose was administered intravenously over 10 minutes prior to the loading dose to all patients. The test dose did not reliably identify patients at risk for severe allergic reactions.
DERMATOLOGIC TOXICITY AND RELATED DISORDERS
Non-suppurative acneform rash described as "acne", "rash", "maculopapular rash", "pustular rash", "dry skin", or "exfoliative dermatitis" was observed in patients receiving ERBITUX (Cetuximab) plus irinotecan or ERBITUX monotherapy. One or more of the dermatological adverse events were reported in 88% (14% Grade 3) of patients receiving ERBITUX plus irinotecan and in 90% (8% Grade 3) of patients receiving ERBITUX monotherapy. Acneform rash most commonly occurred on the face, upper chest, and back, but could extend to the extremities and was characterized by multiple follicular- or pustular-appearing lesions. Skin drying and fissuring were common in some instances, and were associated with inflammatory and infectious sequelae (eg, blepharitis, cellulitis, cyst). Two cases of S. aureus sepsis were reported. The onset of acneform rash was generally within the first two weeks of therapy. Although in a majority of the patients the event resolved following cessation of treatment, in nearly half of the cases, the event continued beyond 28 days. (See WARNINGS: Dermatologic Toxicity and DOSAGE AND ADMINISTRATION: Dose Modifications.)
A related nail disorder, occurring in 14% of patients (0.4% Grade 3), was characterized as a paronychial inflammation with associated swelling of the lateral nail folds of the toes and fingers, with the great toes and thumbs as the most commonly affected digits.
USE WITH RADIATION THERAPY
In a study of 21 patients with locally advanced squamous cell cancer of the head and neck, patients treated with ERBITUX, cisplatin, and radiation had a 95% incidence of rash (19% Grade 3). The incidence and severity of cutaneous reactions with combined modality therapy appears to be additive, particularly within the radiation port. The addition of radiation to ERBITUX therapy in patients with colorectal cancer should be done with appropriate caution.
|
REPORTS OF SUSPECTED ERBITUX SIDE EFFECTS / ADVERSE REACTIONS
Below is a sample of reports where side effects / adverse reactions may be related to Erbitux. The information is not vetted and should not be considered as verified clinical evidence.
Possible Erbitux side effects / adverse reactions in 72 year old male
Reported by a consumer/non-health professional from Germany on 2011-10-02
Patient: 72 year old male
Reactions: Hyperbilirubinaemia, Presyncope, Pyrexia, Neutropenia
Adverse event resulted in: hospitalization
Suspect drug(s):
Erbitux
Other drugs received by patient: Irinotecan HCL; Lederfoline; Lenograstim; Aldactone; Fluorouracil
Possible Erbitux side effects / adverse reactions in 57 year old male
Reported by a health professional (non-physician/pharmacist) from United States on 2011-10-03
Patient: 57 year old male weighing 81.0 kg (178.2 pounds)
Reactions: Stomatitis, Oral Pain, Dehydration
Adverse event resulted in: hospitalization
Suspect drug(s):
Cisplatin
Dosage: last dose on 12jun2007 also delayed for 7 days
Indication: Head and Neck Cancer
Start date: 2007-06-12
Erbitux
Dosage: last dose on 26jun2007 1271.5mg
Indication: Head and Neck Cancer
Start date: 2007-06-26
Possible Erbitux side effects / adverse reactions in 49 year old female
Reported by a health professional (non-physician/pharmacist) from United States on 2011-10-03
Patient: 49 year old female
Reactions: Oesophageal Pain, Vomiting, Dysphonia, Oesophagitis
Adverse event resulted in: hospitalization
Suspect drug(s):
Erbitux
Indication: non-Small Cell Lung Cancer
Start date: 2011-07-25
End date: 2011-08-29
Taxol
Indication: non-Small Cell Lung Cancer
Start date: 2011-07-25
End date: 2011-08-29
Carboplatin
Indication: non-Small Cell Lung Cancer
Start date: 2011-07-25
End date: 2011-08-29
Doxycycline
|
