Lerkamen Duo pills 10+10mg, 28pcs

Composition

>of 1 tab. contains: Active ingredients:  lercanidipine hydrochloride 10 mg, enalapril maleate 10 mg. Auxiliary substances: lactose monohydrate-102 mg, microcrystalline cellulose-40 mg, sodium carboxymethyl starch-20 mg, povidone K 30-8 mg, sodium bicarbonate-8 mg, magnesium stearate-2 mg. Shell composition:  opadray white (02F29056) – 6 mg (hypromellose 5cP-3.825 mg, titanium dioxide (E 171) – 1.275 mg, talc-300 mcg, macrogol 6000-600 mcg).

Pharmacological action

The drug is a combination of an ACE inhibitor and a slow calcium channel blocker. Lercanidipine Lercanidipine is a dihydropyridine derivative that inhibits the transmembrane flow of calcium into cardiac and smooth muscle cells. The mechanism of antihypertensive action is due to a direct relaxing effect on the smooth muscles of blood vessels, as a result of which OPSS decreases. It has a prolonged antihypertensive effect. Due to its high selectivity to vascular smooth muscle cells, there is no negative inotropic effect. Enalapril Enalapril is an ACE inhibitor, inhibits the formation of angiotensin II and eliminates its vasoconstrictive effect. Reduces blood pressure without causing an increase in heart rate and minute volume. Reduces OPSS, reduces afterload and preload on the heart. Reduces pressure in the right atrium and small circle of blood circulation. It does not affect the metabolism of glucose, lipoproteins, as well as the functions of the reproductive system. Pharmacokineticspharmacokinetic interactions have not been observed with concomitant use of enalapril and lercanidipine. Lercanidipineabsorption lercanidipine is completely absorbed in the gastrointestinal tract after oral use. At the” first pass ” through the liver, due to high metabolism, the absolute bioavailability when taken orally after a meal is approximately 10%, when taken on an empty stomach, the bioavailability decreases by 1/3. Bioavailability after the use of lercanidipine increases by 4 times if the drug is taken no later than 2 hours after taking a fatty meal. Therefore, the drug should be taken at least 15 minutes before meals. Cmax in blood plasma is reached in 1.5-3 hours. Does not accumulate with repeated use. The duration of therapeutic action of lercanidipine is 24 hours. The concentration of lercanidipine in blood plasma when taken orally is non-linear with the dose. When taking 10 mg,20 mg or 40 mg, the Cmax of lercanidipine in blood plasma was determined in the ratio of 1: 3: 8, respectively, and the AUC – in the ratio of 1: 4: 18, which suggests progressive saturation at the “first pass” through the liver. Accordingly, bioavailability increases with increasing dose. Distribution lercanidipine is rapidly and intensively distributed from blood plasma to tissues and organs. The binding of lercanidipine to plasma proteins exceeds 98%. Metabolism: Lercanidipine is metabolized by the liver isoenzyme CYP3A4 to form inactive metabolites. Excretionthe drug in unchanged form is practically not detected in the urine and feces. About 50% of the dose of lercanidipine is excreted by the kidneys, the average T1 / 2 of lercanidipine is 8-10 hours. Pharmacokinetics in special clinical cases in elderly patients and patients with mild or moderate renal insufficiency or with mild or moderate hepatic insufficiency, the pharmacokinetic parameters of lercanidipine are the same as in the general group of patients. In patients with severe renal insufficiency or in patients undergoing hemodialysis, lercanidipine is excreted by the kidneys in a higher amount (about 70%). In patients with moderate to severe hepatic insufficiency, the systemic bioavailability of lercanidipine is increased, since the drug is mainly metabolized in the liver. In patients with renal and hepatic insufficiency, the plasma protein content is reduced, so the free fraction of lercanidipine can be increased. Enalaprilabsorption The absorption rate of enalapril after oral use is about 60%. Cmax of enalapril in blood plasma is observed after 1 h. Food intake does not affect the absorption of enalapril. Distribution: When taken orally, it is rapidly hydrolyzed to enalaprilate, which has an ACE inhibitory effect. Cmax of enalaprilate in the blood serum is observed 3-4 hours after taking the drug. The binding of enalapril to plasma proteins does not exceed 60%. Metabolism: When taken orally, it is hydrolyzed to the main metabolite, enalaprilate. Elimination About 40% of enalapril as enalaprilate and about 20% unchanged enalapril is excreted by the kidneys. Pharmacokinetics in special clinical cases in patients with renal insufficiency, the duration of exposure to enalapril and enalaprilat is increased. In patients with mild or moderate renal insufficiency (creatinine clearance 40-60 ml/min) when taking 5 mg of enalapril 1 time/day, the plateau stage of enalaprilate AUC is doubled compared to patients with normal liver function. In patients with severe renal insufficiency (creatinine clearance < 30 ml/min), AUC increases approximately 8-fold. In this stage of renal failure, T1 / 2 enalaprilate increases with repeated use of enalapril maleate and the time to reach the plateau stage of AUC slows down. Enalaprilate can be removed from the general bloodstream by hemodialysis. The dialysis clearance is 62 ml/min.

