Expiration date: 01/2025
Active substances
enalapril
lercanidipine
Dosage form
The drug is available on a prescription Lerkamen ® DUO
Tab., film-coated, 10 mg+10 mg: 7, 10, 14, 28, 30, 35, 42, 50 or 56 PCs.
reg. Number: PL-001184 from 11.11.11 - Indefinitely
Date of re-registration: 16.12.16
Form of production, packaging and composition of Lerkamen® DUO
Tablets covered with a white film coating, round, biconvex; on a cross section - the core is light yellow.
1 tablet contains:
lercanidipine hydrochloride 10 mg
enalapril maleate 10 mg
Excipients: lactose monohydrate-102 mg, microcrystalline cellulose-40 mg, sodium carboxymethyl starch-20 mg, povidone K30-8 mg, sodium bicarbonate-8 mg, magnesium stearate-2 mg.
Shell composition: opadray white (02F29056) - 6 mg (hypromellose 5cP - 3.825 mg, titanium dioxide (E171) - 1.275 mg, talc - 300 mcg, macrogol 6000-600 mcg).
7 PCs. - blisters (1, 2, 3, 4, 5, 6, 7, 8, 9, 10) - bundles of cardboard.
10 PCs. - blisters (1, 2, 3, 4, 5, 6, 7, 8, 9, 10) - packs of cardboard.
14 PCs. - blisters (1, 2, 3, 4, 5, 6, 7, 8, 9, 10) - packs of cardboard.
28 PCs. - blisters (1, 2, 3, 4, 5, 6, 7, 8, 9, 10) - packs of cardboard.
30 PCs. - blisters (1, 2, 3, 4, 5, 6, 7, 8, 9, 10) - packs of cardboard.
35 PCs. - blisters (1, 2, 3, 4, 5, 6, 7, 8, 9, 10) - packs of cardboard.
42 PCs. - blisters (1, 2, 3, 4, 5, 6, 7, 8, 9, 10) - bundles of cardboard.
50 PCs. - blisters (1, 2, 3, 4, 5, 6, 7, 8, 9, 10) - packs of cardboard.
56 PCs. - blisters (1, 2, 3, 4, 5, 6, 7, 8, 9, 10) - packs of cardboard.
Clinical and pharmacological group: Antihypertensive drug
Pharmaco-therapeutic group: Hypotensive combined agent (ACE inhibitor+bmcc)
Pharmacological action
Combined antihypertensive drug.
Lercanidipine is a selective calcium channel blocker, a dihydropyridine derivative. It inhibits the transmembrane flow of calcium ions into the cells of the myocardium and vascular smooth muscle. The mechanism of antihypertensive action is due to a direct relaxing effect on vascular smooth muscle cells, as a result of which the OPSS is reduced. Despite the relatively short T1 / 2 of blood plasma, lercanidipine has a long antihypertensive effect due to the high coefficient of membrane distribution. Due to its high vascular selectivity, lercanildipine does not have a negative inotropic effect.
A marked decrease in blood PRESSURE with reflex tachycardia occurs rarely due to the gradual development of vasodilation when taking lercanidipine.
Lercanidipine is a racemic mixture of (+)R and (-)S - enantiomers. The antihypertensive effect of lercanidipine, as well as other asymmetric derivatives of 1,4-dihydropyridine, is mainly determined by the S-enantiomer.
Enalapril-ACE inhibitor, suppresses 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 postload 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 sexual system.
Pharmacokinetics
When using lercanidipine and enalapril simultaneously, no pharmacokinetic interaction was detected.
Lercanidipine is completely absorbed after oral administration, its Cmax in blood plasma is reached in about 1.5-3 hours. Lercanidipine enantiomers exhibit a similar pharmacokinetic profile: they have the same time to reach the maximum concentration (Tmax), the same T1/2. Cmax in blood plasma and AUC of the S-enantiomer of lercanidipine, on average, 1.2 times more than the R-enantiomer. There is no interconversion of the two enantiomers in vivo.
