Quadropril instructions for use

Use of the drug Quadropril

In patients with dehydration and hyponatremia (due to vomiting, diarrhea or treatment with diuretics), heart failure or severe hypertension (arterial hypertension), a sharp decrease in blood pressure may be observed at the beginning of treatment with Quadropril, therefore, before prescribing the drug, disturbances in the water-electrolyte balance should be eliminated and discontinued diuretics. Due to the risk of developing arterial hypotension as a consequence of the first dose syndrome, as well as when increasing the dose of Quadropril or diuretics, patients should be under medical supervision for 6 hours. Quadropril is prescribed at an initial dose of 3 mg 1 time per day (in the morning). If the effect is insufficient, after 3 weeks the dose is increased to 6 mg/day. The maintenance dose is usually 6 mg once a day. In case of severe renal failure (creatinine clearance 10–30 ml/min), the recommended dose of Quadropril is 3 mg/day; taking into account functional renal parameters and the effectiveness of treatment, it can be increased to 6 mg/day. Quadropril is not prescribed to patients with creatinine clearance ≤10 ml/min. For patients with moderately severe decrease in renal function (creatinine clearance 30–60 ml/min) or liver, as well as for elderly patients, no dose adjustment is required. The tablets are swallowed without chewing during or after meals, washed down with a sufficient amount of liquid.

Quadropril 6mg tab No. 30

Dosage

6 mg

Active substance

Spirapril

Manufacturer

Kloke Pharma-Service GmbH (Germany)

Shelf life

3 years

Storage conditions

At a temperature not exceeding 25 °C

Registration certificate number

P N015520/01 dated 04/02/2012

Compound

Characteristic

Directions for use and doses

Inside

, regardless of food intake, without chewing and drinking plenty of liquid.

Arterial hypertension

The initial dose is 1/2 tablet. (3 mg) per day. If after taking this dose blood pressure does not normalize, the dose can be increased to 1 table. The maintenance dose is usually 1 tablet. per day.

The maximum daily dose is 1 tablet. (6 mg) per day.

Chronic heart failure

The initial dose is 1/2 tablet. (3 mg) per day. If necessary, the dose can be increased to 1 tablet. (6 mg) per day. Maintenance dose - 1 tablet. (6 mg) per day.

The maximum daily dose is 1 tablet. (6 mg) per day.

Dosage for renal impairment (Cl creatinine 10–30 ml/min)

The recommended dose of Quadropril® is 1/2 tablet. (3 mg), which is taken in the morning. Treatment begins when careful clinical monitoring of the patient is established. Depending on the indicators of kidney function, in isolated justified cases, the dose of Quadropril® can be increased to a maximum of 1 tablet, which is taken in the morning.

In patients with impaired renal function (Cl creatinine 30–60 ml/min) or liver, as well as in elderly patients, dose reduction is not required.

The duration of the course of treatment is determined by the doctor.

Conditions for dispensing from pharmacies

On prescription.

Pharmgroups

Angiotensin-converting enzyme (ACE) inhibitor (ACE inhibitors)

Pharmaceutical actions

hypotensive, vasodilator, cardioprotective, natriuretic

Contraindications to the use of the drug Quadropril

Hypersensitivity to the components of the drug; a history of angioedema caused by taking ACE inhibitors; renal artery stenosis (bilateral or solitary kidney); severe renal failure (creatinine clearance ≤10 ml/min); condition after kidney transplantation; impaired blood outflow from the left ventricle of the heart (hemodynamically significant stenosis of the aortic or mitral valve; hypertrophic cardiomyopathy); hyperaldosteronism, pregnancy and breastfeeding (breastfeeding should be stopped). Due to insufficient experience with use, Quadropril should not be used for hemodialysis, decompensated chronic heart failure, or in pediatric practice.

Side effects of the drug Quadropril

Cardiovascular system Sometimes, mainly at the beginning of treatment with Quadropril, as well as in patients with dehydration and electrolyte deficiency (for example, with previous treatment with diuretics), heart failure, as well as with an increase in the dose of diuretics and/or the dose of Quadropril, a sharp decrease in blood pressure may be observed . Kidneys Renal dysfunction may sometimes occur or worsen, and proteinuria may occur rarely. Respiratory system Dry cough, bronchitis, rarely - shortness of breath, sinusitis, rhinitis, isolated cases of bronchospasm, glossitis and dry mouth, angioedema of the tongue, pharynx and larynx. Digestive tract Nausea, discomfort in the epigastric region, less often - vomiting, diarrhea, constipation, anorexia, extremely rarely - liver damage. Isolated cases of hepatitis, pancreatitis and intestinal obstruction have been described during treatment with ACE inhibitors. Skin, blood vessels, allergic reactions Allergic skin reactions are possible (exanthema, itching, urticaria, angioedema of the lips, face and limbs, in isolated cases - severe reactions (exudative multimorphic erythema). Skin reactions may be accompanied by fever, myalgia, arthralgia, vasculitis , eosinophilia and an increase in the titer of antinuclear antibodies. In isolated cases, during treatment with ACE inhibitors, psoriatic rash, photosensitivity, alopecia, onycholysis and an increase in the frequency of vascular spasms in Raynaud's disease were detected. Nervous system Sometimes headache, fatigue may be noted, less often - confusion, depression , sleep disturbances, balance, impotence, paresthesia, tinnitus, blurred vision, as well as changes in taste or temporary loss of taste. Laboratory test indicators Sometimes a decrease in the concentration of hemoglobin in the blood, hematocrit, leukopenia and thrombocytopenia may be noted. Rarely, mainly in patients with impaired renal function, collagenosis, or while taking allopurinol, procainamide or immunosuppressants, thrombocytopenia, neutropenia, eosinophilia may develop, and in some cases - agranulocytosis, pancytopenia. Isolated cases of hemolytic anemia due to glucose-6-phosphate dehydrogenase deficiency have been reported, but a clear cause-and-effect relationship with the use of ACE inhibitors has not been established. Rarely, mainly in patients with impaired renal function, increased concentrations of urea, creatinine and potassium in the blood serum, as well as hyponatremia, may be noted. Hyperkalemia has sometimes been detected in patients with diabetes mellitus. Possible proteinuria, in some cases - hyperbilirubinemia and increased activity of liver enzymes in the blood plasma.

