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
Zoladex Side Effects, and Drug Interactions - Goserelin
Zoladex Side Effects, and Drug Interactions - Goserelin
SIDE EFFECTS
General: Rarely, hypersensitivity reactions (including urticaria
and anaphylaxis) have been reported in patients receiving ZOLADEX.
Males: ZOLADEX has been found to be generally well tolerated
in clinical trials.
Adverse reactions reported in these trials were rarely severe enough
to result in the patients' withdrawal from ZOLADEX treatment. As
seen with other hormonal therapies, the most commonly observed adverse
events during ZOLADEX therapy
were due to the expected physiological
effects from decreased testosterone
levels. These included hot
flashes, sexual dysfunction,
and decreased erections.
Initially, ZOLADEX, like other LHRH agonists, causes transient
increases in serum levels
of testosterone. A small percentage of patients experienced a temporary
worsening of signs and symptoms (see WARNINGS
section), usually manifested by an increase in cancer-related pain
which was managed symptomatically. Isolated cases of exacerbation
of disease symptoms,
either ureteral obstruction
or spinal cord
compression, occurred at similar rates in controlled clinical
trials with both ZOLADEX and orchiectomy. The relationship of these
events to therapy is
uncertain.
In the controlled clinical
trials of ZOLADEX versus orchiectomy, the following events were
reported as adverse reactions in greater than 5% of the patients.
TREATMENT RECEIVED
|
ADVERSE EVENT
|
ZOLADEX
(n=242)
% |
ORCHIECTOMY
(n=254)
% |
| Hot Flashes |
62 |
53 |
| Sexual Dysfunction |
21 |
15 |
| Decreased Erections |
18 |
16 |
| Lower Urinary Tract Symptoms |
13 |
8 |
| Lethargy |
8 |
4 |
| Pain (worsened in the first 30
days) |
8 |
3 |
| Edema |
7 |
8 |
| Upper Respiratory Infection |
7 |
2 |
| Rash |
6 |
1 |
| Sweating |
6 |
4 |
| Anorexia |
5 |
2 |
| Chronic Obstructive Pulmonary
Disease |
5 |
3 |
| Congestive Heart Failure |
5 |
1 |
| Dizziness |
5 |
4 |
| Insomnia |
5 |
1 |
| Nausea |
5 |
2 |
| Complications of Surgery |
0 |
18† |
| †Complications related
to surgery were
reported in 18% of the orchiectomy
patients, while only 3% of ZOLADEX patients reported adverse
reactions at the injection site. The surgical
complications included scrotal infection
(5.9%), groin pain (4.7%), wound
see page (3.1%), scrotal hematoma
(2.8%), incisional discomfort (1.6%), and skin
necrosis (1.2%). |
The following additional adverse reactions were reported in greater
than 1% but less than 5% of the patients treated with ZOLADEX:
- CARDIOVASCULAR - arrhythmia,
cerebrovascular accident, hypertension,
myocardial infarction,
peripheral vascular
disorder, chest pain;
- CENTRAL NERVOUS SYSTEM - anxiety,
depression, headache;
- GASTROINTESTINAL - constipation,
diarrhea, ulcer, vomiting;
- HEMATOLOGIC - anemia;
- METABOLIC/NUTRITIONAL - gout,
hyperglycemia, weight increase;
- MISCELLANEOUS - chills, fever;
- UROGENITAL - renal
insufficiency, urinary obstruction, urinary
tract infection,
breast swelling
and tenderness.
Stage B2-C Prostatic Carcinoma: Treatment with ZOLADEX and
flutamide did not add substantially
to the toxicity of radiation
treatment alone. The
following adverse experiences were reported during a multicenter
clinical trial comparing
ZOLADEX + flutamide + radiation versus radiation
alone. The most frequently reported (greater than 5%) adverse experiences
are listed below.
ADVERSE
EVENTS DURING ACUTE RADIATION THERAPY
(within first 90 days of radiation
therapy) |
|
(n=231)
flutamide + ZOLADEX
+ Radiation
% All |
(n=235)
Radiation Only
% All |
| Rectum/Large Bowel |
80 |
76 |
| Bladder |
58 |
60 |
| Skin |
37 |
37 |
|
|
|
ADVERSE
EVENTS DURING LATE RADIATION THERAPY
(within first 90 days of radiation
therapy) |
|
(n=231)
flutamide + ZOLADEX
+ Radiation
% All |
(n=235)
Radiation Only
% All |
| Diarrhea |
36 |
40 |
| Cystitis |
16 |
16 |
| Rectal Bleeding |
14 |
20 |
| Proctitis |
8 |
8 |
| Hematuria |
7 |
12 |
|
Additional adverse event
data was collected for the combination therapy with radiation
group over both
the hormonal treatment
and hormonal treatment plus radiation
phases of the study. Adverse experiences occurring in more
than 5% of patients in this group, over both parts of the
study, were hot
flashes (46%), diarrhea
(40%), nausea
(9%), and skin
rash (8%).
|
Females: As would be expected with a drug
that results in hypoestrogenism, the most frequently reported adverse
reactions were those related to this effect.
