Diroton - instructions for use, doses, side effects, contraindications

Tablets 2.5 mg: Flat tablets are white or almost white in color, the shape of the disc is chamfered, labeled "2.5" on one side and with a risk on the other.

Tablets 5 mg: Flat tablets are white or almost white in color, the shape of the disc is chamfered, labeled "5" on one side and with a risk on the other.

Tablets 10 mg: Quadrangular, biconvex tablets of white or almost white color, labeled "10" on one side and with a risk on the other.

Tablets of 20 mg: Pentagonal, biconvex tablets of white or almost white color, marked "20" on one side and with a risk on the other.

Pharmacotherapeutic group:ACE inhibitor

ATX: & nbsp

C.09.A.A.03 Lisinopril

C.09.A.A ACE Inhibitors

Pharmacodynamics:

The ACE inhibitor, reduces the formation of angiotensin II from angiotensin I. Reduction of angiotensin content 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, blood pressure (BP), preload, pressure in the pulmonary capillaries,causes an increase in the minute volume of blood and increased tolerance to stress in patients with chronic heart failure. Expands arteries more than veins.

Some effects are explained by the effect on tissue renin-angiotensin systems. With prolonged use, the severity of myocardial hypertrophy and the walls of arteries of resistive type decreases. 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 onset of an antihypertensive effect is after 1 hour. The maximum effect is observed after 6-7 hours. The hypotensive effect persists for 24 hours. The duration of the effect also depends on the amount of the dose. With arterial hypertension, the effect is observed in the first days after the start of treatment, stable action develops after 1-2 months.

With a sharp withdrawal of the drug, there is no pronounced increase in blood pressure.

In addition to reducing blood pressure lisinopril reduces albuminuria.In patients with hyperglycemia contributes to the normalization of the function of the damaged glomerular endothelium.

Lizinopril does not affect the concentration of glucose in the blood in patients with diabetes mellitus and does not increase the risk of developing hypoglycemia.

Pharmacokinetics:

After taking lisinopril, the maximum concentration in the blood serum is reached after 7 hours. It weakly binds to blood plasma proteins. Permeability through the blood-brain and placental barrier is low. The average degree of absorption of lisinopril is about 25%, with a significant interindividual variability (6-60%). Food does not affect the absorption of lisinopril. Lisinopril does not undergo metabolism and is excreted unchanged only by the kidneys. After repeated administration, the effective half-life of lisinopril is 12 hours.

In patients with chronic heart failure Absorption and clearance of lisinopril decreased.

Impaired renal function leads to an increase AUC (the area under the plasma concentration-time curve) and the half-life of lisinopril, but these changes become clinically significant only when the glomerular filtration rate decreases below 30 ml / min.

In elderly patients the concentration of the drug in the blood plasma and the area under the "concentration-time" curve is 2 times greater than in patients of a young age.

Lizinopril is excreted from the body by hemodialysis.

Indications:

- Essential and Renovascular Hypertension (in monotherapy or in combination with other antihypertensive agents).

- Chronic heart failure (as part of combination therapy).

- In acute myocardial infarction with stable parameters of hemodynamics in the first 24 hours in combination therapy for the prevention of left ventricular dysfunction and heart failure.

- Diabetic nephropathy (decreased albuminuria in insulin-dependent patients with normal BP and insulin-independent patients with hypertension).

Contraindications:

Hypersensitivity to lisinopril and other components of the drug, angioedema in the history, including those associated with the use of ACE inhibitors, idiopathic angioedema, hereditary edema of Quincke, age under 18 years (efficacy and safety not established).

