Adverse reactions : תופעות לוואי

4.8 Undesirable effects
The following frequency categories for adverse drug reactions (ADRs) were calculated based on reports from ZOLADEX clinical trials and post-marketing sources. The most commonly observed adverse reactions include hot flushes, sweating and injection site reactions.

The following convention has been used for classification of frequency: Very common (≥1/10), Common (≥1/100 to <1/10), Uncommon (≥1/1,000 to <1/100), Rare (≥1/10,000 to <1/1,000), Very rare (<1/10,000) and Not known (cannot be estimated from the available data).


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Table 1     ZOLADEX 3.6 mg adverse drug reactions presented by MedDRA System Organ Class

SOC                      Frequency                   Males                    Females 
Neoplasms benign,        Very rare                   Pituitary tumour         Pituitary tumour malignant and            Not known                   N/A                      Degeneration of uterine unspecified (including                                                        fibroid cysts and polyps)

Blood and lymphatic      Not knownj                  Anaemia, Leucopenia      Anaemia, Leucopenia system disorders                                     and Thrombocytopenia and Thrombocytopenia 
Immune system            Uncommon                    Drug hypersensitivity    Drug hypersensitivity disorders                Rare                        Anaphylactic reaction    Anaphylactic reaction 
Endocrine disorders      Very rare                   Pituitary haemorrhage    Pituitary haemorrhage 
Metabolism and nutrition Common                      Glucose tolerance        (see Not known) disorders                                            impaireda

Uncommon                    N/A                      Hypercalcaemia

Not knownj                  (see common)             Glucose tolerance impaired

Psychiatric disorders    Very common                 Libido decreasedb        Libido decreasedb 
Common                      Mood changes,            Mood changes,
depression               depression

Very rare                   Psychotic disorder       Psychotic disorder 
Nervous system           Common                      Paraesthesia             Paraesthesia disorders                                            Spinal cord              N/A compression

N/A                      Headache

Not known                   Memory impairment        Memory impairment 
Cardiac disorders        Common                      Cardiac failuref,        N/A myocardial infarctionf

Not known                   QT prolongation (see     QT prolongation (see sections 4.4 and 4.5)    sections 4.4 and 4.5)

Vascular disorders       Very common                 Hot flushb               Hot flushb 
Common                      Blood pressure           Blood pressure abnormalc abnormalc

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Not known                   Pulmonary embolism         Pulmonary embolism 
Hepatobiliary disorders   Not knownj                  Hepatic dysfunction        Hepatic dysfunction and and Jaundice               Jaundice

Skin and subcutaneous     Very common                 Hyperhidrosisb             Hyperhidrosisb, acnei tissue disorders          Common                      Rashd                      Rashd, alopeciag 
Not Known                   Alopeciah                  (see Common)

Musculoskeletal,          Common                      Bone paine                 (see Not known) connective tissue and                                 (see Uncommon)             Arthralgia bone disorders
Uncommon                    Arthralgia                 (see Common)

Not knownj                  (see Common)               Bone pain

Respiratory, thoracic and Not knownj                  Interstitial lung disease Interstitial lung disease mediastinal disorders

Renal and urinary         Uncommon                    Ureteric obstruction       N/A disorders

Reproductive system and Very common                   Erectile dysfunction       N/A breast disorders                                      N/A                        Vulvovaginal dryness 
N/A                        Breast enlargement

Common                      Gynaecomastia              N/A
Uncommon                    Breast tenderness          N/A

Rare                        N/A                        Ovarian cyst

N/A                        Ovarian hyperstimulation syndrome (if concomitantly used with gonadotrophins)
Not known                   N/A                        Withdrawal bleeding (see section 4.4)

General disorders and     Very common                 (see Common)               Injection site reaction administration site       Common                      Injection site reaction    (see Very common) conditions
N/A                        Tumour flare, tumour pain
(on initiation of treatment)

Not knownj                  Tumour flare (on           (see common) initiation of treatment)



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Investigations           Common                      Bone density             Bone density decreased decreased (see section (see section 4.4), weight
4.4), weight increased   increased a       A reduction in glucose tolerance has been observed in males receiving LHRH agonists.
This may manifest as diabetes or loss of glycaemic control in those with pre-existing diabetes mellitus.
b       These are pharmacological effects which seldom require withdrawal of therapy.
Hyperhidrosis and hot flushes may continue after stopping ZOLADEX.
c       These may manifest as hypotension or hypertension, have been occasionally observed in patients administered ZOLADEX.
d       These are generally mild, often regressing without discontinuation of therapy.
e       Initially, prostate cancer patients may experience a temporary increase in bone pain, which can be managed symptomatically.
f       Observed in a pharmaco-epidemiology study of LHRH agonists used in the treatment of prostate cancer. The risk appears to be increased when used in combination with anti- androgens.
g       Loss of head hair has been reported in females, including younger patients treated for benign conditions. This is usually mild but occasionally can be severe.
h       Particularly loss of body hair, an expected effect of lowered androgen levels.
i       In most cases acne was reported within one month after the start of ZOLADEX.
j       Frequency of the adverse drug reactions is based on spontaneous data.


Description of selected adverse event
Blood pressure abnormal: 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.
In addition, the following adverse drug reactions have been reported in women treated for benign gynaecological indications:


Acne, change of body hairs, dry skin, weight gain, increase in serum cholesterol, ovarian hyperstimulation syndrome (if concomitantly used with gonadotropines), vaginitis, vaginal discharge, nervousness, sleep disorder, tiredness, peripheral oedema, myalgias, cramp in the calves, nausea, vomiting, diarrhoea, constipation, abdominal complaints, alterations of voice.
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Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.

Any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by using an online form: https://sideeffects.health.gov.il