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Pharmacological properties

Pharmacodynamic parameters. the combined preparation of coriprene contains an apf enalapril inhibitor (10 or 20 mg) and a calcium antagonist lercanidipine (10 mg), which have a complementary hypotensive effect.

The effectiveness of a fixed combination of enalapril and lercanidipine in reducing systolic and diastolic blood pressure compared with monotherapy has been proven by clinical studies.

Enalapril is a dicarbocyl-containing peptide with antihypertensive activity. Being a prodrug, enalapril is converted by deesterification into the active form - enalaprilat, which competitively binds and inhibits ACE, thereby blocking the conversion of angiotensin I to angiotensin II. This prevents the strong vasoconstrictor effect of angiotensin II and leads to vasodilation. The affinity of enalaprilat to ACE is approximately 200,000 times higher than that of angiotensin I, and 300–1000 times higher than that of enalapril. Enalapril also reduces the adrenal cortex secretion of aldosterone induced by angiotensin II, which leads to an increase in sodium excretion and, accordingly, water outflow.

The antihypertensive effect of a single oral dose of enalapril maleate usually manifests itself within 1 hour and maximum after 4-8 hours. The antihypertensive effect of the usual doses of the drug usually persists for 12-24 hours. Blood pressure when using enalapril decreases with a decrease in heart rate and increased cardiac output (possibly a slight increase in heart rate) and renal blood flow (GFR does not change or rises in case of low values ​​before the start of therapy).

In patients with kidney pathology or diabetes mellitus, the use of enalapril decreases the severity of albuminuria, proteinuria and urinary excretion of IgG.

A rapid increase in blood pressure does not occur with a sharp cessation of enalapril.

Lercanidipine inhibits the influx of extracellular calcium through the membranes of myocardial cells and vascular smooth muscle. A decrease in the concentration of calcium inside the cell leads to a decrease in the contractility of the smooth muscles of the myocardium, causes the expansion of the coronary and systemic arteries, which contributes to an increase in the delivery of oxygen to the myocardial tissue, a decrease in OPSS, systemic blood pressure and afterload.

The vasodilating effect of lercanidipine develops gradually, with prolongation of the antihypertensive effect. Lercanidipine as monotherapy or in combination with enalapril with repeated administration does not cause sympathetic activation secondary to peripheral vasodilation. This aspect is of great clinical importance, given that sympathetic overload may be associated with the development and progression of damage to the target organ and cardiovascular events in patients with hypertension.

Lercanidipine increases the bioavailability of NO and endothelium-dependent vasodilation in patients with hypertension. It also reduces oxidative stress markers. In addition, the drug inhibits the proliferation of neointima and vascular smooth muscle cells, as well as the accumulation of cholesterol by reducing the number of reactive oxygen species in the cells. In patients with hypertension, lercanidipine reduces the number of leukocytes in blood plasma, CRP, E- and P-selectin, lipoprotein (a) and intracellular adhesion molecules involved in thrombotic process and damage to blood vessels / tissues.

At the renal level, lercanidipine expands both afferent and efferent glomerular arteries, while the intraglomerular capillary pressure remains unchanged.

Pharmacokinetic parameters. Changes in the pharmacokinetic parameters of enalapril and lercanidipine during their combined use have not been established.

Pharmacokinetics of enalapril. Enalapril maleate is well absorbed after oral administration.About 55–75% of an orally administered dose of enalapril maleate is rapidly absorbed into the gastrointestinal tract in healthy people and patients with hypertension. Food does not significantly affect the rate or extent of absorption of enalapril maleate.

Cmax in plasma is reached within about 1 hour after oral administration of enalapril.

Stable plasma concentrations of enalaprilat are reached after 4 days in patients with normal renal function.

About 50-60% of enalaprilat binds to plasma proteins.