Carefully:

Stenosis of the aortic estuary, hypertrophic obstructive cardiomyopathy, bilateral stenosis of the renal arteries, stenosis of the single kidney artery, stenosis of the kidney, kidney failure (creatinine clearance less than 30 ml / min), primary hyperaldosteronism, hypotension, oppression of the medullary hematopoiesis, hyponatremia (increased risk of developing arterial hypotension in patients on a low-salt or salt-free diet), hypovolemic conditions (including diarrhea, vomiting), systems (including systemic lupus erythematosus, scleroderma), severe forms of diabetes mellitus, gout, hyperuricemia, hyperkalemia, ischemic heart disease, cerebrovascular diseases (including cerebral circulatory insufficiency), severe chronic heart failure, hemodialysis using high-flow dialysis membranes with high permeability (AN69®), the elderly.

Pregnancy and lactation:

The use of lisinopril during pregnancy is contraindicated. When establishing pregnancy, taking the drug should be stopped as soon as possible. Lisinopril penetrates the placental barrier. Admission of ACE inhibitors in the II and III trimester 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 effects of the drug on the fetus in case of application during the I trimester are not present. For newborns and infants who have undergone intrauterine exposure to ACE inhibitors, it is recommended to monitor for the timely detection of a marked decrease in blood pressure, oliguria, and hyperkalemia.

During the treatment, the drug should be abolished breastfeeding (there is no data on the penetration of lisinopril into breast milk).

Dosing and Administration:

Inside. 1 time per day, regardless of food intake, preferably at the same time.

Essential hypertension

The recommended initial dose for patients not taking antihypertensive drugs, 1 tablet of 10 mg per day. The usual maintenance dose is 1 tablet of 20 mg per day; depending on the parameters of blood pressure can be increased to 40 mg / day. The maximum daily dose is 40 mg / day.When increasing the dose, it should be taken into account that for a full manifestation of the hypotensive effect, it takes 2-4 weeks. If the therapeutic effect is insufficient, it is necessary to supplement therapy with another antihypertensive drug.

For patients taking diuretics, the diuretic medication should be discontinued 2-3 days before therapy with Diroton® is started. In cases where this is not possible, the initial dose of the drug DrTroto® ns should exceed 5 mg / day, while it is recommended to provide medical supervision of the patient after taking the first dose, t. possible development of symptomatic arterial hypotension (maximum effect manifested 6 hours after taking the drug).

Renovascular hypertension and other conditions associated with increased activity of the renin-angiotensin-aldosterone system. The recommended initial dose is 2.5-5 mg / day under enhanced medical supervision (control of blood pressure, kidney function, potassium content in blood serum). The maintenance dose, continuing strict medical control, should be determined depending on the dynamics of blood pressure.

Renal insufficiency

Since the excretion of lisinopril is carried out through the kidneys, the initial dose of the drug Diroton ® depends on the parameters of the CC: with a QC of 30-70 ml / min - 5-10 mg / day, with a KK of 10-30 ml / min - 2.5-5 mg / day , less than 10 ml / min, including patients on hemodialysis - 2.5 mg / day. The maintenance dose depends on the clinical effect and is selected with regular measurement of the renal function, the concentration of potassium and sodium in the blood.

Chronic heart failure

The initial daily dose of the drug Diroton®, equal to 2.5 mg, can be gradually increased 3-5 days before the usual, maintaining a daily dose of 5-20 mg. The dose should not exceed the maximum daily dose of 20 mg. When used simultaneously with diuretics, the dose of a diuretic should be reduced, if possible.

Before starting treatment with Diroton® and later, during treatment, blood pressure, kidney function, potassium and sodium in the blood should be monitored regularly to avoid the development of arterial hypotension and Yen related renal dysfunction.

Diabetic Nephropathy

The daily dose in patients with non-insulin-dependent diabetes mellitus with normal arterial pressure is 10 mg in a single dose.If necessary, the dose may be increased to 20 mg once daily to reduce diastolic blood pressure to 75 mm Hg. measured in the sitting position.

The dose for patients with insulin-dependent diabetes mellitus suffering from arterial hypertension is chosen according to the above scheme, however, the optimal diastolic blood pressure should be below 90 mm Hg.