Indications

• Essential hypertension (if lercanidipine 10 mg monotherapy is ineffective) – a dose of 10 mg+10 mg;
• essential hypertension (if enalapril 20 mg monotherapy is ineffective) – a dose of 10 mg+20 mg.

Contraindications

• Violation of the outflow from the left ventricle, including aortic valve stenosis;
• chronic heart failure in the stage of decompensation;
• hereditary and/or idiopathic angioedema (including in the anamnesis);
• angioneurotic edema with the use of ACE inhibitors (in the anamnesis);
• unstable angina;
• the first month after myocardial infarction (within 28 days);
• severe renal insufficiency (CC < 30 ml/min), including patients on hemodialysis;
• severe hepatic impairment;
• concomitant use with potent inhibitors of isoenzyme CYP3A4 (ketoconazole, Itraconazole, erythromycin, ritonavir, troleandomycin), cyclosporine, grapefruit juice;
• lactase deficiency, lactose intolerance, malabsorption syndrome glucose/galactose;
• childhood and adolescence to 18 years;
• hypersensitivity to lercanidipine, to amlodipine, or to any other ACE inhibitor and other bmkk, a derivative of dihydropyridine, as well as any other component of the drug.

Caution

• syndrome of weakness of the sinus node (without the simultaneous application of an artificial pacemaker of the heart);
• dysfunction of the left ventricle and coronary artery disease;
• renal failure (QC more than 30 ml/min);
• renovascular hypertension;
• condition after kidney transplantation (application experience is limited);
• liver failure;
• the oppression of bone marrow hematopoiesis;
• severe autoimmune connective tissue diseases (including scleroderma, systemic lupus erythematosus);
• concurrent use with immunosuppressive drugs, allopurinol, procainamide;
• diabetes mellitus;
• surgery and General anesthesia;
• patients follow a diet with restriction of salt consumption;
• hyperkalemia;
• state, accompanied by a decrease in BCC, including diarrhea, vomiting, primary aldosteronism.

