Prestans pills 10mg + 5mg №30

Dosage form: tab. 10 mg + 5 mg: 30 pcs.

Pills white, triangular, biconvex, engraved with "10/5" on one side and the company logo on the other.

Excipients: microcrystalline cellulose, lactose monohydrate, Magnesium stearate, colloidal silicon dioxide.

30 pieces - polypropylene bottles with dispenser (1) - cardboard packs with the control of the first opening.

Indications:

- arterial hypertension;

- IHD: stable exertional angina in patients requiring perindopril and amlodipine.

- arterial hypertension;

- IHD: stable exertional angina in patients requiring perindopril and amlodipine.

Application:

The drug is prescribed by mouth, 1 tab. 1 time / day, preferably in the morning before meals. The dose of the drug Prestants is selected after a previously performed titration of doses of individual components of the drug: perindopril and amlodipine in patients with arterial hypertension and stable angina pectoris.

When therapeutic, the dose of Prestans can be changed, based on individual selection of doses of individual components: 5 mg perindopril + 5 mg amlodipine or 5 mg perindopril + 10 mg amlodipine or 10 mg perindopril + 5 mg amlodipine or 10 mg perindopril + 10 mg amlodipine.

Prestans in doses of 10 mg of perindopril + 10 mg of amlodipine is the maximum daily dose of the drug, which is not recommended to exceed.

Removal of perindoprilat elderly patients and patients with renal failure slowed down. Therefore, in such patients, it is necessary to regularly monitor the concentration of creatinine and potassium in the blood plasma. Prestans can be appointed patients withQC ≥ 60 ml / min. Prestans is contraindicated patients withQC <60 ml / min. Such patients are recommended individual selection of doses of perindopril and amlodipine. Changes in the concentration of amlodipine in the blood plasma do not correlate with the severity of renal failure.

Caution must be exercised in the appointment of the drug Prestans in patients with liver failure due to the lack of recommendations on the dosing of the drug in these patients.

Prestans should not be assigned children and teenagers under 18 Due to the lack of data on the efficacy and safety of perindopril and amlodipine in these groups of patients, both as monotherapy and as combination therapy.

Contraindications:

Perindopril

- angioedema (angioedema) in history (including against the background of taking other ACE inhibitors);

- hereditary / idiopathic angioedema;

- age up to 18 years (efficiency and safety have not been established);

- Hypersensitivity to perindopril or other ACE inhibitors.

- severe arterial hypotension (systolic blood pressure less than 90 mm Hg);

- obstruction of the output tract of the left ventricle (for example, severe aortic stenosis);

- unstable angina (with the exception of Prinzmetal stenocardia);

- age up to 18 years (efficiency and safety have not been established);

- Hypersensitivity to amlodipine or other dihydropyridine derivatives.

- renal failure (CC less than 60 ml / min);

- age up to 18 years (efficiency and safety have not been established);

- hereditary lactose intolerance, lactase deficiency and glucose / galactose malabsorption syndrome;

- Hypersensitivity to excipients that are part of the drug.

WITH caution

Renal artery stenosis (including bilateral), the only functioning kidney, liver failure, renal failure, systemic diseases of the connective tissue (including systemic lupus erythematosus, scleroderma), immunosuppressant therapy, Allopurinol, procainamide (risk of developing neutropenia, agranulocytosis), reduced bcc (diuretic intake, salt-free diet, vomiting, diarrhea), atherosclerosis, cerebrovascular diseases, renovascular hypertension, diabetes mellitus, chronic heart failure, Implantation of dantrolene, estramustine, potassium-saving diuretics, potassium preparations, potassium-containing substitutes for edible salt and lithium preparations, hyperkalemia, surgery / general anesthesia, old age, hemodialysis using high-flow membranes (for example, AN69^®), desensitization therapy, LDL apheresis, aortic stenosis / mitral stenosis / hypertrophic cardiomyopathy, patients of the Negroid race.

