Tenliza - instructions for use, dose, side effects, contraindications

Amlodipine + Lysinopril substance - granules 166,60 mg [Active substances of substance - granules: Amlodipine besylate (amlodipine besylate) 6.94 mg, equivalent to amlodipine 5.00 mg, lisinopril dihydrate 10.89 mg, which is equivalent to lisinopril 10.00 mg

Auxiliary substances of substance - granules: calcium hydrogen phosphate dihydrate - 34,00 mg, mannitol 32.67 mg, sodium carboxymethyl starch 26.80 mg, microcrystalline cellulose 54.80 mg, silica colloidal dioxide 0.50 mg]

Excipients: magnesium stearate 3.40 mg

on 1 tablet of 10 mg + 20 mg Active substance:

Amlodipine + Lysinopril substance - granules 333.20 mg [Active substances of substance - granules: Amlodipine besylate (amlodipine besylate) 13.88 mg, equivalent to amlodipine 10,00mg, Lizinopril dihydrate 21.78 mg, which is equivalent to lisinopril 20.00 mg

Auxiliary substances of substance - granules: calcium hydrogen phosphate dihydrate 68.00 mg, mannitol 65.34 mg, sodium carboxymethyl starch 53.60 mg, microcrystalline cellulose 109.60 mg, silica colloidal dioxide 1.00 mg]

Excipients: magnesium stearate 6.80 mg

Description:

Round, biconvex tablets are white or almost white with a risk on one side.

Pharmacotherapeutic group:antihypertensive agent combined (angiotensin-converting enzyme inhibitor + blocker of "slow" calcium channels)

ATX: & nbsp

C.09.A.A.03 Lisinopril

C.08.C.A.01 Amlodipine

Pharmacodynamics:

Combined drug containing active ingredients: lisinopril and amlodipine.

Lysinopril - inhibitor of angiotensin-converting enzyme (ALF), reduces the formation of angiotensin II from angiotensin I. Reduction in angiotensin II leads to a direct decrease in the release of aldosterone. Reduces the degradation of bradykinin and increases the synthesis of prostaglandins.Reduces the overall peripheral vascular resistance (OPSS), arterial pressure (BP), preload, pressure in the pulmonary capillaries, causes an increase in the minute volume of blood and increased tolerance of the myocardium to loads in patients with chronic heart failure. Expands arteries more than veins. Some of the effects are explained by exposure to tissue renin-angiotensin-aldosterone system (RAAS).

With prolonged use, myocardial hypertrophy and the walls of arteries of resistive type decrease. Improves the blood supply of the ischemic myocardium.

ACE inhibitors prolong life expectancy in patients with chronic heart failure, slow the progression of left ventricular dysfunction in patients who underwent myocardial infarction without clinical manifestations of heart failure.

The action begins 1 hour after ingestion. The maximum antihypertensive effect is determined after 6 hours and persists for 24 hours. With hypertension, the antihypertensive effect is observed in the early days after the start of treatment, a stable effect develops after 1-2 months.With a sharp withdrawal of the drug ns marked increase in blood pressure.

Despite the primary effect, manifested in the impact of RAAS, lisinopril It is also effective in arterial hypertension with low renin activity. In addition to reducing blood pressure lisinopril reduces albuminuria. Lisinopril does not affect the concentration of glucose in the blood plasma in patients with diabetes mellitus and ns leads to an increase in cases of hypoglycemia.

Amlodipine - a derivative of dihydropyridine, a blocker of "slow" calcium channels (BCCI), has an antianginal and antihypertensive effect. Blocking calcium channels, reduces the transmembrane passage of calcium ions into the cell (mainly in vascular smooth muscle cells than cardiac myocytes). Antianginal action is due to the expansion of coronary and peripheral arteries and arterioles: with angina decreases the severity of myocardial ischemia, expanding peripheral arterioles, reduces OPSS, reduces afterload on the heart, reduces the need for myocardium in oxygen. Expanding coronary arteries and arterioles in unchanged and ischemic zones of the myocardium,increases the flow of oxygen into the myocardium (especially with vasospastic angina), prevents spasm of the coronary arteries (including those caused by smoking). In patients with stable angina, a single daily dose of amlodipine increases exercise tolerance, slows the development of angina pectoris and the "ischemic" depression of the segment ST, reduces the incidence of angina attacks and consumption of nitroglycerin and other nitrates.

