Enalapril STELLA 10 mg

Rx

Indications

• Treatment of hypertension.
  
• Treatment of symptomatic heart failure. 
• Prevention of symptomatic heart failure in patients with asymptomatic left ventricular dysfunction (ejection fraction ≤ 35%).

Dosage

• Hypertension
  Initial dose: 5 to maximally 20 mg, depending on the degree of hypertension and the condition of the patient. Enalapril maleate is given once daily. In mild hypertension, the recommended initial dose is 5 to 10 mg.
  Patients with a strongly activated renin-angiotensin-aldosterone system, (e.g. renovascular hypertension, salt and/or volume depletion, cardiac decompensation, or severe hypertension) may experience an excessive blood pressure fall following the initial dose. A starting dose of 5 mg or lower is recommended in such patients and the initiation of treatment should take place under medical supervision.
  Prior treatment with high dose diuretics may result in volume depletion and a risk of hypotension when initiating therapy with enalapril. A starting dose of 5 mg or lower is recommended in such patients. If possible, diuretic therapy should be discontinued for 2 – 3 days prior to initiation of therapy with Enalapril STELLA 10 mg.
• Renal function and serum potassium should be monitored.
  The usual maintenance dose: 20 mg daily.
  The maximum maintenance dose is 40 mg daily.
• Heart failure/asymptomatic left ventricular dysfunction
  In the management of symptomatic heart failure, enalapril maleate is used in addition to diuretics and, where appropriate, digitalis or beta-blockers. The initial dose of Enalapril STELLA 10 mg in patients with symptomatic heart failure or asymptomatic left ventricular dysfunction is 2.5 mg, and it should be administered under close medical supervision to determine the initial effect on the blood pressure. In the absence of, or after effective management of, symptomatic hypotension following initiation of therapy with Enalapril STELLA 10 mg in heart failure, the dose should be increased gradually to the usual maintenance dose of 20 mg, given in a single dose or two divided doses, as tolerated by the patient. This dose titration is recommended to be performed over a 2 to 4 week period. The maximum dose is 40 mg daily given in two divided doses.
  Blood pressure and renal function should be monitored closely both before and after starting treatment with Enalapril STELLA 10 mg because hypotension and (more rarely) consequent renal failure have been reported. In patients treated with diuretics, the dose should be reduced if possible before beginning treatment with Enalapril STELLA 10 mg. The appearance of hypotension after the initial dose of Enalapril STELLA 10 mg does not imply that hypotension will recur during chronic therapy with Enalapril STELLA 10 mg and does not preclude continued use of the drug. Serum potassium and renal function also should be monitored.
• In renal insufficiency
  Generally, the intervals between the administration of enalapril should be prolonged and/or the dosage reduced.
• Use in elderly
  The dose should be in line with the renal function of the elderly patient.
• Use in paediatrics
  There is limited clinical trial experience of the use of enalapril in hypertensive paediatric patients.
  For patients who can swallow tablets, the dose should be individualised according to patient profile and blood pressure response. The recommended initial dose is 2.5 mg in patients 20 to < 50 kg and 5 mg in patients ≥ 50 kg. Enalapril maleate is given once daily.
  The dosage should be adjusted according to the needs of the patient to a maximum of 20 mg daily in patients 20 to < 50 kg and 40 mg in patients ≥ 50 kg.
  Enalapril STELLA 10 mg are not recommended in neonates and in paediatric patients with glomerular filtration rate < 30 ml/ min/1.73 m2, as no data are available.

Usage

• Administered orally, regardless to meals.

• Hypersensitivity to the active substance or to any of the excipients listed or any other ACE inhibitor.
• History of angioedema associated with previous ACE-inhibitor therapy.
• Hereditary or idiopathic angioedema.
• Second and third trimesters of pregnancy.
• The concomitant use of Enalapril STELLA 10 mg with aliskiren containing products is contraindicated in patients with diabetes mellitus or renal impairment (GFR < 60 ml/min/1.73m²).
• Combination with sacubitril/valsartan due to the increased risk of angioedema. Do not administer Enalapril STELLA 10 mg within 36 hours of switching to or from sacubitril/valsartan, a product containing a neprilysin inhibitor.

