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
Avonex Side Effects, and Drug Interactions - Interferon beta-1a
Avonex Side Effects, and Drug Interactions - Interferon beta-1a
SIDE EFFECTS
The safety data describing the use of AVONEX® (Interferon
beta-1a) in multiple
sclerosis patients
are based on the placebo-controlled trial in which 158 patients
randomized to AVONEX® were treated for up to 2 years
(see CLINICAL STUDIES).
The five most common adverse events associated (at p £
0.075) with AVONEX® treatment
were flu-like symptoms (otherwise unspecified), muscle ache, fever,
chills and asthenia. The incidence
of all five adverse events diminished with continued treatment.
One patient in the placebo
group attempted suicide;
no AVONEX®-treated
patient attempted suicide. The incidence
of depression was
equal in the two treatment
groups. However, since depression
and suicide have been
reported with other interferon
products, AVONEX® should be used with caution in
patients with depression
(see WARNINGS).
In the placebo-controlled study, four patients receiving AVONEX®
experienced seizures, while no
seizures occurred in the placebo
group. Three of these four patients had no
prior history of seizure.
It is not known whether these events were related to the effects
of multiple sclerosis
alone, to AVONEX®, or to a combination of both (see
PRECAUTIONS).
Table 3 enumerates adverse events and selected laboratory
abnormalities that occurred at an incidence
of 2% or more among the 158 multiple
sclerosis patients treated with 30 mcg
of AVONEX® once weekly by IM injection. Reported
adverse events have been classified using standard COSTART terms.
Terms so general as to be uninformative and those events that were
equal in incidence
or more common in the placebo-treated patients have been excluded.
|
Table 3
Adverse Events and Selected Laboratory Abnormalities in
the Placebo-Controlled Study
|
|
Adverse Event
|
Placebo
(N = 143)
|
AVONEX®
(N = 158)
|
Body as a Whole |
|
| Headache |
57%
|
67%
|
| Flu-like symptoms (otherwise unspecified)* |
40%
|
61%
|
| Pain |
20%
|
24%
|
| Fever* |
13%
|
23%
|
| Asthenia |
13%
|
21%
|
| Chills* |
7%
|
21%
|
| Infection |
6%
|
11%
|
| Abdominal pain |
6%
|
9%
|
| Chest pain |
4%
|
6%
|
| Injection site
reaction |
1%
|
4%
|
| Malaise |
3%
|
4%
|
| Injection site
inflammation |
0%
|
3%
|
| Hypersensitivity reaction |
0%
|
3%
|
| Ovarian cyst |
0%
|
3%
|
| Cardiovascular System |
|
|
| Syncope |
2%
|
4%
|
| Vasodilation |
1%
|
4%
|
| Digestive System |
|
|
| Nausea |
23%
|
33%
|
| Diarrhea |
10%
|
16%
|
| Dyspepsia |
7%
|
11%
|
| Anorexia |
6%
|
7%
|
| Hemic and Lymphatic System |
|
|
| Anemia* |
3%
|
8%
|
| Eosinophils ³
10% |
4%
|
5%
|
| HCT (%) £ 32
(females) or £ 37 (males) |
1%
|
3%
|
| Ecchymosis injection
site |
1%
|
2%
|
| Metabolic and Nutritional Disorders |
|
|
| SGOT ³ 3 x ULN |
1%
|
3%
|
| Musculoskeletal System |
|
|
| Muscle ache* |
15%
|
34%
|
| Arthralgia |
5%
|
9%
|
| Nervous System |
|
|
| Sleep difficult |
16%
|
19%
|
| Dizziness |
13%
|
15%
|
| Muscle spasm |
6%
|
7%
|
| Suicidal tendency |
1%
|
4%
|
| Seizure |
0%
|
3%
|
| Speech disorder |
0%
|
3%
|
| Ataxia |
0%
|
2%
|
| Respiratory System |
|
|
| Upper respiratory
tract infection |
28%
|
31%
|
| Sinusitis |
17%
|
18%
|
| Dyspnea |
3%
|
6%
|
| Skin and Appendages |
|
|
| Urticaria |
2%
|
5%
|
| Alopecia |
1%
|
4%
|
| Nevus |
0%
|
3%
|
| Herpes zoster |
2%
|
3%
|
| Herpes simplex |
1%
|
2%
|
| Special Senses |
|
|
| Otitis media |
5%
|
6%
|
| Hearing decreased |
0%
|
3%
|
| Urogenital |
|
|
| Vaginitis |
2%
|
4%
|
| * Significantly associated with
AVONEX® treatment
(p £ 0.05). |
AVONEX® (Interferon beta-1a) has also been evaluated
in 290 patients with illnesses other than multiple
sclerosis. The majority of these patients were enrolled in studies
to evaluate AVONEX® treatment of chronic
viral hepatitis
B and C, in which the doses studied ranged from 15 mcg
to 75 mcg, given SC, 3 times a week, for up to 6 months. The incidence
of common adverse events in these studies was generally seen at
a frequency similar
to that seen in the placebo-controlled multiple sclerosis study.
