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Zoladex (Goserelin Acetate) - Side Effects and Adverse Reactions

 
 



ADVERSE REACTIONS

General:

Rarely, hypersensitivity reactions (including urticaria and anaphylaxis) have been reported in patients receiving ZOLADEX.

Changes in blood pressure, manifest as hypotension or hypertension, have been occasionally observed in patients administered ZOLADEX. The changes are usually transient, resolving either during continued therapy or after cessation of therapy with ZOLADEX. Rarely, such changes have been sufficient to require medical intervention including withdrawal of treatment from ZOLADEX.

Males - 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.

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.

There have been post-marketing reports of osteoporosis, decreased bone mineral density and bony fracture in men treated with ZOLADEX for prostate cancer.

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

ZOLADEX

ORCHIECTOMY

(n=242)

(n=254)

ADVERSE EVENT

%

%

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 1

1 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.

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 radition therapy)

(n=231)

(n = 235)

flutamide + ZOLADEX + Radiation

Radiation Only

% All

% All

Rectum/Large Bowel

80

76

Bladder

58

60

Skin

37

37

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

(n=231)

(n = 235)

flutamide + ZOLADEX + Radiation

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%).

Females:

As would be expected with a drug that results in hypoestrogenism, the most frequently reported adverse reactions were those related to this effect.

As with other LHRH agonists, there have been reports of ovarian cyst formation and, when ZOLADEX 3.6 mg is used in combination with gonadotropins, of ovarian hyperstimulation syndrome (OHSS).

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

ZOLADEX

DANAZOL

(n=411)

(n=207)

ADVERSE EVENT

%

%

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/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. 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 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 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

ZOLADEX

OOPHORECTOMY

(n=57)

(n=55)

ADVERSE EVENT

% of Pts.

% 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

ZOLADEX 3.6 mg

Placebo

(n=180)

(n=177)

ADVERSE EVENT

%

%

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

Post-Marketing:

Pituitary Apoplexy: During post-marketing surveillance, rare cases of pituitary apoplexy (a clinical syndrome secondary to infarction of the pituitary gland) have been reported after the administration of gonadotropin-releasing hormone agonists. In a majority of these cases, a pituitary adenoma was 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.



REPORTS OF SUSPECTED ZOLADEX SIDE EFFECTS / ADVERSE REACTIONS

Below is a sample of reports where side effects / adverse reactions may be related to Zoladex. The information is not vetted and should not be considered as verified clinical evidence.

Possible Zoladex side effects / adverse reactions in 66 year old male

Reported by a pharmacist from United States on 2011-10-04

Patient: 66 year old male weighing 89.6 kg (197.1 pounds)

Reactions: Drug Rash With Eosinophilia and Systemic Symptoms

Adverse event resulted in: hospitalization

Suspect drug(s):
Zoladex



Possible Zoladex side effects / adverse reactions in 81 year old male

Reported by a consumer/non-health professional from Belgium on 2011-10-06

Patient: 81 year old male

Reactions: Vision Blurred, Headache, Paraesthesia, Blood Glucose Increased, Gynaecomastia, Decreased Appetite

Suspect drug(s):
Zoladex

Other drugs received by patient: Noxin (Aspen); Sotalol HCL; Warfarin Sodium; Celebrex



Possible Zoladex side effects / adverse reactions in 80 year old male

Reported by a pharmacist from United States on 2011-10-07

Patient: 80 year old male weighing 70.0 kg (154.0 pounds)

Reactions: Platelet Count Decreased

Adverse event resulted in: hospitalization

Suspect drug(s):
Zoladex

Avastin



See index of all Zoladex side effect reports >>

Drug label data at the top of this Page last updated: 2007-03-31

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