Expiration date: 03/2025

Release form and composition:

Tablets yellow, round, biconvex, with a corrugated edge, on the one hand engraving MSD 718, on the other - risk.

1 tablet contains:

enalapril maleate 20 mg

hydrochlorothiazide 12.5 mg

Excipients: sodium bicarbonate, lactose, water, corn starch, corn starch pregelatinization, dye iron oxide yellow, magnesium stearate.

7 PCs. - blisters (2) - packs of cardboard.

7 PCs. - blisters (4) - packs of cardboard.

56 PCs. - bottles plastic (1) - packs of cardboard.

Pharmacological action:

Combined antihypertensive drug, which includes ACE inhibitor (enalapril maleate) and thiazide diuretic (hydrochlorothiazide). It has antihypertensive and diuretic effect.

Enalapril – ACE inhibitor, catalytic conversion of angiotensin I to the Pressor substance angiotensin II. After absorption, enalapril is converted by hydrolysis into enalaprilat, which inhibits ACE. Inhibition of ACE leads to a decrease in the concentration of angiotensin II in the blood plasma, which entails an increase in plasma renin activity (due to the elimination of the reverse negative reaction to changes in renin production) and a decrease in aldosterone secretion.

ACE is identical to the enzyme kininase II, so enalapril can also block the destruction of bradykinin, a peptide with vasodilating effect. The significance of this mechanism in the therapeutic effect of enalapril requires clarification. Despite the fact that enalapril reduces blood PRESSURE by suppressing the renin-angiotensin-aldosterone system, which plays an important role in the regulation of blood PRESSURE, the drug reduces blood PRESSURE even in patients with hypertension with low renin content.

Decrease in blood PRESSURE is accompanied by a decrease in heart rate, a small increase in cardiac output and the absence of changes or minor changes in heart rate. As a result of reception of enalapril increases renal blood flow, glomerular filtration rate remains unchanged. However, in patients with initially reduced glomerular filtration, its speed usually increases.

Antihypertensive therapy with enalapril leads to significant regression of left ventricular hypertrophy and preservation of left ventricular systolic function.

Therapy with enalapril is accompanied by a favorable effect on the ratio of lipoprotein fractions and the lack of influence or a favorable effect on the total cholesterol content.

Admission enalapril patients with hypertension leads to a decrease in blood PRESSURE as standing and lying down without a significant increase in heart rate.

Symptomatic postural hypotension is rare. In some patients achievement of optimal blood pressure reduction may require several weeks of therapy. Interruption of therapy with enalapril does not cause a sharp rise in blood PRESSURE.

Effective inhibition of ACE activity usually develops 2-4 hours after a single dose of enalapril inside. The beginning of antihypertensive action occurs within 1 hour, the maximum decrease in blood PRESSURE is observed 4-6 hours after taking the drug. The duration of action depends on the dose. However, when used in the recommended doses of antihypertensive and hemodynamic effects persist for 24 no.

Hydrochlorothiazide has diuretic and antihypertensive effect, increases the activity of renin. Although enalapril itself exhibits antihypertensive effect even in patients with hypertension at a low concentration of renin, concomitant use of hydrochlorothiazide in such patients leads to a more pronounced decrease in blood PRESSURE.

Enalapril reduces the loss of potassium ions caused by the use of hydrochlorothiazide. Enalapril and hydrochlorothiazide have a similar dosing regimen. Therefore, Co-Renitec is a convenient dosage form for the joint administration of enalapril and hydrochlorothiazide.

The use of a combination of enalapril and hydrochlorothiazide leads to a more pronounced decrease in blood PRESSURE compared with monotherapy each drug separately and allows you to maintain the antihypertensive effect of The drug co-Renitec for at least 24 no.

Pharmacokinetics:

Enalapril

Suction

After oral enalapril maleate is rapidly absorbed. Cmax of enalapril in serum is observed within 1 h after administration. After oral absorption is about 60%.

Eating has no effect on the absorption of enalapril. The duration of absorption and hydrolysis of enalapril is similar for the different recommended therapeutic doses.

After absorption, enalapril is rapidly hydrolyzed to form the active substance enalaprilat, a powerful ACE inhibitor. Cmax of enalaprilat in the blood serum is observed in 3-4 h after administration of the dose of enalapril inside.

Breeding

Enalapril is excreted mainly by the kidneys. The main metabolites determined in urine are enalaprilat, which is approximately 40% of the dose, and unchanged enalapril. Data about other important pathways of metabolism of enalapril, except hydrolysis in enalaprilat. The curve of enalaprilat concentration in blood plasma has a long final phase, apparently, due to its binding to ACE. In individuals with normal renal function, a stable concentration of enalaprilat is achieved on the 4th day from the beginning of enalapril. T1/2 enalaprilata in the course of use of the drug inside is 11 no.

