Renitec, 10 mg tablets 14 pcs

Pharmgroup:

The ACE inhibitor.

Pharmic action:

Renitech® (enalapril maleate) refers to agents that affect the renin-angiotensin system – ACE inhibitors and is a highly specific, long-acting, non-sulfhydryl group ACE inhibitor.

Renitec® (enalapril maleate) is a derivative of two amino acids: L-alanine and L-proline. Enalapril is an ACE inhibitor which catalyzes the conversion of angiotensin I into the pressor substance angiotensin II. After absorption, orally ingested enalapril is converted by hydrolysis to enalaprilate, which inhibits ACE. ACE inhibition leads to decrease of angiotensin II concentration in plasma, which leads to increase of plasma renin activity (due to elimination of negative feedback on renin production) and decrease of aldosterone secretion.

The ACE is identical to the enzyme kininase II, so enalapril can also block the breakdown of bradykinin, a peptide with a vasodilatory effect. The significance of this effect in the therapeutic effects of enalapril needs to be clarified. It is now thought that the mechanism by which enalapril lowers BP is the inhibition of the renin-angiotensin-aldosterone system, which plays an important role in regulating BP.

Enalapril shows antihypertensive effect even in patients with decreased concentration of renin. Decrease of BP is accompanied by decrease of total peripheral vascular resistance, increase of cardiac output and no or little change of heart rate. Enalapril administration results in increased renal blood flow, but glomerular filtration rate remains unchanged. However, in patients with initially decreased glomerular filtration, its level usually increases.

Enalapril antihypertensive therapy leads to significant regression of left ventricular hypertrophy and preservation of systolic function.

Enalapril therapy is accompanied by favorable effects on lipoprotein fraction ratios and no or favorable effects on total cholesterol concentrations.

Enalapril administration in patients with arterial hypertension leads to a decrease in BP regardless of body position: both in standing and lying position without a significant increase in HR.

Symptomatic postural hypotension rarely develops. In some patients, it may take several weeks of therapy to achieve optimal BP reduction. Interruption of therapy with enalapril does not cause a sharp rise in BP.

Effective inhibition of ACE activity usually develops 2-4 hours after a single oral dose of enalapril. The onset of hypotensive action occurs within 1 hour, the maximum BP reduction is observed 4-6 hours after taking the drug. Duration of action depends on the dose. However, when using the recommended doses, the antihypertensive effect and hemodynamic effects are maintained for 24 hours.

Enalapril reduces the loss of potassium ions caused by the use of hydrochlorothiazide.

Indications

Heart failure, Hypertension (high blood pressure), Edema

• Essential arterial hypertension (mild, moderate and severe forms);
• Renovascular hypertension;
• Cronic heart failure of all functional classes.

In patients with clinical manifestations of heart failure Renitec is indicated for increase of survival rate of patients, slowing down of heart failure progression, decrease of hospitalization rate.

Active ingredient

Enalapril

Composition

1 tablet contains:

The active ingredient:

Enalapril maleate 10 mg.

Auxiliary substances:

Sodium bicarbonate;

Lactose monohydrate;

Corn starch;

Corn starch pregelatinized;

Magnesium stearate;

Red iron oxide (E172).

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How to take, the dosage

Ingestion, regardless of food intake, since absorption of the tablets is ue dependent on food intake.

– Arterial hypertension

The initial dose is 10-20 mg depending on the severity of arterial hypertension and is prescribed once daily. In mild degree of arterial hypertension, the recommended initial dose is 10 mg/day. In other degrees of arterial hypertension, the initial dose is 20 mg/day at a single dose. The maintenance dose is 1 tablet 20 mg once daily. The dosage is adjusted individually for each patient, but the dose should not exceed 40 mg/day.

– Renovascular hypertension

Because patients in this group may have particularly sensitive BP and renal function to ACE inhibition, therapy is started with a low starting dose of 5 mg or less. The dose is then adjusted according to the patient’s needs. A dose of 20 mg/day with daily administration is usually effective. Caution should be exercised when treating patients who have recently received treatment with diuretics.

