Lisinopril plus

General characteristics. Structure:

Active ingredient: 10 mg of lisinopril in the form of a dihydrate, 5 mg of an amlodipin in the form of a besilat.

Excipients: magnesium stearate, potato starch, lactose.

Structure of a cover of the capsule: gelatin, глицерол, the water purified titanium dioxide, sodium lauryl sulfate, dye red charming (E129).

The combined antihypertensive having hypotensive, vasodilating and angioprotektivny effect.

Pharmacological properties:

Pharmacodynamics. Lisinopril plus – the combined drug containing lisinopril and амлодипин. Pharmacological effect of drug is caused by a combination of separate properties of each of components which combination strengthens action of each other.

Lisinopril concerns to group of APF inhibitors, has hypotensive, vasodilating, angioprotektivny effect. Lowers angiotensin level in blood, reduces products and release of Aldosteronum from adrenal glands, increases formation of a vasodilating mediator of bradikinin. Influences fabric reninangiotenzinovy systems. Reduces OPSS, the ABP (without development of tachycardia), before - and an afterload, pressure in pulmonary capillaries. Expands arteries more than veins. Plays a part in recovery of function of the endothelium damaged as a result of a hyperglycemia.

Improves blood supply of an ischemic myocardium. At prolonged use reduces a hypertrophy of a myocardium and walls of arteries of resistive type. Increases tolerance of a myocardium to exercise stresses at patients with chronic heart failure. Does not influence the frequency of a cordial rhythm, at the same time increase in minute volume of blood and strengthening of a blood-groove in kidneys is possible.

Slows down progressing of dysfunction of a left ventricle after the myocardial infarction which is not complicated by heart failure.

Despite primary effect which is shown in impact on reninangiotenzin-aldosteronovy system (RAAS) it is effective also at arterial hypertension with the low level of a renin.

Lisinopril reduces an albuminuria thanks to decrease in the ABP, and also as a result of change of a hemodynamics of the glomerular device and its fabric structure. Does not influence sugar level in blood at patients with a diabetes mellitus and does not increase the frequency of cases of a hypoglycemia.

Amlodipin – a blocker of slow calcium channels of the III generation, has anti-anginal and hypotensive effect. Reduces intake of calcium in cells of a myocardium and, more, in smooth muscle cells of a vascular wall. Reduces OPSS, the ABP. Anti-anginal action is caused by an arteriectasia and arterioles, decrease in an afterload. Increases supply with oxygen unimpaired (especially at vasospastic stenocardia) a myocardium and ischemic sites of a myocardium. At stenocardia improves portability of an exercise stress. Does not cause reflex tachycardia, interferes with formation of an ischemic interval of ST, does not influence conductivity and contractility of a myocardium. Reduces the frequency of attacks of stenocardia and need for nitroglycerine use. Has long dozozavisimy hypotensive effect. Does not reduce fraction of emission of a left ventricle, reduces degree of a hypertrophy of a myocardium of a left ventricle, has anti-atherosclerotic and cardioprotective effect at an ischemic heart disease. Does not increase risk of death at sick HSN (the III-IV Art. on NYHA) against the background of therapy by digoxin, diuretics, APF inhibitors. Slows down aggregation of thrombocytes, strengthens glomerular filtering, has a weak natriuretic effect; at a diabetic nephropathy does not strengthen a microalbuminuria. Does not exert negative impact on metabolic processes, does not change plasma lipids. It can be applied at patients with the accompanying bronchial asthma, a diabetes mellitus, gout.

Lisinopril plus has the expressed dozozavisimy hypotensive effect on systolic and diastolic the ABP in a prone position and standing, not depending on age and position of a body of the patient, possesses anti-anginal action. Effect of drug continues 24 h. The lasting clinical effect occurs less, than in 1 month from the beginning of therapy and is not followed by arterial hypotension. The termination of treatment is not followed by development of a withdrawal. Drug is recommended in cases when reception of separate components in the same doses is not effective.

Pharmacokinetics. Pharmacokinetic parameters of lisinopril and an amlodipin at a combination do not change in comparison with their separate use. Lisinopril at intake is quickly absorbed from a GIT, in an invariable look comes to a system blood stream. The hypotensive effect develops in 1 hour after reception, Cmax is reached in 6 h. With Absorption makes 30% (6-60%), bioavailability - 29%. Contacts only APF, gets through hematoencephalic and placental barriers. T1/2 - 12,6 h is excreted by kidneys in not changed look. After removal of the most part of free lisinopril the fraction connected with APF is removed, providing long therapeutic effect (24 h). At patients with a renal failure removal of lisinopril is slowed down (correction of the mode of dosing is necessary). It is removed at dialysis.

Amlodipin slowly and almost is completely soaked up from a GIT; bioavailability – 64–80%. Is exposed to effect of the first passing through a liver. Cmax in a blood plasma is reached in 6-10 h after oral administration. Equilibrium concentration is established in 7-8 days of regular reception. Communication with proteins of a blood plasma – 95-98%.

