Zoladex (goserelin acetate) Implant: Side Effects & Warnings

Generic drug: goserelin acetate

Brand name: Zoladex

What is Zoladex (goserelin acetate), and how does it work?

Zoladex (goserelin acetate) implant is a GnRH agonist used to treat a variety of conditions, including advanced breast cancer, prostate cancer, endometriosis, and endometrial thinning.

Stage B2-C Prostatic Carcinoma

Zoladex is indicated for use in combination with flutamide for the management of locally confined Stage T2b-T4 (Stage B2-C) carcinoma of the prostate. Treatment with Zoladex and flutamide should start 8 weeks prior to initiating radiation therapy and continue during radiation therapy.

Prostatic Carcinoma

Zoladex is indicated in the palliative treatment of advanced carcinoma of the prostate.

Endometriosis

Zoladex is indicated for the management of endometriosis, including pain relief and reduction of endometriotic lesions for the duration of therapy. Experience with Zoladex for the management of endometriosis has been limited to women 18 years of age and older treated for 6 months.

Endometrial Thinning

Zoladex is indicated for use as an endometrial-thinning agent prior to endometrial ablation for dysfunctional uterine bleeding.

Advanced Breast Cancer

Zoladex is indicated for use in the palliative treatment of advanced breast cancer in pre- and perimenopausal women.

The estrogen and progesterone receptor values may help to predict whether Zoladex therapy is likely to be beneficial.

The automatic safety feature of the syringe aids in the prevention of needlestick injury.

What are the side effects of Zoladex?

Stage B2-C Prostatic Carcinoma

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:

Table 1 : ADVERSE EVENTS DURING ACUTE RADIATION
THERAPY (within first 90 days of radiation therapy)

(n=231)
flutamide + Zoladex + Radiation
(n=235)
Radiation Only

% All
%All

Rectum/Large Bowel
80
76

Bladder
58
60

Skin
37
37

Table 2 : ADVERSE EVENTS DURING LATE RADIATION PHASE
(after 90 days of radiation therapy)

(n=231)
flutamide + Zoladex + Radiation
(n=235)
Radiation Only

% All
%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%).

Prostatic Carcinoma

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.

Tumor Flare Phenomenon: Initially, Zoladex, like
other GnRH agonists, causes transient increases in serum levels of
testosterone. A small percentage of patients experienced a temporary worsening
of signs and symptoms, 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.

Table 3 : 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 seepage (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.

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:

Table 4 : 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.

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.

Table 5 : 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

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.

Table 6 : 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.

Hormone Replacement Therapy

Clinical studies suggest the addition of Hormone
Replacement Therapy (estrogens and/or 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.
Sixtysix 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 occurs 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: Elevation 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 HDL2) 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.

Postmarketing Experience

The following adverse reactions have been identified
during post-approval use of Zoladex. Because these reactions are reported
voluntarily from a population of uncertain size, it is not always possible to
reliably estimate their frequency or establish a causal relationship to drug
exposure.

Bone Mineral Density:
Osteoporosis, decreased bone
mineral density and bone
fracture
in men.
Cardiovascular:
Deep vein thrombosis, pulmonary
embolism,
myocardial infarction,
stroke, and
transient ischemic attack have
been observed in women treated with GnRH agonists. Although a
temporal relationship
was reported in some cases, most cases were confounded by risk factors or
concomitant medication use. It is unknown if there is a causal association
between the use of GnRH analogs and these events.
Ovarian Cyst:
Ovarian cyst formation and, in
combination with gonadotropins,
ovarian hyperstimulation syndrome (OHSS).
Changes in Blood Pressure:
Hypotension and
hypertension have been reported. These changes are usually transient, resolving
either during continued therapy or after cessation of therapy.
Pituitary Apoplexy and Tumors:
Pituitary
apoplexy
(a clinical syndrome secondary to infarction of the
pituitary gland) and
pituitary adenoma have been diagnosed. Most of the pituitary apoplexy cases occurred
within 2 weeks of the first dose, and some occurred within the first hour. In
these cases, pituitary apoplexy has presented as sudden headache, vomiting,
visual changes, ophthalmoplegia, altered mental status, and sometimes
cardiovascular collapse. Immediate medical attention has been required.
Pituitary tumors have been reported.
Acne: Usually within one month of starting
treatment.
Other Adverse Reactions: Psychotic disorders,
convulsions and mood swings.

