a. Summary of the safety profile The incidence of adverse events in hypertensive patients on imidapril was 34% with 36% for placebo. Cough, dizziness, fatigue/somnolence, dyspepsia and vomiting occurred more frequently in the imidapril group.
The undesirable effects that have been observed and reported during treatment with imidapril in pre-approval studies are presented in the table below with the following frequencies: 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 (cannot be estimated from the available data).
b. Tabulated list of adverse reactions Pyschiatric disorders Rare Insomnia Nervous system disorders Uncommon Headache, dizziness Rare Dysgeusia, dizziness postural Ear and labyrinth disorders Rare Tinnitus Cardiac disorders Rare Palpitations Vascular disorders Uncommon Hypotension* Respiratory, thoracic and mediastinal disorders Common Cough* Not known Oropharyngeal discomfort Gastrointestinal disorders Rare Nausea*, vomiting*, diarrhoea*, abdominal pain* Skin and subcutaneous tissue disorders Uncommon Rash, pruritus Renal and urinary disorders Rare Renal impairment, proteinuria General disorders and administration site conditions Rare Oedema, fatigue Investigations Rare Alanine aminotransferase increased, blood creatinine increased*, blood urea increased, aspartate aminotransferase increased, red blood cell count decreased, blood lactate dehydrogenase increased, white blood cell count decreased, haemoglobin decreased * See also below section c.
c. Description of selected adverse reactions and class-related adverse reactions The following adverse reactions have been observed in association with imidapril or with other ACE inhibitors. 4). In patients with a congenital deficiency concerning G-6-PDH individual cases of haemolytic anaemia have been reported under other ACE inhibitors.
Nervous system disorders:
Dizziness, weariness, somnolence and fatigue have been reported. Rarely depression, sleep disorders, paresthesias, impotence, disorder of balance, confusion, tinnitus, blurred vision, headache and taste disturbance may occur with ACE inhibitors.
Cardiac disorders:
Severe hypotension may occur after initiation of therapy or increase of dose in certain risk groups. Symptoms like feeling of weakness, impaired vision, rarely with disturbance of consciousness (syncope) can occur in association with hypotension.
Individual cases of tachycardia, palpitations, arrhythmias, angina pectoris, myocardial infarction, transient ischemic attacks and cerebral haemorrhage have been reported for ACE inhibitors in association with hypotension.
Respiratory, thoracic and mediastinal disorders:
ACE inhibitors have been documented to induce cough in a substantial number of patients. Rarely dyspnoea, sinusitis, rhinitis, glossitis, bronchitis, bronchiospasm and angioedema involving the upper airways, and very rarely allergic alveolits/eosinophilic pneumonia may occur with ACE inhibitors.
Gastrointestinal disorders:
Diarrhoea, nausea, vomiting, gastritis, abdominal pain, constipation, dry mouth, cholestatic icterus, hepatitis, pancreatitis and ileus may occur with ACE-inhibitors. Intestinal angioedema has been reported rarely in patients treated with ACE inhibitors.
Symptoms are abdominal pain with or without nausea or vomiting.
Hepatobiliary disorders:
Patients receiving ACE inhibitors have developed jaundice or had marked elevations of hepatic enzymes.
Skin and subcutaneous tissue disorders:
Occasionally allergic and hypersensitivity reactions such as rash, pruritus, exanthema and urticaria can occur. ACE inhibitors have been associated with the onset of angioedema involving the face and oropharyngeal tissues. Cases of erythema multiforme, Steven-Johnson syndrome, toxic epidermic necrolysis, psoriasis-like efflorescences, alopecia and dermatitis exfoliative, photosensitivity reaction were reported for ACE inhibitors.
Cutaneous symptoms can be accompanied by fever, myalgia, arthralgia, eosinophilia and/or increased ANA titers.
Renal and urinary disorders:
Renal insufficiency may rarely occur or be intensified. Acute renal failure has been reported for other ACE inhibitors.
Investigations:
Decreases in haemoglobin, haematocrit, platelets and white cell count as well as elevation of liver enzymes gamma-glutamyltransferase increased, blood alkaline phosphatase increased, serum bilirubin and creatine phosphokinase (CPK) have been reported in a few patients.
Elevation of serum potassium may occur since imidapril leads to a decrease in aldosterone secretion. Increases in blood urea and plasma creatinine, reversible on discontinuation, may occur, especially in the presence of renal insufficiency.
Metabolism and nutrition disorders:
Hyperkalaemia Ear and labyrinth disorders: Vertigo 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.
Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.