Hydrochlorothiazide

Metabolism and distribution

Does not undergo metabolism. Hydrochlorothiazide penetrates the placental barrier, but does not penetrate the BBB.

Breeding

T1 / 2 hydrochlorothiazide from 5.6 to 14.8 hours Quickly excreted by the kidneys. At least 61% of the dose taken orally, excreted unchanged for 24 no.

Combination of enalaprilate maleate and hydrochlorothiazide

Regular use of a combination of enalapril and hydrochlorothiazide does not affect or slightly affects the bioavailability of each component of the drug. The use of combination drug pills Co-renitek bioequivalent to the simultaneous reception of his ingredients in separate dosage forms.

Indications:

• treatment of hypertension in patients who are shown combination therapy.
  

Dosage regimen:

The drug is administered orally, regardless of the meal.

When arterial hypertension initial dose of 1 tab. 1 time / day. If necessary, the dose can be increased to 2 tab. 1 time / day.

At the beginning of therapy with Co-Renitec may develop symptomatic hypotension, more often in patients with impaired water-electrolyte balance due to previous treatment with diuretics. Diuretic therapy should be discontinued 2-3 days before the start of Co-renitek.

In patients with impaired renal function, thiazides may not be effective enough, and in QC, e 30 ml/min (i.e., in moderate to severe renal failure) are ineffective.

When QC 80-30 ml / min Co-Renitec should be used only after the preliminary selection of doses of each component.

In mild renal insufficiency, the recommended dose of enalapril maleate, taken separately, is from 5 mg to 10 mg.

Side effect:

In clinical studies, side effects were usually mild, transient, and in most cases did not require discontinuation of treatment.

From the cardiovascular system: 1-2% - orthostatic effects, including arterial hypotension rarely-fainting, hypotension, regardless of body position, heartbeat, tachycardia, chest pain.

From the Central and peripheral nervous system: often-dizziness, fatigue (usually held at a lower dose and rarely required discontinuation of the drug) 1-2% - asthenia, headaches rarely - insomnia, drowsiness, systemic dizziness, paresthesia, increased excitability.

From the respiratory system: 1-2% - cough rarely-shortness of breath.

From the digestive system: 1-2% - rarely nausea-pancreatitis, diarrhea, vomiting, dyspepsia, abdominal pain, flatulence, constipation, dry mouth.

From the musculoskeletal system: 1-2% - muscle cramps rarely-arthralgia.

Allergic reactions: rarely-angioedema of the face, limbs, lips, tongue, glottis and/or larynx. There are rare reports of the development of angioedema of the intestine due to the intake of ACE inhibitors, including enalapril.

Dermatological reactions: rarely-Stevens-Johnson syndrome, hyperhidrosis, skin rash, itching.

From the urinary system: rarely-renal dysfunction, renal failure.

From the reproductive system: 1-2% rare impotence - decreased libido.

From the laboratory indicators: possible hyperglycemia, hyperuricemia, Hypo - or hyperkalemia, increased blood concentrations of urea, serum creatinine, increased activity of liver enzymes and/or increased serum bilirubin (these indicators are usually normalized after discontinuation of Co-renitekom) in some cases - reduction of hemoglobin and hematocrit.

Other: rarely - tinnitus, gout. A symptom complex, possible manifestations of which are fever, serositis, vasculitis, myalgia, myositis, arthralgia/arthritis, a positive test for antinuclear antibodies, acceleration of ESR, eosinophilia and leukocytosis, is described.photosensitization may develop.

Contraindications:

• anuria
  
• swelling angioneuroticeski in history, associated with the appointment earlier ACE inhibitors, as well as hereditary or idiopathic angioedema
  
• hypersensitivity to the components of the drug
  
• hypersensitivity to other sulfonamide derivatives.
  

With caution, the drug should be prescribed for aortic stenosis, cerebrovascular diseases (including cerebrovascular insufficiency), coronary artery disease, chronic heart failure, severe autoimmune systemic connective tissue diseases (including systemic lupus erythematosus, scleroderma), oppression of bone marrow hematopoiesis, diabetes, hyperkalemia, bilateral stenosis of the renal arteries, stenosis of the artery of the sole kidney, the state after kidney transplantation, renal and/or liver failure, against a diet with sodium restriction, in conditions accompanied by a decrease in BCC (including diarrhea, vomiting), elderly patients.

Pregnancy and lactation:

Not recommended the use of drug Co-renitek during pregnancy. If pregnancy is established, the drug should be stopped immediately.