Side effects

The frequency of adverse events was classified as follows: very common (1/10), common (1/100), infrequent (1/1000), rare (1/10 000), very rare (Lercanidipine + Enalapril from the central nervous system: often-dizziness; infrequently-headache. From the side of the psyche: infrequently-anxiety. Skin disorders: infrequently-dermatitis, lip edema, erythema, urticaria, rash. From the genitourinary system: infrequently-erectile dysfunction, pollacuria, polyuria, nocturia. From the immune system: infrequently-hypersensitivity to one of the components of the drug, angioedema. Musculoskeletal disorders: infrequently-arthralgia. From the digestive system: infrequently-abdominal pain, nausea, constipation, dyspepsia, glossitis. From the hematopoietic system: infrequently-thrombocytopenia. From the respiratory system: often-cough; infrequently-dry throat, pharyngopharyngeal pain. From the cardiovascular system: often – “hot flashes” of blood to the skin of the face; infrequently – palpitation and tachycardia, marked decrease in blood pressure, circulatory collapse, congestive heart failure. From the side of the organ of hearing: often-vertigo, including positional vertigo. Laboratory parameters: infrequently-decreased hemoglobin level, increased ALT, ACT activity. Others: often-peripheral edema, infrequently-asthenia, increased fatigue, feeling hot. Enalapril from the central nervous system: very often-dizziness; often-headache; infrequently-paresthesia. From the side of the psyche: often-depression; infrequently-confusion, drowsiness, insomnia, nervousness; rarely-pathological dreams, sleep disorders. From the skin: often-rash; infrequently-increased sweating, itching, urticaria, alopecia; rarely-erythema multiforme, exfoliative dermatitis, Stevens-Jones syndrome, Lyell’s syndrome, pemphigus. From the genitourinary system: infrequently-renal failure, proteinuria, erectile dysfunction; rarely-gynecomastia, oliguria. From the immune system: often-hypersensitivity, angioedema of the face, limbs, lips, tongue, vocal folds and / or larynx; rarely – autoimmune disorders. From the side of metabolism: infrequently-hypoglycemia, anorexia.Musculoskeletal disorders: infrequently-muscle spasm. From the digestive system: very often-nausea; often-diarrhea, abdominal pain, taste disorders; infrequently-intestinal obstruction, pancreatitis, vomiting, dyspepsia, constipation, dry oral mucosa, stomach pain, stomach or duodenal ulcer; rarely-stomatitis, aphthous stomatitis, glossitis; very rarely-intestinal angioedema. From the liver and biliary tract: rarely-liver failure, hepatitis (cholestatic or necrotic), cholestasis. From the hematopoietic system: infrequently-anemia, including aplastic and hemolytic; rarely-thrombocytopenia, neutropenia, agranulocytosis, pancytopenia, lymphadenopathy, insufficiency of bone marrow hematopoiesis. From the respiratory system: very often – cough; often – shortness of breath; infrequently-rhinorrhea, pharyngopharyngeal pain, dysphonia, bronchospasm, asthma; rarely – lung infiltration, rhinitis, alveolar allergic/eosinophilic pneumonia. From the side of the organ of vision: very often – a decrease in visual acuity. From the side of the organ of hearing: infrequently-ringing in the ears, vertigo. From the cardiovascular system: often-arrhythmia, angina pectoris, tachycardia, myocardial infarction, marked decrease in blood pressure, syncope, stroke, due to excessive decrease in blood pressure in patients with increased risk; infrequently-palpitation, “flushes” of blood to the skin of the face, orthostatic hypotension; rarely-Raynaud’s syndrome. Laboratory parameters: often-hyperkalemia, increased creatinine in the blood; infrequently-increased urea content in the blood, decreased sodium content in the blood; rarely – increased hemoglobin and hematocrit levels, increased number of liver enzymes and decreased bilirubin concentration in the blood. Other: very often – asthenia; often-increased fatigue, chest pain; infrequently-malaise. A symptom complex is also described, which includes facial skin hyperemia, nausea, vomiting, and a marked decrease in blood pressure and can develop with the simultaneous use of ACE inhibitors and the preparation of gold (sodium aurothiomalate) iv. Lercanidipine from the central nervous system: infrequently-dizziness, headache. From the side of the psyche: rarely-drowsiness. From the skin: rarely-rash. Immune system disorders: very rare-hypersensitivity. From the genitourinary system: rarely-polyuria. Musculoskeletal disorders: rarely-myalgia. From the digestive system: rarely-nausea, dyspepsia, diarrhea, abdominal pain, vomiting. From the cardiovascular system: infrequently-tachycardia, palpitation, “flushes” of blood to the skin of the face; rarely-angina pectoris; very rarely-fainting. Other: infrequently-peripheral edema; rarely-asthenia, increased fatigue.