– Concomitant treatment of arterial hypertension with diuretics

After the 1st dose of Renitec, arterial hypotension may develop. This effect is most likely in patients who are treated with diuretics. The drug is recommended to be administered with caution, since fluid or sodium deficiency may be observed in such patients. Treatment with diuretics should be discontinued 2-3 days before treatment with Renitec. If this is not possible, the initial dose of Renitec should be reduced (to 5 mg or less) to determine the initial effect of the drug. Thereafter, the dosage should be adjusted according to the patient’s condition.

Interaction

When Renitec is administered in combination with other hypotensive agents, a summation of the effect may be observed.
Serum potassium concentration usually remains within normal limits. In patients with arterial hypertension treated with Renitec for more than 48 weeks, an increase of serum potassium up to 0.2 mEq/L has been observed.

When Renitec is coadministered with diuretics that cause potassium loss, hypokalemia caused by diuretics is usually attenuated by the effect of enalapril.

Risk factors for hyperkalemia include renal insufficiency, diabetes mellitus, concomitant administration of potassium-saving diuretics (spironolactone, triamterene or amiloride), and use of potassium-containing supplements and salts. The use of potassium supplements, potassium-saving diuretics or potassium-containing salts, especially in patients with renal insufficiency, may lead to a significant increase in serum potassium content. If concomitant administration of the above potassium-containing or potassium-enhancing drugs is necessary, caution should be exercised and serum potassium levels should be monitored regularly.

The co-administration of ACE inhibitors and hypoglycemic agents (insulin, oral hypoglycemic agents) may increase the hypoglycemic effect of the latter with the risk of hypoglycemia. This phenomenon was usually most frequently observed during the first weeks of their combined use, as well as in patients with renal insufficiency. In diabetic patients receiving oral hypoglycemic agents or insulin, blood glucose levels should be monitored carefully, especially during the first month of combined use with ACE inhibitors.

The ACE inhibitors decrease renal excretion of lithium and increase the risk of lithium intoxication. Serum lithium levels should be monitored if lithium salts need to be administered.

NSAIDs, including selective COX-2 inhibitors, may decrease the effect of diuretics and other hypotensive agents. Thus, the antihypertensive effect of ACE inhibitors may be weakened by NSAIDs, including COX-2 inhibitors.

In some patients with impaired renal function, and taking NSAIDs including COX-2 inhibitors, concomitant use of ACE inhibitors may lead to further impairment of renal function. These changes are generally reversible.

A symptomcomplex including facial redness, nausea, vomiting and arterial hypotension have been described in rare cases when parenteral gold drugs (sodium aurothiomalate) and ACE inhibitors (enalapril) are used together.

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Special Instructions

Renitec® should be used with caution when treating patients with bilateral renal artery stenosis or stenosis of the artery of a single kidney, in primary hyperaldosteronism, hyperkalemia, condition after kidney transplantation; aortic stenosis, mitral stenosis (with hemodynamic disorders), idiopathic hypertrophic subaortic stenosis; systemic connective tissue diseases; ischemic heart disease; cerebrovascular diseases; diabetes; renal failure (proteinuria – more than 1 g/day.); hepatic insufficiency; patients on a salt restricted diet or undergoing hemodialysis; concomitant use with immunosuppressants and diuretics, elderly patients (over 65 years), suppression of medullar hemopoiesis; states accompanied with decreased volume of circulating blood (including diarrhea, vomiting).

Clinically pronounced arterial hypotension

Clinically pronounced arterial hypotension is rarely observed in patients with uncomplicated arterial hypertension. In patients with arterial hypertension receiving Renitec®, arterial hypotension develops more frequently against the background of hypovolemia resulting, for example, from diuretic therapy, salt restriction, in patients under hemodialysis, and those suffering from diarrhea or vomiting. Clinically pronounced arterial hypotension has also been observed in patients with heart failure accompanied or not accompanied by renal failure.

Arterial hypotension has been observed more frequently in patients with more severe forms of heart failure who use higher doses of loop diuretics, with hyponatremia or impaired renal function. In such patients, treatment with Renitec should be initiated under medical supervision, which should be especially careful when changing the dose of Renitec and/or diuretic. Similarly, patients with coronary heart disease as well as with cerebrovascular disease, in whom a sharp decrease in BP may lead to myocardial infarction or stroke, should be monitored. If arterial hypotension develops, the patient should be laid down and, if necessary, intravenous sodium chloride saline solution should be administered.