Due to the high metabolism during the" first pass " through the liver, the absolute bioavailability of lercanidipine after meals is about 10%. When ingested on an empty stomach, the bioavailability in healthy volunteers was 1/3 of the bioavailability index after meals.
The bioavailability of lercanidipine when taken orally increases by 4 times if it is taken within 2 hours after a meal with a high fat content, therefore, the drug should be taken at least 15 minutes before meals. The pharmacokinetics of lercanidipine in the range of therapeutic doses is nonlinear. When taking lercanidipine in doses of 10 mg, 20 mg or 40 mg, Cmax in blood plasma was determined in a ratio of 1:3:8, respectively, and AUC - in a ratio of 1:4:18, which suggests progressive saturation at the "first pass" through the liver. Accordingly, bioavailability increases with increasing doses.
Lercanidipine is rapidly and actively distributed from blood plasma to tissues and organs. Binding of lercanidipine to plasma proteins exceeds 98%. Since the concentration of protein in blood plasma decreases in patients with severe renal or liver disorders, this may lead to an increase in the free fraction of lercanidipine. Lercanidipine is actively metabolized by the CYP3A4 isoenzyme, mainly turning into inactive metabolites.
Elimination of lercanidipine occurs mainly by biotransformation. About 50 % of the dose taken is excreted by the kidneys. The average value of T1 / 2 is, on average, 8-10 hours. Due to the close binding of lercanidipine to the lipid membrane, the duration of therapeutic action of lercanidipine is 24 hours. Does not accumulate when reused.
The pharmacokinetics of lercanidipine in elderly patients and patients with mild or moderate renal or hepatic impairment are similar to those in healthy volunteers. In patients with severe renal insufficiency and patients on hemodialysis, the concentration of lercanidipine in blood plasma increased by about 70%. In patients with moderate to severe hepatic impairment, the systemic bioavailability of lercanidipine is likely to increase, since lercanidipine is primarily metabolized in the liver.
After ingestion, enalapril is rapidly absorbed. Cmax of enalapril in blood plasma is observed within 1 hour after oral administration. Absorption of enalapril after oral administration is about 60% and does not depend on the time of food intake. After absorption, enalapril is rapidly and actively hydrolyzed to enalaprilate , a powerful ACE inhibitor. Cmax enalaprilat in blood plasma is reached in 3-4 hours after oral administration. Binding of enalaprilat with plasma proteins in the range of therapeutic doses does not exceed 60%. In addition to conversion to enalaprilat, other metabolic changes of enalapril were not detected. Enalapril is excreted by the kidneys: about 40% as enalaprilat and about 20% as unchanged enalapril. The exposure of enalapril and enalaprilat increases in patients with renal insufficiency. In patients with mild to moderate renal impairment (CC 40-60 ml / min) after taking enalapril at a dose of 5 mg once a day, the AUC of enalaprilat is approximately 2 times greater than in patients with normal renal function. In severe renal impairment (CC < 30 ml / min), the AUC increases by about 8 times, and T1/2 enalaprilate is also lengthened. Enalaprilat can be removed from the General bloodstream by hemodialysis. The dialysis clearance is 62 ml / min
The testimony of the drug of Lerkamen® DUO
Essential hypertension (when monotherapy with enalapril or lercanidipine is ineffective).
ICD-10 codes
Dosage regimen
The method of application and dosage regimen of a particular drug depend on its form of release and other factors. The optimal dosage regimen is determined by the doctor. It is necessary to strictly observe the compliance of the used dosage form of a particular drug with the indications for use and the dosage regimen.
For oral administration. A single dose is taken 1 time/day.
Depending on the clinical effect and individual tolerance, the dose may be increased to lercanidipine 10 mg/enalapril 20 mg 1 time/day.
In elderly patients, the dose depends on the state of kidney function.
