Adverse reactions : תופעות לוואי

4.8     Undesirable effects
Although minor side effects are relatively common, significant side effects are infrequent.

Reported side effects are generally associated with diuresis, thiazide therapy, or with the underlying disease.

No increase in the risk of adverse reactions has been seen over those of the individual components.

The following side effects have been reported with Kaluril and additional side-effects of amiloride and hydrochlorothiazide alone:

Immune system disorders: anaphylactic reaction.

Metabolism and nutrition disorders: anorexia, gout, appetite changes, dehydration.
Electrolyte Balance: elevated plasma potassium levels (above 5.5 mmol/l), electrolyte imbalance, hyponatraemia (see 4.4 'Special warnings and precautions for use') and symptomatic hyponatraemia. Hyponatraemia as acomplication is rare, but constitutes a medical emergency as onset may be rapid. The symptoms of hyponatraemia may be non-specific and include nausea, lethargy, weakness, irritability, mental confusion, muscle cramps and anorexia, but it may be an important cause of morbidity. Severe sequelae of hyponatraemia include tonic- clonic seizures and clinical features resembling subarachnoid haemorrhage.

Nervous system disorders: headache, dizziness, sleepiness, syncope, paraesthesia, stupor, poor taste.

Psychiatric disorders: insomnia, nervousness, mental confusion, depression.

Respiratory: dyspnoea.
Eye disorders: visual disturbances.

Ear disorders: vertigo.

Cardiac disorders: arrhythmias, tachycardia, angina pectoris.
Vascular disorders: orthostatic hypotension, flushing.

Respiratory, thoracic and mediastinal disorders: dyspnoea, hiccups, nasal congestion.

Gastrointestinal disorders: nausea, vomiting, diarrhoea, constipation, abdominal pain, gastrointestinal bleeding, abdominal fullness, flatulence.

Skin and subcutaneous tissue disorders: rash, pruritus, diaphoresis.

Musculoskeletal and connective tissue disorders: leg ache, muscle cramps, joint pain, back pain.

Renal and urinary disorders: nocturia, renal dysfunction including renal failure, dysuria, incontinence.

Reproductive system and breast disorders: impotence occurring early in the course of treatment (onset after 2 years unlikely) and reversible on withdrawal of treatment.

General disorders and administration site conditions: chest pain, fatigue, malaise, weakness and thirst.

Injury, poisoning and procedural complications: digitalis toxicity (see 4.5 
Interactions, sub-heading Cardiac Glycosides).

Amiloride:
Gastrointestinal disorders: activation of probable pre-existing peptic ulcer, dyspepsia, dry mouth.

Hepatobiliary disorders: abnormal liver function. A deepening of jaundice has occurred in cirrhotic patients receiving amiloride hydrochloride alone, but the relationship to amiloride is uncertain.
Skin and subcutaneous tissue disorders: alopecia.

Blood and lymphatic system disorders: aplastic anaemia, neutropenia.

Metabolism and nutrition disorders: hyperkalaemia (see also 4.3 Contraindications and 4.4 Special Warnings & Precautions).

Cardiac disorders: one patient with partial heart block developed complete heart block, palpitations.

Psychiatric disorders: decreased libido.

Nervous system disorders: somnolence., encephalopathy, tremors
Respiratory, thoracic and mediastinal disorders: cough.

Ear disorders: tinnitus.
Musculoskeletal and connective tissue disorders: neck/shoulder ache, pain in extremities.

Renal and urinary disorders: polyuria, urinary frequency, bladder spasm.

Investigations: increased intra-ocular pressure.
Hydrochlorothiazide:
Infections and infestations: sialadenitis.

General disorders and administration site conditions: fever.

Vascular disorders: necrotising angiitis, vasculitis.
Gastrointestinal disorders: pancreatitis, cramping, gastric irritation.

Metabolism and nutrition disorders: Hyperglycaemia glycosuria, diabetes mellitus may be aggravated and latent diabetes may become manifest during thiazide administration. Blood-glucose concentrations should be monitored in patients taking antidiabetics, since requirements may change (see 4.5 Interactions).

Hypokalaemia, hypochloraemic alkalosis, the urinary excretion of calcium may be reduced and the potential for hypercalcaemia exists (use in pre- existing hypercalcaemia is contraindicated, see 4.3). Hyperuricaemia may occur or gout may be precipitated or aggravated in patients receiving thiazides.

Nervous system disorders: encephalopathy may be precipitated by hypokalaemia in patients with pre-existing liver disease.

Hepatobiliary disorders: jaundice (intrahepatic cholestatic jaundice).

Skin and subcutaneous tissue disorders: urticaria, photosensitivity, which may persist after thiazide withdrawal, cutaneous vasculitis, purpura, toxic epidermal necrolysis.

Blood and lymphatic system disorders: agranulocytosis, aplastic anaemia, haemolytic anaemia, leucopenia, thrombocytopenia.

Psychiatric disorders: restlessness.

Immune system disorders: hypersensitivity reactions.
Renal and urinary disorders: interstitial nephritis, glycosuria.

Respiratory, thoracic and mediastinal disorders: respiratory distress, including pneumonitis, pulmonary oedema.
Very rare: Acute Respiratory Distress Syndrome (ARDS) (see section 4.4).

Eye disorders: transient blurred vision, xanthopsia, choroidal effusion.

Neoplasms benign, malignant and unspecified (incl cysts and polyps):
Frequency not known: non-melanoma skin cancer (Basal cell carcinoma and Squamous cell carcinoma).

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 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