The volume of distribution about 20 l/kg, gets through a blood-brain barrier. Has effect of "the first passing", 90% are metabolized in a liver, and the most part turns into an inactive metabolite. 10% of an amlodipin are removed with urine in not changed look, 60% - in the form of metabolites; 20-25% - in the form of metabolites with bile through intestines. Gets into breast milk. General clearance of 500 ml/min. Removal has two-phase character. T1/2 of a final phase of 35-50 h. Is not exposed to dialysis.

At patients of advanced age, with arterial hypertension, with a liver failure, with heavy heart failure of T1/2 increases. Dose adjustment for elderly patients is not required because of identical portability.

Indications to use:

Essential arterial hypertension in need of a combination therapy.

Route of administration and doses:

Lisinopril plus is accepted inside, irrespective of meal, 1 times a day (for the patients who are not accepting hypotensive drugs), at the same time - it is preferable in the morning.

If patients accepted diuretics, in 2-3 days prior to treatment by drug stop diuretic reception.

After administration of drug within several hours medical control because of possible development of symptomatic hypotension is necessary.

At a combination of HSN and the expressed arterial hypertension a maintenance dose - 1 capsule a day.

At a renal failure the maintenance dose depends on individual reaction; at such patients during treatment control of function of kidneys, K+ and Na + in blood is necessary.

At a liver disease removal of an amlodipin can be slowed down. Lisinopril use plus demands extra care from this category of patients.

Features of use:

Cautions. In case of dehydration, treatment needs to be begun after correction of a hyponatremia and recovery of OTsK (for the prevention of sharp decrease in the ABP).

After reception of the first dose of Lisinopril plus it is necessary to control the ABP, especially at the dehydrated patients accepting diuretics and/or at a hyponatremia.

At dekompensirovanny HSN, IBS, cerebrovascular diseases drug can cause the expressed decrease in the ABP, a myocardial infarction or a stroke.

During treatment control of body weight and observation at the stomatologist, control of blood are necessary for identification of a possible agranulocytosis.

At HPN (a renal artery stenosis, a hyponatremia, dehydration, HSN) there can be a deterioration in function of kidneys, an acute renal failure, reversible after the treatment termination

At development of a Quincke's disease of the person, extremities, lips, language, an epiglottis or a throat, treatment is immediately stopped. The Quincke's disease of a throat can lead to a lethal outcome. The paraglossa, an epiglottis and a throat can cause obstruction of respiratory tracts. Introduction п / to 0,3-0,5 ml of 0,1% of solution or slowly in/in 0,1 ml, GKS, antihistaminic HP is necessary; control of the vital functions of an organism.

Simultaneous use of poliakrilnitrilovy membranes for dialysis with Lisinopril plus can provoke an acute anaphylaxis; it is necessary to avoid their simultaneous use, or to apply the dialyzing membrane of other type, or another hypotensive HP.

Performing desensitization against arthropods during treatment by Lisinopril plus can cause anaphylactic reaction (it is necessary to interrupt previously temporarily treatment with drug).

At patients of advanced age both active ingredients are defined in blood in bigger concentration, at the same time efficiency does not change (it is necessary to consider at selection of a dose).

During treatment drug recommends to exclude the use of alcoholic beverages and to use adequate measures of contraception.

Pregnancy and lactation. Lisinopril plus is contraindicated to use at pregnancy and during breastfeeding. APF inhibitors are capable to get through a placenta and to lead to increase of incidence and mortality of a fruit and the newborn. Impact of APF inhibitors on a fruit in II and III trimesters of pregnancy can lead to development in the newborn of arterial hypotension, renal failure, deformation of bones of a skull and person and even by a lethal outcome.

If pregnancy occurred against the background of APF inhibitor reception, then to interrupt it there is no need, but it is necessary to stop immediately administration of drug and to conduct ultrasound examination of a skull of a fruit. Women at whom pregnancy occurred during APF inhibitor reception have to be informed on potential health hazard of a fruit.

Lisinopril can get into breast milk. In need of purpose of Lisinopril plus in the period of a lactation breastfeeding should be stopped.

At medicine reception (especially at the beginning of a therapy course) it is necessary to abstain from driving and performance of the work requiring special attention and high speed of psychomotor reactions in connection with danger of development of arterial hypotension and dizziness.

Side effects:

In the recommended doses drug usually well is transferred. The found side reactions usually carry not expressed and passing nature, cancellation of treatment it is required in rare instances.

From a nervous system: most often - a headache (8%), dizziness (3%); seldom - the increased drowsiness, a muscular fastsikulyation of extremities and lips, an adynamy, emotional lability, confusion of consciousness, weakness.

