A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Infergen Side Effects, and Drug Interactions - Interferon alfacon-1
Infergen Side Effects, and Drug Interactions - Interferon alfacon-1
SIDE EFFECTS
Adverse experiences that were reported, regardless of attribution
to treatment, in at least 5% of the patients in the 9 mcg
Infergen or 3 million IU IFN alfa-2b groups of the pivotal study
are presented in Table 2, listed in decreasing order
by the 9 mcg Infergen group.
The incidence of adverse
events is expressed based on the number
of patients experiencing each event at least once during treatment
or post-treatment of the study.
Most adverse events were mild-to-moderate in severity and abated
with cessation of therapy. Flu-like symptoms (ie, headache,
fatigue, fever, rigors,
myalgia, sweating
increased, and arthralgia) were the most frequently reported treatment-related
adverse reactions. Most were short-lived and could be treated symptomatically.
Depression, usually mild-to-moderate in severity, was reported
in 26% of patients who received 9 mcg
Infergen and was the most common adverse event resulting in study
drug discontinuation.
In patients who had tolerated previous interferon
therapy and failed to
normalize ALT concentration
or who had achieved normalization
of ALT concentration during the treatment
period but who relapsed
during the post-treatment observation period, further treatment
with 15 mcg TIW of Infergen
for 24 weeks was generally tolerated (see Table 2). The higher dose
of Infergen used in these patients was associated with a greater
incidence of leukopenia
and granulocytopenia, and one or more dose
reductions for all causes were required in 33% of patients. Patients
who do not tolerate initial
standard interferon therapy
should not receive therapy
with 15 mcg TIW of Infergen.
|
Table 2. Patient Incidence of Adverse
Events in Phase 3 Clinical Trials Regardless of Attributiona
|
|
|
Initial Treatmentb
|
Subsequent Treatmentb
|
|
|
Infergen
9 mcg
(n = 231)
|
IFN alfa-2b
3 Million IU
(n = 236)
|
Infergen
15 mcg
(n = 165)
|
| Body System |
Preferred Term |
%
of Patients
|
%
of Patients
|
| APPLICATION SITE |
Injection Site
Erythema |
23
|
15
|
17
|
|
Injection Site
Pain |
9
|
3
|
8
|
|
Injection Site
Ecchymosis |
6
|
7
|
5
|
BODY AS
A WHOLE |
Body Pain |
54
|
45
|
39
|
|
Influenza-like Symptomsc |
15
|
11
|
8
|
|
Hot Flushes |
13
|
7
|
7
|
|
Pain Chest__
Non-cardiac |
13
|
14
|
5
|
|
Malaise |
11
|
10
|
2
|
|
Asthenia |
9
|
11
|
10
|
|
Edema Peripheral |
9
|
8
|
4
|
|
Access Pain |
8
|
9
|
1
|
|
Allergic Reaction |
7
|
5
|
3
|
|
Weight Decrease |
5
|
7
|
5
|
| CARDIOVASCULAR |
Hypertension |
5
|
3
|
2
|
|
Palpitation |
3
|
6
|
5
|
| CNS/PNS |
Insomnia |
39
|
30
|
24
|
|
Dizziness |
22
|
25
|
18
|
|
Paresthesia |
13
|
10
|
9
|
|
Amnesia |
10
|
6
|
2
|
|
Hypoesthesia |
10
|
8
|
8
|
|
Hypertonia |
7
|
10
|
6
|
|
Confusion |
4
|
6
|
4
|
|
Somnolence |
4
|
8
|
5
|
ENDOCRINE
DISORDERS |
Thyroid Test
Abnormal |
9
|
5
|
4
|
FLU-LIKE
SYMPTOMS |
Headache |
82
|
83
|
78
|
|
Fatigue |
69
|
67
|
65
|
|
Fever |
61
|
45
|
58
|
|
Myalgia |
58
|
56
|
51
|
|
Rigors |
57
|
45
|
62
|
|
Arthralgia |
51
|
45
|
43
|
|
Sweating Increased |
12
|
11
|
13
|
GASTRO-
INTESTINAL |
Abdominal Pain |
41
|
40
|
24
|
|
Nausea |
40
|
36
|
30
|
|
Diarrhea |
29
|
24
|
24
|
|
Anorexia |
24
|
17
|
21
|
|
Dyspepsia |
21
|
18
|
12
|
|
Vomiting |
12
|
11
|
13
|
|
Constipation |
9
|
6
|
5
|
|
Flatulence |
8
|
9
|
6
|
|
Tooth Ache |
7
|
7
|
3
|
|
Hemorrhoids |
6
|
3
|
1
|
|
Saliva Decreased |
6
|
7
|
4
|
HEARING__
VESTIBULAR |
Tinnitus |
6
|
4
|
4
|
|
Earache |
5
|
7
|
5
|
|
Otitis |
2
|
5
|
1
|
| HEMATOLOGIC |
Granulocytopenia |
23
|
25
|
42
|
|
Thrombocytopenia |
19
|
16
|
18
|
|
Leukopenia |
15
|
13
|
19
|
|
Ecchymosis |
6
|
4
|
4
|
|
Lymphadenopathy |
6
|
8
|
4
|
|
Lymphocytosis |
5
|
7
|
11
|
|
PT Increased |
3
|
5
|
1
|
LIVER AND
BILIARY |
Liver Tender |
5
|
3
|
5
|
|
Hepatomegaly |
3
|
5
|
5
|
METABOLIC__
NUTRITION |
Hypertriglyceridemia |
6
|
7
|
5
|
MUSCULO-
SKELETAL |
Back Pain |
42
|
37
|
29
|
|
Limb Pain |
26
|
25
|
13
|
|
Neck Pain |
14
|
13
|
8
|
|
Skeletal Pain |
14
|
14
|
10
|
|
Musculo-skeletal
Disorder |
4
|
4
|
7
|
PSYCHIATRIC
DISORDER |
Nervousness |
31
|
29
|
16
|
|
Depression |
26
|
25
|
18
|
|
Anxiety |
19
|
18
|
10
|
|
Emotional Lability |
12
|
11
|
6
|
|
Thinking Abnormal |
8
|
12
|
10
|
|
Agitation |
6
|
6
|
4
|
|
Libido Decreased |
5
|
5
|
5
|
REPRODUCTIVE__
FEMALE |
Dysmenorrhea |
9
|
9
|
2
|
|
Vaginitis |
8
|
2
|
5
|
|
Menstrual Disorder |
6
|
5
|
2
|
|
Moniliasis Genital |
2
|
6
|
2
|
|
Pain Breast |
0
|
5
|
2
|
RESISTANCE
MECHANISM |
Infection |
3
|
5
|
2
|
| RESPIRATORY |
Pharyngitis |
34
|
31
|
17
|
|
Infection Upper
