Renipril GT pills 12.5mg+10mg, 20pcs

Composition

Composition per tablet:

Active ingredients:

enalapril maleate – 10 mg,

hydrochlorothiazide-12.5 mg.

Auxiliary substances:

potato starch-59.3 mg,

lactose monohydrate (milk sugar) – 111.5 mg,

povidone (polyvinylpyrrolidone low molecular weight medical) – 4 mg,

colloidal silicon dioxide (aerosil) – 0.7 mg,

calcium stearate (calcium stearic acid) – 2 mg

Pharmacological action

Pharmacotherapy group

Antihypertensive combination agent (angiotensin-converting enzyme (ACE) inhibitor)+diuretic)

ATX code: [C 09 VA 02]

Pharmacological properties

Pharmacodynamics

Renipril GT is a combination drug containing the active substances enalapril and hydrochlorothiazide, the action of which is due to the properties of the components that make up its composition.

Enalapril – an angiotensin converting enzyme (ACE) inhibitor, is a “prodrug”: as a result of its hydrolysis, enalaprilate is formed, which inhibits ACE.

Hydrochlorothiazide is a thiazide diuretic. It 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 sodium and fluid excretion, which leads to a decrease in blood pressure (BP) and a decrease in cardiac output. With continued therapy, the hypotensive effect of hydrochlorothiazide is based on a decrease in total peripheral vascular resistance. Enalapril enhances the antihypertensive effect-it inhibits the renin-angiotensin-aldosterone system, i. e. the production of angiotensin II and its effects. Additionally, it reduces the production of aldosterone and enhances the action of bradykinin and prostaglandin release. Since it often has its own diuretic effect, this may increase the effect of hydrochlorothiazide.

Enalapril reduces pre-and post-loading, which unloads the left ventricle, leading to regression of hypertrophy. As a result, the heart rate slows down and the load on the heart decreases (in chronic heart failure), coronary blood flow improves and oxygen consumption by 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 down the course of chronic kidney disease, even in 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 effect of hydrochlorothiazide is independent of serum renin levels. Therefore, the simultaneous use of enalapril and hydrochlorothiazide has an additional antihypertensive effect. In addition, enalapril prevents or reduces the metabolic effects of diuretic therapy and has a beneficial effect on structural changes in the heart and blood vessels.

Simultaneous use of an ACE inhibitor and hydrochlorothiazide is used when each drug alone is not effective enough or monotherapy is carried out using the maximum doses of the drug, which increases the frequency of undesirable effects. The antihypertensive effect of the combination usually persists for 24 hours.

Pharmacokinetics

Enalapril is rapidly 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 is hydrolyzed to the active metabolite enalaprilate. The maximum concentration of enalaprilat in the blood serum is reached after 3-6 hours. Enalapril is excreted in the urine (60%) and feces (33%) mainly in the form of enalaprilat. Enalaprilat penetrates most body tissues, mainly in the lungs, kidneys and blood vessels. The relationship with plasma proteins is 50-60%. Renal clearance of enalapril and enalaprilat 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 multiple doses of enalapril are administered, the serum half-life of enalaprilate is approximately 11 hours. Enalapril and enalaprilat penetrate the placental barrier and are excreted in breast milk.

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

In patients with reduced renal function, excretion slows down, which requires changing the dosage in accordance with renal function, especially in patients with severe renal insufficiency.

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

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

Hydrochlorothiazide is absorbed mainly in the duodenum and proximal small intestine. Absorption is 70% and increases by 10% when taken with food. The maximum serum concentration is reached in 1.5-5 hours. The volume of distribution is about 3 l/kg. Binding to plasma proteins is 40%. The drug accumulates in red blood cells, the mechanism of accumulation is not known. It is not metabolized in the liver and is mainly excreted by the kidneys: 95% unchanged and about 4% in the form of hydrolysate-2-amino-4-chloro-m-benzenedisulfonamide. 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 elimination profile. The half-life (T_1/2) in the initial phase is 2 hours, in the final phase (10-12 hours after use) – about 10 hours. It penetrates 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. The concentration in the amniotic fluid exceeds that in the blood serum from the umbilical vein (19 times). The level of hydrochlorothiazide in breast milk is very low.