Endometriosis: In
controlled clinical trials comparing ZOLADEX every 28 days and danazol
daily for the treatment of endometriosis,
the following events were reported at a frequency of 5% or greater:
| TREATMENT RECEIVED |
| ADVERSE EVENT |
ZOLADEX
(n=411)
% |
DANAZOL
(n=207)
% |
| Hot Flushes |
96 |
67 |
| Vaginitis |
75 |
43 |
| Headache |
75 |
63 |
| Emotional Lability |
60 |
56 |
| Libido Decreased |
61 |
44 |
| Sweating |
45 |
30 |
| Depression |
54 |
48 |
| Acne |
42 |
55 |
| Breast Atrophy |
33 |
42 |
| Seborrhea |
26 |
52 |
| Peripheral Edema |
21 |
34 |
| Breast Enlargement |
18 |
15 |
| Pelvic Symptoms |
18 |
23 |
| Pain |
17 |
16 |
| Dyspareunia |
14 |
5 |
| Libido Increased |
12 |
19 |
| Infection |
13 |
11 |
| Asthenia |
11 |
13 |
| Nausea |
8 |
14 |
| Hirsutism |
7 |
15 |
| Insomnia |
11 |
4 |
| Breast Pain |
7 |
4 |
| Abdominal Pain |
7 |
7 |
| Back Pain |
7 |
13 |
| Flu Syndrome |
5 |
5 |
| Dizziness |
6 |
4 |
| Application Site Reaction |
6 |
- |
| Voice Alterations |
3 |
8 |
| Pharyngitis |
5 |
2 |
| Hair Disorders |
4 |
11 |
| Myalgia |
3 |
11 |
| Nervousness |
3 |
5 |
| Weight Gain |
3 |
23 |
| Leg Cramps |
2 |
6 |
| Increased Appetite |
2 |
5 |
| Pruritus |
2 |
6 |
| Hypertonia |
1 |
10 |
The following adverse events not already listed above were reported
at a frequency of
1% or greater, regardless of causality, in ZOLADEX-treated women
from all clinical trials:
- WHOLE BODY - allergic
reaction, chest pain,
fever, malaise;
- CARDIOVASCULAR - hemorrhage,
hypertension, migraine, palpitations, tachycardia;
- DIGESTIVE - anorexia,
constipation, diarrhea, dry mouth,
dyspepsia, flatulence;
- HEMATOLOGIC - ecchymosis;
- METABOLIC AND NUTRITIONAL - edema;
- MUSCULOSKELETAL - arthralgia,
joint disorder;
- CNS - anxiety, paresthesia,
somnolence, thinking abnormal;
- RESPIRATORY - bronchitis,
cough increased, epistaxis,
rhinitis, sinusitis;
- SKIN - alopecia,
dry skin, rash,
skin discoloration;
- SPECIAL SENSES - amblyopia,
dry eyes;
- UROGENITAL - dysmenorrhea,
urinary frequency, urinary
tract infection,
vaginal hemorrhage.
Hormone Replacement Therapy: Clinical studies suggest the
addition of Hormone
Replacement Therapy (estrogens and/pr progestins) to ZOLADEX may
decrease the occurrence of vasomotor symptoms and vaginal
dryness associated with hypoestrogenism without compromising the
efficacy of ZOLADEX
in relieving pelvic symptoms.
The optimal drugs, dose and duration
of treatment has not
been established.
Changes in Bone Mineral Density: After 6 months of ZOLADEX
treatment, 109 female
patients treated with ZOLADEX showed an average
4.3% decrease of vertebral
trabecular bone
mineral density (BMD)
as compared to pretreatment
values. BMD was measured by dual-photon absorptiometry or dual energy
x-ray absorptiometry. Sixty-six of these patients were assessed
for BMD loss 6 months after
the completion (posttherapy) of the 6-month therapy
period. Data from these patients showed an average 2.4% BMD loss
compared to pretreatment
values. Twenty-eight of the 109 patients were assessed for BMD at
12 months posttherapy. Data from these patients showed an average
decrease of 2.5% in BMD compared to pretreatment values. These data
suggest a possibility of partial reversibility. Clinical studies
suggest the addition
of Hormone Replacement Therapy (estrogens and/or progestins) to
ZOLADEX is effective in reducing the bone
mineral loss which occrrs with ZOLADEX alone without compromising
the efficacy of ZOLADEX in relieving the symptoms of endometriosis.