Transient arterial hypotension while taking Renitec is not a contraindication to further treatment with the drug, which can be continued after fluid replenishment and normalization of BP. In some patients with heart failure and with normal or decreased BP, Renitec® may cause additional BP decrease. Such a reaction to the drug administration may be expected and should not be considered as a reason to discontinue treatment. In cases where arterial hypotension becomes stable, the dose should be reduced and/or treatment with diuretic and/or Renitec® should be discontinued.

Aortic stenosis/hypertrophic cardiomyopathy

As with all vasodilators, ACE inhibitors should be prescribed with caution in patients with left ventricular aortic obstruction.

Renal function impairment

In some patients, arterial hypotension that develops after initiation of treatment with ACE inhibitors may lead to worsening of renal function. In some cases, the development of acute renal failure has been reported, usually reversible.

In patients with renal impairment, it may be necessary to reduce the dose and/or frequency of administration of the drug. In some patients with bilateral renal artery stenosis or artery stenosis of the only kidney, an increase in blood urea and serum creatinine was observed. The changes were usually reversible and the values returned to normal after discontinuation of treatment. This pattern of change is most likely in patients with renal insufficiency. In some patients with no known renal disease before treatment, Renitec® in combination with diuretics usually caused a slight and transient increase in blood urea and serum creatinine. In such cases, dose reduction and/or discontinuation of the diuretic and/or Renitec® may be required.

High sensitivity/Angioneurotic edema

. Rare cases of angioedema of the face, extremities, lips, tongue, vocal cleft and/or larynx have been described when prescribing ACE inhibitors, including Renitec, occurring at different periods of treatment. In such cases, treatment with Renitec should be discontinued immediately and continuous monitoring of the patient should be established to ensure that the symptoms disappear completely. Even in cases where only difficulty in swallowing without respiratory impairment occurs, patients should be kept under medical supervision for a long time, since therapy with antihistamines and corticosteroids may not be sufficient.

The angioedema of the larynx or tongue may be fatal. If the swelling is localized to the tongue, vocal cleft or larynx and may cause airway obstruction, prompt initiation of appropriate therapy, which may include subcutaneous injection of 0.1% (0.3-0.5 ml) epinephrine (adrenaline) solution and/or emergency measures to ensure airway patency.

Patients with a history of angioedema not associated with ACE inhibitor use may have an increased risk of it also when treated with an ACE inhibitor. Patients of the Negro race have a higher incidence of angioedema when taking ACE inhibitors than other races.

Anaphylactic reactions during hyposensitization with Hymenoptera venom allergen

In rare cases, patients receiving ACE inhibitors during hyposensitization with Hymenoptera venom allergen have developed life-threatening anaphylactic reactions. Such reactions can be avoided by temporarily discontinuing the ACE inhibitor prior to hyposensitization.

Patients on hemodialysis

Patients on dialysis using high throughput membranes (e.g., AN69®) and receiving an ACE inhibitor at the same time have in some cases developed anaphylactic reactions. Therefore, a different type of dialysis membrane or a different group of hypotensive agents is recommended for these patients.

Cough

There have been reports of coughing during treatment with ACE inhibitors. The cough is usually non-productive, persistent and stops after discontinuation of the drug. Cough due to treatment with an ACE inhibitor should be considered in the differential diagnosis of cough.

Surgery/General Anesthesia

. During major surgery or during general anesthesia with hypotensive agents, enalapril blocks angiotensin II formation secondary to compensatory renin release. If a pronounced decrease in BP develops due to this mechanism, it can be corrected by increasing the volume of fluid administered.

Hyperkalemia

. Risk factors for hyperkalemia include renal insufficiency, diabetes mellitus, simultaneous prescription of potassium-saving diuretics (spironolactone, triamterene, or amiloride), and use of potassium-containing supplements and salts.