In these non-multiple sclerosis
studies, inflammation at the site
of the SC injection
was seen in 52% of treated patients. In contrast, injection
site inflammation
was seen in 3% of multiple
sclerosis patients receiving AVONEX®, 30 mcg
by IM injection. Subcutaneous injections were also associated with
the following local reactions:
injection site necrosis,
injection site
atrophy, injection
site edema
and injection site hemorrhage.
None of the above was observed in the multiple sclerosis patients
participating in the placebo-controlled study.
Other events observed during premarket evaluation
of AVONEX®, administered either SC or IM in all patient
populations studied, are listed in the paragraph that follows. Because
most of the events were observed in open
and uncontrolled studies, the role
of AVONEX® in their causation cannot be reliably
determined.
Body as a Whole:abscess, ascites, cellulitis,
facial edema,
hernia, injection
site fibrosis,
injection site hypersensitivity,
lipoma, neoplasm, photosensitivity
reaction, sepsis, sinus
headache, toothache;
Cardiovascular System: arrhythmia,
arteritis, heart arrest, hemorrhage,
hypotension, palpitation,
pericarditis, peripheral
ischemia, peripheral
vascular disorder,
postural hypotension,
pulmonary embolus, spider
angioma, telangiectasia, vascular
disorder;
Digestive System: blood
in stool, colitis,
constipation, diverticulitis,
dry mouth, gallbladder
disorder, gastritis,
gastrointestinal
hemorrhage, gingivitis,
gum hemorrhage, hepatoma,
hepatomegaly, increased appetite, intestinal perforation, intestinal
obstruction, periodontal
abscess, periodontitis,
proctitis, thirst, tongue
disorder;
Endocrine System: hypothyroidism;
Hemic and Lymphatic System: coagulation time
increased, ecchymosis, lymphadenopathy, petechia;
Metabolic and Nutritional Disorders: abnormal healing, dehydration,
hypoglycemia, hypomagnesemia,
hypokalemia;
Musculoskeletal System: arthritis,
bone pain,
myasthenia, osteonecrosis, synovitis;
Nervous System: abnormal
gait, amnesia,
Bell's Palsy, clumsiness, depersonalization, drug
dependence, facial
paralysis, hyperesthesia,
increased libido, neurosis,
psychosis;
Respiratory System: emphysema, hemoptysis, hiccup,
hyperventilation,
laryngitis, pharyngeal
edema, pneumonia;
Skin and Appendages: basal
cell carcinoma,
blisters, cold clammy skin,
contact dermatitis,
erythema, furunculosis,
genital pruritus,
nevus, seborrhea, skin
ulcer, skin
discoloration;
Special Senses:abnormal vision, conjunctivitis,
earache, eye pain,
labyrinthitis, vitreous
floaters;
Urogenital: breast
fibroadenosis, breast
mass, dysuria, epididymitis,
fibrocystic change of the breast,
fibroids, gynecomastia,
hematuria, kidney
calculus, kidney pain,
leukorrhea, menopause,
nocturia, pelvic
inflammatory disease, penis
disorder, Peyronies Disease, polyuria,
postmenopausal
hemorrhage, prostatic disorder, pyelonephritis,
testis disorder, urethral
pain, urinary urgency,
urinary retention,
urinary incontinence,
vaginal hemorrhage.
Serum Neutralizing Activity
Throughout the placebo-controlled multiple
sclerosis study, serum
samples from patients were monitored for the development
of Interferon beta-1a neutralizing activity. During the study, 24%
of AVONEX®-treated patients were found to have serum
neutralizing activity
at one or more time points tested. Fifteen percent
of AVONEX®-treated patients tested positive
for neutralizing activity
at a level at which no placebo
patient tested positive. The significance of the appearance
of serum neutralizing
activity is unknown.
Drug Abuse and Dependence
There is no evidence
that abuse or dependence
occurs with AVONEX® (Interferon beta-1a) therapy.
However, the risk of dependence
has not been systematically evaluated.
DRUG INTERACTIONS
No formal drug interaction
studies have been conducted with AVONEX®. In
the placebo-controlled study, corticosteroids or ACTH
were administered for treatment
of exacerbations in some patients concurrently receiving AVONEX®.
In addition, some patients
receiving AVONEX® were also treated with anti-depressant
therapy and/or oral contraceptive
therapy. No unexpected adverse
events were associated with these concomitant
therapies.
Other interferons have been noted to reduce
cytochrome P-450
oxidase-mediated drug metabolism. Formal hepatic
drug metabolism
studies with AVONEX® in humans have not been conducted.
Hepatic microsomes isolated from AVONEX®-treated
rhesus monkeys showed no
influence of AVONEX® on hepatic P-450 enzyme
metabolism activity.
As with all interferon
products, proper monitoring of patients is required if AVONEX®
is given in combination with myelosuppressive agents.
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