Adverse reactions : תופעות לוואי

4.8 Undesirable effects

In controlled clinical studies with candesartan cilexetil/hydrochlorothiazide, the observed side effects were mild and transient. The proportion of patients who discontinued treatment due to side effects were the same for candesartan cilexetil/hydrochlorothiazide (2.3-3.3%) and for placebo (2.7-4.3%).

In clinical studies of candesartan cilexetil/hydrochlorothiazide, the observed side effects were limited to those previously reported with candesartan cilexetil and/or hydrochlorothiazide.

The table below shows the side effects of candesartan cilexetil as observed in clinical studies and from experience following market approval. In a pooled analysis of data from clinical studies on patients with hypertension, the determination of the side effects from candesartan cilexetil was based on an incidence of side effects with candesartan cilexetil that was at least 1% higher than the incidence seen with placebo.


The frequencies used throughout the tables in Section 4.8 are: 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) and no known frequency (cannot be calculated from available data).
System organ class       Frequency       Side effect
Infections and           Common          Respiratory infection infestations
Blood and lymphatic      Very rare       Leukopenia, neutropenia and system disorders                         agranulocytosis
Metabolism and           Very rare       Hyperkalaemia, hyponatremia nutrition disorders
Central and peripheral Common            Dizziness/vertigo, headache nervous system disorders
Respiratory, thoracic    Very rare       Cough and mediastinal disorders
Gastrointestinal         Very rare       Nausea disorders                Frequency       Diarrhoea unknown
Hepatobiliary disorders Very rare        Elevated liver enzymes, abnormal liver function or hepatitis
System organ class       Frequency      Side effect
Skin and                 Very rare      Angioedema, skin rash, urticaria, itching subcutaneous tissue disorders
Musculoskeletal and      Very rare      Back pain, arthralgia, myalgia connective tissue disorders
Renal and urinary        Very rare      Reduced renal function, including renal disorders                               failure in predisposed patients (see Section 4.4)



The table below presents adverse reactions associated with hydrochlorothiazide in monotherapy, usually with doses of 25 mg or higher.
System organ class       Frequency Side effect
Neoplasms benign,        Frequency    Non-melanoma skin cancer (basal cell malignant and            unknown      cancer and squamous cell carcinoma) unspecified (incl cysts and polyps)
Blood and lymphatic      Rare         Leuckpenia, neutropenia/agranulocytosis, system disorders                      thrombocytopenia, aplastic anaemia, bone marrow depression, haemolytic anaemia
Immune system            Rare         Anaphylactic reactions
Metabolism and           Common       Hyperglycaemia, hyperuricaemia, nutrition disorders                   electrolyte disturbances (including hyponatremia and hypokalaemia)

Psychiatric disorders    Rare        Sleep disturbances, depression, restlessness
Central and peripheral   Common      Dizziness, vertigo nervous system disorders
Rare        Paraesthesia

Eye disorders            Rare        Transient blurred vision
Frequency   Acute myopia, acute narrow-angle- unknown     glaucoma, choroidal effusion
Cardiac disorders        Rare        Cardiac arrhythmias
Vascular disorders       Uncommon    Postural hypotension
System organ class        Frequency   Side effect
Rare        Necrotising angiitis (vasculitis, cutaneous vasculitis)
Respiratory, thoracic     Rare        Breathing difficulties (including pneumonitis and mediastinal                       and pulmonary oedema) disorders
Very rare   Acute respiratory distress syndrome
(ARDS) (see section 4.4)
Gastrointestinal          Uncommon    Anorexia, loss of appetite, gastric irritation, disorders                             diarrhoea, constipation
Rare        Pancreatitis


Hepatobiliary disorders   Rare        Icterus (intrahepatic cholestatic icterus) 
Skin and                  Uncommon    Skin rash, urticaria, photosensitivity subcutaneous tissue                   reactions disorders
Rare        Toxic epidermal necrolysis



Frequency   Systemic lupus erythematosus unknown     cutaneous lupus erythematosus

Musculoskeletal and       Rare        Muscle spasm connective tissue disorders
Renal and urinary         Common      Glucosuria disorders
Rare        Renal dysfunction and interstitial nephritis
General disorders and     Common      Weakness administration site       Rare        Fever conditions
Examinations              Common      Elevated cholesterol and triglyceride values Rare        Elevated BUN and serum creatinine values


Description of selected side effects
Non-melanoma skin cancer: Based on available data from epidemiological studies, a cumulative dose-dependent correlation has been observed between HCTZ and NMSC (see also Sections 4.4 and 5.1).
Reporting of suspected side effects
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