Adverse reactions : תופעות לוואי

4.8   Undesirable effects

The adverse reactions below are classified where appropriate by system organ class and frequency according to the following convention:

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
Not known:       cannot be estimated from the available data

In clinical trials with losartan potassium salt and hydrochlorothiazide, no adverse reactions peculiar to this combination of substances were observed. The adverse reactions were restricted to those which were formerly observed with losartan potassium salt and/or hydrochlorothiazide.

In controlled clinical trials for essential hypertension, dizziness was the only adverse reaction reported as substance-related that occurred with an incidence greater than placebo in 1% or more of patients treated with losartan and hydrochlorothiazide.

Next to these effects, there are further adverse reactions reported after the introduction of the product to the market as follows:

System organ class             Adverse reaction                                   Frequency Hepato-biliary disorders       hepatitis                                          rare Investigations                 hyperkalaemia, elevation of ALT                    rare 
The adverse reactions that have been seen with one of the individual components and may be potential adverse reactions with losartan potassium/hydrochlorothiazide are the following: 
Losartan:

The following adverse reactions have been reported for losartan in clinical studies and in post- marketing experience:

System organ class             Adverse reaction                                   Frequency Blood and lymphatic            anaemia, Henoch-Schönlein purpura,                 uncommon system disorders               ecchymosis, haemolysis thrombocytopaenia                                  not known
System organ class            Adverse reaction                                  Frequency Cardiac disorders             hypotension, orthostatic hypotension,             uncommon sternalgia, angina pectoris, grade II-AV block,
cerebrovascular event, myocardial infarction,
palpitation, arrhythmias (atrial fibrillations,
sinus bradycardia, tachycardia, ventricular tachycardia, ventricular fibrillation)

Ear and labyrinth disorders   vertigo, tinnitus                                 uncommon Eye disorders                 blurred vision, burning/stinging in the eye,      uncommon conjunctivitis, decrease in visual acuity
Gastrointestinal disorders    abdominal pain, nausea, diarrhea, dyspepsia       common constipation, dental pain, dry mouth,             uncommon flatulence, gastritis, vomiting, obstipation pancreatitis                                      not known
General disorders and         asthenia, fatigue, chest pain                     common administration site           facial oedema, oedema, fever                      uncommon conditions                    flu-like symptoms, malaise                        not known Hepatobiliary disorders       liver function abnormalities                      not known Immune system disorders       hypersensitivity: anaphylactic reactions,         rare angioedema including swelling of the larynx and glottis causing airway obstruction and/or swelling of the face, lips, pharynx, and/or tongue; in some of these patients angioedema had been reported in the past in connection with the administration of other medicines,
including ACE inhibitors;
Metabolism and nutrition      anorexia, gout                                    uncommon disorders
Musculoskeletal and           muscle cramp, back pain, leg pain, myalgia        common connective tissue disorders   arm pain, joint swelling, knee pain,              uncommon musculoskeletal pain, shoulder pain, stiffness,
arthralgia, arthritis, coxalgia, fibromyalgia,
muscle weakness rhabdomyolysis                                    not known
Nervous system disorders      headache, dizziness                               common nervousness, paraesthesia, peripheral             uncommon neuropathy, tremor, migraine, syncope dysgeusia                                         not known
System organ class          Adverse reaction                                  Frequency Psychiatric disorders       insomnia                                          common anxiety, anxiety disorder, panic disorder,        uncommon confusion, depression, abnormal dreams,
sleep disorder, somnolence, memory impairment

Renal and urinary           renal impairment, renal failure                   common disorders                   nocturia, urinary frequency, urinary tract        uncommon infection
Reproductive system and     decreased libido, erectile                        uncommon breast disorders            dysfunction/impotence

Respiratory, thoracic and   cough, upper respiratory infection, nasal         common mediastinal disorders       congestion, sinusitis, sinus disorder pharyngeal discomfort, pharyngitis, laryngitis,   uncommon dyspnoea, bronchitis, epistaxis, rhinitis,
respiratory congestion
Skin and subcutaneous       alopecia, dermatitis, dry skin, erythema,         uncommon tissue disorders            flushing, photosensitivity, pruritus, rash, urticaria, sweating

Vascular disorders          vasculitis                                        uncommon 
 dose-related orthostatic effects                  not known

Investigations              hyperkalaemia, mild reduction of haematocrit      common and haemoglobin, hypoglycaemia mild increase in urea and creatinine serum        uncommon levels increase in hepatic enzymes and bilirubin         very rare hyponatraemia                                     non known

Hydrochlorothiazide

System organ class          Adverse reaction                                  Frequency Blood and lymphatic         agranulocytosis, aplastic anaemia, haemolytic     uncommon system disorders            anaemia, leukopenia, purpura,
thrombocytopaenia

Immune system disorders     anaphylactic reaction                             rare 
Metabolism and nutrition    anorexia, hyperglycaemia, hyperuricaemia,         uncommon disorders                   hypokalaemia, hyponatraemia

Psychiatric disorders       insomnia                                          uncommon 
Nervous system disorders    cephalalgia                                       common 
Eye disorders               transient blurred vision, xanthopsia              uncommon choroidal effusion, acute myopia, acute angle-    not known closure glaucoma
Vascular disorders          necrotizing angiitis (vasculitis, cutaneous       uncommon vasculitis)
System organ class            Adverse reaction                                   Frequency Respiratory, thoracic and     respiratory disorders including pneumonitis        uncommon mediastinal disorders         and pulmonary oedema
 acute respiratory distress syndrome (ARDS)         very rare
(see section 4.4)
Gastrointestinal disorders    sialoadenitis, spasms, stomach irritation,         uncommon nausea, vomiting, diarrhoea, constipation
Hepato-biliary disorders      icterus (intrahepatic cholestasis), pancreatitis   uncommon 
Skin and subcutaneous         photosensitivity, urticaria, toxic epidermal       uncommon tissue disorders              necrolysis
 cutaneous lupus erythematosus                      not known
Musculoskeletal and           muscle cramps                                      uncommon connective tissue disorders



Neoplasms benign,             Non-melanoma skin cancer (basal cell               not known malignant and unspecified     carcinoma and squamous cell carcinoma)
(incl. cysts and polyps)
Renal and urinary             glycosuria, interstitial nephritis, renal          uncommon disorders                     dysfunction, renal failure

General disorders and         fever, dizziness                                   uncommon administration site conditions


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