Side effects:

The frequency of adverse reactions that were noted during monotherapy with perindopril and amlodipine is given in the form of the following gradation: very often (≥1 / 10); often (≥1 / 100, <1/10); infrequently (≥1 / 1000, <1/100); rarely (≥1 / 10,000, <1/1000); very rarely (<1/10 000), including individual messages; unspecified frequency (frequency cannot be calculated from available data).

Hemic and lymphatic: very rarely - leukopenia, neutropenia, agranulocytosis, pancytopenia, thrombocytopenia, hemolytic anemia in patients with congenital deficiency of glucose-6-phosphate dehydrogenase, a decrease in the concentration of hemoglobin and hematocrit.

Allergic reactions: infrequently - urticaria.

Metabolic disorders: infrequently - weight gain, weight loss; very rarely - hyperglycemia.

From the side of the central nervous system: often - drowsiness, dizziness, headache, paresthesias; infrequently - insomnia, mood lability, sleep disturbance, tremor, hypoesthesia; very rarely - peripheral neuropathy, confusion.

Special senses: often - visual disturbances.

From the organ of hearing: often - tinnitus.

Since the cardiovascular system: often - palpitations, flushing of blood to the skin of the face, a pronounced decrease in blood pressure; infrequently - fainting; rarely - pain behind the sternum; very rarely - stenocardia, myocardial infarction, possibly due to an excessive decrease in blood pressure in patients from the high-risk group, arrhythmias (including bradycardia, ventricular tachycardia and atrial fibrillation), stroke, possibly due to an excessive decrease in blood pressure in patients from the high risk, vasculitis.

Respiratory: often - shortness of breath, cough; infrequently - rhinitis, bronchospasm; very rarely - eosinophilic pneumonia.

From the digestive system: often - abdominal pain, nausea, vomiting, dyspepsia, a violation of taste perception, diarrhea, constipation; infrequently - constipation, dryness of the oral mucosa; rarely, increased bilirubin levels; very rarely - pancreatitis, gum hyperplasia, gastritis, hepatitis, cholestatic jaundice, cytolytic or cholestatic hepatitis, increased activity of liver enzymes ACT, ALT (most often in combination with cholestasis).

From the skin: often - pruritus, rash; infrequently - angioedema of the face, extremities, lips, mucous membranes, tongue, glottis and / or larynx, alopecia, hemorrhagic rash, photosensitization, increased sweating; very rarely - angioedema, erythema multiforme, Stevens-Johnson syndrome.

From the musculoskeletal system: often - muscle spasms; infrequently - arthralgia, myalgia, back pain.

From the kidneys and urinary tract: infrequently - a violation of urination, nocturia, frequent urination, renal failure; very rarely - severe renal failure.

From the reproductive system: infrequently - impotence, gynecomastia.

On the part of the body as a whole: often - peripheral edema, asthenia, fatigue; infrequently - chest pain, malaise.

Laboratory values: unspecified frequency - increased concentration of urea and serum creatinine, hyperkalemia.

Overdose:

Information about drug overdose Prestans is absent.

Information on overdose of amlodipine is limited.

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

Treatment: gastric lavage, the appointment of Activated carbon (especially in the first 2 h after overdose), maintaining the function of the cardiovascular system, the elevated position of the extremities, control of BCC and diuresis, symptomatic and supportive therapy, intravenous Calcium gluconate and dopamine. Dialysis is ineffective. With a significant decrease in blood pressure should be monitored for the patient in a cardiological ICU. In the absence of contraindications, vasoconstrictors can be used to restore vascular tone and blood pressure.

Data on overdose of perindopril is limited.

Symptoms: a significant reduction in blood pressure, shock, electrolyte disturbances, renal failure, hyperventilation, tachycardia, palpitations, bradycardia, dizziness, anxiety, and cough.