Side effect
Determining the frequency of side effects: very common (> 1/10); common (> 1/100 to < 1/10); infrequent (> 1/1000 to < 1/100); rare (>1/10000 to < 1/1000); very rare (< 1/10 000); frequency unknown (cannot be estimated from available data).
Lercanidipine + enalapril
From the blood and lymphatic system: infrequently-thrombocytopenia, decreased hemoglobin in the blood serum.
On the part of the immune system: infrequently-hypersensitivity to one of the components of the drug, Quincke's edema.
From the side of metabolism and nutrition: infrequently-hypertriglyceridemia.
Mental disorders: infrequent-anxiety.
From the nervous system: often-dizziness; infrequently: headache.
On the part of the organ of hearing and labyrinth disorders: common - vertigo, including positional.
From the cardiovascular system: often-a feeling of" tides " of blood to the skin of the face; infrequently-a marked decrease in blood PRESSURE, vascular collapse, palpitations and tachycardia, decompensation of CHF.
The respiratory system: often - cough, pharyngeal-laryngeal pain; rarely, dryness of the mucous membrane of the oral cavity.
From the digestive system: infrequently-abdominal pain, nausea, constipation, dyspepsia, glossitis, increased ALT activity, ACT.
The skin and subcutaneous tissue: often - dermatitis, swelling of the lips, erythema, urticaria, skin rash.
From the side of musculoskeletal system: infrequently - artralgia.
From the urinary system: infrequently-pollakiuria, polyuria, nycturia.
From the sexual system: infrequently-erectile dysfunction.
Other: often-peripheral edema; infrequently-asthenia, fatigue, feeling of heat.
Enalapril
From the hematopoietic system: infrequently-anemia (including aplastic and hemolytic); rarely-neutropenia, decreased hemoglobin and hematocrit in the blood serum, thrombocytopenia, agranulocytosis, inhibition of bone marrow hematopoiesis, pancytopenia, lymphadenopathy, autoimmune diseases.
From the immune system: often-hypersensitivity reactions/angioedema (described angioedema of the face, limbs, lips, tongue, pharynx and/or larynx).
From the endocrine system: infrequently-hypoglycemia; frequency unknown-syndrome of inadequate ADH secretion.
Mental disorders: often-depression; infrequently-confusion, drowsiness, insomnia, nervousness; rarely-pathological dreams, sleep disorders.
From the nervous system: very often-dizziness; often-headache; infrequently-paresthesia.
On the part of the visual organ: very often-blurred visual perception.
On the part of the organ of hearing and labyrinth disorders: infrequent - tinnitus, vertigo.
Of the cardiovascular system: often - pain in the chest, arrhythmia, angina, tachycardia, myocardial infarction (possibly due to a sharp drop in blood pressure in patients of high risk group), marked reduction in blood pressure (including orthostatic hypotension), syncope, stroke (possibly due to a sharp drop in blood pressure in patients at high risk); rarely, palpitations, feeling "tides" of blood to the skin; rarely, Raynaud's syndrome.
From the respiratory system: very often - cough; often-shortness of breath, pharyngeal pain; infrequently - rhinorrhea, sore throat and hoarseness of voice, bronchospasm/asthma; rarely - pulmonary infiltrates, rhinitis, allergic alveolitis/eosinophilic pneumonia.
From the digestive system: very often-nausea; often-diarrhea, abdominal pain, flatulence, changes in taste perception; infrequently-ileitis, intestinal obstruction, pancreatitis, vomiting, dyspepsia, constipation, anorexia, dry mouth, stomach pain, peptic ulcer; rarely - stomatitis / aphthous ulcers, glossitis; very rarely - angioedema of the intestine.
From the liver and biliary tract: rarely-liver failure, hepatitis (hepatocellular or cholestatic), including hepatic necrosis, cholestasis (including jaundice).
