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  • Enaladex
    / Dexcel


    Active Ingredient
    Enalapril Maleate 5, 10, 20 mg

    Status in Israel
    RX

    Presentation and Status in Health Basket

    Presentation Basket Yarpa Pharmasoft

    Tablets

    30 X 5 mg

    full basket chart 22582 5028

    Tablets

    30 X 10 mg

    full basket chart 22583 5029

    Tablets

    30 X 20 mg

    full basket chart 22584 5152

    Related information


    Dosage

    Posology: The absorption of enalapril maleate is not affected by food.
    The dose should be individualized according to patient profile and blood pressure response.
    Paediatric population: There is limited clinical trial experience of the use of enalapril in hypertensive paediatric patients.
    Hypertension: The initial dose is 5 to maximally 20 mg, depending on the degree of hypertension and the condition of the patient (see below). 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 Maleate Tablets. Renal function and serum potassium should be monitored.
    The usual maintenance dose is 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 Enaladex 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 Maleate Tablets 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.
    Suggested Dosage Titration of Enaladex in Patients with Heart Failure/Asymptomatic Left Ventricular Dysfunction:
    Week 1: 
    Days 1 to 3: 2.5 mg/day1 in a single dose; Days 4 to 7: 5 mg/day in two divided doses.
    Week 2: 10 mg/day in a single dose or in two divided doses.
    Weeks 3 and 4: 20 mg/day in a single dose or in two divided doses.
    1Special precautions should be followed in patients with impaired renal function or taking diuretics.

    Blood pressure and renal function should be monitored closely both before and after starting treatment with Enaladex 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 Enaladex. The appearance of hypotension after the initial dose of Enaladex does not imply that hypotension will recur during chronic therapy with Enaladex and does not preclude continued use of the drug. Serum potassium and renal function also should be monitored.
    Dosage in Renal Insufficiency: Generally, the intervals between the administration of enalapril should be prolonged and/or the dosage reduced.
    Creatinine Clearance (CrCL) mL/min: 30<CrCL<80 ml/min: Initial Dose is 5-10 mg/day.
    Creatinine Clearance (CrCL) mL/min: 10<CrCL≤30 ml/min: Initial Dose is 2.5 mg/day.
    Creatinine Clearance (CrCL) mL/min: ≤10 ml/min: Initial Dose is 2.5 mg on dialysis days.

    Enalaprilat is dialysable. Dosage on non-dialysis days should be adjusted depending on the blood pressure response.
    Use in Elderly: The dose should be in line with the renal function of the elderly patient.
    Use in Paediatrics: 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.
    Enaladex Tablets are not recommended in neonates and in paediatric patients with glomerular filtration rate <30 ml/min/1.73 m2, as no data are available.
    Method of administration: Oral use.


    Indications

    Treatment of essential hypertension.
    Treatment of renovascular hypertension.
    Treatment of congestive heart failure and to reduce mortality in patients with all degrees of heart failure.
    To retard the development of symptomatic heart failure in asymptomatic patients with left ventricular dysfunction.


    Contra-Indications

    Hypersensitivity to the active substance or to any of the excipients 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 Enaladex with aliskiren containing products is contraindicated in patients with diabetes mellitus or renal impairment (GFR <60ml/min/1.73 m²).
    Combination with sacubitril/valsartan due to the increased risk of angioedema. Do not administer Enaladex within 36 hours of switching to or from sacubitril/valsartan, a product containing a neprilysin inhibitor.