Amlodipine has a long-term dose-dependent antihypertensive effect. Antihypertensive action is due to direct vasodilating effect on smooth muscle vessels. With arterial hypertension, a single dose provides a clinically significant reduction in blood pressure for 24 hours (in the patient's "lying" and "standing" position). Orthostatic hypotension with amlodipine is rare. Does not cause a decrease in exercise tolerance, a fraction of the ejection of the left ventricle. Reduces the degree of myocardial hypertrophy of the left ventricle. Does not affect the contractility and conductance of the myocardium, does not cause a reflex increase in the heart rate (heart rate),inhibits the aggregation of platelets, increases the rate of glomerular filtration, has a weak natriuretic effect. When diabetic nephropathy does not increase the severity of microalbuminuria. Does not have any adverse effect on the metabolism and concentration of plasma lipids and can be used when therapy in patients with bronchial asthma, diabetes and gout. A significant reduction in blood pressure is observed after 6-10 hours, the duration of the effect is 24 hours.

Amlodipine + lisinopril

The combination of lisinopril with amlodipine in a single medicine can prevent the development of possible undesirable effects caused by one of the active substances. So, BCCC, directly expanding the arterioles, can lead to a delay in sodium and fluid in the body and, therefore, can activate RAAS. The ACE inhibitor blocks this process.

Pharmacokinetics:

Lisinopril

Suction

After oral administration lisinopril absorbed from the gastrointestinal (GI), its absorption varies from 6 to 60%. Bioavailability is 29%. Eating does not affect the absorption of lisinopril.

Distribution

Almost does not bind to blood plasma proteins. The maximum concentration (Cmah) in blood plasma 90 ng / ml is achieved after 6-7 hours. Permeability through blood-brain and placental barriers is low.

Metabolism

Lizinopril is not biotransformed in the body.

Excretion

It is excreted by the kidneys unchanged. The half-life (T1 / 2) is 12.6 hours.

Pharmacokinetics in selected patient groups

In elderly patients, the concentration of lisinopril in the blood plasma and the area under the concentration-time curve (AUC) twice as many as in young patients.

In patients with chronic heart failure, the absorption and clearance of lisinopril are reduced.

In patients with renal insufficiency, the concentration of lisinopril is several times higher than the concentration in the blood plasma in healthy volunteers, with an increase in the time to reach the maximum concentration in the blood plasma and an elongation of T1 / 2.

Lizinopril is excreted from the body by hemodialysis.

Amlodipine

Suction

After oral administration amlodipine slowly and almost completely (90%) is absorbed from

GIT. Bioavailability of amlodipine is 64-80%.Eating does not affect

absorption of amlodipine.

Distribution

Most of the amlodipine, which is in the blood (95-98%), binds to blood plasma proteins. FROM_m_Oh in the serum is observed after 6-10 hours. The equilibrium concentrations (Css) are achieved after 7-8 days of therapy. The average volume of distribution is 20 l / kg body weight, indicating that most of the amlodipine is in the tissues, and the smaller is in the blood.

Metabolism

Amlodipine undergoes a slow but active metabolism in the liver with

absence of a significant effect of "primary passage". Metabolites do not have significant pharmacological activity.

Excretion

The derivation consists of two phases, T1 / 2 the final phase is 30-50 hours. About 60% of the dose taken internally is excreted by the kidneys mainly in the form of metabolites, 10% - in unchanged form, and 20-25% - is excreted as metabolites through the intestine with bile. The total clearance of amlodipine is 0.116 ml / s / kg (7 ml / min / kg, 0.42 l / h / kg).

Pharmacokinetics in selected patient groups

In elderly patients (over 65 beds), the withdrawal of amlodipine is slowed down (T1 / 2 - 65 hours) compared with young patients, but this difference is not of clinical significance.

In patients with hepatic insufficiency, prolongation of T1 / 2 suggests that with prolonged use, amlodipine cumulation in the body will be higher (T1 / 2 - up to 60 hours).

Renal failure does not significantly affect the pharmacokinetics of amlodipine.

Amlodipine penetrates the blood-brain barrier. When hemodialysis is not removed.

Amlodipine + lisinopril

Interaction between the active substances that make up the preparation of Tenliza is unlikely. AUC, the time of reaching and the value of the maximum concentration, T1 / 2 do not change in comparison with the indices of each individual active substance. Eating does not affect the absorption of active substances.

Indications:

Essential hypertension (patients who are shown combined therapy).

Contraindications:

Hypersensitivity to lisinopril or other ACE inhibitors. Hypersensitivity to amlodipine or other dihydropyridine derivatives.