About 60% of the absorbed dose of enalapril is intensively hydrolyzed by esterases to enalaprilat, mainly in the liver. About 20% are hydrolyzed upon first passage through the liver. The hydrolysis of enalapril to enalaprilate may be delayed and / or impaired in patients with severe hepatic impairment.

Effective T½ for the accumulation of enalaprilat on average is about 11 hours in patients with normal renal function. In patients with creatinine clearance of 30 ml / min, effective T½ increases.

Enalapril does not penetrate the BBB; crosses the placenta, distributed in milk in trace amounts.

After oral administration, enalapril and enalaprilat are excreted in urine and feces. In healthy people, an average of 60–78% (43–56% in the form of enalaprilat and the rest in the form of an unchanged drug) enalapril maleate is excreted in the urine and about 33% (about 27% in the form of enalaprilat and 6% unchanged) - with feces within 24–48 hours after a dose of 10 mg.

Enalapril renal clearance may be reduced in patients with hypertension. In the elderly, renal clearance and / or volume of distribution may also decrease.

Pharmacokinetics of lercanidipine. After oral administration, lercanidipine is well absorbed in the digestive tract. The absorption of lercanidipine increases with a high-fat meal, so it should be taken before meals. Cmax achieved within about 1.5–3 hours. Lercanidipine has high binding to plasma proteins (98%) and quickly accumulates in the membranes of arteriolar cells.

In patients with hypertension, the mean terminal T½ after a single oral dose of 10–20 mg is 8–10.5 hours. Despite a short T½ in plasma, the pharmacodynamic effect covers 24 hours. A high coefficient of membrane separation of lercanidipine provides a lasting effect at the level of receptors and membranes, allowing it to be administered once a day.

Lercanidipine is metabolized in the liver by CYP 3A4 and converted into inactive metabolites, which are excreted in urine (50%) and feces.

The pharmacokinetic properties of lercanidipine do not change depending on age, the presence of mild or moderate hepatic or renal failure.


Primary ag.


Per os 1 tablet per day, mainly in the morning (before breakfast for ≥15 min).


  • Hypersensitivity to any active pharmaceutical ingredient, any APF inhibitor or dihydropyridine calcium antagonist, or any other component of the drug; Quinckes edema (idiopathic, hereditary or transferred in connection with the use of APF inhibitors); pregnancy or its planning; combined use with drugs containing aliskiren against diabetes mellitus or impaired renal function (SCF 60 ml / min / 1.73 m2); obstruction of the outflow of blood from the left ventricle; heart failure in a large circle of blood circulation (in patients who have not received treatment for this reason); angina pectoris (unstable form); myocardial infarction (within 1 month); severe impaired renal function (creatinine clearance 30 ml / min), also in patients receiving hemodialysis treatment; severe impaired liver function; combined use of cyclosporine, strong inhibitors of cyp 3a4, grapefruit juice.

Side effects

  • Decrease in the level of hemoglobin, platelets (150-109 / l); hypersensitivity; increased potassium in the blood; anxiety; cephalgia and dizziness (including postural), tinnitus; increased heart rate (90 beats / min), palpitation; decreased hell (90/60 mm Hg), insufficientia vascularis; cough, dryness, sore throat; abdominal pain, nausea, constipation, dyspeptic manifestations, swelling of the lips, speech disorders, xerostomia, diarrhea, inflammation of the mucous membrane of the gums; increased activity of aminotransferases; Quinckes edema, facial edema, dermatitis, rashes, urticaria; arthralgia; pollakiuria, the prevalence of the night part of diuresis over the daytime, increased urine output; impotence; weakness, fatigue, peripheral edema, sensation of heat.

special instructions

Coripren 20 mg / 10 mg is not used for starting therapy with ag.

Therapy of elderly patients is determined by the functional state of the kidneys.

Care must be taken at the start of therapy for patients with mild or moderate severity of liver or kidney function.

