Renipril GT - instructions for use, dose, side effects, contraindications

potato starch - 59.3 mg, lactose monohydrate (sugar milk) - 111.5 mg, povidone (polyvinylpyrrolidone low molecular weight medical) - 4 mg, silicon dioxide colloid (aerosil) - 0.7 mg, calcium stearate (calcium stearic acid) - 2 mg.

Description:Tablets are white or white with a creamy shade of color, flat-cylindrical with a risk and a facet. Marble is allowed on the surface of the tablets.

Pharmacotherapeutic group:hypotensive combined agent (angiotensin-converting enzyme inhibitor + diuretic).

ATX: & nbsp

C.09.B.A.02 Enalapril in combination with diuretics

Pharmacodynamics:

Renipril® GT is a combined preparation containing active substances: enalapril and hydrochlorothiazide, the effect of which is due to the properties of the components that make up its composition.

Enalapril, an inhibitor of the angiotensin converting enzyme (ACE), is a "prodrug": as a result of its hydrolysis, a enalaprilate, which inhibits ACE. Hydrochlorothiazide - Thiazide diuretic. Acts at the level of the distal renal tubules, increasing the excretion of sodium and chlorine ions. At the beginning of treatment with hydrochlorothiazide, the volume of fluid in the vessels decreases as a result of increased excretion of sodium and liquid, which leads to a reduction in blood pressure (BP) and a decrease in cardiac output. With the continuation of therapy, the hypotensive effect of hydrochlorothiazide is based on a decrease in the total peripheral vascular resistance. Enalapril enhances the antihypertensive effect - inhibits the renin-angiotensin-aldosterone system, i.e. production of angio-tensin II and its effects. In addition, it reduces the production of aldosterone and enhances the effect of bradykinin and the release of prostaglandins. Since it often has its own diuretic effect, it can enhance the action of hydrochlorothiazide. Enalapril reduces pre- and postnagruzku, which unloads the left ventricle, leading to regression of hypertrophy. As a result, the heart rate slows down and the heart load decreases (with chronic heart failure), coronary blood flow improves and oxygen consumption of cardiomyocytes decreases. Thus, the sensitivity of the heart to ischemia decreases. It has a beneficial effect on cerebral blood flow in patients with arterial hypertension and chronic cardiovascular diseases. Prevents the development of glomerulosclerosis, supports and improves kidney function and slows the course of chronic kidney disease, even in those patients who have not yet developed hypertension.

The antihypertensive effect of ACE inhibitors is higher in patients with hyponatremia, hypovolemia and elevated serum renin levels, whereas the hydrochlorothiazide effect does not depend on the level of renin in the serum. Therefore, the simultaneous administration of enalapril and hydrochlorothiazide has an additional antihypertensive effect. Besides, enalapril prevents or weakens the metabolic effects of diuretic therapy and has a beneficial effect on structural changes in the heart and blood vessels. Simultaneous administration of an ACE inhibitor and hydrochlorothiazide is applied when each drug is not sufficiently effective alone or monotherapy is performed using the maximum doses of the drug, which increases the incidence of unwanted effects. The antihypertensive effect of the combination is usually maintained for 24 hours.

Pharmacokinetics:

Enalapril quickly absorbed from the gastrointestinal tract. The suction volume is 60%. Food does not affect the absorption of enalapril. The maximum concentration in the blood plasma is reached after 1 hour. In the liver enalapril hydrolyzed to the active metabolite-enalaprilata. The maximum concentration of enalaprilat in the blood serum is achieved in 3-6 hours. Displayed enalapril with urine (60%) and feces (33%), mainly in the form of enalaprilate. Enalaprilat penetrates into most tissues of the body, mainly in the lungs, kidneys and blood vessels. Communication with blood plasma proteins - 50 - 60%. Renal clearance of enalapril and enalaprilate is 0.005 ml / s (18 l / h) and 0.00225 - 0.00264 ml / s (8.1 - 9.5 l / h), respectively. It is displayed in several stages. When appointing multiple doses of enalapril, the half-life of enalaprilate from serum is approximately 11 hours. Enalapril and enalaprilate penetrate the placental barrier and are excreted in breast milk.

Enalaprilat is removed from the bloodstream during hemodialysis or peritoneal dialysis. Hemodialysis clearance of enalaprilate 0.63 - 1.03 ml / s (38-62 ml / min); serum concentration of enalaprilat after 4-hour hemodialysis is reduced by 45 - 57%.

In patients with reduced renal function, excretion slows down, which requires a change in dosage in accordance with renal function, especially in patients with severe renal failure.

In patients with hepatic insufficiency, metabolism of enalapril may be slowed down, and its pharmacodynamic effect does not change.

In patients with heart failure, the absorption and metabolism of enalaprilat slows down, and the volume of distribution also decreases.