Hypersensitivity to other components of the drug.

Quincke's edema in the anamnesis, including against the background of the use of ACE inhibitors. Hereditary or idiopathic angioedema.

Hemodynamically significant stenosis of the aorta or mitral valve.

Hypertrophic obstructive cardiomyopathy.

Severe arterial hypotension (systolic blood pressure less than 90 mm Hg). Cardiogenic shock.

Unstable angina (with the exception of Prinzmetal angina).

Heart failure after acute myocardial infarction (within the first 28 days).

Pregnancy and the period of breastfeeding.

Age to 18 years (effectiveness and safety not established).

Carefully:

Severe renal failure, bilateral renal artery stenosis or stenosis of the single kidney with progressive azotemia, condition after kidney transplantation, azotemia, hyperkalemia, primary hyperaldosteronism, impaired liver function, arterial hypotension, cerebrovascular disease (including cerebral circulatory insufficiency), coronary heart disease , coronary insufficiency, syndrome of weakness of the sinus node (pronounced bradycardia, tachycardia), chronic cardiac insufficiency (CHF) nonischemic etiology III-IV functional class by classification NYHA, aortic stenosis, mitral stenosis, acute myocardial infarction (and within 1 month after myocardial infarction), autoimmune systemic connective tissue diseases (including scleroderma, systemic lupus erythematosus), oppression of bone marrow hematopoiesis, diabetes mellitus, diet with restriction of table salt, hypovolemic conditions (including as a result of diarrhea, vomiting), use in elderly patients, Hemodialysis using high-permeability dialysis membranes with high permeability (AN69®).

Pregnancy and lactation:

The use of the drug Tenlise is not recommended during pregnancy.

When diagnosing pregnancy, taking Tenliza should be stopped immediately.

Admission of ACE inhibitors in the II and III trimesters of pregnancy has an adverse effect on the fetus (there may be a marked decrease in blood pressure, renal failure, hyperkalemia, hypoplasia of the skull bones, fetal death). Data on the negative effect of the drug on the fetus in the case of application during the first trimester of pregnancy is not. For newborns and infants who have been exposed to intrauterine exposure to ACE inhibitors,it is recommended to carefully monitor for the timely detection of a marked decrease in blood pressure, oliguria, hyperkalemia. The safety of amlodipine during pregnancy is not established, so the use of amlodipine is not recommended during pregnancy.

Lizinopril penetrates the placenta and can be excreted in breast milk. There is no evidence that amlodipine is excreted in breast milk. However, it is known that other BCCC - dihydropyridine derivatives are excreted in breast milk.

The use of the drug Tenliza during breastfeeding is not recommended. If you need to use the drug Tenliza during lactation, breastfeeding should be discontinued.

Dosing and Administration:

Inside, regardless of meal time. The recommended dose is one tablet of the drug Tenlize daily. The maximum daily dose is one tablet of the drug Tenliza.

Patients with renal insufficiency

To determine the optimal initial and maintenance dose for patients with renal insufficiency, the dose should be titrated and determined individually, using in monotherapy lisinopril and amlodipine. The TENLIZA preparation is indicated only for those patients in whom the optimal maintenance dose of lisinopril and amlodipine is titrated to 10 mg and 5 mg or 20 mg and 10 mg, respectively. During treatment with the drug Tenliza, it is necessary to monitor the kidney function, the content

potassium and sodium in the blood serum. In case of impaired renal function, the preparation of Tenliza should be discarded and replaced with lisinopril and amlodipine in adequate doses.

Patients with hepatic insufficiency

Excretion of amlodipine may be delayed in patients with impaired hepatic function. Clear recommendations on the dosage regimen in such cases are not established, so the drug Tenliza should be used with caution in patients with hepatic insufficiency.

Patients of advanced age (over 65 years)

In clinical studies, age-related changes in efficacy or safety profile for amlodipine and lisinopril have not been observed. To determine the optimal maintenance dose, it is necessary to determine the dosing regimen individually, using in monotherapy lisinopril and amlodipine. The TENLIZA preparation is indicated only for those patients in whom the optimal maintenance dose of lisinopril and amlodipine is titrated to 10 mg and 5 mg or 20 mg and 10 mg, respectively.