The use of potassium supplements, potassium-saving diuretics or potassium-containing salts, especially in patients with renal insufficiency, may lead to a significant increase in serum potassium. Hyperkalemia can cause serious, in some cases fatal, heart rhythm disturbances.

When concomitant administration of the above potassium-containing or potassium-boosting drugs is necessary, caution should be exercised and serum potassium levels should be monitored regularly.

Hypoglycemia

. Patients with diabetes who are receiving oral hypoglycemic agents or insulin should be informed of the need for close monitoring of blood glucose levels (hypoglycemia) before starting ACE inhibitors, especially during the first month of co-administration of these drugs.

Use in elderly patients

Clinical studies of efficacy and tolerability of enalapril have been similar in elderly and younger patients.

Effects on ability to drive and/or operate machinery

. During the treatment period one should be careful when driving motor transport and engaging in other potentially dangerous activities which require increased concentration and quick psychomotor reactions (dizziness is possible especially after taking the initial dose of ACE inhibitor in patients taking diuretic drugs).

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Contraindications

• Angeoneurotic edema in history associated with previous administration of ACE inhibitors;
• Hereditary or idiopathic angioedema;
• Age under 18 years of age (efficacy and safety not established);
• High sensitivity to any of the components of Renitec.

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Side effects

In general, the drug is well tolerated. The cumulative incidence of side effects when using Renitec does not exceed that of placebo prescription. In most cases the side effects are minor, temporary and do not require discontinuation of therapy.

The following side effects are observed while prescribing Renitec: Dizziness and headache are the most common. Increased fatigability and asthenia are observed in 2-3 % of patients. Other side effects (arterial hypotension, orthostatic hypotension, fainting, nausea, diarrhea, muscle cramps, skin rash and cough) occur in less than 2% of patients. There are rare reports of renal dysfunction, renal failure, oliguria, and proteinuria.

Ensensitivity/Angeoneurotic edema

In rare cases, angioedema of the face, extremities, lips, tongue, vocal cleft and/or larynx, very rarely – intestinal angioedema were observed.

In very rare cases, the following side effects occur:

Cardiovascular side effects:in less than 2% of patients, arterial hypotension, orthostatic hypotension, syncope; in very rare cases, chest pain, palpitations, heart rhythm disorders, angina pectoris. Acute myocardial infarction or stroke may develop in patients belonging to the risk group.

CNS and peripheral nervous system disorders: Most commonly, dizziness, headache; in 2-3% of cases, increased fatigue, asthenia; in very rare cases, depression, confusion, sleep disturbances, paresthesias, tinnitus, blurred vision.

Digestive system disorders: in less than 2% of patients – nausea, diarrhea; in very rare cases – intestinal obstruction, pancreatitis, liver failure, hepatitis, jaundice, abdominal pain, vomiting, dyspepsia, constipation, anorexia, stomatitis, increased liver transaminase activity and plasma bilirubin concentration (these changes are usually reversible and normalize after stopping Renitec administration).

In less than 2% of patients – cough; in very rare cases – pulmonary infiltrates, bronchospasm, dyspnea, rhinorrhea, pharyngitis, dysphonia (hoarseness of voice).

Urinary system disorders:in rare cases – renal dysfunction, renal failure, oliguria; increased urea, creatinine (these changes are usually reversible and normalize after stopping Renitec).

Allergic reactions: in less than 2% of patients, skin rash; rarely, angioedema of the face, extremities, lips, tongue, vocal cleft and/or larynx; in very rare cases, erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis, pemphigus, pruritus, urticaria. A complex symptom complex including fever, serositis, vasculitis, myalgia/myositis, arthralgia/arthritis, positive antinuclear antibody test, elevated sedimentation rate, eosinophilia, and leukocytosis has been reported.

With regard to the hematopoietic system:in some cases, neutropenia, thrombocytopenia, agranulocytosis.

Dermatological reactions: itching, alopecia, facial skin hyperemia.

In terms of laboratory parameters: possible development of hyperkalemia and hyponatremia; decrease in hemoglobin and hematocrit levels.

Others:increased sweating, seizures, impotence, glossitis, changes in taste sensation, tinnitus.

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