Acetec

Enalapril maleate.

Each tablet contains: Enalapril maleate 5 mg and 20 mg.

Pharmacology: Pharmacodynamics: Enalapril is an angiotensin converting enzyme inhibitors, acts primarily through suppression of the renin-angiotensin-aldosterone system.
Following oral administration, enalapril is rapidly absorbed and then hydrolysed to enalaprilat, which a highly specific, long-acting, non-sulfhydryl angiotensin-converting enzyme inhibitors.
It prevents the conversion of angiotensin I to angiotensin II by inhibiting angiotensin converting enzyme (ACE) and also inhibit local angiotensin II at vascular and renal sites and attenuate the release of catecholamine from adrenal nerve endings.
Inhibiting ACE results in decrease plasma angiotensin II and increased plasma renin activity (PRA). This leads to decrease aldosterone secretion, resulting in small increase in serum potassium, and sodium and fluid loss.
Enalaprilat produce a reduction of peripheral arterial resistance in hypertensive patients, and either no change or an increase in cardiac output. Renal blood flow increases, but glomerular filtration rate is usually unchanged. Peak blood pressure reduction is achieved by 4 to 6 hours. To achieve maximum effects, several weeks of therapy may be required.
Pharmacokinetics: Enalapril maleate is rapidly absorbed from gastro-intestinal tract, approximately 60% of a dose is absorbed and peak serum concentrations occur within about one hour. Enalapril absorption is not influenced by the presence of food.
Enalapril is metabolised in the liver by hydrolysis to enalaprilat, the active metabolite. Excretion of enalapriat and enalapril is primarily renal.
Approximately 94% of the dose is recovered in the urine and feces as enalaprilat or enalapril. The principle components in urine are enalaprilat, accounting for about 40% of the dose, and intact Enalapril. The elimination half-life is approximately 11 hours, and is increased in patients with renal failure.

High blood pressure, whether alone or in combination with other anti-hypertensive drugs especially diuretics.
Congestive heart failure: Should be used as an adjunctive therapy with digitalis and/or diuretics.

Essential Hypertension: The initial dose is 10 - 20 mg, depending on the degree of hypertension, and is given once daily. In mild hypertension the recommended initial dose is 10 mg daily. For other degrees of hypertension the initial dose is 20 mg daily. The usual maintenance dose is one 20 mg tab taken once daily. The dosage should be adjusted according to the needs of the patient to a maximum of 40 mg daily.
Renovascular Hypertension: Since blood pressure and renal function in such patients may be particularly sensitive to ACE inhibition, therapy should be initiated with a lower starting dose (e.g. 5 mg or less). The dosage should then be adjusted according to the needs of the patient. Most patients may be expected to respond to one 20 mg tab taken once daily. For patients with hypertension who have been treated recently with diuretics, caution is recommended.
Concomitant Diuretic Therapy in Hypertension: Symptomatic hypotension may occur following the initial dose of ACETEC; this is more likely in patients who are being treated currently with diuretics. Caution is recommended, therefore, since these patients may be volume or salt-depleted. The diuretic therapy should be discontinued for 2 - 3 days prior to initiation of therapy with ACETEC. If this is not possible, the initial dose of ACETEC should be low (5 mg or less) to determine the initial effect on the blood pressure. Dosage should then be adjusted according to the needs of the patient.
Dosage in Renal Insufficiency: Generally, the intervals between the administration of enalapril should be prolonged and/or the dosage reduced. (See table.)

Click on icon to see table/diagram/image

Heart Failure and/or Symptomatic Left Ventricular Dysfunction: The initial dose of ACETEC in patients with symptomatic heart failure or symptomatic 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 ACETEC in heart failure, the dose should be increased gradually to the usual maintenance dose of 20 mg, given in a single dose or 2 divided doses, as tolerated by the patient. This dose titration may be performed over a 2 to 4 weeks period, or more rapidly if indicated by the presence of residual signs and symptoms of heart failure. In patients with symptomatic heart failure, this dosage regimen was effective in reducing mortality. Blood pressure and renal function should be monitored closely both before and after starting treatment with ACETEC because hypotension and consequent renal failure have been reported. In patients treated with diuretics, the dose should be reduced if possible before beginning treatment with ACETEC. The appearance of hypotension after the initial dose of ACETEC does not imply that hypotension will recur during chronic therapy with ACETEC and does not preclude continued use of the drug. Serum potassium also should be monitored.

The common symptom is hypotension. The recommended treatment of overdosage is IV infusion of normal saline solution.
If ingestion is recent, induce emesis. ACETEC may be removed from the circulation by hemodialysis.