Side effects:

The incidence of adverse reactions in patients receiving combination therapy was not higher than in patients receiving one of the active substances. Adverse reactions corresponded to the previously obtained data on amlodipine and / or lisinopril. Adverse reactions were mild, transient and rarely required the withdrawal of treatment. The most common adverse reactions when receiving a combination Amlodipine / lisinopril were: headache (8%), cough (5%) and dizziness (3%). The frequency of adverse reactions is given separately for lisinopril and amlodipine.

The data are presented to the system-organ classes according to the classification MedDRA and with the following frequency: very often (> 1/10); often from (> 1/100 to <1/10); infrequently (from> 1/1000 to <1/100); rarely (from> 1/10000 to <1/1000); very rarely (from <1/10000); frequency is unknown (can not be established based on available data).

The class of the organ system according to MedDRA

Frequency

Undesirable effects of lisinopril

The undesirable effects of amlodipine

Violations of the blood and lymphatic

systems

Highly

Rarely

Frequency

unknown

Inhibition of bone marrow hemopoiesis, agranulocytosis, leukopenia, neutropenia, thrombocytopenia, hemolytic anemia, anemia, lymphadenopathy

Eosinophilia, leukocytosis

Thrombocytopenia

Immune system disorders

Rarely

Vasculitis, an increase in the titer of antinuclear antibodies

Hypersensitivity

Disorders from the metabolism and nutrition

Rarely

Hypoglycaemia

Hyperglycaemia

Disorders of the psyche

Infrequently

Rarely

Lability of mood, sleep disorders

Disorders of the psyche

Insomnia, unusual dreams, mood changes, increased excitability, depression, anxiety

Apathy, agitation

Disturbances from the nervous system

Often

Infrequently

Rarely

Dizziness, headache, drowsiness

Systemic dizziness, paresthesia, dysgeusia (a taste disorder), convulsive twitching of the muscles of the extremities and lips

Confusion of consciousness

Drowsiness, dizziness, headache

Syncope (syncope), tremor, dysgeusia (taste disorder), hypoesthesia, paresthesia

Migraine

Peripheral neuropathy, ataxia, amnesia, parosmia

Disturbances on the part of the organ of sight

Infrequently

Visual disturbances (diplopia, accommodation disorder), xerophthalmia, conjunctivitis, eye pain

Hearing disorders and labyrinthine disorders

Infrequently

Noise in ears

Heart Disease

Often

Infrequently

Rarely

Myocardial infarction, violation of atrioventricular conduction, bradycardia, tachycardia, heart palpitations, worsening of CHF, chest pain

Cardiopalmus

Exacerbation of CHF flow

Myocardial infarction,

ventricular

tachycardia, atrial fibrillation, arrhythmia

Vascular disorders

Often

Infrequently

Rarely

The pronounced decrease

AD, orthostatic

hypotension

Disturbance of the cerebral

blood circulation, syndrome

Reynaud

Hyperemia of the skin

The pronounced decrease

AD, orthostatic

Hypotension

Vasculitis

Infringements from respiratory system, organs of the chest and mediastinum

Often

Infrequently

Rarely

Dry cough

Rhinitis

Dyspnea

Bronchospasm, allergic alveolitis / eosinophilic pneumonia, sinusitis

Disnea, rhinitis, nasal

Bleeding

Cough

Disorders from the digestive system

Often

Infrequently

Rarely

Diarrhea, vomiting

Pain in the abdomen, nausea,

disorder

digestion

Dryness of the oral mucosa

Pancreatitis,

angioedema of the intestine

Abdominal pain, nausea

Vomiting, indigestion, constipation

or diarrhea, dryness

mucous membrane of the mouth, anorexia, thirst

Increased appetite

Pancreatitis, gastritis,

gingival hyperplasia

Disorders from the liver and

bile excretory

ways

Rarely

Hepatic

insufficiency, hepatitis, cholestatic jaundice

Hepatitis, jaundice,

cholestasis

Disturbances from the skin and subcutaneous tissues

Infrequently

Rarely

Allergic reactions /

angioedema, swelling of the face, extremities, lips, tongue, vocal folds and / or larynx, skin rash, skin itching, photosensitivity

Psoriasis, urticaria rash, alopecia

Toxic

epidermal necrolysis, Stevens-Johnson syndrome,

erythema multiforme,

vulgar pemphigus, increased sweating, pseudolymphoma of the skin.