From the skin and subcutaneous tissues: often-skin rash; infrequently-increased sweating, itching, urticaria, alopecia; rarely-erythema multiforme, Stevens-Johnson syndrome, exfoliative dermatitis, toxic epidermal necrolysis, pemphigus (pemphigus), erythroderma. A symptom complex is described that may include: fever, myalgia/myositis, arthralgia/arthritis, serositis, vasculitis, increased ESR, leukocytosis and eosinophilia, and a positive test for antinuclear antibodies. There may also be a skin rash, photosensitization reactions, or other skin manifestations.
From the musculoskeletal system: infrequently-muscle cramps.
From the urinary system: impaired renal function, proteinuria, renal failure; rarely-oliguria.
From the sexual system: infrequently-erectile dysfunction; rarely-gynecomastia.
General reactions: very often - asthenia; often-increased fatigue; infrequently-malaise.
Laboratory and instrumental data: often-hyperkalemia, increased serum creatinine concentration; infrequently-increased serum urea concentration, hyponatremia; rarely-increased liver enzyme activity, increased serum bilirubin concentration.
When using ACE inhibitors, including enalapril, in patients receiving an intravenous drug of gold (sodium aurothiomalate), a symptom complex was described, including: facial skin hyperemia, nausea, vomiting and a marked decrease in blood PRESSURE.
Lercanidipine
From the immune system: very rarely - hypersensitivity reactions.
Mental disorders: rarely-drowsiness.
From the nervous system: infrequently-dizziness, headache.
From the cardiovascular system: infrequently-tachycardia, palpitations, a feeling of" rush " of blood to the skin of the face; rarely - angina, pain behind the sternum; very rarely - patients with angina may increase the frequency, duration and severity of attacks, fainting.
From the esophageal system: rarely-nausea, dyspepsia, diarrhea, abdominal pain, vomiting.
From the skin and subcutaneous tissues: rarely-skin rash.
From the musculoskeletal system: rarely-myalgia.
From the urinary system: rarely-polyuria.
General reactions: infrequently-peripheral edema; rarely-asthenia, fatigue.
There are reports of the following very rare side effects: myocardial infarction, gum hyperplasia, reversible increase in the activity of liver transaminases, a marked decrease in blood PRESSURE, pollakiuria (increased frequency of urination), chest pain.
Contraindications to use
Left ventricular outflow tract obstruction, including aortic stenosis; chronic heart failure in the decompensation stage; unstable angina; the first month after a myocardial infarction (for 28 days); severe liver failure (more than 9 points on the child-Pugh scale); simultaneous use with cyclosporine, powerful inhibitors of the CYP3A4 isoenzyme (ketoconazole, Itraconazole, erythromycin, ritonavir, troleandomycin), grapefruit juice; pregnancy, breastfeeding; use in women of childbearing age who do not use reliable methods of contraception; severe renal failure (CC less than 30 ml/min), including patients on hemodialysis; a history of angioedema associated with previous use of ACE inhibitors; a history of episodes of angioedema (idiopathic, hereditary); simultaneous use with aliskiren in patients with diabetes mellitus or moderate or severe renal impairment (CC less than 60 ml/min); age up to 18 years; increased individual sensitivity to one of the components of the combination, any ACE inhibitors, dihydropyridine derivatives.
With caution
Renovascular hypertension (bilateral stenosis of the renal arteries or stenosis of the artery of a single kidney), primary hyperaldosteronism, hyperkalemia, conditions with reduced BCC (including diarrhea, vomiting), systemic connective tissue diseases (including scleroderma, systemic lupus erythematosus), CHD, inhibition of bone marrow hematopoiesis, diabetes mellitus, renal failure (CC more than 30 ml/min), mild to moderate liver failure, use in patients who follow a diet with limited consumption of table salt, simultaneous use with immunosuppressants, allopurinol, procainamide and diuretics, use in elderly patients, the state after kidney transplantation, SSS (without simultaneous use artificial pacemaker), left ventricular dysfunction, aortic or mitral stenosis, GOCMP, before the procedure of LDL apheresis with dextran sulfate, CHF, severe hypotension (systolic blood PRESSURE less than 90 mm Hg), simultaneous desensitizing therapy with hymenopteran venom (risk of anaphylactoid reactions), use in patients of the black race, surgery and General anesthesia.