Treatment: with a significant decrease in blood pressure, the patient should be placed in a supine position with legs elevated; if necessary, correction of hypovolemia should be carried out (for example, IV infusion of a 0.9% sodium chloride solution). It is also possible to / in the introduction of angiotensin II and / or catecholamines. With hemodialysis, perindopril can be removed from the systemic circulation.In bradycardia resistant to therapy, it may be necessary to install an artificial pacemaker. Dynamic control of the physical state, concentration of creatinine and plasma electrolytes is necessary.

Emergency measures are reduced to the removal of the drug from the body: gastric lavage and / or the appointment of activated carbon, followed by the restoration of water and electrolyte balance.

Pharmachologic effect:

Combined antihypertensive and antianginal drug.

Perindopril is an inhibitor of the enzyme that converts angiotensin I to angiotensin II (ACE inhibitor). ACE, or kininase II, is exopeptidase, which carries out both the conversion of angiotensin I into a vasoconstrictor substance angiotensin II, and the destruction of bradykinin, which has a vasodilator, to an inactive heptapeptide.

Since ACE inactivates bradykinin, ACE suppression is accompanied by an increase in the activity of both the circulating and tissue kallikrein-kinin system, and the prostaglandin system is also activated.

Perindopril has a therapeutic effect due to its active metabolite, perindoprilat. Other metabolites have no inhibitory effect on ACE in vitro.

Arterial hypertension

Perindopril is a drug for treating hypertension of any severity. Against the background of its use, a decrease in both systolic and diastolic blood pressure in the prone and standing position is noted. Perindopril reduces OPSS, which leads to a decrease in elevated blood pressure and improvement of peripheral blood flow without changing heart rate.

As a rule, perindopril increases renal blood flow, while the glomerular filtration rate does not change.

The antihypertensive effect of the drug reaches a maximum after 4-6 hours after a single dose and remains for 24 hours.

The antihypertensive effect 24 hours after a single dose is about 87-100% of the maximum antihypertensive effect. Reduced blood pressure is achieved quite quickly.

The therapeutic effect occurs less than 1 month from the start of therapy and is not accompanied by tachycardia. Discontinuation of treatment does not cause withdrawal syndrome.Perindopril has a vasodilating effect, helps to restore the elasticity of large arteries and the structure of the vascular wall of small arteries, and also reduces left ventricular hypertrophy.

Stable ischemic heart disease

The efficacy of perindopril in patients (12,218 patients over 18 years old) with stable coronary artery disease without the clinical symptoms of chronic heart failure was studied during a 4-year study (EUROPA). 90% of study participants previously had acute myocardial infarction or coronary revascularization. Therapy with perindopril tertbutylamine at a dose of 8 mg / day (equivalent to 10 mg of perindopril arginine) resulted in a significant reduction in the absolute risk of complications by 1.9%, in patients who had previously suffered a myocardial infarction or coronary revascularization, the absolute risk decreased by 2.2% compared with the placebo group.

Amlodipine is a blocker of slow calcium channels, a derivative of the dihydropyridine series. Amlodipine inhibits the transmembrane transition of calcium ions into cardiomyocytes and smooth muscle cells of the vascular wall.

The antihypertensive effect of amlodipine is due to a direct effect on the smooth muscle cells of the vascular wall. It is established that amlodipine causes expansion of peripheral arterioles, reducing OPSS (afterload), since the heart rate does not change, and the need of myocardium for oxygen decreases. It causes the expansion of coronary arteries and arterioles in both ischemic and intact areas. In patients with Prinzmetal angina, coronary blood flow is improved.

In patients with arterial hypertension, taking amlodipine 1 time per day provides a clinically significant reduction in blood pressure while standing and lying down for 24 hours. The antihypertensive effect develops slowly, and therefore the development of acute arterial hypotension is not typical.

