Adverse reactions : תופעות לוואי

4.8     Undesirable effects

Adverse drug reactions reported in clinical trials and laboratory findings occurring more frequently with valsartan plus hydrochlorothiazide versus placebo and individual postmarketing reports are presented below according to system organ class. Adverse drug reactions known to occur with each component given individually but which have not been seen in clinical trials may occur during treatment with valsartan/hydrochlorothiazide.

Adverse Drug Reactions
Adverse drug reactions are ranked by frequency, the most frequent first, using the following convention: 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 (frequency cannot be estimated from the available data).

Within each frequency grouping, adverse drug reactions are ranked in order of decreasing seriousness.

Table 1. Frequency of adverse reactions with valsartan/hydrochlorothiazide 
Metabolism and nutrition disorders
Uncommon                           Dehydration
CO-DIO API APR22 V1                                        Page 8 of 18      Sweden SmPC 03.2022 Nervous system disorders
Very rare                            Dizziness
Uncommon                             Paraesthesia
Not known                            Syncope
Eye disorders
Uncommon                             Vision blurred
Ear and labyrinth disorders
Uncommon                             Tinnitus
Vascular disorders
Uncommon                             Hypotension
Respiratory, thoracic and mediastinal disorders
Uncommon                             Cough
Not known                            Non cardiogenic pulmonary oedema Gastrointestinal disorders
Very rare                            Diarrhoea
Musculoskeletal and connective tissue disorders
Uncommon                             Myalgia
Very rare                            Arthralgia
Renal and urinary disorders
Not known                            Impaired renal function
General disorders and administration site conditions
Uncommon                             Fatigue
Investigations
Not known                            Serum uric acid increased, Serum bilirubin and Serum creatinine increased, Hypokalaemia, Hyponatraemia,
Elevation of Blood Urea Nitrogen, Neutropenia

Additional information on the individual components
Adverse reactions previously reported with one of the individual components may be potential undesirable effects with Co-Diovan as well, even if not observed in clinical trials or during postmarketing period.

Table 2. Frequency of adverse reactions with valsartan

Blood and lymphatic system disorders
Not known                                         Decrease in haemoglobin, decrease in haematocrit, thrombocytopenia
Immune system disorders
Not known                                         Other hypersensitivity/allergic reactions including serum sickness
Metabolism and nutrition disorders
Not known                                         Increase of serum potassium, hyponatraemia Ear and labyrinth disorders
Uncommon                                          Vertigo
Vascular disorders
Not known                                         Vasculitis
Gastrointestinal disorders
Uncommon                                          Abdominal pain
Hepatobiliary disorders
Not known                                         Elevation of liver function values Skin and subcutaneous tissue disorders
Not known                                         Angioedema, dermatitis bullous, rash, pruritus Renal and urinary disorders
Not known                                         Renal failure

CO-DIO API APR22 V1                                         Page 9 of 18    Sweden SmPC 03.2022 Table 3: Frequency of adverse reactions with hydrochlorothiazide

Hydrochlorothiazide has been extensively prescribed for many years, frequently in higher doses than those administered with Co-Diovan. The following adverse reactions have been reported in patients treated with monotherapy of thiazide diuretics, including hydrochlorothiazide: 
Neoplasms benign, malignant and unspecified (incl. cysts and polyps)
Not known                                     Non-melanoma skin cancer (Basal cell carcinoma and Squamous cell carcinoma)
Blood and lymphatic system disorders
Rare                                          Thrombocytopenia sometimes with purpura Very rare                                     Agranulocytosis, leucopenia, haemolytic anaemia, bone marrow failure
Not known                                     Aplastic anemia
Immune system disorders
Very rare                                     Hypersensitivity reactions Metabolism and nutrition disorders
Very common                                   Hypokalaemia, blood lipids increased (mainly at higher doses)
Common                                        Hyponatraemia, hypomagnesaemia, hyperuricaemia
Rare                                          Hypercalcaemia, hyperglycaemia, glycosuria and worsening of diabetic metabolic state
Very rare                                     Hypochloraemic alkalosis Psychiatric disorders
Rare                                          Depression, sleep disturbances Nervous system disorders
Rare                                          Headache, dizziness, paraesthesia Eye disorders
Rare                                          Visual impairment
Not known                                     Choroidal effusion, acute angle-closure glaucoma
Cardiac disorders
Rare                                          Cardiac arrhythmias
Vascular disorders
Common                                        Postural hypotension
Respiratory, thoracic and mediastinal disorders
Very rare                                     Acute respiratory distress syndrome (ARDS) (see section 4.4), respiratory distress including pneumonitis and pulmonary oedema
Gastrointestinal disorders
Common                                          Loss of appetite, mild nausea and vomiting Rare                                            Constipation, gastrointestinal discomfort, diarrhoea
Very rare                                       Pancreatitis
Hepatobiliary disorders
Rare                                            Intrahepatic cholestasis or jaundice Renal and urinary disorders
Not known                                       Renal dysfunction, acute renal failure Skin and subcutaneous tissue disorders
Common                                          Urticaria and other forms of rash Rare                                            Photosensitisation
Very rare                                       Necrotising vasculitis and toxic epidermal necrolysis, cutaneous lupus erythematosus-like

CO-DIO API APR22 V1                                       Page 10 of 18      Sweden SmPC 03.2022 reactions, reactivation of cutaneous lupus erythematosus
Not known                                       Erythema multiforme
General disorders and administration site conditions
Not known                                       Pyrexia, asthenia
Musculoskeletal and connective tissue disorders
Not known                                       Muscle spasm
Reproductive system and breast disorders
Common                                          Impotence

Description of selected adverse reactions
Non-melanoma skin cancer: based on available data from epidemiological studies, cumulative dose-dependent association between hydrochlorothiazide and NMSC has been observed (see also sections 4.4 and 5.1).


Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorization 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/