Skin rash, purpura,

cutaneous itching, xeroderma

Dermatitis

The erythema multiforme,

angioedema, urticaria rash, increased sweating,

"cold" sweat, alopecia, skin discoloration

Disturbances from musculoskeletal and connective tissue

Infrequently

Rarely

Arthralgia, myalgia,

arthritis

Arthralgia, myalgia,

muscle cramps, pain

in the back, arthrosis

Myasthenia gravis

Disorders from the kidneys and urinary tract

Often

Infrequently

Rarely

Frequency unknown

Impaired renal function

Acute renal failure, uremia

Oliguria / anuria

Proteinuria

Dysuria (disorder

urination),

nocturia, increase

frequency of urination

Violations of the genitals and mammary gland

Infrequently

Rarely

Impotence

Gynecomastia

Impotence, gynecomastia

General disorders and disorders at the site of administration

Often

Infrequently

Frequency unknown

Increased

fatigue, asthenia

Anorexia

Peripheral edema,

increased

fatigue

Pain in the chest, pain,

malaise, asthenia

Laboratory and instrumental data

Infrequently

Rarely

Increase in concentration

urea and creatinine in

blood serum,

hyperkalemia,

increased activity

"hepatic" enzymes

Reduction of hemoglobin and

hematocrit, erythropenia,

hyperbilirubinemia,

hyponatremia

An increase in body weight,

weight loss

Increased activity

"hepatic" enzymes

A complex symptom complex has been reported that may include all or some of the following symptoms: fever, vasculitis, myalgia, arthralgia / arthritis, increased titer of antinuclear antibodies, increased erythrocyte sedimentation rate (ESR), eosinophilia and leukocytosis, rash, photosensitivity, or other skin-related changes.

With the simultaneous use of inhibitors of LPF and gold preparations (sodium aurotomy malate) intravenously, a symptom complex is described, which includes facial flushing, nausea, vomiting and arterial hypotension.

Overdose:

Amlodipine

Symptoms: a marked decrease in blood pressure with the possible development of reflex tachycardia and excessive peripheral vasodilation (the risk of development of severe and persistent arterial hypotension, including with the development of shock and death).

Treatment: gastric lavage, reception of activated charcoal, maintenance of cardiovascular and respiratory systems, giving the patient a horizontal position with raised legs, monitoring the volume of circulating blood (BCC) and diuresis.To restore the vascular tone - the use of vasoconstrictors (in the absence of contraindications to their use), to eliminate the effects of calcium channel blockade - intravenous calcium gluconate. Hemodialysis is ineffective.

Lisinopril

Symptoms: marked decrease in blood pressure, dryness of the oral mucosa, drowsiness, urinary retention, constipation, anxiety, increased irritability.

Treatment: gastric lavage, taking activated charcoal, giving the patient a horizontal position with raised legs, replenishment of BCC - intravenous administration of plasma-substituting solutions, symptomatic therapy, monitoring of cardiovascular and respiratory functions, bcc, urea, creatinine and electrolytes in serum, and diuresis. Lisinopril can be removed from the body by hemodialysis.

Interaction:

Lisinopril

Double blockade of RAAS angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with an increased risk of arterial hypotension, hyperkalemia, and impaired renal function (including acute renal failure) compared with monotherapy with these drugs.It is necessary to carefully monitor blood pressure, night function and electrolyte balance in patients receiving lisinopril simultaneously with other drugs that affect RAAS.

Drugs affecting the potassium content in blood plasma: potassium-sparing diuretics (for example, spironolactone, amiloride, triamterene and eplerenone), potassium-containing dietary supplements, potassium-containing salt substitutes and any other drugs that lead to an increase in serum potassium (for example, heparin), can lead to hyperkalemia with simultaneous use with ACE inhibitors, especially in patients with renal insufficiency and other kidney diseases in the anamnesis. When using a drug that affects the content of potassium, simultaneously with lisinopril should monitor the potassium content in the serum. Therefore, simultaneous application should be carefully justified and carried out with extreme caution and regular monitoring of both the potassium content in the blood serum and the function of the nights. Potassium-sparing diuretics can be taken concomitantly with the preparation of Tenlise only under the condition of careful medical supervision. Diuretics: in the case of diuretics against the background of therapy with the preparation of Tenliza, the antihypertensive effect is usually increased. Simultaneous application should be conducted with caution. Lisinopril reduces the potassium -uretic effect of diuretics.

Other antihypertensive drugs: simultaneous administration of these drugs can enhance the antihypertensive effect of the drug Tenliza. Simultaneous reception with nitroglycerin, other nitrates or vasodilators can lead to a marked decrease in blood pressure.