Respiratory |
31
|
34
|
16
|
|
Cough |
22
|
17
|
12
|
|
Sinusitis |
17
|
22
|
12
|
|
Rhinitis |
13
|
16
|
7
|
|
Respiratory
Tract Congestion |
12
|
7
|
5
|
|
Upper Respiratory
Tract Congestion |
10
|
14
|
7
|
|
Epistaxis |
8
|
12
|
6
|
|
Dyspnea |
7
|
12
|
8
|
|
Bronchitis |
6
|
6
|
2
|
SKIN AND
APPENDAGES |
Alopecia |
14
|
25
|
10
|
|
Pruritus |
14
|
14
|
11
|
|
Rash |
13
|
15
|
13
|
|
Erythema |
6
|
6
|
6
|
|
Skin Dry |
6
|
5
|
2
|
|
Wound |
4
|
7
|
3
|
SPECIAL
SENSES |
Taste Perversion |
3
|
6
|
3
|
VISION
DISORDERS |
Conjunctivitis |
8
|
8
|
4
|
|
Eye Pain |
5
|
6
|
4
|
|
Vision Abnormal |
3
|
5
|
5
|
- a Only events that occurred
at a frequency
of ³ 5% in any
treatment
group are
included. Patients can appear more than once in Table
2. Because the two studies were conducted at different
times with nonidentical patient
groups, the adverse events profile
for the subsequent treatment study is not directly comparable
to the initial
treatment
study.
- b Adverse events reported
in patients during treatment
or post-treatment observation in the pivotal initial
treatment
and subsequent treatment studies are listed regardless
of attribution to treatment.
- c Influenza-like Symptoms:
presumed viral
etiology.
|
Laboratory Values
The following laboratory
variables were found to be affected by therapy with Infergen in
the 231 patients who received treatment
with 9 mcg Infergen.
Hemoglobin and Hematocrit: Treatment with Infergen
was associated with gradual decreases in mean
values for hemoglobin
and hematocrit, which
were 4% and 5% below baseline
at the end of treatment.
Decreases from baseline of 20% or more in hemoglobin
or hematocrit were
seen in 1% of patients or less.
White Blood Cells: Infergen treatment
was associated with decreases in mean
values for both total white
blood cell
(WBC) count and ANC
within the first 2 weeks of treatment. By the end
of treatment, mean
decreases from baseline
of 19% for WBCs and 23% for ANC
were observed. These effects reversed during the post-treatment
observation period. In two
Infergen-treated patients in the phase
3 trial, decreases in ANC
to levels below 500 x 106 cells/L were seen. In
both cases, the ANC returned
to clinically acceptable levels with reduction
of the dose of Infergen,
and these transient decreases in neutrophils were not associated
with infections.
Platelets: Infergen treatment
was associated with alterations in platelet
count. Decreases in mean
platelet count
of 16% compared to baseline were seen by the end
of treatment. These decreases were reversed during the post-treatment
observation period. Values below normal
were common during treatment
with 3% of patients developing values less than 50 x 109
cells/L, usually necessitating dose
reduction.
Triglycerides: Mean values for serum
triglyceride increased shortly after the start of administration
of Infergen, with increases of 41%, compared with baseline,
at the end of the treatment
period. Seven percent
of the patients developed values which were at least three times
above pretreatment levels during treatment. This effect
was promptly reversed after discontinuation of treatment.
Thyroid Function: Infergen treatment
was associated with biochemical changes consistent with hypothyroidism
including increases in TSH
and decreases in T4 mean
values. Increases in TSH
to greater than 7 mU/L were seen in 10% of 9 mcg
Infergen-treated patients either during the treatment period or
the 24-week post-treatment observation period. Thyroid supplements
were instituted in approximately one third of these patients.
Laboratory Values for Subsequent Treatment: From
a database of 165 patients receiving treatment
with 15 mcg of Infergen
after failing initial interferon
therapy, similar changes
in the laboratory
variables as outlined above were observed. However, mean
decreases from baseline of 23% for WBCs and 27% for ANC
were observed, which was greater than during initial treatment.
Reductions in WBCs and ANC
resulted in alteration of doses in 11 patients (7%). Two patients
experienced reversible
reductions in ANC to <
500 x 106 cells/L, which were not associated with infectious
complications. No patients
discontinued as a result of hematologic toxicity.
DRUG INTERACTIONS
No formal drug interaction
studies have been conducted with Infergen. Infergen should be used
cautiously in patients who are receiving agents that are known to
cause myelosuppression
or with agents known to be metabolized via the cytochrome
P-450 pathway.7 Patients taking drugs that are metabolized
by this pathway should
be monitored closely for changes in the therapeutic
and/or toxic levels of
concomitant drugs.
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