The optimal drugs, dose and duration
of treatment has not
been established.
Changes in Laboratory Values During Treatment
Plasma Enzymes: Elevations of liver enzymes (AST, ALT) have
been reported in female
patients exposed to ZOLADEX (representing less than 1% of all patients).
Lipids: In a controlled
trial, ZOLADEX therapy
resulted in a minor, but statistically significant
effect on serum lipids.
In patients treated for endometriosis
at 6 months following initiation of therapy,
danazol treatment
resulted in a mean increase
in LDL cholesterol
of 33.3 mg/dL and a decrease in HDL
cholesterol of 21.3
mg/dL compared to increases of 21.3 and 2.7 mg/dL in LDL
cholesterol and
HDL cholesterol,
respectively, for ZOLADEX-treated patients. Triglycerides increased
by 8.0 mg/dL in ZOLADEX-treated patients compared to a decrease
of 8.9 mg/dL in danazol-treated patients.
In patients treated for endometriosis, ZOLADEX increased total
cholesterol and
LDL cholesterol
during 6 months of treatment. However, ZOLADEX therapy
resulted in HDL cholesterol
levels which were significantly higher relative to danazol
therapy. At the end of 6
months of treatment,
HDL cholesterol
fractions (HDL2 and HDL3) were decreased by
13.5 and 7.7 mg/dL, respectively, for danazol-treated patients compared
to treatment increases
of 1.9 and 0.8 mg/dL, respectively, for ZOLADEX treated patients.
Breast Cancer: The adverse event profile for women with
advanced breast cancer
treated with ZOLADEX is consistent with the profile
described above for women treated with ZOLADEX for endometriosis.
In a controlled clinical
trial (SWOG-8692) comparing ZOLADEX with oophorectomy in premenopausal
and perimenopausal women with advanced breast
cancer, the following events were reported at a frequency
of 5% or greater in either treatment group
regardless of causality.
TREATMENT RECEIVED
|
ADVERSE EVENT
|
ZOLADEX
(n=57)
% of Pts.
|
OOPHORECTOMY
(n=55)
% of Pts.
|
| Hot Flashes |
70
|
47
|
| Tumor Flare |
23
|
4
|
| Nausea |
11
|
7
|
| Edema |
5
|
0
|
| Malaise/Fatigue/Lethargy |
5
|
2
|
| Vomiting |
4
|
7
|
In the Phase II clinical
trial program in 333 pre- and perimenopausal women with advanced
breast cancer,
hot flashes were reported
in 75.9% of patients and decreased libido
was noted in 47.7% of patients. These two adverse events reflect
the pharmacological actions of ZOLADEX.
Injection site reactions
were reported in less than 1% of patients.
Endometrial Thinning: The following adverse events were
reported at a frequency
of 5% or greater in premenopausal women presenting with dysfunctional
uterine bleeding
in Trial 0022 for endometrial thinning. These results indicate that
headache, hot
flushes and sweating
were more common in the ZOLADEX group
than in the placebo group.
ADVERSE EVENTS REPORTED AT A FREQUENCY OF
5% OR GREATER IN ZOLADEX
AND PLACEBO TREATMENT GROUPS OF TRIAL 0022
|
ADVERSE EVENT
|
ZOLADEX 3.6 mg
(n=180)
%
|
Placebo
(n=177)
%
|
| Whole body |
| Headache |
32
|
22
|
| Abdominal Pain |
11
|
10
|
| Pelvic Pain |
9
|
6
|
| Back Pain |
4
|
7
|
| Cardiovascular |
| Vasodilatation |
57
|
18
|
| Migraine |
7
|
4
|
| Hypertension |
6
|
2
|
| Digestive |
| Nausea |
5
|
6
|
| Nervous |
| Nervousness |
5
|
3
|
| Depression |
3
|
7
|
| Respiratory |
| Pharyngitis |
6
|
9
|
| Sinusitis |
3
|
6
|
| Skin and appendages |
| Sweating |
16
|
5
|
| Urogenital |
| Dysmenorrhea |
7
|
9
|
| Uterine Hemorrhage |
6
|
4
|
| Vulvovaginitis |
5
|
1
|
| Menorrhagia |
4
|
5
|
| Vaginitis |
1
|
6
|
DRUG INTERACTIONS
No formal drug-drug interaction studies have been performed. No
confirmed interactions have been reported between ZOLADEX and other
drugs.
top
