Adverse reactions : תופעות לוואי

4.8 Undesirable effects

Clinical studies
• Overview
Clinical studies have shown that cetirizine at the recommended dosage has minor undesirable effects on the CNS, including somnolence, fatigue, dizziness and headache. In some cases, paradoxical CNS stimulation has been reported.
Although cetirizine is a selective antagonist of peripheral H1-receptors and is relatively free of anticholinergic activity, isolated cases of micturition difficulty, eye accommodation disorders and dry mouth have been reported.
Instances of abnormal hepatic function with elevated hepatic enzymes accompanied by elevated bilirubin have been reported. Mostly this resolves upon discontinuation of the treatment with cetirizine dihydrochloride.
• Listing of ADRs
Double blind controlled clinical trials comparing cetirizine to placebo or other antihistamines at the recommended dosage (10 mg daily for cetirizine), of which quantified safety data are available, included more than 3200 subjects exposed to cetirizine.
From this pooling, the following adverse reactions were reported for cetirizine 10 mg in the placebo- controlled trials at rates of 1.0 % or greater:
Adverse reactions                             Cetirizine 10 mg                  Placebo (WHO-ART)                                      (n= 3260)                  (n = 3061) 
General disorders and administration site conditions
Fatigue                                                                       1.63 %                      0.95 % 
Nervous system disorders
Dizziness                                                                     1.10 %                      0.98 % Headache                                                                      7.42 %                      8.07 % 
Gastro-intestinal disorders
Abdominal pain                                                                0.98 %                      1.08 % Dry mouth                                                                     2.09 %                      0.82 % Nausea                                                                        1.07 %                      1.14 % 
Psychiatric disorders
Somnolence                                                                    9.63 %                      5.00 % 
Respiratory, thoracic and mediastinal disorders
Pharyngitis                                                                   1.29 %                      1.34 % 
Although statistically more common than under placebo, somnolence was mild to moderate in the majority of cases. Objective tests as demonstrated by other studies have demonstrated that usual daily activities are unaffected at the recommended daily dose in healthy young volunteers.
Paediatric population
Adverse reactions at rates of 1 % or greater in children aged from 6 months to 12 years, included in placebo-controlled clinical trials are:


Adverse reactions                                 Cetirizine                     Placebo (WHO-ART)                                   (n=1656)                     (n =1294) 
Gastro-intestinal disorders
Diarrhoea                                                               1.0 %                            0.6 % 
Psychiatric disorders
Somnolence                                                              1.8 %                            1. 4 % 
Respiratory, thoracic and mediastinal disorders
Rhinitis                                                                1.4 %                            1.1 % 
General disorders and administration site conditions
Fatigue                                                                 1.0 %                            0.3 % 

Post-marketing experience
In addition to the adverse reactions reported during clinical studies and listed above, the following undesirable effects have been reported in post-marketing experience.
Undesirable effects are described according to MedDRA System Organ Class and by estimated frequency based on post-marketing experience.
Frequencies are defined as follows: Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), not known (cannot be estimated from the available data)
Blood and lymphatic disorders
Very rare: thrombocytopenia
Immune system disorders
Rare: hypersensitivity
Very rare: anaphylactic shock
Metabolism and nutrition disorders
Not known: increased appetite
Psychiatric disorders
Uncommon: agitation
Rare: aggression, confusion, depression, hallucination, insomnia
Very rare: tics
Not known: suicidal ideation, nightmare
Nervous system disorders
Uncommon: paraesthesia
Rare: convulsions
Very rare: dysgeusia, syncope, tremor, dystonia, dyskinesia
Not known: amnesia, memory impairment
Eye disorders
Very rare: accommodation disorder, blurred vision, oculogyration
Ear and labyrinth disorders
Not known: vertigo
Cardiac disorders
Rare: tachycardia
Gastro-intestinal disorders
Uncommon: diarrhoea
Hepatobiliary disorders
Rare: hepatic function abnormal (increased transaminases, alkaline phosphatase, γ-GT and bilirubin) 
Not known: hepatitis
Skin and subcutaneous tissue disorders
Uncommon: pruritus, rash
Rare: urticaria
Very rare: angioneurotic oedema, fixed drug eruption
Not known: acute generalized exanthematous pustulosis
Musculoskeletal and connective tissue disorders
Not known: arthralgia
Renal and urinary disorders
Very rare: dysuria, enuresis
Not known: urinary retention
General disorders and administration site conditions
Uncommon: asthenia, malaise
Rare: oedema
Investigations
Rare: weight increased
Description of selected adverse reactions
After discontinuation of cetirizine, pruritus (intense itching) and/or urticaria 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 Side effects can also be reported to the following email: safety@trima.co.il