Interaction

The antihypertensive effect of Coripren can be potentiated by other drugs that reduce blood pressure, such as diuretics, beta-blockers, alpha-blockers, and others. In addition, when used concomitantly with other drugs, the following interaction effects may occur. Lercanidipine should not be taken in combination with CYP3A4 inhibitors, such as ketoconazole, itraconazole, erythromycin and others, with cyclosporine and grapefruit juice (they increase the concentration in the blood and lead to potentiation of the antihypertensive effect). Caution should be exercised when taking concomitant medications such as terfenadine, astemizole, Class III antiarrhythmic drugs (for example, amiodarone). and quinidine. Concomitant use with anticonvulsants (e. g., phenytoin, carbamazepine) and rifamycin may reduce the antihypertensive effect of lercanidipine. Digoxin intake should be carefully monitored for clinical signs of digoxin toxicity. Taking the drug with midazolam leads to an increase in the absorption of lercanidipine in the gastrointestinal tract and a decrease in the rate of absorption. Metaprolol reduces the bioavailability of lercanidipine by 50%. Cimetidine at a dose of 800 mg / day does not cause significant changes in the content and concentration of lercanidipine in the blood serum, however, with such a combination, special caution is required, because with higher doses of cimetidine, the bioavailability of lercanidipine, and, consequently, its antihypertensive effect, may increase. Fluoxetine has no effect on the pharmacokinetics of lercanidipine. In the case of taking the drug with simvastatin, the drug should be taken in the morning, and simvastatin-in the evening. Taking lercanidipine concomitantly with warfarin does not affect the pharmacokinetics of the latter. Simultaneous use of Enalapril with potassium salts, potassium-sparing diuretics (spironolactone, triamterene, eplerenone, amiloride), ACE inhibitors, angiotensin II receptor antagonists, NSAIDs, heparins (low molecular weight or unfractionated), cyclosporine, tacrolimus and trimethoprim increases the risk of hyperkalemia. He is also recommended to be used together with lithium salts (if such a combination is necessary, then careful monitoring of the concentration of lithium in the blood plasma is carried out). Concomitant use with antidiabetic drugs (both oral and insulins) may cause hypoglycemia in the first week of treatment. Diuretics (“loop” and thiazide) can cause a decrease in BCC and thus increase the risk of a pronounced decrease in blood pressure during treatment with the drug. Long-term use of NSAIDs may reduce the antihypertensive effect of ACE inhibitors. Both NSAIDs and ACE inhibitors (enalapril) they contribute to an increase in the potassium content in the blood, which can lead to impaired kidney function. Baclofen enhances the antihypertensive effect. Cyclosporine increases the risk of hyperkalemia. Ethanol enhances the antihypertensive effect of ACE inhibitors. Tricyclic antidepressants, antipsychotics, general anaesthetics, and opioid analgesics may lead to a further decrease in blood pressure. Corticosteroids (except hydrocortisone as a replacement therapy for Addison’s disease) reduce the antihypertensive effect (fluid retention followed by an increase in BCC). Concomitant use with other antihypertensive agents may enhance the antihypertensive effect of enalapril. Combined use with nitroglycerin and other nitrates and vasodilators leads to an even more pronounced decrease in blood pressure. Allopurinol, cytostatics, immunosuppressants, systemic corticosteroids, and procainamide may lead to an increased risk of leukopenia. Antacids reduce the bioavailability of ACE inhibitors. Sympathomimetics may reduce the antihypertensive effect. Enalapril can be used simultaneously with acetylsalicylic acid (as an antiplatelet agent). When used concomitantly with the preparation of gold (sodium aurothiomalate) intravenously, side effects may develop.

How to take, course of use and dosage

Tablets are taken orally, preferably in the morning, at least 15 minutes before meals, without chewing, with a sufficient amount of water. Do not drink grapefruit juice. Coripren® is not intended for the initial treatment of hypertension. If lercanidipine 10 mg monotherapy is ineffective, you should start taking Coripren® 10 mg lercanidipine + 10 mg enalapril. If monotherapy with enalapril 20 mg is ineffective, you should start taking Coripren® 10 mg lercanidipine + 20 mg enalapril. The dose of the drug is selected by the doctor.

Overdose

There is no information about overdose with the drug. Presumably, in case of overdose, it can cause conditions caused by an overdose of any of the active substances. Lercanidipin Symptoms: peripheral vasodilation with a marked decrease in blood pressure and reflex tachycardia, vomiting. Treatment: treatment is symptomatic, the choice of treatment method depends on the degree of overdose and on the observed symptoms. The following methods of medical care are used: gastric lavage, taking high doses of catecholamines, furosemide, cardiac glycosides and plasma substitutes, activated charcoal, laxatives, and intravenous use of dopamine. Intravenous use of atropine is also possible to prevent the development of bradycardia. Enalapril symptoms: the main sign of overdose is a marked decrease in blood pressure, which is accompanied by blockade of the renin-angiotensin-aldosterone system. You may also develop a collapse, electrolyte imbalance, kidney failure, hyperventilation, tachycardia, rapid heartbeat, bradycardia, dizziness, anxiety, and coughing. Treatment: treatment is symptomatic. In severe cases, intravenous use of 0.9% sodium chloride solution and, if possible, infusion of angiotensin II and/or catecholamines is recommended. If symptoms of overdose develop immediately after taking the drug, then it is necessary to induce vomiting, perform gastric lavage and take drugs from the group of adsorbents or sodium sulfate.