In patients with angina, taking amlodipine 1 time / day increases exercise tolerance, delaying the onset of an attack of angina and "ischemic" depression of the ST segment, and also reduces the frequency of strokes and Nitroglycerin (short-acting form).

Amlodipine does not affect the lipid profile and does not cause changes in the hypolipidemic parameters of blood plasma.

The drug can be used in patients with concomitant bronchial asthma, diabetes mellitus and gout.

The efficacy and safety of using amlodipine at a dose of 2.5-10 mg / day, an ACE inhibitor lisinopril at a dose of 10-40 mg / day and thiazide diuretic chlortalidone at a dose of 12.5-25 mg / day as a first-line drug was studied in a 5-year study ALLHAT ( involving 33,357 patients aged 55 years and older) in patients with mild or moderate arterial hypertension and at least one of the additional risk factors for coronary complications, such as myocardial infarction or stroke, more than 6 months before inclusion in the study ment, or other evidence of cardiovascular disease of atherosclerotic; diabetes; HDL cholesterol levels of less than 35 mg / dL; left ventricular hypertrophy according to ECG or echocardiography; smoking.

The main criterion for evaluating the effectiveness is a combined indicator of the frequency of deaths from IHD and the frequency of nonfatal myocardial infarction. There were no significant differences between the amlodipine and chlorthalidone groups in the main evaluation criteria. The incidence of heart failure in the amlodipine group was significantly higher than in the chlorthalidone group — 10.2% and 7.7%, respectively; the overall incidence of deaths in the amlodipine and chlorthalidone groups did not differ significantly.

Effectiveness with long-term use of amlodipine in combination with perindopril and Atenolol in combination with bendroflumethiazide in patients aged 40 to 79 years with arterial hypertension and at least 3 of the additional risk factors: left ventricular hypertrophy according to ECG or echocardiography; type 2 diabetes; peripheral artery atherosclerosis; previous stroke or transient ischemic attack; male; age 55 years and older; microalbuminuria or proteinuria; smoking; total cholesterol / HDL cholesterol ≥ 6; The early development of coronary artery disease in next of kin was studied in an ASCOT-BPLA study.

The main criterion for evaluating the effectiveness is a combined indicator of the frequency of nonfatal myocardial infarction (including painless) and deaths of IHD.The incidence of complications provided for by the main evaluation criteria in the amlodipine / perindopril group was 10% lower than in the atenolol / bendroflumethiazide group, but this difference was not statistically significant. In the amlodipine / perindopril group, there was a significant decrease in the incidence of complications, provided by additional criteria of effectiveness (except for fatal and nonfatal heart failure).

Pharmacokinetics:

The amount of absorption of perindopril and amlodipine when using the drug Prestanc does not significantly differ from that when using monopreparations.

Suction

When taken inside, perindopril is rapidly absorbed, C_max in blood plasma is achieved within 1 hour. Perindopril does not possess pharmacological activity. Approximately 27% of the total amount of perindopril ingested enters the bloodstream as an active metabolite of perindoprilat. In addition to perindoprilat, 5 more metabolites are formed that do not possess pharmacological activity. C_max Perindoprilat in blood plasma is achieved 3-4 hours after ingestion. Eating slows down the conversion of perindopril to perindoprilat, thereby affecting bioavailability. Therefore, the drug should be taken 1 time / day, in the morning, before eating.

Distribution

There is a linear dependence of the concentration of perindopril in plasma from its dose. V_d free perindoprilat is approximately 0.2 l / kg. Binding of perindoprilat with plasma proteins, mainly with ACE, is about 20% and is dose-dependent.

Removal

T_1/2 perindopril from blood plasma is 1 h.

Perindoprilat is excreted by the kidneys. Final t_1/2 free fraction is about 17 hours, so the equilibrium state is reached within 4 days.

Pharmacokinetics in special clinical situations

Removal of perindoprilat is delayed in old age, as well as in patients with cardiac and renal failure. Therefore, in these groups of patients, it is necessary to regularly monitor the concentration of creatinine and potassium in the blood plasma.