Hydrochlorothiazide absorbed, mainly in the duodenum and proximal part of the small intestine. Absorption is 70% and increases by 10% when taken with food. The level of maximum serum concentration is reached after 1.5-5 hours. The volume of distribution is about 3 l / kg. Connection with blood plasma proteins - 40%. The drug accumulates in erythrocytes, the mechanism of accumulation is not known. It is not metabolized in the liver, is excreted mainly by the kidneys: 95% unchanged and about 4% in the form of hydrolyzate-2-amino-4-chloro-t-benzene disulfonamide. The renal clearance of hydrochlorothiazide in healthy volunteers and patients with arterial hypertension is approximately 5.58 ml / s (335 ml / min). Hydrochlorothiazide has a two-phase withdrawal profile. The half-life period (T1 / 2) in the initial phase is 2 hours, in the final phase (10-12 hours after administration) - about 10 hours. It penetrates through the placental barrier and accumulates in the amniotic fluid.The serum concentration of hydrochlorothiazide in the blood of the umbilical vein is almost the same as in the maternal blood. Concentration in the amniotic fluid exceeds that in the blood serum from the umbilical vein (by 19 times). The level of hydrochlorothiazide in breast milk is very low.

When hydrochlorothiazide was prescribed, patients with heart failure were found to have a decrease in proportion to the degree of disease, by 20 -70%. T1 / 2 hydrochlorothiazide increased to 28.9 hours; renal clearance of 0.17 - 3.12 ml / s (10 - 187 ml / min) (mean values of 1.28 ml / s (77 ml / min)).

In patients undergoing surgery of the intestinal bypass surgery for obesity, hydrochlorothiazide absorption can be reduced by 30% and the serum concentration of 50%, than in healthy volunteers.

Simultaneous administration of enalapril and hydrochlorothiazide does not affect the pharmacokinetics of each of them.

Indications:Arterial hypertension (patients who are shown combined therapy).

Contraindications:

- hypersensitivity (including to individual components of the drug or sulfonamides)

- anuria, marked renal impairment (creatinine clearance less than 30 ml / min)

- bilateral stenosis of the renal arteries or stenosis of the arteries of a single kidney

- angioedema in history, associated with the use of ACE inhibitors, as well as hereditary or idiopathic angioedema

- primary hyperaldosteronism

- Addison's disease

- porphyria

- pregnancy, lactation

- age to 18 years (efficacy and safety not established).

Carefully:

- impaired renal function (creatinine clearance 30-75 ml / min)

- severe stenosis of the aortic aorta or idiopathic hypertrophic subaortic stenosis

- ischemic heart disease and cerebrovascular diseases (including cerebral circulatory insufficiency)

- chronic heart failure

- severe autoimmune systemic diseases of connective tissue (including

- systemic lupus erythematosus, scleroderma)

- oppression of bone marrow hematopoiesis

- diabetes

- hyperkalemia

- state after kidney transplantation,

- severe liver dysfunction

- states, accompanied by a decrease in the volume of circulating blood (as a result of therapy with diuretics, while limiting consumption of table salt, diarrhea and vomiting)

- elderly age

- gout.

Pregnancy and lactation:The drug is contraindicated in pregnancy. At the onset of pregnancy, the drug should be stopped immediately. If it is necessary to prescribe the drug during lactation, lactating mothers should refuse breastfeeding.

Dosing and Administration:

Treatment of hypertension does not begin with a combination of drugs. Initially, adequate doses of individual components should be determined. Dosage should always be selected individually for each patient.

The usual dose is 1 tablet a day. Patients should take the pill completely during or after a meal, with a small amount of liquid, preferably in the morning. In case of missed intake of the next dose of the drug, it must be taken as soon as possible, if a sufficiently large amount of time remains before the next dose. If several hours are left before taking the next dose, you should wait and accept only it. Never double the dose.

If a satisfactory therapeutic effect is not achieved, it is recommended to add another medication or change the therapy.

In patients on diuretic therapy, it is recommended to cancel treatment or to reduce the dose of diuretics at least 3 days before the start of treatment with Renipril® GT to prevent the development of symptomatic hypotension. Before the beginning of treatment, the function of the kidneys should be investigated.

Dosage with impaired renal function

Patients with a creatinine clearance greater than 0.5 mL / s or serum creatinine of less than 265 mol / L (3 mg / 100 mL) may be given a normal dose of Renipril® GT.

Side effects:

General: weakness, hypersensitivity reactions, necrotizing angiitis, respiratory distress syndrome, including pneumonitis and pulmonary edema.

From the cardiovascular system: heart palpitations, fainting, chest pain, various heart rhythm disorders, marked decrease in blood pressure, orthostatic hypotension.

