AQUMELDI 0.25 MG Orodispersible tablet

Symptomatic hypotension Symptomatic hypotension has been observed in patients with heart failure, with or without associated renal insufficiency.‍‍‍‍‍‍​​​‍​​​​​​ It occurs most commonly in patients with more severe degrees of heart failure, as reflected by the use of high doses of loop diuretics, hyponatraemia or functional renal impairment. In these patients, therapy should be started under medical supervision and patients should be closely monitored whenever the dose of AQUMELDI and/or the diuretic is adjusted. Similar precautions may apply to patients with ischaemic heart disease or cerebrovascular disease, in whom an excessive fall in blood pressure could result in myocardial infarction or cerebrovascular accident. In some patients with heart failure who have normal or low blood pressure, additional lowering of systemic blood pressure may occur with AQUMELDI. This effect is anticipated and is usually not a reason to discontinue treatment. If hypotension becomes symptomatic, it may be necessary to reduce the dose of the diuretic and/or AQUMELDI, or to discontinue treatment. If hypotension occurs, the patient should be placed in a supine position and, if necessary, should receive an intravenous infusion of sodium chloride 9 mg/mL (0.9%) solution. A transient hypotensive response is not a contraindication to further doses, which can usually be administered without difficulty once the blood pressure has risen following volume expansion. Aortic or mitral valve stenosis/hypertrophic cardiomyopathy As with all vasodilators, ACE inhibitors should be used with caution in patients with valvular and left ventricular outflow obstruction and should be avoided in cases of cardiogenic shock and haemodynamically significant obstruction. Renal impairment Renal failure has been reported in association with enalapril, observed particularly in patients with severe heart failure or underlying renal disease, including renal artery stenosis. If promptly recognised and appropriately treated, renal failure associated with enalapril therapy is usually reversible (see section 4.8). In some hypertensive patients with no apparent pre-existing renal disease, increases in blood urea and creatinine have occurred when enalapril was given concomitantly with a diuretic. Dose reduction of enalapril and/or discontinuation of the diuretic may be required (see section 4.2). This situation should raise the possibility of renal artery stenosis (see Renovascular hypertension below). Renovascular hypertension Patients with bilateral renal artery stenosis or stenosis of the artery to a single functioning kidney treated with ACE inhibitors are at increased risk of hypotension and renal insufficiency. 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. Renal transplantation There is no experience with the administration of AQUMELDI in patients with a recent renal transplant; therefore, treatment with AQUMELDI is not recommended in these patients. Hepatic failure Rarely, ACE inhibitor therapy has been associated with a syndrome that starts with cholestatic jaundice or hepatitis and progresses to fulminant hepatic necrosis and (sometimes) death. The mechanism of this syndrome is not understood. Patients receiving ACE inhibitors who develop jaundice or marked elevations of hepatic enzymes should discontinue ACE inhibitor therapy and receive appropriate medical follow-up. Neutropenia/agranulocytosis Neutropenia/agranulocytosis, thrombocytopenia and anaemia have been reported in patients receiving ACE inhibitors. In patients with normal renal function and no other complicating factors, neutropenia occurs rarely. Enalapril 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 enalapril is used in such patients, periodic monitoring of white blood cell counts is advised and patients should be instructed to report any sign of infection. Hypersensitivity/angioedema Angioedema of the face, extremities, lips, tongue, glottis and/or larynx has been reported in patients treated with ACE inhibitors, including enalapril. This may occur at any time during treatment. In such cases, AQUMELDI should be promptly discontinued and appropriate monitoring should be instituted to ensure complete resolution of symptoms before the patient is discharged. Even in those cases where swelling of only the tongue is involved, without respiratory distress, patients may require prolonged observation since treatment with antihistamines and corticosteroids may not be sufficient. Very rarely, fatalities have been reported due to angioedema associated with laryngeal oedema or oedema of the tongue. Patients with involvement of the tongue, glottis or larynx are likely to experience airway obstruction, especially those with a history of airway surgery. Where there is involvement of the tongue, glottis or larynx likely to cause airway obstruction, appropriate therapy should be promptly administered, which may include subcutaneous epinephrine solution 1:1,000 and/or measures to ensure a patent airway. A higher incidence of angioedema has been reported in Black patients receiving ACE inhibitors compared with non-Black patients. Patients with a history of angioedema unrelated to ACE inhibitor therapy may be at increased risk of angioedema while receiving an ACE inhibitor (see section 4.3). Caution should be exercised when starting racecadotril, mTOR inhibitors (e.g. sirolimus, everolimus, temsirolimus) and vildagliptin in patients already taking an ACE inhibitor. Patients taking a concomitant ACE inhibitor and neprilysin inhibitor (e.g. sacubitril, racecadotril) may be at increased risk of