Adverse reactions : תופעות לוואי

4.8 Undesirable effects

Summary of safety profile
The most commonly reported adverse drug reactions were those related to withdrawal symptoms (e.g. insomnia, headache, nausea and hyperhidrosis) and pain.

Tabulated list of adverse reactions
Table 1 summarises:
• adverse reactions reported from pivotal clinical studies. The frequency of possible side effects listed below is defined using the following convention: Very common (≥1/10), common (≥1/100 to <1/10), not known (cannot be estimated from the available data).
• the most commonly reported adverse drug reactions during post-marketing surveillance. Events occurring in at least 1% of reports by healthcare professionals and considered expected are included. Frequency of events not reported in pivotal studies cannot be estimated and is given as not known.

Table 1: Adverse effects observed in pivotal clinical studies and / or post marketing surveillance listed by body system
System Organ       Very common           Common (≥1/100          Not known Class           (≥1/10)               to <1/10)

Infections and                              Bronchitis infestations                                Infection
Influenza
Pharyngitis
Rhinitis
Blood and                                   Lymphadenopathy lymphatic system disorders
Metabolism and                              Decreased appetite nutrition disorders
Psychiatric           Insomnia              Agitation              Drug dependence disorders                                   Anxiety                (see section 4.4) Depression
Hostility
Nervousness
Paranoia
Thinking abnormal
Nervous system        Headache              Dizziness              Seizures disorders                                   Hypertonia
Migraine
Paraesthesia
Somnolence
Syncope
Tremor
Eye disorders                               Lacrimal disorder
Mydriasis
Cardiac disorders                           Palpitations
Vascular disorders                          Vasodilatation
Respiratory,                                Cough thoracic and                                Dyspnoea mediastinal                                 Yawning disorders
Gastrointestinal      Nausea                Abdominal pain disorders                                   Constipation
Diarrhoea
Dry mouth
Dyspepsia
Gastrointestinal disorder
Flatulence
Tooth disorder
Vomiting
Skin and              Hyperhidrosis        Rash subcutaneous tissue disorders
Musculoskeletal,                           Arthralgia connective tissue                          Back pain and bone disorders                         Bone pain
Muscle spasms
Myalgia
Neck pain
Reproductive                               Dysmenorrhoea system and breast disorders
General disorders     Drug withdrawal      Asthenia               Drug withdrawal and administration    syndrome             Chest pain             syndrome site conditions       Pain                 Chills                 neonatal Malaise
Oedema peripheral
Pyrexia

Description of selected adverse reactions
The following is a summary of other post-marketing adverse event reports that are considered serious or otherwise noteworthy:

•   In cases of intravenous misuse, 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 withdrawal effect similar to that associated with naloxone.
•   The most common signs and symptoms of hypersensitivity include rashes, urticaria, and pruritus.
Cases of bronchospasm, angioedema, and anaphylactic shock have been reported (see section     4.3).
•   Transaminase increase, hepatitis, acute hepatitis, cytolytic hepatitis, jaundice, hepatorenal syndrome, hepatic encephalopathy, and hepatic necrosis have occurred (see section 4.4).
•   Neonatal drug withdrawal syndrome has been reported among newborns of women who have received buprenorphine during pregnancy. The syndrome may be milder than that seen with a full µ-opioid agonist and may be delayed in onset. The nature of the syndrome may vary depending upon the mother’s drug use history (see section 4.6).
•   Hallucination, orthostatic hypotension, urinary retention and vertigo have been reported 
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/