Tricyclic antidepressants / antipsychotics / general anesthetics / narcotic analgesics: simultaneous administration with inhibitors of PSA can lead to a marked decrease in blood pressure.

Ethanol enhances the antihypertensive effect.

Allopurinol, procainamide, cytostatics or immunosuppressants (systemic glucocorticosteroids) may lead to an increased risk of developing leukopenia when used concomitantly with ACE inhibitors.

Antacids and colstiraamine when administered simultaneously with ACE inhibitors, reduce the bioavailability of ACE inhibitors.

Sympathomimetics can reduce the antihypertensive effect of ACE inhibitors, it is necessary to carefully monitor the achievement of the desired effect.

Hypoglycemic drugs: with the simultaneous administration of ACE inhibitors and hypoglycemic drugs (insulin and hypoglycemic agents for oral administration), the likelihood of a decrease in serum glucose and the risk of hypoglycemia may increase. This phenomenon is most often observed during the first week of combined treatment and in patients with renal insufficiency.

Non-steroidal anti-inflammatory drugs (NSAIDs) (including selective inhibitors of cyclooxygenase-2 (COX-2)): long-term use of NSAIDs, including high doses of acetylsalicylic acid more than 3 g / day, can reduce the antihypertensive effect of ACE inhibitors. The additive effect of NSAIDs and ACE inhibitors is manifested in an increase in serum potassium levels and can lead to impaired renal function. These effects are usually reversible. It is very rare to develop acute renal failure, especially in elderly patients and dehydrated patients.

Lithium preparations: the elimination of lithium can be slowed down by simultaneous administration with ACE inhibitors, and therefore, the concentration of lithium in serum should be monitored during this period. When used simultaneously with lithium preparations, it is possible increased manifestation of their neurotoxicity (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus).

Preparations of gold: at simultaneous application of inhibitors of LPF and preparations of gold (sodium aurotomy malate) intravenously, a symptom complex is described, which includes facial flushing, nausea, vomiting and arterial hypotension.

Amlodipine

Inhibitor inhibitors CYP3A4: studies in elderly patients have shown that diltiazem Suppresses the metabolism of amlodipine, probably through isoenzyme CYP3A4 (concentration in plasma / serum increases by almost 50% and the effect of amlodipine increases). It is impossible to exclude the possibility that stronger inhibitors of the isoenzyme CYP3A4 (eg, ketoconazole, itraconazole, ritonavir) can increase the concentration of amlodipine in the blood serum more than diltiazem. Simultaneous use should be carried out with caution.

Inductors of isoenzyme CYP3A4: simultaneous use with antiepileptic drugs (for example, carbamazepine, phenobarbital, phenytoin, fosphenytoin, primidone), rifampicin, herbal preparations containing St. John's Wort, can lead to a decrease in the concentration of amlodipine in the blood plasma. Control with possible correction of amlodipine dose during treatment with isoenzyme inducers is shown CYP3A4 and after their cancellation. Simultaneous use should be carried out with caution.

As a monotherapy amlodipine blended well with thiazide and "loop" diuretics, means for general anesthesia, beta-blockers. ACE inhibitors, long-acting nitrates, nitroglycerin, digoxin, warfarin, atorvastatin, sildenafil, antacid preparations (aluminum hydroxide, magnesium hydroxide), simethicone, cimetidine, NSAIDs. antibiotics and hypoglycemic agents for oral administration.

It is possible to increase the anti-anginal and antihypertensive action of BCCC when used simultaneously with thiazide and loop diuretics, verapamil, ACE inhibitors, beta-adrenoblockers and nitrates, as well as an increase in their antihypertensive effect when used simultaneously with alpha-adrenoblockers, neuroleptics.

A single dose of 100 mg sildenafil in patients with essential hypertension does not affect the pharmacokinetics parameters of amlodipine.

Repeated use of amlodipine in a dose of 10 mg and atorvastatin in a dose of 80 mg is not accompanied by significant changes in the pharmacokinetics of atorvastatin.

Antiviral drugs (ritonavir) increase plasma concentrations of BCCC, including amlodipine.

Neuroleptics and isoflurane - increased antihypertensive action of dihydropyridine derivatives.

Amlodipine does not significantly affect the pharmacokinetics ethanol. Calcium preparations can reduce the effect of BCCI.

With the simultaneous use of amlodipine with lithium preparations possibly increased manifestation of neurotoxicity (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus). Amlodipine does not cause significant changes in pharmacokinetics cyclosporine.