From the side of the digestive tract: dry mouth, glossitis, stomatitis, inflammation of the salivary glands, anorexia, nausea, vomiting, diarrhea, constipation, flatulence, epigastric pain, intestinal colic, ileus, pancreatitis, hepatic insufficiency, hepatitis, jaundice.

On the part of the respiratory system, unproductive "dry" cough, rhinitis, sinusitis, pharyngitis, hoarseness, bronchospasm, eosinophilic pneumonia.

From the genitourinary system: oliguria, gynecomastia, decreased potency, decreased libido, renal failure, impaired renal function, interstitial nephritis.

Allergic reactions: angioedema, swelling, exfoliative dermatitis, toxic epidermal necrolysis, erythema multiforme, Stephen-Johnson syndrome.

From the skin: skin rash, itching, alopecia.

From the sense organs: impaired vision, impaired taste, impaired sense of smell, tinnitus, conjunctivitis.

From the central nervous system: dizziness, headache, fatigue, depression, ataxia, asthenia, drowsiness, insomnia, anxiety, nervousness, peripheral neuropathy (paresthesia, dysesthesia).

Laboratory indicators: hypomagnesemia, hypercalcemia, hyponatremia, hypochloraemic alkalosis, hyperglycemia, hypercreatininemia, hyper- or hypokalemia, glucosuria, hyperuricemia, hypercholesterolemia, hypertriglyceridemia, increased activity of "hepatic" enzymes, hyperbilirubinemia, leukocytosis, eosinophilia, neutropenia, leukopenia, agranulocytosis, anemia, pancytopenia, hemoglobin and hematocrit.

Other: lupus-like syndrome (fever, myalgia / myositis and arthralgia / arthritis, serositis, vasculitis, increased erythrocyte sedimentation rate, positive antinuclear antibody test), photosensitivity, muscle cramps.

Overdose:

Symptoms: increased diuresis, marked decrease in blood pressure with bradycardia or other heart rhythm disturbances, convulsions, paresis, paralytic ileus, impaired consciousness (including coma), renal insufficiency, acid-base balance disturbance, electrolyte balance disturbance.

Treatment: the patient is transferred to a horizontal position with a low headboard. In mild cases, gastric lavage and ingestion of saline are indicated, in more serious cases, measures aimed at stabilizing blood pressure in / in the administration of physiological solution, plasma substitutes. The patient needs to monitor the level of blood pressure, heart rate, respiratory rate, serum urea concentration, creatinine, electrolytes and diuresis, if necessary - intravenous angiotensin II, hemodialysis (enalaprilate removal rate -62 ml / min).

Interaction:

Simultaneous reception of other antihypertensive agents, barbiturates, tricyclic antidepressants, phenothiazines and narcotics, as well as alcohol intake, increases the antihypertensive effect of Renipril® GT.

Analgesics and non-steroidal anti-inflammatory drugs, large amounts of salt in the diet, simultaneous reception of colestyramine or colestipol reduce the effect of Renipril® GT. Simultaneous use with lithium preparations can lead to lithium intoxication, since enalapril and hydrochlorothiazide reduce the excretion of lithium. It is necessary to monitor the concentration of lithium in the blood serum and correct its dosage. If possible, simultaneous treatment with Renipril® GT and lithium preparations should be avoided.

The simultaneous use of Renipril® GT and non-steroidal anti-inflammatory drugs and analgesics (due to inhibition of prostaglandin synthesis) can reduce the efficacy of enalapril and increase the risk of impaired renal function and / or heart failure. In some patients, the antihypertensive effect of enalapril may also decrease with simultaneous treatment.Simultaneous treatment with potassium-sparing diuretics (spironolactone, amiloride, triamterene) or the addition of potassium can lead to hyperkalemia.

Simultaneous administration with allopurinol, cytostatics, immunosuppressants or systemic corticosteroids may cause leukopenia, anemia or pancytopenia, therefore periodic monitoring of the hemogram is required.

Caution is necessary when used concomitantly with cardiac glycosides. Possible hydrochlorothiazidine-induced hypovolemia, hypokalemia and hypomagnesemia can increase the toxicity of glycosides.

Simultaneous administration with corticosteroids increases the risk of hypokalemia. When used concomitantly with theophylline enalapril can reduce the half-life of theophylline.

With simultaneous application with cimetidine, the half-life of enalapril may be increased. The risk of arterial hypotension increases during general anesthesia or the use of nondepolarizing muscle relaxants (eg, tubocurarine).

Special instructions:

A marked reduction in blood pressure with all clinical consequences can be observed after the first administration of Renipril® GT tablets in patients withsevere heart failure and hyponatremia, severe renal failure, left ventricular dysfunction, and especially in patients who are in a state of hypovolemia as a result of diuretic therapy, salt-free diets, diarrhea, vomiting or hemodialysis. Arterial hypotension after taking the first dose and its more serious consequences is a rare and ongoing phenomenon. It can be avoided by removing diuretics, if possible, before starting treatment with Renipril® GT.

