Adverse reactions : תופעות לוואי

4.8     Undesirable effects
At the beginning of the treatment, a rise in the serum testosterone level usually develops and may lead to temporary activation of the tumour with secondary reactions such as: 
-     occurrence or exacerbation of bone pain in patients with metastases . In very rare cases slight, transient increase in tumor pain.
-     signs of neurologic deficit due to tumour compression with e.g. muscle weakness in the legs
-     impaired micturition, hydronephrosis or lymphostasis
-     thrombosis with pulmonary embolism

These reactions can be largely avoided when an anti-androgen is given concomitantly in the initial phase of buserelin treatment (see also section 4.4).

The following categories are used for stating the frequency of undesirable effects: very common (>1/10); common (>1/100,<1/10); uncommon (>1/1,000, <1/100), rare (>1/10,000, <1/1,000); very rare (<1/10,000), Not known (frequency cannot be estimated from the available data).

Investigations:
Uncommon: increase in serum liver enzyme levels (e.g. transaminases), increase or decrease in weight.
Rare: changes in blood lipids, increase in serum bilirubin

Cardiac disorders:
Rare: palpitations
Not known: Androgen deprivation therapy treatment may lead to QT prolongation (see sections 4.4 and 4.5).

Blood and lymphatic system disorders:
Very rare: thrombopenia, leucopenia

Nervous system disorders:
Common: headache
Uncommon: drowsiness, dizziness
Rare: sleep disturbances, disturbances in memory and concentration
In isolated cases, paraesthesia has been observed with other presentations of buserelin.
Eye disorders:
Very rare: impaired vision (e.g. blurred vision), and a feeling of pressure behind the eyes 
Ear and labyrinth disorders:
Very rare: tinnitus, hearing disorders

Gastrointestinal disorders:
Uncommon: constipation
Rare: Nausea, vomiting, diarrhoea

Skin and subcutaneous tissue disorders:
Rare: increase or decrease in scalp and body hair

Musculoskeletal and connective tissue disorders:
Very rare: musculoskeletal discomfort and pain.
The use of LHRH-agonists may be associated with decreased bone density and may lead to osteoporosis and an increased risk of bone fracture. The risk of skeletal fracture increases with the duration of therapy.
Metabolism and nutrition disorders:
Very rare: increased thirst, changes in appetite, reduction in glucose tolerance (which in diabetic patients may lead to a deterioration of metabolic control), 
Neoplasm benign, malignant and unspecified (incl cysts and polyps)
Very rare: cases of pituitary adenomas were reported during treatment with LHRH-agonists- including buserelin. Even with concomitant anti-androgen therapy, mild transient increase in tumour pain.

Vascular disorders:
Common: hot flushes
Rare: deterioration in blood pressure levels in patients with hypertension 
General disorders and administration site reactions:
Common: pain or other local reactions (e.g. reddening, swelling) at the injection site.
Uncommon: oedema (mild) round the ankles and lower parts of the legs, tiredness Very rare: deterioration in general well-being

Immune system disorders:
Uncommon: hypersensitivity reactions such as reddening of the skin, itching, rashes (including urticaria)
Rare: severe hypersensitivity reactions with bronchospasm and allergic asthma with dyspnoea as well as, in isolated cases lead to anaphylactic/anaphylactoid shock.
In cases of anaphylactic/anaphylactoid reactions it may be necessary to remove the implant surgically.
Reproductive system and breast disorders:
Common: loss of potency, atrophy of the testes
Uncommon: gynaecomastia (painless)

Psychiatric disorders:
Common: loss of libido, mood changes and depression (long term use).
Uncommon: mood changes and depression (short term use).
Rare: nervousness, emotional instability, feeling of anxiety, depression (may develop or worsen).

Most of the effects listed above are directly or indirectly related to the suppression of testosterone by buserelin (symptoms of androgen deficiency).

Pharmacoepidemiological information indicates that androgen deprivation may increase the risk for cardiovascular disease, diabetes mellitus and anaemia (frequencies unknown) (see section 4.4).

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.
Healthcare professionals are asked to report any suspected adverse reactions to the Ministry of Health according to the National Regulation by using an online form
(http://forms.gov.il/globaldata/getsequence/getsequence.aspx?formType=AdversEffectMedic @moh.health.gov.il)