With caution, patients with coronary artery disease are prescribed either with a pathology of the cerebral vessels (an excessive decrease in blood pressure can cause a stroke or myocardial infarction), as well as Shorts syndrome without an implanted pacemaker and in patients with left ventricular dysfunction.

Secondary hypotension in the treatment of enalapril is possible in patients with heart failure. Medical supervision is required for patients with severe heart failure amid a decrease in sodium in the blood, impaired renal function or high-dose loop diuretics (risk of secondary hypotension).

With a decrease in BCC in patients with enalapril, hypertension, the likelihood of secondary hypotension increases.

If secondary hypotension develops, a dose reduction or discontinuation of diuretics and / or enalapril may be necessary.

Patients with impaired renal function of mild or moderate degree require constant monitoring of creatinine and potassium in the blood plasma. An increase in plasma levels of creatinine and potassium can occur in a number of hypertensive patients who have no history of kidney pathology, while using a diuretic in combination with enalapril.

With the use of enalapril, the development of renal failure is possible (usually in patients with pathology of the kidneys or with severe impairment of cardiac function), reversible when the drug is discontinued.

Careful observation by a physician of patients with stenosis is required a. renalis (bilateral or the only functioning kidney) receiving treatment with ACE inhibitors, due to the likelihood of impaired renal function or decreased blood pressure (90/60 mm Hg). Treatment begins with low doses with a gradual increase against the background of renal function control.

Do not take coriprene in patients after kidney transplantation.

Patients with diabetic nephropathy should not take ACE inhibitors in combination with aliskiren.

If it is necessary to use ACE inhibitors in combination with aliskiren or angiotensin II antagonists, medical supervision and careful monitoring of blood pressure, plasma electrolytes, and renal functions are required.

Possible increased antihypertensive effect of lercanidipine in patients with impaired hepatic function. The use of ACE inhibitors ceases in patients with an increase in aminotransferase activity or the development of jaundice.

With caution, enalapril is prescribed to patients with collagenosis (with vascular damage) receiving therapy with immunosuppressants, procainamide or allopurinol (regular monitoring of the leukogram and alertness regarding the development of infectious diseases is required).

The likelihood of developing Quincke edema with the use of an ACE inhibitor increases in patients with a history of Quincke edema (not associated with the use of drugs of this group).

In rare cases, anaphylactoid reactions may develop with the use of ACE inhibitors in combination with desensitizing therapy (insect venom) or LDL-apheresis (dextran sulfate).

Patients receiving ACE inhibitors may experience coughing.

At the beginning (1st month) of therapy with ACE inhibitors in patients with diabetes mellitus receiving insulin or sugar-lowering drugs per os, careful monitoring of glycemia is required.

In the case of lowering blood pressure 90/60 mm RT. Art. during major surgery or the use of blood pressure lowering anesthetics, measures are taken to increase the BCC.

With the use of ACE inhibitors, the development of hyperkalemia is possible. Regular monitoring of potassium in the blood plasma is required if necessary, the combined use of enalapril with potassium-sparing diuretics, dietary supplements, or salt substitutes containing potassium.

The antihypertensive effect of enalapril is reduced in representatives of the black race compared with the Caucasian.

Due to the lactose content, the drug is contraindicated in patients with galactosemia, lactase deficiency or glucose-galactose malabsorption syndrome.

The use of calcium antagonists can cause reversible changes in sperm and, consequently, impaired fertilization.

With the development of pregnancy in patients receiving Coripren, the drug is immediately canceled.

During lactation, Coripren is not used.

Persons driving vehicles, or when working with other mechanisms while taking Coripren, should take into account the likelihood of fatigue, weakness, dizziness, drowsiness.


Investigated only in adults.

It is possible to enhance the antihypertensive effect of the drug when combined with other antihypertensive drugs.

The combined use of enalapril maleate with other ACE inhibitors, aliskiren, angiotensin II receptor antagonists increases the likelihood of side effects (lowering blood pressure 90/60 mm Hg, elevated levels of potassium in the blood, impaired renal function).