The dialysis clearance of perindoprilat is 70 ml / min.

The pharmacokinetics of perindopril changed in patients with cirrhosis of the liver: its hepatic clearance is reduced by 2 times.However, the amount of perindoprilat formed does not decrease, which does not require dose adjustment.

Suction

C_max amlodipine in the blood plasma is achieved 6-12 hours after ingestion. Absolute bioavailability is about 64-80%.

Distribution

Eating does not affect the bioavailability of amlodipine. V_d - approximately 21 l / kg. In vitro studies have shown that about 97.5% of circulating amlodipine is associated with plasma proteins.

Metabolism and excretion

Amlodipine is metabolized in the liver to form inactive metabolites. Final t_1/2 amlodipine from blood plasma is 35-50 hours, which allows you to take the drug 1 time / day. About 60% of the dose of amlodipine is excreted by the kidneys, 10% - unchanged.

Pharmacokinetics in special clinical situations

The time from taking the drug to achieve C_max Amlodipine does not differ in patients of older and younger age. In elderly patients, there is a slowdown in the clearance of amlodipine, which leads to an increase in AUC. Elderly patients do not require dose adjustment of the drug, but it is necessary to increase the dose of amlodipine with caution.

In patients with hepatic insufficiency T_1/2 amlodipine increases.

During pregnancy:

The drug is contraindicated for use in pregnancy.

Except for cases when therapy with Prestans is necessary for health reasons, when planning a pregnancy, the drug should be discontinued and other antihypertensive agents prescribed for pregnancy should be prescribed. If pregnancy occurs, you should immediately discontinue taking Prestans and, if necessary, prescribe another therapy.

It is known that the effect of ACE inhibitors on the fetus in the II and III trimesters of pregnancy can lead to a violation of its development (reduced renal function, oligohydramnios, delayed ossification of the skull bones) and the development of complications in the newborn (renal failure, arterial hypotension, hyperkalemia). If the patient received ACE inhibitors in the II or III trimester of pregnancy, it is recommended to conduct an ultrasound examination of the fetus to assess the state of the skull and kidney function.

Newborns whose mothers received ACE inhibitors during pregnancy need careful medical supervision because of the risk of arterial hypotension, oliguria and hyperkalemia.The limited data available on taking amlodipine and other slow calcium channel blockers during pregnancy indicate that the drug does not adversely affect the fetus. However, there is a risk of prolonged delivery.

It is not recommended to take Prestans in the period of lactation due to the lack of appropriate clinical experience in the use of perindopril and amlodipine, both in monotherapy and in combination. If you need to take the drug, you should stop breastfeeding.

When liver failure:

Caution must be exercised in the appointment of the drug Prestans in patients with liver failure due to the lack of recommendations on the dosing of the drug in these patients.

Storage:

Special storage conditions are not required. Keep vial tightly closed. Store in original packaging. Keep out of the reach of children. Shelf life - 2 years. Do not use after the expiration date printed on the package.

Special instructions:

Removal of perindoprilat patients with renal failure slowed down. Therefore, in such patients, it is necessary to regularly monitor the concentration of creatinine and potassium in the blood plasma. Prestans can be appointed patients with QC ≥ 60 ml / min. Prestans is contraindicated patients with QC <60 ml / min. Such patients are recommended individual selection of doses of perindopril and amlodipine. Changes in the concentration of amlodipine in the blood plasma do not correlate with the severity of renal failure.

Special instructions:

Removal of perindoprilat elderly patients and patients with renal failure slowed down. Therefore, in such patients, it is necessary to regularly monitor the concentration of creatinine and potassium in the blood plasma.

Special instructions (children's age): Prestans should not be appointed children and teenagers under 18 Due to the lack of data on the efficacy and safety of perindopril and amlodipine in these groups of patients, both as monotherapy and as combination therapy.