Adverse reactions : תופעות לוואי

4.8   Undesirable effects

Adverse reactions seen with ELIGARD 45 mg are mainly subject to the specific pharmacological action of leuprorelin acetate, namely increases and decreases in certain hormone levels. The most commonly reported adverse reactions are hot flashes, nausea, malaise and fatigue and transient local irritation at the site of injection. Mild or moderate hot flashes occur in approximately 58 % of patients.

Tabulated list of adverse reactions
The following adverse events were reported during clinical trials with ELIGARD 45 mg in patients with advanced prostate carcinoma. Adverse events are classified, by frequency, as very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1,000, <1/100), rare (≥1/10,000, <1/1,000) and very rare (<1/10,000), not known (cannot be estimated from the available data).

Table 1: Undesirable effects in clinical studies with Eligard
Infections and infestations common                                   nasopharyngitis uncommon                                 urinary tract infection, local skin infection Metabolism and nutrition disorders uncommon                                 aggravated diabetes mellitus Psychiatric disorders uncommon                                 abnormal dreams, depression, decreased libido Nervous system disorders uncommon                                 dizziness, headache, hypoaesthesia, insomnia, taste disturbance, smell disturbance, vertigo rare                                     abnormal involuntary movements not known                                idiopathic intracranial hypertension (pseudotumor cerebri) (see section 4.4)
Cardiac disorders not known                                QT prolongation (see sections 4.4 and 4.5) Vascular disorders very common                              hot flashes uncommon                                 hypertension, hypotension rare                                     syncope, collapse
Respiratory, thoracic and mediastinal disorders uncommon                                 rhinorrhoea, dyspnoea not known                                interstitial lung disease
Gastrointestinal disorders common                                   nausea, diarrhoea, gastroenteritis/colitis uncommon                                 constipation, dry mouth, dyspepsia, vomiting rare                                     flatulence, eructation
Table 1: Undesirable effects in clinical studies with Eligard
Skin and subcutaneous tissue disorders very common                               ecchymoses, erythema common                                    pruritus, night sweats uncommon                                  clamminess, increased sweating rare                                      alopecia, skin eruption
Musculoskeletal and connective tissues disorders common                                    arthralgia, limb pain, myalgia, rigors, weakness uncommon                                  back pain, muscle cramps
Renal and urinary disorders common                                    urinary infrequency, difficulty in micturation, dysuria, nocturia, oliguria uncommon                                  bladder spasm, haematuria, aggravated urinary frequency, urinary retention
Reproductive system and breast disorders common                                    breast tenderness, testicular atrophy, testicular pain infertility, breast hypertrophy, erectile dysfunction, reduced penis size uncommon                                  gynaecomastia, impotence, testicular disorder rare                                      breast pain
General disorders and administration site conditions very common                               fatigue, injection site burning, injection site paraesthesia common                                    malaise, injection site pain, injection site bruising, injection site stinging uncommon                                  injection site pruritus, injection site induration, lethargy, pain, pyrexia rare                                      injection site ulceration very rare                                 injection site necrosis
Blood and lymphatic system disorders common                                    hematology changes, anaemia Investigations common                                    increased blood creatinine phosphokinase, prolonged coagulation time uncommon                                  increased alanine aminotransferase, increased blood triglycerides, prolonged prothrombin time, increased weight

Other adverse events which have been reported in general to occur with leuprorelin acetate treatment include peripheral oedema, pulmonary embolism, palpitations, myalgia, an alteration in the skin sensation, muscle weakness, chills, rash, amnesia, and visual disturbances. Muscular atrophy has been observed with long term use of products in this class. Infarction of pre-existing pituitary apoplexy has been reported rarely after administration of both short and long acting GnRH agonists. There have been rare reports of thrombocytopenia and leucopenia. Changes in glucose tolerance have been reported.

Convulsions have been reported after GnRH agonist analogue administration (see section 4.4).

Local adverse events reported after injection of ELIGARD 45 mg are similar to the local adverse events associated with similar subcutaneously injected products.

Generally, these localised adverse events following subcutaneous injection are mild and described as being of brief duration.

Anaphylactic/anaphylactoid reactions have been reported rarely after GnRH agonist analogue administration.

Changes in Bone Density
Decreased bone density has been reported in the medical literature in men who have had orchiectomy or who have been treated with a GnRH analogue. It can be anticipated that long periods of treatment with leuprorelin may show increasing signs of osteoporosis. Regarding the increased risk for fractures owing to osteoporosis (see section 4.4).

Exacerbation of signs and symptoms of the disease
Treatment with leuprorelin acetate can cause exacerbations of signs and symptoms of the disease during the first few weeks. If conditions such as vertebral metastases and/or urinary obstruction or haematuria are aggravated, neurological problems such as weakness and/or paraesthesia of the lower limbs or worsening of urinary symptoms may occur.

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.
Additionally, you should also report to Kamada Ltd. to email address: pharmacovigilance@kamada.com