Adverse reactions : תופעות לוואי

4.8    Undesirable effects

Summary of the safety profile
Typical opioid adverse reactions are to be expected with Fentora. Frequently, these will cease or decrease in intensity with continued use of the medicinal product, as the patient is titrated to the most appropriate dose. However, the most serious adverse reactions are respiratory depression (potentially leading to apnoea or respiratory arrest), circulatory depression, hypotension and shock and all patients should be closely monitored for these.
The clinical studies of Fentora were designed to evaluate safety and efficacy in treating BTP and all patients were also taking concomitant opioids, such as sustained-release morphine or transdermal fentanyl, for their persistent pain. Therefore it is not possible to definitively separate the effects of Fentora alone.

Tabulated list of adverse reactions
The following adverse reactions have been reported with Fentora and/or other fentanyl- containing compounds during clinical studies and post marketing experience. Adverse reactions are listed below as MedDRA preferred term by system organ class and frequency (frequencies are defined as: 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), not known (cannot be estimated from the available data); within each frequency group, undesirable effects are presented in order of decreasing seriousness:

Very common          Common          Uncommon           Rare             Not known Infections and                           Oral            Pharyngitis        Oral pustule infestations                             candidiasis
Blood and                               Anaemia         Thrombocyto- lymphatic                               Neutropenia     penia system disorders
Immune                                                                     Hyper- system                                                                     senstivity* disorders
Endocrine                                                                 Hypogonadis      Adrenal disorders                                                                 m                insufficiency , Androgen deficiency
Metabolism                              Anorexia and nutrition disorders
Psychiatric                             Depression      Euphoric mood                       Drug disorders                               Anxiety         Nervousness                         dependence Confusional     Hallucination                       (addiction)* state           Visual                              Drug abuse
Insomnia        hallucination                       (see sec. 4.4)
Mental status                       Delirium changes
Disorientation



Very common          Common           Uncommon         Rare            Not known Nervous            Dizziness            Dysgeusia        Depressed        Cognitive       Loss of system             Headache             Somnolence       level of         disorder        consciousness disorders                               Lethargy         consciousness    Motor           * Tremor           Disturbance in   dysfunction     Convulsion
Sedation         attention
Hypoaesthesia    Balance
Migraine         disorder
Dysarthria
Eye                                                      Visual           Abnormal disorders                                                disturbance      sensation in Ocular           eye hyperaemia       Photopsia
Blurred vision
Visual acuity reduced
Ear and                                                  Vertigo labyrinth                                                Tinnitus disorders                                                Ear discomfort Cardiac                                 Tachycardia      Bradycardia disorders
Vascular                                Hypotension      Flushing disorders                               Hypertension     Hot flush
Respiratory,                            Dyspnoea         Respiratory                      Respiratory thoracic and                            Pharyngolaryn-   depression                       arrest* mediastinal                             geal pain        Sleep apnoea disorders                                                syndrome
Gastro-            Nausea               Constipation     Ileus             Oral mucosal intestinal         Vomiting             Stomatitis       Mouth             blistering disorders                               Dry mouth        ulceration        Dry lip Diarrhoea        Oral
Abdominal        hypoaesthesia pain             Oral
Gastro-          discomfort oesophageal      Oral mucosal reflux disease   discolouration
Stomach          Oral soft tissue discomfort       disorder
Dyspepsia        Glossodynia
Toothache        Tongue blistering
Gingival pain
Tongue ulceration
Tongue disorder
Oesophagitis
Chapped lips
Tooth disorder
Hepatobiliary                                            Biliary disorders                                                dilatation
Skin and                               Pruritus          Cold sweat       Onychorrhexi subcutaneous                           Hyperhidrosis     Facial swelling s tissue                                 Rash              Generalised disorders                                                pruritus
Alopecia


Very common          Common        Uncommon          Rare            Not known Musculoskel                            Myalgia       Muscle etal and                               Back pain     twitching connective                                           Muscular tissue                                               weakness disorders
Renal and                                            Urinary urinary                                              retention disorders
General            Application site     Peripheral    Malaise                           Pyrexia disorders and      reactions            oedema        Sluggishness                      Neonatal administration     including            Fatigue       Chest                             withdrawal site conditions    bleeding, pain,      Asthenia      discomfort                        syndrome (see ulcer, irritation,   Drug          Feeling                           section 4.6) paraesthesia,        withdrawal    abnormal                          Drug anaesthesia,         syndrome*     Feeling jittery                   tolerance erythema,            Chills        Thirst oedema,                            Feeling cold swelling and                       Feeling hot vesicles
Investigations                          Weight        Platelet count decreased     decreased
Heart rate increased
Haematocrit decreased
Haemoglobin decreased
Injury,                             Fall poisoning and procedural complications
* See section Description of selected adverse reactions

Description of selected adverse reactions
Tolerance
Tolerance can develop on repeated use.

Drug dependence
Repeated use of Fentora lead to drug dependence, even at therapeutic doses. The risk of drug dependence may vary depending on a patient's individual risk factors, dosage, and duration of opioid treatment (see section 4.4).

Opioid withdrawal symptoms such as nausea, vomiting, diarrhoea, anxiety, chills, tremor and sweating have been observed with transmucosal fentanyl.

Loss of consciousness and respiratory arrest have been observed in the context of overdose (see section 4.9).

Hypersensitivity reactions have been reported in post-marketing experience, including rash, erythema, lip and face swelling, and urticaria (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.
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