The elimination of potassium from the body caused by the use of diuretics decreases with the use of ACE inhibitors. The use of potassium-sparing diuretics, dietary supplements with potassium, or substances containing salts of this macroelement in combination with enalapril maleate can lead to hyperkalemia.

The combined use of diuretics (loop or thiazide series) at the beginning of enalapril therapy can cause a decrease in bcc and increase the likelihood of a decrease in blood pressure (90/60 mm Hg).

The combined use of enalapril maleate with vasodilators (including nitroglycerin preparations, other nitrates) can enhance the hypotensive effect.

Enalapril maleate should not be used in combination with lithium preparations due to the increase in blood levels and, accordingly, the toxicity of the latter. If it is necessary to use this combination, careful monitoring of the plasma content of lithium is required.

In rare cases, patients who received injections of sodium aurothiomalate and at the same time treatment with ACE inhibitors (including enalapril), observed vasomotor reactions.

Combined use with mTOR kinase inhibitors may increase the likelihood of developing Quincke edema.

The antihypertensive effect of ACE inhibitors is potentiated by alcohol, antipsychotics, as well as drugs used for anesthesia, and tricyclic antidepressants.

The antihypertensive effect of ACE inhibitors decreases with combined use with indirect action adrenomimetics, NSAIDs.

The combination with NSAIDs also contributes to an increase in potassium in the blood and possible impaired renal function (rarely - acute renal failure).

The likelihood of hyperglycemia increases with the combination of ACE inhibitors with sugar-lowering drugs, especially at the start of such therapy and in patients with impaired renal function.

Do not use lercanidipine in combination with potent CYP 3A4 inhibitors, cyclosporine or grapefruit juice.

With care, lercanidipine is used in combination with other CYP 3A4 substrates.

In view of the possible decrease in the hypotensive effect with the combination of lercanidipine with CYP 3A4 inducers (rifampicin, anticonvulsants), their simultaneous use requires more frequent monitoring of the patients blood pressure.

Due to the increase in the hypotensive effect, the combined use of lercanidipine with alcohol is not recommended; for the same reason, caution is required when combined with cimetidine at a dose of 800 mg / day (increased bioavailability of lercanidipine).

The absorption of lercanidipine increases (with a simultaneous slowdown in its speed) with combined use with midazolam at a dose of 20 mg in the elderly.

In the case of simultaneous use of lercanidipine with digoxin, careful monitoring of the clinical manifestations of the toxic effects of digoxin is necessary.


Excessive use of enalapril is manifested by a decrease in hell (90/60 mm Hg) approximately 6 hours after administration and the development of stupor. when taking an excessive dose of APF inhibitors, vascular shock, electrolyte imbalance, kidney function, hyperventilation, increased heart rate (90 beats / min) or decreased heart rate (60 beats / min), palpitations, dizziness, anxiety and cough may occur.

Intravenous infusion of 0.9% NaCl solution is carried out. In the event of a decrease in blood pressure (90/60 mm RT. Art.) Give the patient an anti-shock position of the body; catecholamines or angiotensin II are administered iv. With a recent dose, they artificially induce vomiting, perform gastric lavage, prescribe adsorbents and Na2SO4. In the case of a steady-state reduction in heart rate (60 beats / min), a pacemaker is used. Effectively hemodialysis. Constant monitoring of plasma creatinine and electrolytes, indicators of the functions of vital organs and systems is necessary.

Excessive use of lercanidipine can manifest an excessive vasodilating effect in the peripheral vasculature with a significant decrease in blood pressure (90/60 mm Hg) and a reflex increase in heart rate (90 bpm).

It is advisable to use iv atropine. Dialysis is ineffective. Monitoring of the patients condition for 1 day is recommended.

Storage conditions

In a place inaccessible to children, at a temperature of ≤25 ° C in the original packaging.

Tags: Coripen® [Lercanidipine Hydrochloride, enalapril]