When prescribing hydrochlorothiazide to patients with heart failure, it was found that its absorption decreases in proportion to the degree of the disease – by 20-70%. T_1/2 of hydrochlorothiazide increases to 28.9 hours; renal clearance is 0.17-3.12 ml / s (10-187 ml / min) (mean values are 1.28 ml / s (77 ml / min)).

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

Concomitant use of enalapril and hydrochlorothiazide does not affect the pharmacokinetics of either drug.

Indications

Arterial hypertension (including renovascular hypertension), congestive heart failure.

Use during pregnancy and lactation

Contraindicated in pregnancy.

Breast-feeding should be discontinued for the duration of treatment.

Contraindications

-hypersensitivity (including to certain components of the drug or sulfonamides)- anuria, severe renal impairment (creatinine clearance less than 30 ml / min) – bilateral renal artery stenosis or stenosis of the arteries of a single kidney – a history of angioedema associated with the use of ACE inhibitors, as well as hereditary or idiopathic angioedema-primary hyperaldosteronism-Addison’s disease-porphyria-pregnancy, lactation – age up to 18 years (efficacy and safety have not been established).

With caution-impaired renal function (creatinine clearance 30-75 ml / min) – severe aortic stenosis or idiopathic hypertrophic subaortic stenosis-coronary heart disease and cerebrovascular diseases (including cerebrovascular insufficiency)- chronic heart failure – severe autoimmune systemic connective tissue diseases (including systemic lupus erythematosus, scleroderma) – inhibition of bone marrow hematopoiesis-diabetes mellitus-hyperkalemia-conditions after kidney transplantation-severe liver function disorders-conditions accompanied by a decrease in the volume of circulating blood (as a result of diuretic therapy, with limited consumption of table salt, diarrhea and vomiting)- old age – gout.

Side effects

Nervous system and sensory disorders:  dizziness, headache, weakness, fatigue, decreased libido.

Cardiovascular and blood disorders (hematopoiesis, hemostasis):  hypotension, collapse, neutropenia, hyperkalemia.

From the digestive tract:  nausea, impaired liver function (increased activity of hepatic transaminases, bilirubin levels), diarrhea.

Other services:  cough, skin rashes, impaired renal function, proteinuria, muscle spasms, angioedema.

Interaction

Enhances the effect of other antihypertensive agents, barbiturates. NSAIDs-weaken the antihypertensive effect, potassium-sparing diuretics, potassium preparations increase the risk of hyperkalemia.

Slows down the elimination of lithium, increases the toxicity of cardiac glycosides.Hydrochlorothiazide weakens the effect of antidiabetic agents, renipril-enhances.

How to take, course of use and dosage

Treatment of hypertension does not start with a combination of medications. Initially, adequate doses of individual components should be determined. The dosage should always be selected individually for each patient.

The usual dose is 1 tablet per day. Patients should take the whole tablet during or after a meal, with a small amount of liquid, preferably in the morning. If you miss the next dose of the drug, it should be taken as soon as possible, if there is a sufficiently large amount of time left before taking the next dose. If there are several hours left before taking the next dose, you should wait and take only it. Never double the dose.

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

In patients receiving diuretic therapy, it is recommended to discontinue treatment or reduce the dose of diuretics at least 3 days before the start of treatment with Renipril® GT to prevent the development of symptomatic hypotension. Renal function should be evaluated before starting treatment.

Dosage for impaired renal function

Patients with creatinine clearance greater than 0.5 ml / s or serum creatinine less than 265 mol / L (3 mg/100 ml) may be prescribed the usual dose of Renipril GT.

Composition

Tablet Form of production

Storage conditions

In a dry place, protected from light

Shelf life

3 years

Active ingredient

Hydrochlorothiazide, Enalapril

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as directed by your doctor

Indications

Hypertension