Enap-N, tablets 25 mg+10 mg 20 pcs

Pharmgroup:

Hypertensive combination drug (ACE inhibitor+diuretic).

Pharm Action:

Enap-H is a combination drug whose action is due to the properties of its constituent components. It has an antihypertensive effect.

– Enalapril inhibits ACE, which promotes transformation of angiotensin I into angiotensin II, reduces the concentration of aldosterone in blood, increases renin release by juxtaglomerular cells in the walls of arterioles of renal tubules, improves functioning of kallikrein-kinin system, stimulates release of prostaglandins and endothelial relaxing factor (NO), inhibits sympathetic nervous system.

Taken together, these effects eliminate spasm and dilate peripheral arteries, reduce RPS, systolic and diastolic BP, post- and preload on the myocardium. It dilates arteries to a greater extent than veins, and there is no reflex increase in HR. Hypotensive effect is more pronounced at high plasma renin concentration than at normal or reduced concentration. Reduction of BP within therapeutic limits has no effect on cerebral blood flow. Improves blood supply to ischemic myocardium. Increases renal blood flow without changing glomerular filtration rate. In patients with initially decreased glomerular filtration, its rate usually increases.

The maximum effect of enalapril develops after 6-8 hours and lasts up to 24 hours.

Hydrochlorothiazide is a medium-acting thiazide diuretic. It reduces the reabsorption of sodium ions at the level of the cortical segment of the loop of Genle without affecting its section in the medullary layer of the kidney. It blocks carboanhydrase in the proximal part of the convoluted tubules, increases renal excretion of potassium ions, hydrocarbonates and phosphates.

It has practically no effect on the acid-base state. Increases the excretion of magnesium ions. Delays calcium ions in the body. Diuretic effect develops after 1-2 hours, reaches a maximum after 4 hours, lasts for 10-12 hours. The action decreases with decreasing glomerular filtration rate and stops when its value is less than 30 ml/min. It decreases BP by decreasing the BCC and changing the reactivity of the vascular wall.

The use of combination of enalapril and hydrochlorothiazide causes more significant decrease of BP in comparison with monotherapy of each of agents separately and allows to maintain hypotensive effect of Enap®-N at least for 24 hours.

Indications

Active ingredient

Composition

1 tablet:

– enalapril maleate 10 mg

– hydrochlorothiazide 25 mg

Supplementary substances:

Sodium bicarbonate,

Quinoline yellow dye (E104),

Lactose monohydrate,

calcium hydrophosphate anhydrous,

corn starch,

talk,

Magnesium stearate.

How to take, the dosage

The usual starting and maintenance dose of Enap-H is 1 tablet daily.

In the absence of a good effect, the dose may be increased to 2 tablets daily. In general, the maximum effect is achieved within 3 weeks after the start of treatment.

Interaction

The use of potassium supplements, potassium-saving agents or potassium-containing drugs, salt substitutes, especially in patients with renal insufficiency, may lead to a significant increase in serum potassium.

Potassium loss with thiazide diuretics is generally reduced with enalapril. Serum potassium content usually remains within normal limits.

When concomitant use with lithium preparations the excretion of lithium is delayed (increase of cardiotoxic and neurotoxic effects of lithium).
Thiazide diuretics may increase the effect of tubocurarine chloride.

The simultaneous use of thiazide diuretics, opioid analgesics or phenothiazine derivatives may lead to orthostatic hypotension.

The concomitant use of beta-adrenoblockers, alpha-adrenoblockers, ganglioblockers, methyldopa, or slow calcium channel blockers with enalapril may further decrease BP.

The concomitant use of allopurinol, cytostatics and immunosuppressants with ACE inhibitors may increase the risk of leukopenia.

The concomitant use of thiazide diuretics with GCS, calcitonin may lead to hypokalemia.

The concomitant use of cyclosporine with ACE inhibitors may increase the risk of hyperkalemia.

The concomitant use of NSAIDs (including selective COX-2 inhibitors) may weaken the antihypertensive effect of ACE inhibitors. NSAIDs and ACE inhibitors have an additive effect on the increase in serum potassium, which may lead to worsening of renal function, especially in patients with impaired renal function. This effect is reversible. NSAIDs may reduce the diuretic and antihypertensive effects of diuretics.

Antacids may decrease the bioavailability of ACE inhibitors.
Sympathomimetics may decrease the antihypertensive effect of ACE inhibitors.

Thiazide diuretics may decrease the effect of adrenomimetics (epinephrine).
Ethanol increases the hypotensive effect of ACE inhibitors and thiazide diuretics, which may cause orthostatic hypotension.
Epidemiological studies suggest that simultaneous use of ACE inhibitors and hypoglycemic agents may lead to hypoglycemia.

Hypoglycemia most often develops in the first weeks of therapy in patients with impaired renal function. Long-term and controlled clinical trials of enalapril do not support these findings and do not limit the use of enalapril in patients with diabetes mellitus. Nevertheless, such patients should be under regular medical supervision. The use of oral hypoglycemic agents and insulin with thiazide diuretics may require adjustment of their doses.

Single administration of colestyramine or colestipol decreases absorption of hydrochlorothiazide in the gastrointestinal tract by 85% and 43%, respectively.
When ACE inhibitors and gold drugs (sodium aurothiomalate) are used concomitantly by IV, a symptomcomplex including facial hyperemia, nausea, vomiting and arterial hypotension is described.

Special Instructions

During treatment with Enap-H, regular monitoring of liver and kidney function as well as blood picture is necessary.

Two to three days before starting treatment with Enap-H, therapy with diuretics should be stopped. Concomitant use of Enap-H with drugs of lithium and potassium is not recommended.

Combination of Enap-H with beta-blockers is possible.

Contraindications

Side effects

Overdose

Symptoms: increased diuresis, marked BP decrease with bradycardia or other cardiac rhythm disturbances, convulsions, consciousness disorders (including coma), acute renal failure, impaired acid and blood water-electrolyte balance.

Treatment: the patient is transferred to the horizontal position with elevated legs. In mild cases gastric lavage and intake of activated charcoal are indicated, in more severe cases – measures aimed at BP stabilization – intravenous infusion of plasma substitutes, infusion of 0.9% sodium chloride solution.

The patient’s blood pressure, HR, respiratory rate, serum concentrations of urea, creatinine, electrolytes and urine output should be controlled, and if necessary – intravenous angiotensin II infusion, hemodialysis (enalaprilat excretion rate – 62 ml/min).

Similarities