Adverse reactions : תופעות לוואי

4.8   Undesirable effects
The safety of fentanyl transdermal patch was evaluated in 1,565 adult and 289 paediatric subjects who participated in 11 clinical studies (1 double-blind, placebo-controlled; 7 open-label, active-controlled; 3 open-label, uncontrolled) used for the management of chronic malignant or non-malignant pain. These subjects received at least one dose of fentanyl transdermal patch and provided safety data. Based on pooled safety data from these clinical studies, the most commonly reported (i.e. ≥10% incidence) adverse reactions were: nausea (35.7%), vomiting (23.2%), constipation (23.1%), somnolence (15.0%), dizziness (13.1%), and headache (11.8%).
The adverse reactions reported with the use of fentanyl transdermal patch from these clinical studies including the above-mentioned adverse reactions, and from post-marketing experiences are listed below in Table 5.
The displayed frequency categories use the following convention: 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); not known (cannot be estimated from the available clinical data). The adverse reactions are presented by System Organ Class and in order of decreasing seriousness within each frequency category.
Table 5: Adverse reactions in adult and paediatric patients
System/organ class                                          Frequency category Very common          Common              Uncommon                    Rare           Not known Immune system                            Hypersensitivity                                                 Anaphylactic disorders                                                                                                     shock, Anaphylactic reaction,
Anaphylactoid reaction
Endocrine                                                                                                   Androgen disorders                                                                                                  deficiency Metabolism and                              Anorexia nutrition disorders
Psychiatric                                Insomnia,             Agitation,                                 Delirium disorders                                 Depression,          Disorientation, Anxiety,           Euphoric mood
Confusional state,
Hallucination
Nervous system         Somnolence,          Tremor,           Hypoaesthesia, disorders               Dizziness,        Paraesthesia      Convulsion (including Headache                             clonic convulsions and grand mal convulsion),
Amnesia, Depressed level of consciousness, Loss of consciousness
Eye disorders                                                   Vision blurred             Miosis Ear and labyrinth                            Vertigo disorders
Cardiac disorders                         Palpitations,        Bradycardia, Tachycardia           Cyanosis
Vascular disorders                        Hypertension         Hypotension Respiratory,                               Dyspnoea            Respiratory                Apnoea,         Bradypnoea thoracic and                                                   depression,             Hypoventilation mediastinal                                                 Respiratory distress disorders
Gastrointestinal         Nausea,         Diarrhoea, Dry              Ileus                Subileus disorders                Vomiting,     mouth, Abdominal
Constipation    pain, Abdominal pain upper,
Dyspepsia

Skin and                                 Hyperhidrosis,     Eczema, Dermatitis subcutaneous                             Pruritus, Rash,        allergic, Skin tissue disorders                           Erythema         disorder, Dermatitis, Dermatitis contact


Musculoskeletal                          Muscle spasms        Muscle twitching and connective tissue disorders
Renal and urinary                       Urinary retention disorders
Reproductive                                                Erectile dysfunction, system and breast                                           Sexual dysfunction disorders

General disorders                       Fatigue, Oedema         Application site       Application site and administration                         peripheral,        reaction, Influenza-       dermatitis, site conditions                             Asthenia,       like illness, Feeling of   Application site Malaise, Feeling       body temperature           eczema cold            change, Application site hypersensitivity,
Drug withdrawal syndrome, Pyrexia*
* The assigned frequency (uncommon) is based on analyses of incidence including only adult and paediatric clinical study subjects with non-cancer pain.
Paediatric population
The safety of fentanyl transdermal patch was evaluated in 289 paediatric subjects (<18 years) who participated in 3 clinical studies for the management of chronic or continuous pain of malignant or non-malignant origin. These subjects received at least one dose of fentanyl transdermal patch and provided safety data (see section 5.1).
The safety profile in children and adolescents treated with fentanyl transdermal patch was similar to that observed in adults. No risk was identified in the paediatric population beyond that expected with the use of opioids for the relief of pain associated with serious illness and there does not appear to be any paediatric-specific risk associated with fentanyl transdermal patch use in children as young as 2 years old when used as directed.
Based on pooled safety data from these 3 clinical studies in paediatric subjects, the most commonly reported (i.e. ≥10% incidence) adverse reactions were vomiting (33.9%), nausea (23.5%), headache (16.3%), constipation (13.5%), diarrhoea (12.8%), and pruritus (12.8%).

Tolerance, physical dependence, and psychological dependence can develop on repeated use of Fenta TDP (see section 4.4).
Opioid withdrawal symptoms (such as nausea, vomiting, diarrhoea, anxiety, and shivering) are possible in some patients after conversion from their previous opioid analgesic to Fenta TDP or if therapy is stopped suddenly (see sections 4.2 and 4.4).
There have been very rare reports of newborn infants experiencing neonatal withdrawal syndrome when mothers chronically used fentanyl transdermal patch during pregnancy (see section 4.6).
Cases of serotonin syndrome have been reported when fentanyl was administered concomitantly with highly serotonergic drugs (see sections 4.4. and 4.5).
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/