Acute myocardial infarction

In the case of the use of the drug Diroton ® on the first day after myocardial infarction, the initial dose of the drug is 5 mg, on the second day re-administered 5 mg, on the third day - 10 mg, later maintaining a dose of 10 mg per day. In patients with acute myocardial infarction, the drug should be applied for at least 6 weeks.

With low systolic blood pressure (less than 120 mm Hg), treatment starts with a low dose (2.5 mg / day). In the case of development of arterial hypotension, when the systolic blood pressure is less than 100 mm Hg, the maintenance dose is reduced to 5 mg / day, if necessary, 2.5 mg / day may be temporarily prescribed.

In the case of a long pronounced decrease in blood pressure (systolic blood pressure below 90 mm Hg.more than 1 hour) it is necessary to stop treatment with the drug.

Side effects:

The most common side effects: dizziness, headache (5-6% of patients), weakness, diarrhea, dry cough (3%), nausea, vomiting, orthostatic hypotension, skin rash, chest pain (1-3%).

The incidence of other adverse reactions is less than 1%:

From the side of the cardiovascular system: marked decrease in blood pressure, chest pain, rarely - orthostatic hypotension, tachycardia, bradycardia, the appearance of symptoms of heart failure, violation of atrioventricular conduction, myocardial infarction.

From the side of the digestive tract: nausea, vomiting, abdominal pain, dry mouth, diarrhea, dyspepsia, anorexia, taste disorder, pancreatitis, hepatitis (hepatocellular and cholestatic), jaundice (hepatocellular or cholestatic).

From the skin: urticaria, increased sweating, photosensitivity, skin itching, hair loss.

From the central nervous system: mood lability concentration of attention, paresthesia, increased fatigue, drowsiness, convulsive twitching of the muscles of the extremities and lips; rarely - asthenic syndrome, confusion.

From the respiratory system: dyspnea, dry cough, bronchospasm, apnea.

On the part of the hematopoiesis system: leukopenia, thrombocytopenia, neutropenia, agranulocytosis, anemia (decrease in the concentration of hemoglobin, hematocrit, erythrocytopenia).

Allergic reactions: angioedema, facial edema, extremities, lips, tongue, epiglottis and / or larynx, intestinal angioedema, vasculitis, positive responses to antinuclear antibodies, increased ESR, eosinophilia.

In very rare cases - interstitial angioedema (edema of the interstitial tissue of the lungs without the release of the transudate into the lumen of the alveoli).

From the genitourinary system: uremia, oliguria, anuria, impaired renal function, acute renal failure, decreased potency.

Laboratory indicatorshyperkalemia and / or hypokalemia, hyponatremia, hypomagnesemia, hypochloraemia, hypercalcemia, hyperuricemia, increased urea concentration and creatinine in blood plasma, hyperbilirubinemia, hypercholesterolemia, hypertriglyceridemia, decreased glucose tolerance, increased activity of "liver" transaminases, with prolonged treatment, a slight decrease hemoglobin and hematocrit, in some cases agranulocytosis.

Other: arthralgia, arthritis, myalgia, fever, exacerbation of gout.

Overdose:

Symptoms: marked decrease in blood pressure, dry mouth, drowsiness, urinary retention, constipation, anxiety, increased irritability.

Treatment: gastric lavage, taking activated charcoal, giving the patient a horizontal position with raised legs, replenishing the volume of circulating blood (BCC) - intravenous administration of plasma-interfering solutions, symptomatic therapy, control of cardiovascular and respiratory systems, bcc, urea, creatinine and electrolytes in blood serum , as well as diuresis. Lisinopril can be removed from the body by hemodialysis.

Interaction:

When used simultaneously with potassium-sparing diuretics (spironolactone, triamterene, amiloride), potassium preparations, salt substitutes containing potassium - increases the risk of hyperkalemia, especially in patients with impaired renal function. Therefore, they can be jointly administered only on the basis of an individual doctor's decision with regular monitoring of potassium content in the blood serum and kidney function.