    Special Precautions

    Symptomatic hypotension is rarely seen in uncomplicated hypertensive patients. In hypertensive patients receiving Enaladex, 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 Enaladex 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.
    If hypotension occurs, the patient should be placed in the supine position and, if necessary, should receive an intravenous infusion of normal saline. A transient hypotensive response is not a contraindication to further doses, which can be given usually without difficulty once the blood pressure has increased after volume expansion.
    In some patients with heart failure who have normal or low blood pressure, additional lowering of systemic blood pressure may occur with Enaladex. 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 Enaladex may be necessary.
    Aortic or Mitral Valve Stenosis/Hypertrophic Cardiomyopathy: 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.
    Renal Function Impairment: 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.
    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.
    Kidney Transplantation: There is no experience regarding the administration of enalapril maleate in patients with a recent kidney transplantation. Treatment with Enaladex is therefore not recommended.
    Hepatic Failure: Rarely, ACE inhibitors have 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 the ACE inhibitor 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/Angioneurotic Oedema: 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, Enaladex 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.
    Very rarely, fatalities have been reported due to angioedema associated with laryngeal oedema or tongue oedema. 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, which may include subcutaneous epinephrine solution 1:1000 (0.3 ml to 0.5 ml) and/or measures to ensure a patent airway, should be administered promptly.
    Black patients receiving ACE inhibitors have been reported to have a higher incidence of angioedema compared to non-blacks.
    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.
    Anaphylactoid Reactions during Hymenoptera Desensitisation: Rarely, patients receiving ACE inhibitors during desensitization with hymenoptera venom have experienced life-threatening anaphylactoid reactions. These reactions were avoided by temporarily withholding ACE-inhibitor therapy prior to each desensitization.
    Anaphylactoid Reactions during LDL Apheresis: 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.
    Haemodialysis Patients: 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.
    Hypoglycaemia: 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: 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 rennin 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 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 co-trimoxazole). 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.
    Lithium: The combination of lithium and enalapril is generally not recommended.
    Dual blockade of the renin-angiotensin-aldosterone system (RAAS): There is evidence that the concomitant use of ACE-inhibitors, angiotensin II receptor blockers or aliskiren increases the risk of hypotension, hyperkaleaemia 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.
    Lactose: Enaladex contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.
    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. Enaladex Tablets are not recommended in children in other indications than hypertension.
    Enaladex Tablets are not recommended in neonates and in paediatric patients with glomerular filtration rate <30 ml/min/1.73m2, as no data are available.
    Pregnancy: 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.
    Ethnic Differences: 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.


    Side Effects

    Undesirable effects reported for enalapril include:
    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).
    Blood and the lymphatic system disorders:
    uncommon: anaemia (including aplastic and hemolytic)
    rare: neutropenia, decreases in haemoglobin, decreases in haematocrit, thrombocytopenia, agranulocytosis, bone marrow depression, pancytopenia, lymphadenopathy, autoimmune diseases.
    Endocrine disorders:
    not known: syndrome of inappropriate antidiuretic hormone secretion (SIADH).
    Metabolism and nutrition disorders:
    uncommon: hypoglycaemia
    Psychiatric disorders:
    common: depression
    uncommon: confusion, insomnia, nervousness
    rare: dream abnormality, sleep disorders
    Nervous system disorders:
    very common: dizziness
    common: headache, syncope, taste alteration
    uncommon: somnolence, paresthesia, vertigo
    Eye disorders:
    very common: blurred vision
    Ear and labyrinth disorders:
    uncommon: tinnitus
    Cardiac disorders:
    common: chest pain, rhythm disturbances, angina pectoris, tachycardia
    uncommon: palpitations, myocardial infarction or cerebrovascular accident*, possibly secondary to excessive hypotension in high-risk patients
    Vascular disorders:
    common: hypotension (including orthostatic hypotension)
    uncommon: flushing, orthostatic hypotension
    rare: Raynaud’s phenomenon
    Respiratory, thoracic and mediastinal disorders:
    very common: cough
    common: dyspnoea
    uncommon: rhinorrhoea, sore throat and hoarseness, bronchospasm/asthma
    rare: pulmonary infiltrates, rhinitis, allergic alveolitis/eosinophilic pneumonia
    Gastro-intestinal disorders:
    very common: nausea
    common: diarrhoea, abdominal pain
    uncommon: ileus, pancreatitis, vomiting, dyspepsia, constipation, anorexia, gastric irritations, dry mouth, peptic ulcer
    rare: stomatitis/aphthous ulcerations, glossitis
    very rare: intestinal angioedema.
    Hepatobiliary disorders:
    rare: hepatic failure, hepatitis – either hepatocellular or cholestatic, hepatitis including necrosis, cholestasis (including jaundice)
    Skin and subcutaneous tissue disorders:
    common: rash, hypersensitivity/angioneurotic oedema: angioneurotic oedema of the face, extremities, lips, tongue, glottis and/or larynx has been reported
    uncommon: diaphoresis, pruritus, urticaria, alopecia
    rare: erythema multiforme, Stevens-Johnson syndrome, exfoliative dermatitis, toxic epidermal necrolysis, pemphigus, erythroderma
    not known: A symptom complex has been reported which may include some or all of the following: fever, serositis, vasculitis, myalgia/myositis, arthralgia/arthritis, a positive ANA, elevated ESR, eosinophilia, and leukocytosis. Rash, photosensitivity or other dermatologic manifestations may occur.
    Musculoskeletal, connective tissue, and bone disorders
    Uncommon: muscle cramps
    Renal and urinary disorders:
    uncommon: renal dysfunction, renal failure, proteinuria
    rare: oliguria
    Reproductive system and breast disorders:
    uncommon: impotence
    rare: gynecomastia
    General disorders and administration site conditions:
    very common: asthenia
    common: fatigue
    uncommon: malaise, fever
    Investigations:
    common: hyperkalaemia, increases in serum creatinine
    uncommon: increases in blood urea, hyponatraemia
    rare: elevations of liver enzymes, elevations of serum bilirubin.
    * Incidence rates were comparable to those in the placebo and active control groups in the clinical trials