Use during pregnancy and lactation
Contraindicated use during pregnancy and lactation (breastfeeding).
Use in children
It is contraindicated for children and adolescents under 18 years of age (lack of data on efficacy and safety).
Use in elderly patients
The dose for elderly patients depends on the state of kidney function.
Special instruction
Do not use in patients with cardiogenic shock and hemodynamically significant left ventricular obstruction.
In patients with mild or moderate renal impairment, therapy should be started with extreme caution.
In patients with bilateral renal artery stenosis or stenosis of the artery of the only functioning kidney, treatment with ACE inhibitors increases the risk of hypotension and renal failure. Only minor changes in serum creatinine concentration can indicate a decrease in kidney function. In such patients, treatment should begin with small doses of Enap L Combi under close medical supervision. It is necessary to carefully titrate the dose and monitor kidney function.
Use in patients who have recently undergone kidney transplantation is not recommended.
The antihypertensive effect of lercanidipine may increase in patients with impaired liver function.
In rare cases, treatment with ACE inhibitors is marked by a syndrome that begins with cholestatic jaundice and ends with lightning-fast necrosis of hepatocytes (sometimes fatal). The mechanism of development of this syndrome is not established. If jaundice develops and the activity of liver enzymes significantly increases, you should immediately cancel the ACE inhibitor and prescribe adequate treatment.
Use with great caution in patients with connective tissue diseases (including systemic lupus erythematosus, scleroderma), simultaneously receiving immunosuppressive therapy, allopurinol or procainamide, as well as with a combination of these factors, especially with existing renal dysfunction. These patients may develop severe infections that do not respond to intensive antibiotic therapy. If patients still take drugs containing this combination, it is recommended to periodically monitor the number of white blood cells in the blood.
In patients, taking ACE inhibitors during desensitization with Hymenoptera venom, and in rare cases develop life-threatening anaphylactoid reactions. To prevent such reactions, it is necessary to temporarily stop taking the combined drug during desensitization procedures.
Patients who took ACE inhibitors during LDL apheresis with dextran sulfate rarely developed life-threatening anaphylactoid reactions. It should be temporarily replaced with medicines of another group.
Due to the increased risk of anaphylactoid reactions, this combination should not be used in patients undergoing hemodialysis with high-flow polyacrylonitrile membranes (AN69®) undergoing LDL apheresis with dextran sulfate. If it is necessary to perform hemodialysis, it is advisable to use dialysis membranes of another type, or hypotensive drugs of another group.
In patients with diabetes who receive hypoglycemic agents for oral administration or insulin, during the first month of treatment with an ACE inhibitor, blood glucose concentrations should be carefully monitored.
It is necessary to take into account the differential diagnosis of cough with the use of an ACE inhibitor.
This combination, as well as other drugs containing ACE inhibitors, has a less pronounced antihypertensive effect in patients of the black race compared to representatives of other races.
Patients treated with ACE inhibitors, including enalapril, have reported developing angioedema of the face, extremities, lips, vocal folds, and/or larynx at any time after starting treatment. Even if there is only swelling of the tongue, when there is only difficulty swallowing without respiratory distress syndrome, patients may need long-term monitoring, as the use of antihistamines and corticosteroids may be insufficient.
Angioedema of the larynx or tongue can be fatal in very rare cases. Swelling of the tongue, vocal folds, or larynx can lead to airway obstruction, especially after a history of airway surgery.
Among patients of a black race 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 dental procedures), the surgeon/anaesthetist should be warned about the use of this combination.
In extensive surgery or General anesthesia with hypotension-inducing agents, ACE inhibitors may block the formation of angiotensin II in response to compensatory renin release. If this develops a pronounced decrease in blood PRESSURE, explained by a similar mechanism, it can be corrected by the introduction of plasma substitutes.