Very common

• Dizziness;
• Blurred vision;
• Cough;
• Nausea;
• Asthenia.

Common

• Depression;
• Headache, syncope, taste alteration;
• Chest pain, rhythm disturbances, angina pectoris, tachycardia;
• Hypotension (including orthostatic hypotension);
• Dyspnoea;
• Diarrhoea, abdominal pain;
• Angioneurotic oedema of the face, extremities, lips, tongue, glottis and/or larynx;
• Fatigue;
• Hyperkalaemia, increases in serum creatinine.

• In hypertensive patients receiving Enalapril STELLA 10 mg, symptomatic hypotension is more likely to occur if the patient has been volume-depleted, e.g. by diuretic therapy, dietary salt restriction, dialysis, diarrhoea or vomiting. In patients with heart failure, with or without associated renal insufficiency, symptomatic hypotension has been observed.
  This is most likely to occur in those 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 the patients should be followed closely whenever the dose of Enalapril STELLA 10 mg and/or diuretic is adjusted. Similar considerations may apply to patients with ischaemic heart or cerebrovascular disease in whom an excessive fall in blood pressure could result in a 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 enalapril. This effect is anticipated,and usually is not a reason to discontinue treatment. If hypotension becomes symptomatic, a reduction of dose and/or discontinuation of the diuretic and/or Enalapril STELLA 10 mg may be necessary.
• As with all vasodilators, ACE inhibitors should be given with caution in patients with left ventricular valvular and outflow tract obstruction and avoided in cases of cardiogenic shock and haemodynamically significant obstruction.
• In cases of renal impairment (creatinine clearance < 80 ml/min) the initial enalapril dosage should be adjusted according to the patient’s creatinine clearance and then as a function of the patient’s response to treatment.
  Routine monitoring of potassium and creatinine are part of normal medical practice for these patients.
  Renal failure has been reported in association with enalapril and has been mainly in patients with severe heart failure or underlying renal disease, including renal artery stenosis. If recognized promptly and treated appropriately, renal failure when associated with therapy with enalapril is usually reversible.
  Some hypertensive patients, with no apparent pre-existing renal disease have developed increases in blood urea and creatinine when enalapril has been given concurrently with a diuretic. Dosage reduction of enalapril and/or discontinuation of the diuretic may be required. This situation should raise the possibility of underlying renal artery stenosis.
• 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..
• There is no experience regarding the administration of enalapril maleate in patients with a recent kidney transplantation. Treatment with Enalapril STELLA 10 mg is therefore not recommended.
• Rarely, ACE inhibitors have been associated with a syndrome that starts with cholestatic eath. The mechanism of this syndrome is not understood. Patients receiving ACE inhibitors who develop jaundice or marked elevations of hepatic enzymes should discontinue the ACE inhibitor and receive appropriate medical follow-up.
• 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.
• Angioneurotic oedema of the face, extremities, lips, tongue, glottis and/or larynx has been reported in patients treated with angiotensin-converting enzyme inhibitors, including enalapril maleate. This may occur at any time during treatment. In such cases, Enalapril STELLA 10 mg should be discontinued promptly and appropriate monitoring should be instituted to ensure complete resolution of symptoms prior to dismissing the patient. Even in those instances 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.
• Black patients receiving ACE inhibitors have been reported to have a higher incidence of angioedema compared to nonblacks. Patients with a history of angioedema unrelated to ACE inhibitor therapy may be at increased risk of angioedema while receiving an ACE inhibitor.
• Patients receiving co-administration of ACE inhibitor and mTOR (mammalian target of rapamycin) inhibitor (e.g., temsirolimus, sirolimus, everolimus) therapy may be at increased risk for angioedema.
  Patients receiving concomitant ACE inhibitor and neprilysin inhibitor therapy (e.g., sacubitril, racecadotril) may be at increased risk for angioedema. The combination of enalapril with sacubitril/valsartan is contraindicated due to the increased risk of angioedema.
  Sacubitril/valsartan must not be initiated until 36 hours after taking the last dose of enalapril therapy. If treatment with sacubitril/valsartan is stopped, enalapril therapy must not be initiated until 36 hours after the last dose of sacubitril/valsartan.
