TANATRIL

Posology- Adults Treatment should be initiated with a daily dose of 5 mg. If optimum control of blood pressure has not been achieved after at least 3 weeks of treatment, the daily dose should be increased to 10 mg, the dose that has been determined to be most effective.

However, for a small number of patients it may be necessary to increase the daily dose to 20 mg (the recommended maximum dose) or preferably, to consider combination therapy with a diuretic. It has not been assessed whether hypertensive patients would benefit from a combination of imidapril with other antihypertensive therapies.

5 mg once a day. The dose should be titrated according to the blood pressure response. The recommended maximum dose is 10 mg once a day. - Renal impairment Imidapril and its pharmacologically active metabolite, imidaprilat, are predominantly excreted via the kidney.

Renal function should be evaluated before commencing therapy with imidapril in patients suspected of renal impairment. 5 mg. 2), imidapril should not be administered to these patients. 3). 5 mg once a day. Imidapril should be used with caution in patients with hepatic impairment.

4). Initiation of therapy requires, if possible, correction in salt and/or body fluids deficiencies, and discontinuation of an existing diuretic therapy for two to three days before ACE inhibition. 5 mg. In hypertensive patients with concomitant cardiac failure symptomatic hypotension has been observed after treatment with ACE inhibitors.

5 mg imidapril once a day under close medical supervision. Patients at high risk for severe acute first dose hypotension should be monitored medically, preferably in hospital, for up to 6-8 hours after administration of the first dose of imidapril and whenever the dose of imidapril or a concomitant diuretic is increased.

5 mg. This also applies to patients with angina pectoris and cerebrovascular disease. These patients are at increased risk to experience myocardial infarction or cerebrovascular accident following excessive hypotension. - Paediatric population The safety and efficacy of this medicine in children have not been established.

No data are available. Method of administration Oral use. It is recommended that the tablets be taken at about the same time of day about 15 minutes before meals, conditions under which efficacy has been demonstrated.

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.

Hypotension Imidapril like other ACE inhibitors may cause a profound fall in blood pressure especially after the first dose. Symptomatic hypotension is rare in uncomplicated hypertensive patients. It is more likely to occur in patients who have been volume depleted by diuretic therapy, dietary salt restriction, dialysis, diarrhoea or vomiting.

It has been reported mainly in patients with severe cardiac failure with or without associated renal insufficiency. This is more likely in patients on high doses of loop diuretics, or those with hyponatraemia or functional renal impairment.

5 mg and careful dose titration. If possible, diuretic treatment should be discontinued temporarily. Such considerations apply also to patients with ischaemic heart- or cerebrovascular disease in whom excessive hypotension could result in a myocardial infarction or cerebrovascular accident.

If the patient develops hypotension, they should be placed in a supine position. Volume repletion with intravenous normal saline may be required. The appearance of hypotension after the initial dose does not preclude subsequent careful dose titration with imidapril after effective management.

- Aortic or mitral valve stenosis/Hypertrophic cardiomyopathy As with others ACE inhibitors, imidapril should be used with caution in patients with an obstruction in the outflow tract of the left ventricle. - Neutropenia/Agranulocytosis Neutropenia/agranulocytosis, thrombocytopenia and anaemia have been reported rarely in patients receiving ACE inhibitors, including imidapril.

In patients with normal renal function and no other complicating factors, neutropenia occurs rarely. Imidapril should be used with extreme caution in patients with collagen vascular disease, immunosuppressant therapy, treatment with allopurinol or procainamide, or a combination of these complicating factors, especially if there is pre-existing impaired renal function.

Some of these patients developed serious infections which in a few instances did not respond to intensive antibiotic therapy. If imidapril is used in such patients, it is advised that white blood cell count and differential counts should be performed prior to therapy, every 2 weeks during the first 3 months of imidapril therapy, and periodically thereafter.

g. sore throat, fever) when a differential white blood cell count should be performed. Imidapril and other concomitant medication should be withdrawn if neutropenia (neutrophils less than 1000/mm3) is detected or suspected. In most patients neutrophil counts rapidly return to normal upon discontinuing imidapril.

- Patients with renal insufficiency Changes in renal function may be anticipated in susceptible individuals due to the inhibition of the renin-angiotensin-aldosterone system. Therefore imidapril like other ACE inhibitors should be used with caution in patients with renal insufficiency.

2). 2). Close monitoring of renal function during therapy should be performed as deemed appropriate. Renal failure has been reported in association with ACE inhibitors, mainly in patients with severe cardiac failure or underlying renal disease, including renal artery stenosis.

Some patients, with no apparent pre-existing renal disease, may develop increases in blood urea and creatinine concentrations when a diuretic is given concomitantly. Dosage reduction of the ACE inhibitor and/or discontinuation of the diuretic may be required.

It is recommended that the renal function be monitored during the first weeks of therapy. - Patients with renovascular hypertension There is an increased risk of hypotension and renal insufficiency when patients with bilateral renal artery stenosis or stenosis of the artery to a single functioning kidney are treated with ACE inhibitors.

Loss of renal function may occur with only mild changes in serum creatinine. In these patients, therapy should be initiated under close medical supervision with low doses, careful titration, and monitoring of renal function. - Patients on haemodialysis Anaphylactoid reactions have been reported in patients dialysed with high-flux membranes and treated concomitantly with an ACE inhibitor.

In these patients consideration should be given to using a different type of dialysis membrane or a different class of antihypertensive agent. - Kidney transplantation There is no experience regarding the administration of imidapril in patients with a recent kidney transplantation - Angioedema Angioedema of the face, extremities, lips, tongue, glottis and/or larynx has been reported in patients treated with ACE inhibitors, including imidapril.

Angioedema can occur immediately after starting ACE inhibitor treatment, however severe angioedema may also develop after months or years of long-term treatment with an ACE inhibitor. In such cases, imidapril should be discontinued promptly and appropriate monitoring should be instituted to ensure complete resolution of symptoms prior to dismissing the patient.

In those instances where swelling has been confined to the face and lips the condition generally resolved without treatment, although antihistamines have been useful in relieving symptoms. Healthcare professionals should review the response to treatment noting standard therapies for histamine-mediated angioedema may be ineffective for bradykinin-mediated angioedema.

Angioedema associated with laryngeal oedema may be fatal. If the tongue, glottis or larynx are involved and airway obstruction is likely, appropriate therapy should be […]

1. - History of angioedema associated with previous ACE inhibitor therapy. - Hereditary/idiopathic angioedema. 6). - Renal failure with or without haemodialysis (creatinine clearance < 10 ml/min). 1). - Concomitant use with sacubitril/valsartan.