Adverse reactions : תופעות לוואי

4.8 Undesirable effects
Since Symbicort Turbuhaler contains both budesonide and formoterol, the same pattern of undesirable effects as reported for these substances may occur. No increased incidence of adverse reactions has been seen following concurrent administration of the two compounds. The most common drug related adverse reactions are pharmacologically predictable side-effects of β2 adrenoceptor agonist therapy, such as tremor and palpitations. These tend to be mild and usually disappear within a few days of treatment.

Adverse reactions, which have been associated with budesonide or formoterol, are given below, listed by system organ class and frequency. Frequency are defined as: very common (1/10), common (1/100 and <1/10), uncommon (1/1000 to <1/100), rare (1/10 000 to <1/1000) and very rare (<1/10 000).
Table 1
SOC                               Frequency Adverse Drug Reaction
Infections and infestations       Common       Candida infections in the oropharynx, Pneumonia (in COPD patients)
Immune system disorders           Rare         Immediate and delayed hypersensitivity reactions, e.g. exanthema, urticaria, pruritus,
dermatitis, angioedema and anaphylactic reaction
Endocrine disorders               Very rare    Cushing's syndrome, adrenal suppression, growth retardation, decrease in bone mineral density
Metabolism and nutrition          Rare         Hypokalaemia disorders                         Very rare    Hyperglycaemia
Psychiatric disorders             Uncommon Aggression, psychomotor hyperactivity, anxiety, sleep disorders
Very rare    Depression, behavioural changes
(predominantly in children)
Nervous system disorders          Common       Headache, tremor
Uncommon Dizziness
Very rare    Taste disturbances
Eye disorders                     Uncommon Vision blurred (see also section 4.4) Very rare    Cataract and glaucoma
Cardiac disorders                 Common       Palpitations
Uncommon Tachycardia
Rare         Cardiac arrhythmias, e.g. atrial fibrillation,
supraventricular tachycardia, extrasystoles
Very rare    Angina pectoris, prolongation of QTc-interval
Vascular disorders                Very rare    Variations in blood pressure Respiratory, thoracic and         Common       Mild irritation in the throat, coughing, dysphonia mediastinal disorders                          including hoarseness
Rare         Bronchospasm
Gastrointestinal disorders        Uncommon Nausea
Skin and subcutaneous tissue      Uncommon Bruises disorders
Musculoskeletal and connective Uncommon Muscle cramps tissue disorders

Candida infection in the oropharynx is due to drug deposition. Advising the patient to rinse the mouth out with water after each maintenance dose will minimise the risk. Oropharyngeal Candida infection usually responds to topical anti-fungal treatment without the need to discontinue the inhaled corticosteroid. If oropharyngeal thrush occurs, patients should also rinse their mouth with water after the as-needed inhalations.
As with other inhalation therapy, paradoxical bronchospasm may occur very rarely affecting less than 1 in 10,000 people, with an immediate increase in wheezing and shortness of breath after dosing. Paradoxical bronchospasm responds to a rapid-acting inhaled bronchodilator and should be treated straightaway. Symbicort Turbuhaler 160/4.5 mcg/dose should be discontinued immediately, the patient should be assessed and an alternative therapy instituted if necessary (see section 4.4).

Systemic effects of inhaled corticosteroids may occur particularly at high doses prescribed for prolonged periods. These effects are much less likely to occur than with oral corticosteroids.
Possible systemic effects include Cushing’s Syndrome, Cushingoid features, adrenal suppression, growth retardation in children and adolescents, decrease in bone mineral density, cataract and glaucoma. Increased susceptibility to infections and impairment of the ability to adapt to stress may also occur. Effects are probably dependent on dose, exposure time, concomitant and previous steroid exposure and individual sensitivity.

Treatment with β2 adrenoceptor-agonists may result in an increase in blood levels of insulin, free fatty acids, glycerol and ketone bodies.

Paediatric populations
It is recommended that the height of children receiving prolonged treatment with inhaled corticosteroids is regularly monitored (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/