    Drug interactions

    Dual blockade of the renin-angiotensin-aldosterone system (RAAS): Clinical trial data has shown that dual blockade of the renin-angiotensin-aldosterone-system (RAAS) through the combined use of ACE-inhibitors, angiotensin II receptor blockers or aliskiren is associated with a higher frequency of adverse events such as hypotension, hyperkalaemia and decreased renal function (including acute renal failure) compared to the use of a single RAAS-acting agent.
    Potassium sparing diuretics, potassium supplements, or other drugs that may increase serum potassium: ACE inhibitors attenuate diuretic-induced potassium loss. Potassium sparing diuretics (e.g. spironolactone, eplerenone, triamterene or amiloride), potassium supplements, potassium-containing salt substitutes, or other drugs that may increase serum potassium (e.g., heparin, trimethoprim-containing products such as co-trimoxazole) may lead to significant increases in serum potassium. 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.
    Diuretics (thiazide or loop diuretics): Prior treatment with high dose diuretics may result in volume depletion and a risk of hypotension when initiating therapy with enalapril. The hypotensive effects can be reduced by discontinuation of the diuretic, by increasing volume or salt intake or by initiating therapy with a low dose of enalapril.
    Other antihypertensive agents: Concomitant use of these agents may increase the hypotensive effects of enalapril.
    Concomitant use with nitroglycerine and other nitrates, or other vasodilators, may further reduce blood pressure.
    Lithium: Reversible increases in serum lithium concentrations and toxicity have been reported during concomitant administration of lithium with ACE inhibitors. Concomitant use of thiazide diuretics may further increase lithium levels and enhance the risk of lithium toxicity with ACE inhibitors. Use of enalapril with lithium is not recommended, but if the combination proves necessary, careful monitoring of serum lithium levels should be performed.
    Tricyclic antidepressants/Antipsychotics/Anaesthetics/Narcotics:
    Concomitant use of certain anaesthetic medicinal products, tricyclic antidepressants and antipsychotics with ACE inhibitors may result in further reduction of blood pressure.
    Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) Including Selective Cyclooxygenase-2 (COX-2) Inhibitors: Non-steroidal anti-inflammatory drugs (NSAIDs) including selective cyclooxygenase-2 Inhibitors (COX-2 inhibitors) may reduce the effect of diuretics and other antihypertensive drugs. Therefore, the antihypertensive effect of angiotensin II receptor antagonists or ACE inhibitors may be attenuated by NSAIDs including selective COX-2 inhibitors.
    The co-administration of NSAIDs (including COX-2 inhibitors) and angiotensin II receptor antagonists or ACE inhibitors exert an additive effect on the increase in serum potassium, and may result in a deterioration of renal function. These effects are usually reversible. Rarely, acute renal failure may occur, especially in patients with compromised renal function (such as the elderly or patients who are volume-depleted, including those on diuretic therapy). Therefore, the combination should be administered with caution in patients with compromised renal function. Patients should be adequately hydrated and consideration should be given to monitoring renal function after initiation of concomitant therapy and periodically thereafter.
    Gold: Nitritoid reactions (symptoms include facial flushing, nausea, vomiting and hypotension) have been reported rarely in patients on therapy with injectable gold (sodium aurothiomalate) and concomitant ACE inhibitor therapy including enalapril.
    Mammalian Target of Rapamycin (mTOR) Inhibitors: Patients taking concomitant mTOR inhibitor (e.g., temsirolimus, sirolimus, everolimus) therapy may be at increased risk for angioedema.
    Neprilysin Inhibitors: Patients receiving concomitant ACE inhibitor and neprilysin inhibitor therapy (e.g., sacubitril, racecadotril) may be at increased risk for angioedema. The concomitant use of enalapril with sacubitril/valsartan is contraindicated, as the concomitant inhibition of neprilysin and ACE may increase the risk of angioedema.
    Sacubitril/valsartan must not be started until 36 hours after taking the last dose of enalapril therapy. Enalapril therapy must not be started until 36 hours after the last dose of sacubitril/valsartan.
    Sympathomimetics: Sympathomimetics may reduce the antihypertensive effects of ACE inhibitors.
    Antidiabetics: Epidemiological studies have suggested that concomitant administration of ACE inhibitors and antidiabetic medicines (insulins, oral hypoglycemic agents) may cause an increased blood-glucose-lowering effect with risk of hypoglycemia. This phenomenon appeared to be more likely to occur during the first weeks of combined treatment and in patients with renal impairment.
    Alcohol: Alcohol enhances the hypotensive effect of ACE inhibitors.
    Acetylsalicylic acid, thrombolytics and β- blockers: Enalapril can be safely administered concomitantly with acetyl salicylic acid (at cardiologic doses), thrombolytics and β- blockers.
    Paediatric population: Interaction studies have only been performed in adults.