What is the dosage for Zoladex?

Zoladex, at a dose of 3.6 mg, should be administered
subcutaneously every 28 days into the
anterior abdominal wall below the navel
line using an
aseptic
technique under the supervision of a physician.
While a delay of a few days is permissible, every effort
should be made to adhere to the 28-day schedule.

Stage B2-C Prostatic Carcinoma

When Zoladex is given in combination with
radiotherapy
and flutamide for patients with Stage T2b- T4 (Stage B2-C) prostatic carcinoma,
treatment should be started 8 weeks prior to initiating radiotherapy and should
continue during radiation therapy.
A treatment regimen using a Zoladex 3.6 mg
depot 8 weeks before radiotherapy, followed in 28 days by the Zoladex 10.8 mg
depot, can be administered. Alternatively, four injections of 3.6 mg depot can
be administered at 28-day intervals, two depots preceding and two during
radiotherapy.

Prostatic Carcinoma

For the management of advanced
prostate cancer,
Zoladex
is intended for long-term administration unless clinically inappropriate.

Endometriosis

For the management of endometriosis, the recommended
duration of administration is 6 months. Currently, there are no clinical data
on the effect of treatment of
benign gynecological conditions with
Zoladex for
periods in excess of 6 months.
Retreatment cannot be recommended for the management of
endometriosis since safety data for retreatment are not available.
If the
symptoms of endometriosis recur after a course of therapy, and further
treatment with Zoladex is contemplated, consideration should be given to monitoring
bone mineral density.
Clinical studies suggest the addition of Hormone
Replacement Therapy (estrogens and/or progestins) to
Zoladex is effective in
reducing the bone mineral loss which occurs with Zoladex alone without
compromising the efficacy of Zoladex in relieving the symptoms of endometriosis.
The addition of Hormone Replacement Therapy may also reduce the occurrence of
vasomotor
symptoms and vaginal dryness associated with hypoestrogenism. The optimal
drugs, dose and duration of treatment has not been established.

Endometrial Thinning

For use as an endometrial-thinning agent prior to
endometrial
ablation, the dosing recommendation is one or two depots (with each
depot given four weeks apart).
When one depot is administered, surgery should
be performed at four weeks. When two depots are administered, surgery should be
performed within two to four weeks following administration of the second
depot.

Breast Cancer

For the management of advanced breast cancer, Zoladex is
intended for long-term administration unless clinically inappropriate.

Renal Or Hepatic Impairment

No dosage adjustment is necessary for patients with renal
or hepatic impairment.

Latest Cancer News

Daily Health News

Trending on MedicineNet

What Is Polycythemia Vera?

Learn More on

What drugs interact with Zoladex?

No formal drug-drug interaction studies have been
performed. No confirmed interactions have been reported between Zoladex and
other drugs.

Drug/Laboratory Test Interactions

Administration of Zoladex in therapeutic doses results in
suppression of the pituitary-gonadal system.
Because of this suppression,
diagnostic tests of pituitary-gonadotropic and gonadal functions conducted
during treatment and until the resumption of menses may show results which are
misleading. Normal function is usually restored within 12 weeks after treatment
is discontinued.

Is Zoladex safe to use while pregnant or breastfeeding?

Zoladex is contraindicated during pregnancy unless Zoladex is being used for palliative treatment of advanced breast cancer. There are no adequate and well-controlled studies in pregnant women using
Zoladex.
Based on mechanism of action in humans and findings of increased pregnancy loss in animal studies,
Zoladex can cause fetal harm when administered to a pregnant woman. If this drug is used during pregnancy, the patient should be apprised of the potential hazard to the fetus. There is an increased risk for pregnancy loss due to expected hormone changes that occur with
Zoladex treatment.
It is not known if goserelin is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from
Zoladex, a decision should be made to either discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

UrbanObserver

Subscribe to newsletter

Movies

TV Shows

Music

Celebrity

Scandals

Drama

Lifestyle

Health

Technology

Company

Movies

TV Shows

Music

Celebrity

Scandals

Drama

Lifestyle

Health

Technology

Company