Does not affect serum concentration digoxin and its renal clearance.

Has no significant effect on the action warfarin (prothrombin time). Cimetidine does not affect the pharmacokinetics of amlodipine.

It is possible to reduce the antihypertensive effect of the TENLIZA preparation with simultaneous use with estrogen, sympathomimetics.

Procainamide, quinidine and other drugs extending the RT interval, can contribute to its considerable elongation.

In studies in vitro Amlodipine does not affect the binding to plasma proteins digoxin, phenytoin, warfarin and indomethacin.

Reception of amlodipine with grapefruit juice is not recommended, as in some patients this can lead to an increase in the bioavailability of amlodipine, resulting in increased its antihypertensive effect.

Special instructions:

Arterial hypotension

A marked decrease in blood pressure with the development of clinical symptoms can be observed in patients with reduced circulating blood volume and / or sodium content in the blood serum due to diuretics, fluid loss or other reasons, for example, increased sweating, prolonged vomiting and / or diarrhea. It is necessary that the restoration of loss of fluid and / or sodium is carried out before the start of therapy with the drug Tenliza.It is necessary to monitor BP after taking the initial dose. Similar conditions apply to patients with ischemic disease heart or cerebrovascular diseases in which a pronounced decrease in blood pressure can lead to the development of myocardial infarction or stroke.

Aortic and mitral stenosis

Like all vasodilating drugs, the Tenliz preparation should be used with caution in patients with obstruction of the left ventricular outflow tract and stenosis of the mitral valve.

Impaired renal function

In some patients with arterial hypertension without pronounced manifestations of renovascular diseases, an increase in the concentration of serum creatinine and urea was observed, in most cases minimal or transient, more pronounced with concurrent administration of an ACE inhibitor and a diuretic. This is most typical for patients with a history of kidney disease.

To determine the optimal maintenance dose, it is necessary to determine the dosage regimen on an individual basis, using in monotherapy lisinopril and amlodipine, with simultaneous monitoring of kidney function.The TENLIZA preparation is indicated only for those patients in whom the optimal maintenance dose of lisinopril and amlodipine is titrated to 10 mg and 5 mg or 20 mg and 10 mg, respectively. In the case of a decrease in kidney function, the preparation of Tenliz should be discontinued and replaced by monotherapy with drugs in adequate doses. In addition, a dose reduction or elimination of diuretics may be required.

Angioedema

Angioedema of the face, extremities, lips, tongue, vocal folds and / or larynx was recorded in patients taking ACE inhibitors, including lisinopril. In such cases, taking Tenliza should be stopped immediately and the patient carefully followed up with the patient until the symptoms disappear completely.

Edema of the face, lips and extremities usually passes independently, however, to reduce the severity of symptoms should use antihistamines. Angioedema, accompanied by swelling of the larynx, can lead to death. If you detect edema of the tongue, pharynx or larynx, which are the cause of airway obstruction, emergency measures should be urgently started.The proper measures include: the use of 0.1% epinephrine (adrenaline) solution subcutaneously in a dose of 0.3-0.5 mg or 0.1 mg intravenously slowly, followed by the use of glucocorticosteroids (intravenously) and antihistamines under the control of vital functions .

In patients taking inhibitors of AMP, in rare cases, the development of angioedema edema of the intestine. Such patients complained of pain in the abdomen (with or without nausea and vomiting), in some cases of the previous angioedema, the face was not observed, and the activity of C-1 esterase was within normal limits. Angioedema of the intestine was diagnosed by computed tomography of the gastrointestinal tract, either after ultrasound or in surgical intervention. Symptoms disappeared after the withdrawal of the ACE inhibitor. When performing differential diagnosis of abdominal pain in patients taking ACE inhibitors, you should also consider angioedema of the intestine.

Anaphylactic reactions in patients on hemodialysis

In patients who underwent hemodialysis through polyacrylonitrile membranes (for example, AN69®) and who at the same time received ACE inhibitors, cases of anaphylactic shock have been reported, so it is necessary to avoid this combination. Patients are recommended to use either another type of dialysis membrane, or an antihypertensive drug of another pharmacotherapeutic group. Anaphylactic reactions in patients during apheresis of low-density lipoproteins (LDL)

Rarely in patients who used ACE inhibitors during apheresis of LDL using dextran sulfate, life-threatening anaphylactic reactions developed. Such reactions were prevented by withdrawal of an ACE inhibitor before each apheresis procedure.