From cardiovascular system: seldom - arrhythmias, heartbeat, tachycardia (owing to decrease in the ABP at patients with high risk of a myocardial infarction, cerebrovascular stroke), orthostatic hypotension.

From respiratory system: most often - dry cough (5%).

From the alimentary system: seldom - dysfunction of intestines, a hyperplasia of gums, dryness in a mouth, an abdominal pain, pancreatitis, hepatocellular or cholestatic jaundice, hepatitis, a loss of appetite; diarrhea, nausea, vomiting.

From bodies of a hemopoiesis: a leukopenia, a neutropenia, an agranulocytosis (at the expense of APF inhibitor), thrombocytopenia, an erythropenia; small decrease in Hb and hematocrit (at prolonged treatment).

From integuments: seldom - a small tortoiseshell, the increased sweating, an alopecia, a mnogoformny erythema; skin itch, rash, erubescence of the person.

From urinogenital system: seldom - a renal failure, the speeded-up urination, an oliguria, an anury, an acute renal failure, uraemia, a proteinuria, impotence.

From a musculoskeletal system: an arthralgia (1-3%), swelled ankles of legs. Allergic reactions: Quincke's disease of the person, extremities, lips, language, epiglottis and throat (0,1%).

Others: seldom - a mialgiya, fever; the stethalgia is possible.

Laboratory indicators: hyperpotassemia, giperkreatininemiya, increase in an urea nitrogen, activity of "hepatic" enzymes, hyperbilirubinemia; seldom - emergence of antinuclear antibodies, acceleration of SOE.

Interaction with other medicines:

Inhibitors of a microsomal oxidation increase concentration of an amlodipin in plasma, increasing risk of development of side effects, and inductors of microsomal enzymes of a liver - reduce.

At simultaneous use with kaliysberegayushchy diuretics (Spironolactonum, amiloride, Triamterenum) and the drugs K+ the hyperpotassemia is possible. Lisinopril plus is appointed taking into account assessment of advantage and risk, under control of K+ in blood and function of kidneys.

At a concomitant use with diuretics perhaps sharp decrease in the ABP, with other antihypertensives (beta adrenoblockers, BMKK, including verapamil, APF inhibitors, nitrates) - the additive action

NPVP, estrogen, adrenostimulyator, sympathomimetics reduce therapeutic effect.

Antacids and Colestyraminum slow down absorption of drug in a GIT.

Amiodaronum, quinidine, alfa1-adrenoblockers, antipsychotic HP (neuroleptics) can strengthen hypotensive action.

Delay of removal of the drugs Li+ is possible, control of Li + in a blood plasma is necessary.

Cimetidinum does not influence pharmacokinetics of an amlodipin.

The HP containing Ca2+ can reduce effect of BMKK.

The procaineamide, quinidine and other HP extending Q-T interval increase risk of considerable lengthening of an interval of Q-T.

Does not exert impact on pharmacokinetics of digoxin and warfarin.

Lisinopril reduces loss of K+ at treatment by diuretics.

Contraindications:

• Hypersensitivity (including to other dihydropyridines);
• hereditary or idiopathic Quincke's disease,
• a Quincke's disease in the anamnesis against the background of therapy by APF inhibitors;
• hemodynamically significant aortal stenosis;
• mitral stenosis;
• heavy arterial hypotension;
• cardiogenic shock;
• hypertrophic cardiomyopathy;
• pregnancy;
• breastfeeding;
• hypersensitivity to lisinopril and/or derivatives of dihydropyridine;
• children and teenagers up to 18 years.

With care it is necessary to apply Lisinopril plus at cerebrovascular diseases (including at insufficiency of cerebral circulation), an ischemic heart disease, the coronary insufficiency expressed to bradycardia, tachycardia, dekompensirovanny HSN, arterial hypotension (easy or moderate), an acute myocardial infarction and within one month after it, a serious autoimmune illness (including sclerodermas, hard currency), at oppression of a marrowy hemopoiesis, a diabetes mellitus, a hyperpotassemia, a state after transplantation of kidneys, a diet with restriction of maintenance of Na+, a renal and/or liver failure, advanced age.

Overdose:

Symptoms: an excessive peripheral vazodilatation, the expressed decrease in the ABP, tachycardia.

Treatment: considering slow absorption of an amlodipin the gastric lavage, purpose of absorbent carbon is necessary; symptomatic therapy (at the expressed decrease in the ABP - sublime position of extremities, in/in administration of calcium of a gluconate, dopamine), control of the ABP, a diuresis, water and electrolytic balance. The hemodialysis is inefficient: lisinopril is dialyzed; амлодипин, due to the expressed communication with blood proteins, a hemodialysis is not removed.

Storage conditions:

Drug should be stored in the unavailable to children, protected from moisture and light place at a temperature from 15 °C to 25 °C. A period of validity - 2 years.

Issue conditions:

According to the recipe

Packaging:

On in blister strip packagings, on strip packagings in a cardboard box.