Hyperkalemia may develop during treatment with ACE inhibitors, including this combination. Risk factors for hyperkalemia are renal failure, advanced age (over 70 years), diabetes, some related condition (a decrease in the BCC, cardiac decompensation, metabolic acidosis), the simultaneous use of kalisberegath dioretikov (spironolactone, eplerenone, triamterene, amiloride) and potassium supplements or potassium-containing substitutes and the use of other drugs that increase potassium levels in the blood plasma (e.g., heparin). The use of potassium preparations, potassium-sparing diuretics and potassium-containing substitutes can lead to a significant increase in serum potassium, especially in patients with impaired renal function. Hyperkalemia can lead to serious heart rhythm disorders, sometimes with fatal results. Simultaneous use of the above drugs should be carried out with caution under the control of potassium in the blood serum.
During treatment, you should avoid drinking alcohol, because it may increase the antihypertensive effect.
During in vitro fertilization, in some cases, the use of slow calcium channel blockers caused changes in the head of the sperm, which can lead to impaired sperm function. In cases where repeated in vitro fertilization was not performed for an unclear reason, the use of bmcc is considered a possible cause of failure.
Influence on the ability to drive vehicles and mechanisms
Keep in mind the possibility of dizziness, asthenia, weakness, fatigue, and in rare cases, drowsiness. Therefore, care should be taken when driving vehicles and performing work that requires increased attention, especially at the beginning of treatment and when increasing the dose of the combination components.
Drug interaction
Antihypertensive effect may be enhanced when used simultaneously with other antihypertensive drugs, such as: diuretics, beta-blockers, alpha-blockers, and others.
Enalapril
The risk of arterial hypotension, hyperkalemia and renal dysfunction (including acute renal failure) is higher in the case of double blockade of the RAAS, that is, when angiotensin II receptor antagonists (ARA II), ACE inhibitors or aliskiren are used simultaneously, in comparison with the use of the drug in one of the listed groups.
ACE inhibitors reduce the loss of potassium under the action of diuretics. The simultaneous use of enalapril and potassium-sparing diuretics (such as: spironolactone, eplerenone, triamterene, amiloride), potassium preparations or potassium-containing substitutes, as well as the use of other drugs that increase the content of potassium in the blood plasma (for example, heparin) can lead to hyperkalemia.
Prior therapy with high doses of diuretics may lead to a decrease in BCC and an increase in the risk of hypotension during the beginning of enalapril therapy. Excessive antihypertensive effects can be reduced by discontinuing the diuretic, increasing the intake of liquid or table salt, and if treatment with enalapril begins at a low dose.
Simultaneous use of beta-blockers, alpha-blockers, ganglioblockers, methyldopa, bmcc, nitroglycerin or other nitrates with enalapril may further reduce blood PRESSURE.
With simultaneous use of ACE inhibitors with lithium preparations, a transient increase in serum lithium concentration and the development of lithium intoxication were observed. The use of thiazide diuretics may lead to an additional increase in serum lithium concentration and the risk of developing lithium intoxication with the simultaneous use of ACE inhibitors. Simultaneous use of enalapril with lithium is not recommended. If such a combination is necessary, serum lithium concentrations should be carefully monitored.
Simultaneous use of certain analgesics, tricyclic antidepressants and antipsychotic agents (neuroleptics) with ACE inhibitors may lead to an additional decrease in blood PRESSURE.
Simultaneous 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 increasing serum potassium, which can lead to impaired renal function, especially in patients with impaired renal function. This effect is reversible. In rare cases, acute renal failure may develop, especially in patients with already impaired renal function (for example, in elderly patients or in patients with severe hypovolemia, including the use of diuretics).
Epidemiological studies suggest that the simultaneous use of ACE inhibitors and hypoglycemic agents (insulin and hypoglycemic agents for oral administration) may lead to an increased hypoglycemic effect with the risk of hypoglycemia. More often, hypoglycemia develops in the first weeks of therapy in patients with impaired renal function.