The appointment of ACE inhibitors in groups II and III trimestrah pregnancy can cause disease or death of the fetus or newborn. The negative effect of ACE inhibitors on the fetus and newborn is manifested by arterial hypotension, renal failure, hyperkalemia and/or hypoplasia of the skull. Perhaps the development of oligohydramnios, apparently due to dysfunction of the kidneys of the fetus. This complication can lead to contracture of the limbs, deformation of the skull, including its front part, to hypoplasia of the lungs.

The use of diuretics in women during pregnancy is not recommended, since there is a risk of jaundice in the fetus and newborn, thrombocytopenia and, possibly, other side effects observed in adult patients.

If Co-Renitec is prescribed during pregnancy, the patient should be warned about the existing potential risk to the fetus. In those rare cases, when the appointment of the drug during pregnancy is considered necessary, periodic ultrasound examinations should be carried out to assess the condition of the fetus, as well as intraamniotic space.

Newborns whose mothers took Co-Renitec should be carefully monitored for the development of hypotension, oliguria and hyperkalemia. Enalapril, which penetrates the placental barrier, was removed from the blood circulation of the newborn by peritoneal dialysis with some favorable clinical effect, theoretically it can be removed by exchange blood transfusion.

Enalapril and thiazides, including hydrochlorothiazide, are excreted in breast milk. If necessary, use of the drug during lactation breastfeeding should be discontinued.

Special instruction:

During treatment, Co-renitek like to change antihypertensive therapy may develop symptomatic hypertension. Patients should be examined for clinical signs of impaired water-electrolyte balance, i.e. dehydration, hyponatremia, hypochloremic alkalosis, hypomagnesemia or hypokalemia, which may occur as a result of episodes of diarrhea or vomiting. In such patients during therapy should be carried out periodic determination of the electrolyte composition of the blood at regular intervals.

With caution should appoint drug patients with coronary artery disease or cerebrovascular disease, because excessive reduction in blood pressure may lead to myocardial infarction or stroke.

With the development of hypotension shows bed rest and, if necessary-in / in the introduction of saline. Transient arterial hypotension in the appointment of Co-Renitec is not a contraindication to its further use. After normalization of blood PRESSURE and BCC therapy can be resumed either in a few reduced doses, or each of the components of the drug can be used separately.

Co-renitek should not be administered to patients with renal insufficiency (??t80 ml/min) as long as the selection of the individual components of the drug do not show that the required dose for the patient present in the dosage form.

In some patients without any signs of kidney disease before treatment with enalapril in combination with diuretic there was usually a slight and transient increase in blood urea and serum creatinine. In such cases, the treatment of Co-renitek should be discontinued. In the future, it is possible to resume therapy in reduced doses or the appointment of each of the components of the drug separately.

Like all drugs that have vasodilating effect, ACE inhibitors should be used with caution in patients who have difficulty in blood flow from the left ventricle of the heart.

Some patients with bilateral renal artery stenosis or stenosis of the artery only kidneys, when the treatment with ACE inhibitors there was an increase in the content of blood urea and creatinine in serum. These changes were reversible, as a rule, the indicators returned to normal after discontinuation of treatment.

It should be used with caution thiazide diuretics in patients with impaired liver function or with progressive liver disease, because even small changes in the water-electrolyte balance can lead to hepatic coma.

When performing large surgical operations or during General anesthesia using drugs that cause arterial hypotension, enalaprilat blocks the formation of angiotensin II, caused by compensatory release of renin. If this develops severe hypotension, explained by such a mechanism, it can be corrected by increasing BCC.

Thiazide diuretics may not be effective enough in patients with impaired renal function and are ineffective in CC e 30 ml/min (i.e., moderate to severe renal failure).

Thiazide diuretics can cause impaired glucose tolerance. Correction of doses of hypoglycemic drugs, including insulin, may be required.

Thiazide diuretics can reduce calcium excretion in the urine, as well as cause a slight and transient increase in serum calcium. Severe hypercalcemia may be a sign of latent hyperparathyroidism. Thiazides should be discontinued before the study of the function of the parathyroid glands.

An increase in cholesterol and TG levels may also be associated with thiazide diuretic therapy, but at a dose of hydrochlorothiazide 12.5 mg contained in 1 tablet Of co-Renitec, such effects were either not observed or were insignificant.

Thiazide therapy may lead to hyperuricemia and/or gout in some patients. However, enalapril can increase the content of uric acid in the urine and thereby weaken the hyperuricemic effect of hydrochlorothiazide.

