Adverse reactions : תופעות לוואי

4.8   Undesirable effects

Summary of the safety profile
The most commonly reported treatment related adverse reactions reported during the pivotal clinical studies were constipation and symptoms commonly associated with drug withdrawal (i.e. insomnia, headache, nausea, hyperhidrosis and pain). Some reports of seizure, vomiting, diarrhoea, and elevated liver function tests were considered serious.


Tabulated list of adverse reactions
Table 1 summarizes adverse reactions reported from pivotal clinical trials in which, 342 of         472 patients (72.5 %) reported adverse reactions and adverse reactions reported during post-marketing surveillance.

The frequency of possible undesirable effects listed below is defined using the following convention: Very common (1/10), Common (1/100 to <1/10), Uncommon (1/1,000 to <1/100), Not known (cannot be estimated from available data).

Table 1: Treatment-related adverse reactions reported in clinical trials and post-marketing surveillance of buprenorphine/naloxone

System Organ Class      Very common               Common                   Uncommon                       Not known 
Infections and                                    Influenza                Urinary tract infection infestations                                      Infection                Vaginal infection Pharyngitis
Rhinitis
Blood and lymphatic                                                        Anaemia system disorders                                                           Leukocytosis Leukopenia
Lymphadenopathy
Thrombocytopenia
Immune system                                                              Hypersensitivity          Anaphylactic shock disorders
Metabolism and                                                             Decreased appetite nutrition disorders                                                        Hyperglycaemia Hyperlipidaemia
Hypoglycaemia
Psychiatric disorders   Insomnia                  Anxiety                  Abnormal dreams           Hallucination Depression               Agitation
Libido decreased         Apathy
Nervousness              Depersonalisation
Thinking abnormal        Drug dependence
Euphoric mood
Hostility
Nervous system          Headache                  Migraine                 Amnesia                   Hepatic disorders                                         Dizziness                Hyperkinesia              encephalopathy Hypertonia               Seizure                   Syncope
Paraesthesia             Speech disorder
Somnolence               Tremor
Eye disorders                                     Amblyopia                Conjunctivitis Lacrimal disorder        Miosis
Ear and labyrinth                                                                                    Vertigo disorders
Cardiac disorders                                                          Angina pectoris Bradycardia
Myocardial infarction
Palpitations
Tachycardia
Vascular disorders                                Hypertension             Hypotension               Orthostatic Vasodilatation                                     hypotension
Respiratory, thoracic                             Cough                    Asthma                    Bronchospasm and mediastinal                                                            Dyspnea                   Respiratory depression disorders                                                                  Yawning 
Gastrointestinal        Constipation              Abdominal pain            Mouth ulceration disorders               Nausea                    Diarrhoea                 Tongue discolouration Dyspepsia
Flatulence
Vomiting
Hepatobiliary                                                                                         Hepatitis disorders                                                                                             Hepatitis acute Jaundice
Hepatic necrosis
Hepatorenal syndrome
Skin and subcutaneous   Hyperhidrosis             Pruritus                  Acne                      Angioedema tissue disorders                                  Rash                      Alopecia Urticaria                 Dermatitis exfoliative
Dry skin
Skin mass
Musculoskeletal and                               Back pain                 Arthritis connective tissue                                 Arthralgia disorders                                         Muscle spasms
Myalgia
Renal and urinary                                 Urine abnormality         Albuminuria disorders                                                                   Dysuria Haematuria
Nephrolithiasis
Urinary retention
Reproductive system                               Erectile dysfunction      Amenorrhoea and breast disorders                                                        Ejaculation disorder Menorrhagia
Metrorrhagia
General disorders and   Drug withdrawal           Asthenia                  Hypothermia               Drug withdrawal administration site     syndrome                  Chest pain                                          syndrome neonatal conditions                                        Chills
Pyrexia
Malaise
Pain
Oedema peripheral
Investigations                                    Liver function test       Blood creatinine          Transaminases abnormal                  increased                 increased
Weight decreased
Injury, poisoning and                             Injury                    Heat stroke procedural complications


Description of selected adverse reactions
In cases of intravenous drug misuse, some adverse reactions are attributed to the act of misuse rather than the medicinal product and include local reactions, sometimes septic (abscess, cellulitis), and potentially serious acute hepatitis, and other infections such as pneumonia, endocarditis have been reported (see section 4.4).

In patients presenting with marked drug dependence, initial administration of buprenorphine can produce a drug withdrawal syndrome similar to that associated with naloxone (see sections 4.2 and         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/