In the case of arterial hypotension, it is necessary to place the patient on the back with a low headboard and, if necessary, adjust the volume of plasma by infusing saline. Transient arterial hypotension is not a contraindication for continuing treatment. After normalizing blood pressure and replenishing the volume of circulating blood, patients usually tolerate subsequent doses well.

Caution is necessary when used in patients with impaired renal function (creatinine clearance from 0.5 to 1.3 ml / s). In patients receiving hydrochlorothiazide, can develop azotemia. Patients with impaired renal function may show signs of accumulation of the drug. If necessary, a combination of enalapril with

a lower amount of hydrochlorothiazide or a combination therapy with enalapril and hydrochlorothiazide should be abolished.

A regular monitoring of the serum concentration of electrolytes during the treatment period is necessary to identify possible imbalances. Determination of the serum concentration of electrolytes is mandatory for patients with prolonged diarrhea, vomiting and receiving intravenous infusions.

In patients taking Renipril ® HT, signs of electrolyte imbalance should be identified, such as dry mouth, thirst, weakness, drowsiness, lethargy, agitation, muscle pain and cramps (mainly calf muscles), lowering blood pressure, tachycardia, oliguria and gastrointestinal tract, intestinal disorders (nausea, vomiting).

During treatment with Renipril® HT, hypomagnesemia and sometimes hypercalcemia may occur, resulting from an increase in the excretion of magnesium and a delay in the excretion of calcium in the urine by hydrochlorothiazide. A significant increase in serum calcium levels may be a sign of latent hyperparathyroidism. In some patients, the action of hydrochlorothiazide may indicate hyperuricemia or worsening of gout.If there is an increase in the concentration of uric acid in the serum, treatment should be discontinued. It can be resumed after the normalization of laboratory indicators and in the future, under their control. Caution is necessary in all patients receiving oral hypoglycemic agents or insulin, since hydrochlorothiazide can weaken, and enalapril strengthen their action. Patients with diabetes should be more frequently observed, and if necessary, some change in the dose of hypoglycemic agents may be required. When an angioedema develops in the face or neck, it is usually sufficient to discontinue therapy and prescribe antihistamines to the patient. In more severe cases (edema of the tongue, throat and larynx) angio-neurotic edema treated with adrenaline, it is necessary to maintain the patency of the airways (intubation or laryngotomy). The antihypertensive effect of Renipril® HT may be enhanced after sympathectomy. Due to the increased risk of anaphylactic reactions, Renipril® GT should not be administered to patients on hemodialysis using polyacrylonitrile membranes,subject to apheresis with dextran sulfate and immediately prior to the procedure of desensitization to aspen or bee venom. During treatment with Renipril® HT, hypersensitivity reactions may occur in patients without previous allergies or bronchial asthma. Reported worsening of the course of systemic lupus erythematosus.

When jaundice occurs and the activity of "liver" enzymes increases, treatment should be stopped immediately, patients should be monitored. Caution is also needed in patients taking sulfonamides or oral hypoglycemic agents from the sulfonylurea group (cross-sensitivity is possible).

During treatment, periodic monitoring of the number of white blood cells is required, especially in patients with connective tissue or kidney disease.

During treatment, periodic monitoring of the serum concentration of electrolytes, glucose, urea, creatinine and the activity of "liver" enzymes, as well as urine protein, is necessary. Treatment of Renipril® HT should be discontinued before the study of parathyroid function.

Effect on the ability to drive transp. cf. and fur:In some patients, primarily at the beginning of treatment, arterial hypotension and dizziness may occur, which may reduce the ability to drive and operate machinery. At the beginning of treatment it is recommended to avoid work that requires concentration of attention, until an answer to treatment is established.

Form release / dosage:Tablets 12.5 mg + 10 mg.

Packaging:For 10 or 20 tablets in a planar cell pack. 1, 2 or 3 contourcell packs with instructions for use in the pack.

Storage conditions:Store at a temperature not higher than 25 ° C. Keep out of the reach of children.

Shelf life:

3 years. After the expiration date indicated on the package, do not use the drug.

Terms of leave from pharmacies:On prescription

Registration number:P N000156 / 01

Date of registration:28.06.2010

The owner of the registration certificate:PHARMSTANDART-FORESTRY, OJSC PHARMSTANDART-FORESTRY, OJSC Russia

Manufacturer: & nbsp

PHARMSTANDART-FORESTRY, OJSC Russia

Information update date: & nbsp02.01.2016

Illustrated instructions

Instructions

Renipril® GT (Renipril® HT)