Adverse reactions : תופעות לוואי

4.8    Undesirable effects

Treatment of Hypertension

In controlled clinical studies adverse reactions were mild and transient. The overall incidence of adverse events showed no association with dose or age. Withdrawals from treatment due to adverse events were similar with candesartan cilexetil (3.1%) and placebo (3.2%).


In a pooled analysis of clinical trial data of hypertensive patients, adverse reactions with candesartan cilexetil were defined based on an incidence of adverse events with candesartan cilexetil at least 1% higher than the incidence seen with placebo.
By this definition, the most commonly reported adverse reactions were dizziness/vertigo, headache and respiratory infection.


The table below presents adverse reactions from clinical trials and post-marketing experience.


The frequencies used in the tables throughout section 4.8 are: 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) and very rare (< 1/10,000) and not known (cannot be estimated from the available data).



System Organ Class            Frequency                   Undesirable Effect Infections and infestations   Common                      Respiratory infection Blood and lymphatic           Very rare                   Leukopenia, neutropenia system disorders                                          and agranulocytosis Metabolism and nutrition      Very rare                   Hyperkalaemia, disorders                                               hyponatraemia Nervous system disorders     Common                     Dizziness/vertigo, headache
Respiratory, thoracic and    Very rare                  Cough mediastinal disorders
Gastrointestinal disorders   Very rare                  Nausea Not known                  Diarrhoea
Hepato-biliary disorders     Very rare                  Increased liver enzymes, abnormal hepatic function or hepatitis
Skin and subcutaneous        Very rare                  Angioedema, rash, tissue disorders                                        urticaria, pruritus Musculoskeletal and          Very rare                  Back pain, arthralgia, connective tissue                                       myalgia disorders
Renal and urinary            Very rare                  Renal impairment, disorders                                               including renal failure in susceptible patients (see section 4.4)

Laboratory findings
In general, there were no clinically important influences of Atacand on routine laboratory variables. As for other inhibitors of the renin-angiotensin-aldosterone system, small decreases in haemoglobin have been seen. No routine monitoring of laboratory variables is usually necessary for patients receiving Atacand. However, in patients with renal impairment, periodic monitoring of serum potassium and creatinine levels is recommended.


Treatment of Heart Failure
The adverse experience profile of Atacand in adult heart failure patients was consistent with the pharmacology of the drug and the health status of the patients.
In the CHARM clinical programme, comparing Atacand in doses up to 32 mg (n=3,803) to placebo (n=3,796), 21.0% of the candesartan cilexetil group and 16.1% of the placebo group discontinued treatment because of adverse events. The most commonly reported adverse reactions were hyperkalaemia, hypotension and renal impairment. These events were more common in patients over 70 years of age, diabetics, or subjects who received other medicinal products which affect the renin-angiotensin-aldosterone system, in particular an ACE-inhibitor and/or spironolactone. The table below presents adverse reactions from clinical trials and post-marketing experience.

System Organ Class            Frequency                   Undesirable Effect Blood and lymphatic           Very rare                   Leukopenia, neutropenia system                                                    and agranulocytosis disorders
Metabolism and nutrition      Common                      Hyperkalaemia disorders                     Very rare                   hyponatraemia Nervous system disorders      Very rare                   Dizziness, headache Vascular disorders            Common                      Hypotension Respiratory, thoracic and     Very rare                   Cough mediastinal disorders
Gastrointestinal disorders    Very rare                   Nausea Not known                   Diarrhoea
Hepato-biliary disorders      Very rare                   Increased liver enzymes, abnormal hepatic function or hepatitis
Skin and subcutaneous         Very rare                   Angioedema, rash, tissue disorders                                          urticaria, pruritus Musculoskeletal and           Very rare                   Back pain, arthralgia, connective tissue                                         myalgia disorders
Renal and urinary             Common                      Renal impairment, disorders                                                 including renal failure in susceptible patients (see section 4.4)


Laboratory findings:
Hyperkalaemia and renal impairment are common in patients treated with Atacand for the indication of heart failure. Periodic monitoring of serum creatinine and potassium is recommended (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