Ethanol increases the antihypertensive effect of ACE inhibitors.
Sympathomimetics can reduce the antihypertensive effect of ACE inhibitors.
It weakens the effect of medications containing theophylline.
Allopurinol, cytostatics and immunosuppressants (including methotrexate, cyclophosphamide): concomitant use with ACE inhibitors may increase the risk of developing leukopenia. When used simultaneously with allopurinol, the risk of developing an allergic reaction increases, especially in patients with impaired renal function.
Cyclosporine: concomitant use with ACE inhibitors may increase the risk of hyperkalemia.
Antacids may reduce the bioavailability of ACE inhibitors.
When using ACE inhibitors, including enalapril, patients receiving intravenous gold (sodium aurothiomalate), a symptom complex was described, including: facial skin hyperemia, nausea, vomiting, and a marked decrease in blood PRESSURE.
Lercanidipine
Lercanidipine can be used simultaneously with beta-blockers, diuretics, ACE inhibitors.
When used simultaneously with metoprolol, the bioavailability of lercanidipine decreases by 50 %. This effect can also occur when used simultaneously with other beta-blockers, so it may be necessary to adjust the dose of lercanidipine to achieve a therapeutic effect in this combination.
Lercanidipine is metabolized with the participation of the CYP3A4 isoenzyme, so inhibitors and inducers of the CYP3A4 isoenzyme can simultaneously affect the metabolism and excretion of lercanidipine. Simultaneous use of lercanidipine with inhibitors of the CYP3A4 isoenzyme (ketoconazole, Itraconazole, ritonavir, erythromycin, troleandomycin) is not recommended.
Simultaneous use of cyclosporine and lercanidipine is not recommended, since there is an increase in the concentration of both substances in the blood plasma.
Caution should be exercised when using lercanidipine with other substrates of the CYP3A4 isoenzyme (terfenadine, astemizole, class III antiarrhythmic drugs, for example, amiodarone, quinidine).
When using lercanidipine at a dose of 20 mg with midazolam, the bioavailability of lercanidipine in elderly patients may increase by approximately 40%.
Lercanidipine should be used with caution simultaneously with inducers of the CYP3A4 isoenzyme, such as anticonvulsants (phenytoin, carbamazepine) and rifampicin, since it is possible to reduce the antihypertensive effect of lercanidipine. Regular blood PRESSURE monitoring is required.
In patients who are constantly taking digoxin, while using lercanidipine at a dose of 20 mg, no pharmacokinetic interaction was observed. However, in healthy volunteers who took digoxin, there was an increase in the Cmax of digoxin in blood plasma, on average, by 33 % after ingestion on an empty stomach of 20 mg of lercanidipine, while the AUC and renal clearance of digoxin changed slightly. It is necessary to monitor the presence of signs of digoxin intoxication in patients taking digoxin and lercanidipine simultaneously.
Simultaneous use of lercanidipine with cimetidine (up to 800 mg) does not cause significant changes in the concentration of lercanidipine in blood plasma. When using high doses of cimetidine, the bioavailability of lercanidipine and its antihypertensive effect may increase.
With simultaneous use of lercanidipine (20 mg) and simvastatin (40 mg), the AUC value for simvastatin increased by 56 %, and for its active metabolite (beta-hydroxy acids) - by 28 %. When taking drugs at different times of the day (lercanidipine - in the morning, simvastatin — in the evening), you can avoid unwanted interaction.
There were no changes in the pharmacokinetics of warfarin with simultaneous use of 20 mg of lercanidipine and warfarin in healthy volunteers.
When used simultaneously with fluoxetine (an inhibitor of CYP2D6 and CYP3A4 isoenzymes) in elderly patients, clinically significant changes in the pharmacokinetics of lercanidipine were not detected.
It is possible to increase the antihypertensive effect with the simultaneous use of grapefruit juice and lercanidipine .
Ethanol can potentiate the antihypertensive effect of lercanidipine.