ACETEC is contraindicated in patients with a history of angioneurotic edema relating to previous treatment with an ACE inhibitor.
Hypersensitivity to the product or any of its component.

ACETEC should be used with caution for the simultaneous intake with potassium supplement or potassium sparing diuretics, all drugs which may increase the resistance of blood vessels.
For the patients with renal dysfunctions, the dosage must be reduced.
For the patients with liver dysfunction, the active metabolite of Enalapril becomes low and the dosage may be increased but there is no sufficient experience in these patients.
Neutropenia, thrombocytopenia, bone marrow depression and agranulocytosis have occurred rarely; a causal relationship can not be excluded.
ACETEC should not be recommended for children because there is no sufficient report of safety of the drug in children.
If increased BUN and creatinine concentration occur, reduction in dosage and/or withdrawal of the diuretic may be required. The possibility of renovascular hypertension should also be consider, especially in the presence of a solitary kidney, transplanted kidney, or bilateral renal artery stenosis.
Symptomatic hypotension is likely to occur in volume-depleted patients, patients with congestive heart failure. 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, hyponatremia 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 ACETEC and/or diuretic is adjusted. Similar considerations may apply to patients with ischemic heart or cerebrovascular disease in whom an excessive fall in blood pressure could result in a myocardial infarction or cerebrovascular accident.
If hypotension occurs, place patients in supine position and, if necessary, give IV 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 ACETEC. 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 ACETEC may be necessary. No differences in blood pressure response or adverse effects have been noted in elderly patients receiving enalapril.
In patients undergoing major surgery or during anesthesia with agents that produce hypotension, enalapril will block 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.
Use in pregnancy: When used in pregnancy during the second and third trimesters ACE inhibitors can cause injury and even death to the developing fetus. When pregnancy is detected, this drug should be discontinued as soon as possible.
Use in lactation: Enalapril and enalaprilat are secreted in human milk in trace amounts. Cautions should be exercised if ACETEC is given to a nursing mother.

Use in pregnancy: When used in pregnancy during the second and third trimesters ACE inhibitors can cause injury and even death to the developing fetus. When pregnancy is detected, this drug should be discontinued as soon as possible.
Use in lactation: Enalapril and enalaprilat are secreted in human milk in trace amounts. Cautions should be exercised if ACETEC is given to a nursing mother.

Hypotensive especially with high dosage or simultaneous intake with diuretics or dehydration states or salt-limited diet.
Renal function disturbances such as glycosuria or proteinuria and in some cases may lead to acute renal failure.
Skin: Diaphoresis, erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis, pemphigus, pruritus, urticaria, alopecia.
Gastrointestinal: Ileus, pancreatitis, hepatic failure, hepatitis (either hepatocellular or cholestatic), jaundice, abdominal pain, vomiting, dyspepsia, constipation, anorexia, stomatitis.
Laboratory Test Findings: Increases in blood urea and serum creatinine and elevations of liver enzymes and/or serum bilirubin have been seen. These are usually reversible upon discontinuation of ACETEC. Hyperkalemia and hyponatremia have occurred. Decreases in hemoglobin and hematocrit have been reported, a small number of cases of neutropenia, thrombocytopenia, bone marrow depression and agranulocytosis have been reported.
Hypersensitivity/Angioneurotic Edema: Angioneurotic edema of the face, extremities, lips, tongue, glottis and/or larynx has been reported rarely.
Respiratory: Pulmonary infiltrates, bronchospasm/asthma, dyspnea, rhinorrhea, sore throat and hoarseness.
Nervous System/Psychiatric: Depression, confusion, somnolence, insomnia, nervousness, paresthesia, vertigo.

When administered concurrently, the following drugs may interact with Enalapril: Antihypertensive drug: Additive hypotensive effect may occur.
Potassium-sparing diuretics or potassium preparation: Hyperkalemia may occur (particularly in patient with impaired renal function).
Potassium-losing diuretics: The potassium-losing effect was attenuated.
Lithium: Lithium clearance may be reduced. Frequent monitoring of serum lithium concentrations is recommended.
Digoxin: Increase plasma digoxin level.
Allopurinol: High risk of hypersensitivity reaction possible.
Rifampin: Pharmacologic effects of enalapril may be decreased.
Phenothiazine: Pharmacologic effects of enalapril may be increased.
Indomethacin: Reduce hypotensive effect of enalapril.

Store at room at temperature not exceeding 30°C, protect from moisture.
Shelf-life: 3 years.

ACE Inhibitors/Direct Renin Inhibitors

C09AA02 - enalapril ; Belongs to the class of ACE inhibitors. Used in the treatment of cardiovascular disease.

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