Rare cases of angioedema of the face, limbs, lips, tongue, glottis and/or larynx were described in the treatment with ACE inhibitors, including enalapril maleate. These reactions can occur at any stage of therapy. In such cases, it is necessary to immediately stop taking enalapril maleate and establish careful monitoring of the patient's condition in order to control and correct clinical symptoms. Even in cases where there is only swelling of the tongue without swelling of the respiratory organs, patients may require long-term follow-up, since therapy with antihistamines and corticosteroids may not be enough.

There are rare reports of death due to angioedema accompanied by laryngeal edema or swelling of the tongue. Swelling of the tongue, glottis, or larynx can lead to airway obstruction, especially in patients undergoing respiratory surgery.

In cases where swelling is localized in the tongue, glottis or larynx, which can lead to airway obstruction, should immediately enter p/to 0.3-0.5 ml of 0.1% solution of epinephrine (adrenaline) and quickly provide airway patency.

In patients of the Negroid race, taking ACE inhibitors, angioedema was observed more often than in other patients.

When indicated in the history of angioedema, not associated with the reception of ACE inhibitors, significantly increases the risk of angioedema during therapy with ACE inhibitors.

In patients receiving thiazides, allergic reactions may occur regardless of the presence of a history of allergic conditions or bronchial asthma. Relapses or worsening of the severity of SLE in patients receiving thiazides have been reported.

In rare cases, patients receiving ACE inhibitors, developed life-threatening anaphylactoid reactions during desensitization an allergen from the venom of the Hymenoptera. Such reactions can be avoided if prior to hyposensitization temporarily stop taking ACE inhibitor.

Co-Renitec administration is contraindicated in patients with renal insufficiency who are on hemodialysis. Anaphylactoid reactions were observed in patients on dialysis using high-throughput membranes (such as AN69) and treated simultaneously with ACE inhibitors. In these patients, dialysis membranes of another type or antihypertensive drugs of other classes should be used.

Against the background of therapy with ACE, cases of cough were noted. As a rule, the cough is dry, has a constant character and disappears after the end of therapy. Cough associated with the use of ACE inhibitors should be considered in the differential diagnosis of cough.

The results of clinical studies of the efficacy and tolerability of enalapril maleate and hydrochlorothiazide with simultaneous administration were similar in elderly and younger patients.

Use in Pediatrics

The safety and efficacy of Co-Renitec in children have not been established, so the use in Pediatrics is not recommended.

Overdose:

Symptoms: severe hypotension, starting approximately 6 hours after taking the drug, and stupor. After administration of enalapril maleate at doses of 330 mg and 440 mg, plasma concentrations of enalaprilate were 100 and 200 times higher, respectively, at therapeutic doses.

When an overdose of hydrochlorothiazide is most often observed symptoms caused by hypokalemia, hypochloremia, hyponatremia and dehydration due to excessive diuresis. If earlier therapy with digitalis preparations was carried out, it is possible to aggravate the course of arrhythmia due to hypokalemia.

Treatment: Co-renitek should abolish the careful supervision of a physician. Gastric lavage is recommended if the drug was recently taken symptomatic and maintenance therapy to correct violations of water-electrolyte balance and hypotension. Data on specific treatment of overdose is not available.

When an overdose of enalapril maleate is recommended in / infusion of saline, effective administration of angiotensin II. Enalaprilat can be removed from the systemic circulation by hemodialysis.

Drug interaction:

In the appointment of enalapril in combination with other antihypertensive drugs possible summation effect.

The loss of potassium, which is caused by diuretics of the thiazide series, usually decreases under the action of enalaprilat. Serum potassium concentration usually remains within normal limits.

The use of potassium supplements, potassium-sparing diuretics or potassium-containing salts, especially in patients with renal insufficiency, can lead to a significant increase in serum potassium.

Diuretics and ACE inhibitors reduce the excretion of lithium by the kidneys and increase the risk of lithium intoxication. Lithium drugs are usually not administered with diuretics or ACE inhibitors.

NSAIDs, including selective COX-2 inhibitors can reduce the efficacy of diuretics and other antihypertensive drugs. Therefore, it is possible to reduce the hypotensive effect of ACE inhibitors while prescribing with NSAIDs, including selective COX-2 inhibitors.

In patients with impaired renal function receiving NSAIDs, including selective COX-2 inhibitors, with concomitant taking ACE inhibitors, may further deterioration of kidney function. These changes are usually reversible.

Thiazide diuretics can enhance the effect of tubocurarine.

The hypotensive effect of the drug reduces NSAIDs, estrogens, ethanol.

Immunosuppressants, allopurinol, cytostatics increase the risk of hematotoxicity.

Terms and conditions of storage:

The drug should be stored out of reach of children at a temperature not exceeding 30°C. shelf life for tablets in blisters – 3 years, for tablets in high – density bottles-2 years.