    Pregnancy and Lactation

    Pregnancy: ACE inhibitors: The use of ACE inhibitors is not recommended during the first trimester of pregnancy. The use of ACE inhibitors is contraindicated during the second and third trimesters of pregnancy.
    Epidemiological evidence regarding the risk of teratogenicity following exposure to ACE inhibitors during the first trimester of pregnancy has not been conclusive; however a small increase in risk cannot be excluded. 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. Exposure to ACE inhibitor therapy during the second and third trimesters is known to induce human foetotoxicity (decreased renal function, oligohydramnios, skull ossification retardation) and neonatal toxicity (renal failure, hypotension, hyperkalaemia). Maternal oligohydramnios, presumably representing decreased fetal renal function, has occurred and may result in limb contractures, craniofacial deformations and hypoplastic lung development.
    Should exposure to ACE inhibitor have occurred from the second trimester of pregnancy, ultrasound check of renal function and skull is recommended.
    Infants whose mothers have taken ACE inhibitors should be closely observed for hypotension.
    Lactation: Limited pharmacokinetic data demonstrate very low concentrations in breast milk. Although these concentrations seem to be clinically irrelevant, the use of Enaladex 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 Enaladex 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.


    Overdose

    Limited data are available for overdosage in humans. The most prominent features of overdosage reported to date are marked hypotension, beginning some six hours after ingestion of tablets, concomitant with blockade of the renin-angiotensin system, and stupor. Symptoms associated with overdosage of ACE inhibitors may include circulatory shock, electrolyte disturbances, renal failure, hyperventilation, tachycardia, palpitations, bradycardia, dizziness, anxiety, and cough. Serum enalaprilat levels 100- and 200-fold higher than usually seen after therapeutic doses have been reported after ingestion of 300 mg and 440 mg of enalapril, respectively.
    The recommended treatment of overdosage is intravenous infusion of normal saline solution. If hypotension occurs, the patient should be placed in the shock position. If available, treatment with angiotensin II infusion and/or intravenous catecholamines may also be considered. If ingestion is recent, take measures aimed at eliminating enalapril maleate (e.g. emesis, gastric lavage, administration of absorbents, and sodium sulfate). Enalaprilat may be removed from the general circulation by haemodialysis.
    Pacemaker therapy is indicated for therapy-resistant bradycardia. Vital signs, serum electrolytes and creatinine concentrations should be monitored continuously.


    Important notes

    Lactose: Enaladex contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.
    Alcohol: Alcohol enhances the hypotensive effect of ACE inhibitors.
    See prescribing information for full details.


    Manufacturer
    Dexcel Ltd.
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