Desensitization with bee or aspen poison

In some patients who took ACE inhibitors, anaphylactic reactions developed during the desensitization of Hymenoptera (eg, wasps or bees). Such life-threatening situations can be avoided with the abolition of the ACE inhibitor before the desensitization procedure.

Effects on the liver

In rare cases, the administration of ACE inhibitors was accompanied by a syndrome that began with cholestatic jaundice or hepatitis and subsequently led to fulminant necrosis of the liver and, in some cases, a lethal outcome.

The mechanism of this syndrome is not established.Patients who take the drug Tenliza, who develop jaundice or have an increase in the activity of "liver" enzymes, you should cancel the drug with a subsequent observation of their condition.

Liver failure

In patients with impaired T1 / 2 liver function, amlodipine is elongated. At the moment, there are no recommendations on the dosing regimen, so this drug should be used with caution, having previously estimated the expected benefit and the potential risk of treatment.

Neutropenia / agranulocytosis

In rare cases, neutropenia, agranulocytosis, thrombocytopenia and anemia have been reported in patients receiving ACE inhibitors. In patients with normal renal function and in the absence of other aggravating factors, neutropenia is rare. Neutropenia and agranulocytosis are reversible and disappear after the withdrawal of the ACE inhibitor. The preparation of Tenliza should be used with extreme caution in patients with systemic connective tissue diseases, with immunosuppressive therapy, during treatment with allopurinol or procainamide, or in a combination of these aggravating factors, especially in the presence of a previous impairment of kidney function.Some of these patients developed serious infectious diseases, in which, in several cases, a response to antibiotic treatment was not received. During treatment with the Tenliza preparation, periodic monitoring of leukocytes (blood count with counting of the leukocyte formula) in such patients is necessary, as well as to warn patients about the need to report the appearance of the first signs of an infectious disease.

Cough

Cough was often recorded during the use of ACE inhibitors. As a rule, cough is unproductive, persistent and stopped after the drug was discontinued. With a differential diagnosis of cough, you need to consider the cough caused by the use of ACE inhibitors.

Surgery / general anesthesia

In patients who undergo extensive surgery or during general anesthesia with drugs leading to hypotension, lisinopril can block the formation of angiotensin II after compensatory release of renin. If arterial hypotension develops, probably as a result of the above mechanism, it is possible to correct the increase in BCC.

Elderly patients

In elderly patients with impaired renal function, dose adjustment should be performed using monotherapy lisinopril and amlodipine.

Hyperkalemia

In some patients who received ACE inhibitors, an increase in serum potassium was observed. Risk group for the development of hyperkalemia consists of patients with renal failure, diabetes, congestive heart failure, dehydration, metabolic acidosis or while receiving potassium-sparing diuretics, potassium-containing food additives, potassium-based salt substitutes or any other medications, leading to an increase of potassium in blood serum (e.g., heparin). If it is necessary to simultaneously take the above drugs, you need to monitor the potassium content in the blood serum.

Patients with reduced body weight, low growth patients and patients with severe liver dysfunction may need a dose reduction. The preparation of Tenlise does not have any adverse effect on the metabolism and concentration of lipids in the blood plasma and can be used to treat patients with bronchial asthma, diabetes and gout.

During treatment, it is necessary to control body weight and monitor the dentist (to prevent soreness, bleeding and gingival hyperplasia).

Effect on the ability to drive transp. cf. and fur:

It is necessary to use the preparation of Tenliza with caution (the risk of a pronounced decrease in blood pressure and dizziness). Therefore, at the beginning of treatment, it is recommended to avoid driving vehicles, working with mechanisms and performing other work requiring increased concentration of attention.

Form release / dosage:

Tablets, 5 mg + 10 mg, 10 mg + 20 mg.

Packaging:

For 10 tablets in a contour mesh package made of a combined material OPA / Al / PVC and aluminum foil.

1, 2, 3, 6 or 9 contour mesh packages together with the instruction for use are placed in a pack of cardboard.

Storage conditions:

At a temperature of no higher than 25 ° C, in the original packaging. Keep out of the reach of children.

Shelf life:

2 years.

Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-002857

Date of registration:10.02.2015

The owner of the registration certificate:KRKA-RUS, LLC KRKA-RUS, LLC Russia

Manufacturer: & nbsp

KRKA, d.d. Slovenia

Representation: & nbspKRKA KRKA Slovenia

Information update date: & nbsp10.02.2015

Illustrated instructions

Instructions

Tenliza (Tenlisa)