With simultaneous use with beta-blockers, blockers of "slow" calcium channels, diuretics and other antihypertensive drugs, there is an increase in the hypotensive effect of the drug.

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

With simultaneous use with vasodilators, barbiturates, phenothiazines, tricyclic antidepressants, ethanol - strengthening of the hypotensive effect of the drug.

When used simultaneously with non-steroidal anti-inflammatory drugs (NSAIDs) (including selective inhibitors of cyclooxygenase-2), estrogens, as well as adrenostimulators - a decrease in the antihypertensive effect of lisinopril.

With simultaneous use with lithium preparations - slowing the excretion of lithium from the body (increased cardiotoxic and neurotoxic action of lithium).

With simultaneous use with antacids and colestyramine - reduced absorption in the gastrointestinal tract.

The drug enhances the neurotoxicity of salicylates, weakens the effect of hypoglycemic agents for oral administration, norepinephrine, epinephrine and antidotal drugs, increases the effects (including side effects) of cardiac glycosides, the action of peripheral muscle relaxants, reduces the excretion of quinidine.

Reduces the effect of oral contraceptives.

With the simultaneous administration of methyldopa, the risk of hemolysis increases.

Special instructions:

A pronounced decrease in blood pressure most often occurs with a decrease in the volume of circulating blood caused by diuretic therapy, a decrease in the amount of salt in the food, dialysis, diarrhea, or vomiting.

In patients with chronic heart failure with simultaneous renal failure or without it, a marked decrease in blood pressure is possible. It is more often detected in patients with a severe stage of chronic heart failure as a consequence of the use of large doses of diuretics, hyponatremia or impaired renal function. In such patients, treatment should be started under the strict supervision of a doctor (with care to select the dose of the drug and diuretics).

Similar rules should be adhered to when assigning patients with coronary heart disease, cerebrovascular insufficiency, in which a sharp decrease in blood pressure can lead to myocardial infarction or stroke.

Transient arterial hypotension is not a contraindication for taking the next dose of the drug. Prior to treatment, if possible, normalize the concentration of sodium and / or replenish the volume of circulating blood, carefully monitor the effect of the initial dose of the drug on the patient. Treatment of symptomatic arterial hypotension consists of providing bed rest and, if necessary, with / in the administration of fluid (infusion of physiological solution). Transient arterial hypotension is not a contraindication (for treatment with Diroton®, however, it may be necessary to temporarily abolish it or reduce the dose.

Treatment with Diroton® is contraindicated in case of cardiogenic shock and acute myocardial infarction, if the appointment of a vasodilator can significantly worsen hemodynamics, for example, when systolic blood pressure does not exceed 100 mm Hg. Art.

In patients with acute myocardial infarction, a decrease in renal function (creatinine concentration in the blood plasma greater than 177 μmol / L and / or proteinuria more than 500 mg / 24 h) is a contraindication for the use of the drug Diroton ®.

In case of development of renal failure during treatment with lisinopril (the creatinine concentration in the blood plasma is more than 265 μmol / l or twice as high as the baseline level), the doctor should decide whether to stop treatment.

In bilateral renal artery stenosis and renal artery stenosis of a single kidney, as well as in hyponatremia and / or a decrease in the volume of circulating blood or circulatory failure, arterial hypotension caused by taking Diroton® can lead to a decrease in kidney function followed by development of reversible (after drug withdrawal) acute renal failure. A small temporary increase in the concentration of urea in the blood and creatinine can be observed in cases of impaired renal function, especially against a background of simultaneous treatment with diuretics. In cases of significant decrease in kidney function (creatinine clearance less than 30 ml / min) caution and monitoring of renal function is required.