Special instructions

Patients with severe hypotension and systolic blood pressure of less than 90 mm Hg, as well as patients with decompensated heart failure, require special attention in the treatment of arterial hypertension. Transient arterial hypotension is not a contraindication to continuing treatment, because after filling the BCC, an adequate response to the drug can be expected. Special care should be taken in the initial stages of treatment of patients with mild to moderate renal insufficiency. Patients with bilateral renal artery stenosis or stenosis of the artery of a single functioning kidney are particularly at risk of developing hypotension or renal failure due to taking ACE inhibitors. For this group of patients, treatment should be carried out under strict medical supervision, with careful dose selection and the appointment of low doses of the drug. Renal function should be monitored before and during treatment. Special care should be taken in the initial stages of treatment of patients with mild to moderate hepatic insufficiency.If jaundice occurs and there is a significant increase in the activity of liver enzymes, it is necessary to immediately stop taking ACE inhibitors and consult a doctor. Due to the increased risk of anaphylactic reactions, the drug should not be prescribed to patients undergoing hemodialysis using high-strength polyacrylonitrile membranes (AN69), undergoing low-density lipoprotein apheresis with dextran sulfate and immediately before the procedure of desensitization to wasp or bee venom. Like other ACE inhibitors, it has a less pronounced antihypertensive effect in patients of the black race compared to representatives of other races. Angioedema of the face, extremities, tongue, pharynx, or larynx may develop due to the use of enalapril. In this case, you should immediately stop taking the drug. Angioedema of the larynx can be fatal. Angioedema of the tongue, pharynx or larynx can lead to airway obstruction, it is necessary to immediately introduce 0.3-0.5 ml of epinephrine (epinephrine) solution subcutaneously in a ratio of 1: 1000 and maintain airway patency (intubation or tracheostomy). Among black patients receiving ACE inhibitor therapy, the incidence of angioedema is higher than among patients of other races. Patients with a history of angioedema that is not associated with the use of ACE inhibitors have an increased risk of developing angioedema when using any ACE inhibitor. Before surgery (including dentistry), the surgeon/anesthesiologist should be warned about the use of ACE inhibitors. During surgical procedures and/or during general anesthesia with hypotensive agents, ACE inhibitors can block the formation of angiotensin II in response to the compensatory release of renin. If a marked decrease in blood pressure occurs due to such a mechanism, it can be corrected by increasing the BCC. Hyperkalemia may develop during therapy with ACE inhibitors, including enalapril. Risk factors for hyperkalemia include renal failure, advanced age, diabetes mellitus, certain concomitant conditions (decreased BCC, acute heart failure in the decompensation stage, metabolic acidosis), concomitant use of potassium-sparing diuretics (such as spironolactone, eplerenone, triamterene, amiloride), as well as potassium preparations or potassium-containing substitutes for table salt, and the use of other drugs that contribute to an increase in the content of potassium in blood plasma (for example, heparin). Hyperkalemia can lead to serious cardiac arrhythmias, sometimes fatal. The combined use of the above drugs should be carried out with caution. It is not recommended to drink alcohol during drug therapy. There is evidence of reversible biochemical changes in sperm heads during the use of calcium channel blockers, which may interfere with their ability to fertilize. Effects on the ability to drive motor vehicles and control mechanisms should be borne in mind the possibility of weakness and drowsiness, so care should be taken when performing work that requires increased attention, especially at the beginning of treatment, when increasing the dose of the drug and when driving vehicles.

Storage conditions

The drug should be stored out of the reach of children at a temperature not exceeding 25°C.

Shelf

life is 2 years.

Active ingredient

Lercanidipine, Enalapril

Conditions of release from pharmacies

By prescription

Dosage form

Tablets