Adverse reactions : תופעות לוואי

4.8   Undesirable effects

Effects of smoking Cessation
Some symptoms may be related to nicotine withdrawal associated with stopping smoking. These can include the following: dysphoria or depressed mood; insomnia; irritability, frustration or anger; anxiety; difficulty concentrating, restlessness or impatience; decreased heart rate; and increased appetite or weight gain. These have been observed in those using the mouthspray.

Increased frequency of aphthous ulcer, cough and nasopharyngitis may occur after abstinence from smoking. The causality is unclear.

In addition to this, other cessation-associated symptoms were seen in those using the mouth spray: dizziness, presyncopal symptoms, constipation, and gingival bleeding.

Nicotine craving, which is recognised as a clinically relevant symptom, is an important element in nicotine withdrawal after smoking cessation.

Effects of vaping Cessation
The nicotine withdrawal effects of vaping cessation have not been established, however it is anticipated that many of the effects relating to nicotine withdrawal will be the same as those seen with tobacco smoking cessation.

Adverse Drug Reactions
This product may cause adverse reactions similar to those associated with nicotine given by other means, including smoking and vaping, and these are mainly dose- dependent.

Most adverse events reported with this product occur during the early phase of treatment and are similar to those seen with other orally delivered forms. During the first few days of treatment irritation to the mouth and throat may be experienced and hiccups are particularly common. Tolerance is normal with continued use.

Daily collection of data from trial subjects demonstrated that very commonly occurring adverse events were reported with onset in the first 2-3 weeks of use of the spray, and declined thereafter.

Allergic reactions (including symptoms of anaphylaxis) occur rarely during use of this product.
The adverse reactions observed in patients treated with oral nicotine formulations during clinical trials and post-marketing experience are listed below by System Organ Class (SOC).

Frequencies are defined in accordance with current guidance, as: Very common (≥1/10); common (≥1/100, <1/10); uncommon (≥1/1 000, <1/100); rare (≥1/10 000, <1/1 000); very rare (<1/10 000); not known (cannot be estimated from the available data).


Body System                   Incidence                     Reported Adverse Event (Preferred Term)
Immune System Disorders       Common                        Hypersensitivitya Not known                     Anaphylactic reactiona
Psychiatric disorders         Uncommon                      Abnormal dreams* Nervous System Disorders      Very common                   Headachea# Common                        Burning sensationc
Common                        Dizziness
Common                        Dysgeusia
Common                        Paraesthesiaa
Not known                     Seizures
Eye Disorders                 Not known                     Blurred Vision Not known                     Lacrimation increased
Cardiac Disorders             Uncommon                      Palpitationsa Uncommon                      Tachycardiaa
Not known                     Atrial fibrillation
Vascular Disorders            Uncommon                      Flushinga Uncommon                      Hypertensiona
Respiratory, Thoracic and     Common                        Cough** Mediastinal Disorders         Very common                   Hiccups**** Very common                   Throat irritation**
Uncommon                      Bronchospasm
Uncommon                      Dysphonia
Uncommon                      Dyspnoeaa
Uncommon                      Nasal congestion
Uncommon                      Oropharyngeal pain
Uncommon                      Rhinorrhoea
Uncommon                      Sneezing
Uncommon                      Throat tightness

Gastrointestinal Disorders    Very common                   Nauseaa Common                        Abdominal pain
Common                        Diarrhoea***
Common                        Dry mouth
Common                        Dyspepsia
Common                        Flatulence
Common                        Salivary hypersecretion
Common                        Stomatitis
Common                        Toothache
Common                        Vomitinga
Uncommon                      Eructation
Uncommon                      Gingivitis
Uncommon                      Glossitis
Uncommon                      Oral mucosal blistering and exfoliation
Uncommon                      Paraesthesia oral***
Rare                          Dysphagia
Rare                               Hypoaesthesia oral***
Rare                               Retching
Not known                          Dry throat
Not known                          Gastrointestinal discomforta
Not known                          Lip pain
Musculoskeletal and                Uncommon                           Pain in jawb connective tissue disorders        Uncommon                           Musculoskeletal pain Not known                          Muscle tightnessb
Skin and Subcutaneous Tissue       Uncommon                           Dry skin Disorders                          Uncommon                           Hyperhidrosisa Uncommon                           Pruritusa
Uncommon                           Rasha
Uncommon                           Urticaria**
Not known                          Angioedemaa
Not known                          Erythemaa

General disorders and               Common                              Fatiguea administration site conditions:     Uncommon                            Astheniaa Uncommon                            Chest discomfort and paina
Uncommon                            Malaise a
Systemic effects; b Tightness of jaw and pain in jaw with nicotine gum formulation c
At the application site
*
Identified only for formulations applied during the night
**
Higher frequency observed in clinical studies with inhaler formulation.
***Reported the same or less frequently than placebo
**** Higher frequency observed in clinical studies with mouth spray formulation #
Although the frequency in the active group is less than that of the placebo group, the frequency in the specific formulation in which the PT was identified as a systemic ADR was greater in the active group than the placebo group.

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