Adverse reactions : תופעות לוואי

4.8   Undesirable effects
Since patients suffering from locally advanced or metastatic, hormone-dependent prostate cancer are generally old and have other diseases frequently encountered in this aged population, more than 90 % of the patients included in clinical trials reported adverse events, and often the causality is difficult to assess. As seen with other GnRH agonist therapies or after surgical castration, the most commonly observed adverse events related to triptorelin treatment were due to its expected pharmacological effects. These effects included hot flushes and decreased libido.
With the exception of immuno-allergic (rare) and injection site (< 5%) reactions, all adverse events are known to be related to testosterone changes.
The following adverse reactions considered as at least possibly related to triptorelin treatment were reported. Most of these events are known to be related to biochemical or surgical castration.
The frequency of the adverse reactions is classified as follows: very common (≥1/10); common (≥1/100, <1/10); uncommon (≥1/1000, <1/100); rare (≥1/10000, <1/1000); not known (cannot be estimated fromthe available data).

System             Very Common             Common                Uncommon                    Rare                 Additional post-
Organ Class marketing
Frequency notknown
Infections and                                                                               nasopharyngitis infestations
Investigations                             weight increase       alanine                     blood alkaline aminotransferase phosphatase increased, aspartate
- aminotransferase          increased increased, blood creatinine increased,
blood pressure increased, blood urea increased, gamma- glutamyltransferase increased, weight decreased
Blood and lymphatic system                                                 thrombocytosis disorders

Cardiac                                                          palpitations                                     QT prolongation* disorders
(see sections
4.4 and 4.5)
Immune system                              hypersensitivity                                  anaphylactic         anaphylactic disorders                                                                                    reaction             shock 
Endocrine                                                                                                         pituitary disorders                                                                                                         apoplexy** Metabolism and                                                   anorexia, diabetes nutrition                                                        mellitus, gout, disorders                                                        hyperlipidaemia increased appetite
Psychiatric        libido decreased        loss of libido        insomnia                    confusional state    anxiety disorders                                  depression* mood      irritability                decreased activity changes*                                          euphoric mood
Nervous system     paraesthesia in lower   dizziness, headache   paraesthesia                memory disorders          limbs                                                                     impairment Eye disorders                                                    visual impairment           abnormal sensation in the eye,
visual disturbances
Ear and                                                          Tinnitus, vertigo labyrinth disorders vascular           hot flash               hypertension                                      hypotension disorders
Respiratory                                                      dyspnoea                    orthopnoea thoracic and                                                     epistaxis mediastinal disorders



System              Very Common             Common                Uncommon                    Rare               Additional post-
Organ Class marketing
Frequency notknown
Gastro-                                     dry mouth, nausea,    abdominal pain, intestinal                                                        constipation, diarrhoea,    abdominal disorders                                                         vomiting                    distension dysgeusia flatulence


Skin and            hyperhidrosis                                 acne, alopecia, erythema,   Blister, purpura   angioneurotic pruritus, rash subcutaneous                                                                                                     oedema urticaria tissue disorders
Musculo-skeletal    back pain               musculoskeletal       arthralgia, bone pain,      joint stiffness pain                  muscle cramp,
disorders                                                                                     joint swelling pain in extremity,    muscular weakness,
musculoskeletal myalgia stiffness osteoarthritis
Renal and                                                         nocturia                                       urinary urinary                                                           urinary retention                              incontinence disorders
Reproductive        erectile dysfunction    pelvic plain          gynaecomastia (including system and                                                        breast pain ejaculation failure,
breasts disorders   ejaculation disorder)                         testicular atrophy testicular pain

General             asthenia                injection site        Lethargy, oedema            chest pain ,       malaise peripheral, pain, rigors,
disorders and                               reaction (including                               dysstasia , somnolence administration                              erythema,                                         influenza like site conditions                             inflammation, and                                 illness, pyrexia pain), oedema

*This frequency is based on class-effect frequencies common for all GnRH agonists.
**Reported following initial administration in patients with pituitary adenoma Triptorelin causes a transient increase in circulating testosterone levels within the first week afterthe initial injection of the sustained release formulation. With this initial increase in circulating testosterone levels, a small percentage of patients (≤ 5 %) may experience a temporary worseningof signs and symptoms of their prostate cancer (tumour flare), usually manifested by an increasein urinary symptoms (< 2%) and metastatic pain (5%), which can be managed symptomatically.These symptoms are transient and usually disappear in one to two weeks.
Isolated cases of exacerbation of disease symptoms, either urethral obstruction or spinal cord compression by metastasis have occurred. Therefore, patients with metastatic vertebral lesions and/or with upper or lower urinary tract obstruction should be closely observed during the first few weeks of therapy (see section 4.4 Special warnings and precautions for use).
The use of GnRH agonists, to treat prostate cancer may be associated with increased bone loss and may lead to osteoporosis and increases the risk of bone fracture. This may also lead to an incorrect diagnosis of bone metastases.
Increased lymphocytes count has been reported with patients undergoing GnRH analoguetreatment.
This secondary lymphocytosis is apparently related to GnRH induced castration and seems to indicate that gonadal hormones are involved in thymic involution.


Patients receiving long-term treatment with GnRH analogue in combination with radiation therapy may have more side effects, mostly gastrointestinal and related to radiotherapy.

Reporting suspected adverse reactions after authorization 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.