Adverse reactions : תופעות לוואי

4.8    Undesirable effects

Typical opioid adverse reactions are to be expected with ACTIQ. Frequently, these will cease or decrease in intensity with continued use of the product, as the patient is titrated to the most appropriate dose. However, the most serious adverse events are respiratory depression (potentially leading to apnoea or respiratory arrest), circulatory depression, hypotension and shock and all patients should be closely monitored for these.

Application site reactions, including gum bleeding, irritation, pain and ulcer have been reported in post-marketing use.

Because the clinical trials of ACTIQ were designed to evaluate safety and efficacy in treating breakthrough pain, all patients were also taking concomitant opioids, such as sustained-release morphine or transdermal fentanyl, for their persistent pain. Thus it is not possible to definitively separate the effects of ACTIQ alone.

The following adverse reactions have been reported with ACTIQ 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, not known (cannot be estimated from the available data):


System organ       Very common     common                       uncommon             Not known class
Immune system                                                                        anaphylactic disorders                                                                            reaction, tongue oedema,
lip oedema
Endocrine                                                                            adrenal disorders                                                                            insufficiency, androgen deficiency
Metabolism and                     anorexia nutrition disorders
Psychiatric                        confusion,                   abnormal dreams,     Insomnia, drug disorders                          anxiety,                     depersonalisation,   dependence hallucinations,              abnormal             (addiction),
depression,                  thinking,            drug abuse (see emotional lability           euphoria             section 4.4),
delirium
Nervous system     somnolence,     loss of consciousness,       coma, disorders          dizziness,      convulsion,                  slurred speech headache        vertigo,
myoclonus,
sedation,
paraesthesia (including hyperaesthesia/circumor al paraesthesia),
abnormal gait/incoordination,
taste perversion
Eye disorders                      abnormal vision
(blurred, double vision)
Vascular                                                        vasodilatation       flushing, disorders                                                                            hot flush 
Respiratory,       dyspnoea                                                          pharyngeal thoracic and                                                                         oedema, mediastinal                                                                          respiratory disorders                                                                            depression, sleep apnoea syndrome
Gastrointestinal   nausea,         dry mouth,                   ileus,               tooth loss, disorders          vomiting,       dyspepsia,                   mouth ulcers,        gingival constipation,   stomatitis,                  dental caries,       recession, abdominal       tongue disorder (for         gingival bleeding    gingivitis, pain            example, burning                                  diarrhoea sensation, ulcers),
flatulence,
abdomen enlarged
Skin and                           pruritus,                    urticaria subcutaneous                       sweating,
tissue disorders                   rash

Renal and                          urinary retention urinary disorders
General            asthenia        application site reactions                        fatigue, System organ         Very common       common                       uncommon            Not known class disorders and                          including irritation, pain                       peripheral administration                         and ulcer,                                       oedema, site conditions                        malaise                                          pyrexia, withdrawal syndrome*,
neonatal withdrawal syndrome (see section 4.6),
drug tolerance,
bleeding at the site of application
Investigations                         weight decreased

Injury,                                accidental injury (for poisoning and                          example, falls) procedural complications

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

Description of selected adverse reactions

Tolerance
Tolerance can develop on repeated use.
Drug dependence
Repeated use of ACTIQ leads 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).

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/