angioedema (see section 4.3). Sacubitril/valsartan must not be started until 36 hours after the last dose of enalapril. If sacubitril/valsartan therapy is discontinued, enalapril therapy must not be started until 36 hours after the last dose of sacubitril/valsartan (see section 4.5). Anaphylactoid reactions during hymenoptera venom desensitisation Rarely, patients receiving ACE inhibitors during desensitisation with hymenoptera venom have experienced life-threatening anaphylactoid reactions. These reactions were avoided by temporarily withholding ACE inhibitor therapy prior to each desensitisation. Anaphylactoid reactions during LDL apheresis Rarely, patients receiving ACE inhibitors during low-density lipoprotein (LDL) apheresis with dextran sulphate have experienced life-threatening anaphylactoid reactions. These reactions were avoided by temporarily withholding ACE inhibitor therapy prior to each apheresis. Haemodialysis patients Anaphylactoid reactions have been reported in patients dialysed with high-flux membranes (e.g. AN 69®) and concomitantly treated 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. Hypoglycaemia Diabetic patients treated with oral antidiabetic agents or insulin starting ACE inhibitor therapy should be told to closely monitor for hypoglycaemia, especially during the first month of combined use (see section 4.5). Cough Cough has been reported with the use of ACE inhibitors. Characteristically, the cough is non-productive, persistent and resolves after discontinuation of therapy. ACE inhibitor-induced cough should be considered as part of the differential diagnosis of cough. Surgery/anaesthesia In patients undergoing major surgery or during anaesthesia with agents that produce hypotension, enalapril blocks angiotensin II formation secondary to compensatory renin release. If hypotension occurs and is considered to be due to this mechanism, it can be corrected by volume expansion. Hyperkalaemia Elevations in serum potassium have been observed in some patients treated with ACE inhibitors, including enalapril. Risk factors for the development of hyperkalaemia include renal insufficiency, worsening of renal function, older age (over 70 years), diabetes mellitus, intercurrent events, in particular dehydration, acute cardiac decompensation, metabolic acidosis and concomitant use of potassium-sparing diuretics (such as spironolactone, eplerenone, triamterene or amiloride), potassium supplements or potassium-containing salt substitutes; or use of other medicinal products associated with increases in serum potassium (such as heparin or trimethoprim-containing products, for example co-trimoxazole). Neonates are at increased risk of hyperkalaemia. The use of potassium supplements, potassium-sparing diuretics, potassium-containing salt substitutes or other medicinal products that may increase serum potassium levels, especially in patients with impaired renal function, may lead to a significant increase in serum potassium. Hyperkalaemia can cause serious, sometimes fatal arrhythmia. If concomitant use of enalapril and any of the above-mentioned agents is deemed appropriate, they should be used with caution and with frequent monitoring of serum potassium (see section 4.5). Lithium The combination of lithium and enalapril is generally not recommended (see section 4.5). Dual blockade of the renin-angiotensin-aldosterone system (RAAS) Concomitant use of ACE inhibitors, angiotensin II receptor blockers or aliskiren has been shown to increase the risk of hypotension, hyperkalaemia and decreased renal function (including acute renal failure). Dual blockade of RAAS through the combined use of ACE inhibitors, angiotensin II receptor blockers or aliskiren is therefore not recommended (see section 5.1). If dual blockade therapy is considered absolutely necessary, this should only occur under specialist supervision and subject to frequent close monitoring of renal function, electrolytes and blood pressure. ACE inhibitors and angiotensin II receptor blockers should not be used concomitantly in patients with diabetic nephropathy. Pregnancy ACE inhibitor therapy should not be initiated during pregnancy. Unless continued ACE inhibitor therapy is considered essential, patients planning pregnancy should be switched to alternative treatments with an established safety profile for use in pregnancy. When pregnancy is diagnosed, ACE inhibitor therapy should be stopped immediately and, if appropriate, alternative therapy should be started (see section 4.6). Ethnic differences As with other ACE inhibitors, enalapril appears to be less effective in lowering blood pressure in Black individuals compared with other ethnicities, possibly because of a higher prevalence of low-renin states in the Black hypertensive population. Paediatric population AQUMELDI is not recommended in children for indications other than heart failure. Caution is recommended in children younger than 1 month, as these children may be very sensitive to the medicinal product. Data on the use of AQUMELDI in clinical studies with children younger than 1 month are limited (n = 4). All signs of adverse events and electrolytes should be carefully monitored. Hepatic impairment No data are available on the treatment of paediatric patients with pre-existing liver disease. Therefore, paediatric patients with pre-existing hepatic impairment may only be treated with enalapril under strict monitoring. Treatment is not recommended in children with hepatic impairment who are younger than 1 month. Sodium AQUMELDI contains less than 1 mmol (23 mg) sodium per tablet, that is to say it is essentially 'sodium-free'.