• Rarely, patients receiving ACE inhibitors during desensitization with hymenoptera venom have experienced lifethreatening anaphylactoid reactions. These reactions were avoided by temporarily withholding ACE-inhibitor therapy prior to each desensitisation.
• Rarely, patients receiving ACE inhibitors during low density lipoprotein (LDL)-apheresis with dextran sulfate have experienced life-threatening anaphylactoid reactions. These reactions were avoided by temporarily withholding ACE inhibitor therapy prior to each apheresis.
• Anaphylactoid reactions have been reported in patients dialysed with high-flux membranes (e.g. AN 69®) 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.
• Diabetic patients treated with oral antidiabetic agents or insulin, starting an ACE inhibitor, should be told to closely monitor for hypoglycaemia, especially during the first month of combined use.
• Cough has been reported with the use of ACE inhibitors. Characteristically, the cough is non-productive, persistent and resolves after discontinuation of therapy.
• In patients undergoing major surgery or during anaesthesia with agents that produce hypotension, enalapril blocks angiotensin II formation secondary to compensatory rennin release. If hypotension occurs and is considered to be due to this mechanism, it can be corrected by volume expansion.
• Elevations in serum potassium have been observed in some patients treated with ACE inhibitors, including enalapril. Risk factors for the development of hyperkalaemia include those with renal insufficiency, worsening of renal function, age (> 70 years), diabetes mellitus, inter-current events in particular dehydration, acute cardiac decompensation, metabolic acidosis, and concomitant use of potassium-sparing diuretics (e.g., spironolactone, eplerenone, triamterene, or amiloride), potassium supplements or potassium-containing salt substitutes; or those patients taking other drugs associated with increases in serum potassium, (e.g. heparin, trimethoprim-containing products such as cotrimoxazole).
  The use of potassium supplements, potassium-sparing diuretics, potassium-containing salt substitutes, or other drugs that may increase serum potassium, particularly in patients with impaired renal function may lead to a significant increase in serum potassium.
  Hyperkalaemia can cause serious, sometimes fatal arrhythmias. 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.
• The combination of lithium and enalapril is generally not recommended.
• There is evidence that the concomitant use of ACE-inhibitors, angiotensin II receptor blockers or aliskiren increases the risk of hypotension, hyperkalaemia and decreased renal function (including acute renal failure). Dual blockage of RAAS through the combined use of ACE inhibitors, angiotensin II receptor blockers (ARB) or aliskiren is therefore not recommended.
  If dual blockage 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.
• Paediatric population
  There is limited efficacy and safety experience in hypertensive children > 6 years old, but no experience in other indications. Limited pharmacokinetic data are available in children above 2 months of age. Enalapril STELLA 10 mg are not recommended in children in other indications than hypertension.
  Enalapril STELLA 10 mg are not recommended in neonates and in paediatric patients with glomerular filtration rate < 30 ml/min/1.73 m2, as no data are available.
• As with other angiotensin converting enzyme inhibitors, enalapril is apparently less effective in lowering blood pressure in black people than in non-blacks, possibly because of a higher prevalence of low-renin states in the black hypertensive population.
• Enalapril STELLA 10 mg contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.
• Pregnancy n lactation
  ACE inhibitors should not be initiated during pregnancy. Unless continued ACE inhibitor therapy is considered essential, patients planning pregnancy should be changed to alternative antihypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with ACE inhibitors should be stopped immediately, and, if appropriate, alternative therapy should be started.
  The use of Enalapril STELLA 10 mg in breastfeeding is not recommended for preterm infants and for the first few weeks after delivery, because of the hypothetical risk of cardiovascular and renal effects and because there is not enough clinical experience. In the case of an older infant, the use of Enalapril STELLA 10 mg in a breast-feeding mother may be considered if this treatment is necessary for the mother and the child is observed for any adverse effect.
• When driving vehicles or operating machines it should be taken into account that occasionally dizziness or weariness may occur.