Angioedema of the face, extremities, lips, tongue, epiglottis and / or larynx was rarely seen in patients treated with ACE inhibitors, including Diroton®, which may occur during any treatment period. In this case, the treatment with Diroton® should be stopped as soon as possible and the patient should be observed before the symptoms regress completely. In cases where there was only edema of the face and lips, the condition usually passes without treatment, but it is possible to prescribe antihistamines. Angioedema with edema of the larynx can be fatal. When the tongue, epiglottis or larynx are covered, airway obstruction may occur, therefore, appropriate therapy (0.3-0.5 ml epinephrine (adrenaline) 1: 1000 subcutaneously, administration of glucocorticosteroids, antihistamines) and / or measures to ensure patency of the respiratory tract.

Patients who have had an angioneurotic edema that is not associated with previous treatment with ACE inhibitors may have an increased risk of developing it during treatment with an ACE inhibitor (also see "Contraindications"),

Anaphylactic reaction was noted in patients on hemodialysis using highly flowing dialysis membranes (AN69®), which simultaneously take Diroton®. In such cases, one should consider the possibility of using another type of membrane for dialysis or another antihypertensive agent.

In some cases of desensitization against arthropod allergens, treatment with ACE inhibitors was accompanied by hypersensitivity reactions. This can be avoided by interrupting the administration of ACE inhibitors.

In patients with extensive surgical intervention or during general anesthesia, ACE inhibitors (in particular, lisinopril) can block the formation of angiotensin II. The decrease in blood pressure associated with this mechanism of action is corrected by an increase in the volume of circulating blood.

Before surgery (including dentistry), an anesthesiologist must be warned about the use of Diroton®.

The use of recommended doses of the drug in elderly patients can be accompanied by an increase in the concentration of lisinopril in the blood, so the selection of a dose requires special attention and is carried out depending on the function of the kidneys and blood pressure of the patient.However, in elderly and young patients, the antihypertensive effect of Diroton® is equally pronounced.

Cough was used in the use of ACE inhibitors. Cough is dry, prolonged, which disappears after discontinuation of treatment with ACE inhibitors. With a differential diagnosis of cough, one must also consider the cough caused by the use of ACE inhibitors.

In some cases, hyperkalemia was noted. Risk factors for the development of hyperkalemia include renal failure, diabetes mellitus, the use of potassium drugs or drugs that cause an increase in potassium in the blood (eg, heparin), especially in large patients with impaired renal function. During the treatment with the drug, regular monitoring of the potassium ions, glucose, urea, lipids in the blood plasma is necessary.

During the period of treatment it is not recommended to drink alcoholic beverages, since alcohol enhances the hypotensive effect of the drug.

Care should be taken when doing physical exercises, hot weather (the risk of dehydration and excessive blood pressure lowering due to a decrease in the volume of circulating blood).

Because the potential risk of agranulocytosis can not be ruled out, periodic monitoring of the blood picture is required.

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

When there are side effects from the central nervous system, it is not recommended to drive vehicles, as well as perform work associated with increased risk.

Form release / dosage:

Tablets, 2.5 mg, 5 mg, 10 mg and 20 mg.

Packaging:

Tablets, 2.5 mg.

14 tablets in a blister pack AL/ PVC. 1 or 2 blisters with instructions for use in a cardboard bundle.

Tablets, 5 mg, 10 mg and 20 mg.

14 tablets in a blister pack AL/ PVC. 1, 2 or 4 blisters with instructions for use in a cardboard bundle.

Storage conditions:

Store at a temperature of 15-30 FROM.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N011426 / 01

Date of registration:04.06.2009 / 18.11.2013

Expiration Date:Unlimited

The owner of the registration certificate:GEDEON RICHTER, OJSC GEDEON RICHTER, OJSC Hungary

Manufacturer: & nbsp

GEDEON RICHTER-RUS, CJSC Russia

GEDEON RICHTER, Ltd. Hungary

Representation: & nbspGEDEON RICHTER OJSC GEDEON RICHTER OJSC Hungary

Information update date: & nbsp10.11.2016

Illustrated instructions

Instructions

Diroton® (Diroton®)