Quadropril

From the cardiovascular system: decreased blood pressure, orthostatic hypotension; in isolated cases - tachycardia, arrhythmias, angina pectoris, myocardial infarction, increased manifestations of peripheral circulatory failure.

From the genitourinary system: development or worsening of chronic renal failure, proteinuria, decreased potency.

From the nervous system: cerebral stroke, cerebral ischemia, dizziness, headache, weakness; when used in high doses - insomnia, anxiety, depression, confusion, fainting, paresthesia.

From the senses: disorders of the vestibular apparatus, hearing and vision impairment, tinnitus.

From the digestive system: nausea, diarrhea, cholestatic jaundice, dyspepsia, constipation, loss of appetite, stomatitis, glossitis, disturbance or temporary loss of taste, dry mouth, in isolated cases - intestinal obstruction.

From the respiratory system: “dry” cough, pulmonary infiltrates, bronchospasm, shortness of breath, rhinorrhea, pharyngitis, dysphonia.

Allergic reactions: skin rash, itching, urticaria, photosensitivity; angioedema of the tissues of the face, extremities, lips, tongue, glottis and/or larynx, exfoliative dermatitis, exudative erythema multiforme (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome).

From the hematopoietic organs: anemia, leukopenia, thrombocytopenia, rarely - eosinophilia, in isolated cases - agranulocytosis or pancytopenia.

Laboratory indicators: hypercreatininemia, increased urea concentration, increased activity of “liver” transaminases, hyperbilirubinemia, hyperkalemia, hyponatremia.

Effect on the fetus: impaired development of the fetal kidneys, decreased blood pressure in the fetus and newborns, impaired renal function, hyperkalemia, cranial hypoplasia, oligohydramnios, contracture of the limbs, cranial deformation, pulmonary hypoplasia.

Other: alopecia, onycholysis. Overdose. Symptoms: marked decrease in blood pressure, bradycardia, collapse, shock, water-electrolyte imbalance, acute renal failure, stupor.

Treatment: place the patient in the “lying” position with raised legs. In mild cases of overdose - gastric lavage, administration of adsorbents and sodium sulfate within 30 minutes after administration. When blood pressure decreases - intravenous administration of catecholamines, angiotensin II; for bradycardia - use of a pacemaker. Dialysis is effective.

Special instructions for the use of the drug Quadropril

With extreme caution and only subject to periodic monitoring of the relevant indicators of clinical and laboratory studies, Quadropril can be used for electrolyte imbalance, collagenosis (systemic lupus erythematosus, scleroderma), simultaneous treatment with corticosteroids, cytostatics, antimetabolites, allopurinol, procainamide or lithium salts, with severe proteinuria (1 g/day), liver dysfunction, severe renal failure (creatinine clearance 10–30 ml/min). During treatment with Quadropril, hemodialysis cannot be performed using polyacrylonitrile-methalylsulfonate high-performance membranes (for example AN 69), since there is a risk of developing hypersensitivity reactions (anaphylactoid reactions, anaphylactic shock). When performing plasmapheresis for severe hypercholesterolemia using dextran sulfate, hypersensitivity reactions may occur that threaten the patient's life. During a course of desensitization to bee or wasp venom, hypersensitivity reactions may develop (decreased blood pressure, shortness of breath, skin rash). Laboratory tests (see SIDE EFFECTS) must be monitored before and systematically during treatment with Quadropril. Due to the individual reaction to the drug, a decrease in the reaction rate may be noted, especially at the beginning of treatment, with increasing doses and simultaneous consumption of alcohol. With the development of angioedema spreading to the larynx, urgent subcutaneous administration of epinephrine in a dose of 0.3–0.5 mg or its slow intravenous administration in a dose of 0.1 mg under ECG and blood pressure monitoring, and the administration of corticosteroids are indicated. After this, intravenous administration of antihistamines is recommended. If jaundice occurs or if there is a significant increase in the activity of liver enzymes in the blood serum, the drug is discontinued.

Quadropril instructions for use

Antihypertensive drug. A metabolite of the active substance of the drug, spiraprilat, has pharmacological activity. An ACE inhibitor, an enzyme that converts angiotensin I into angiotensin II, which has a vasoconstrictor effect. In arterial hypertension, the therapeutic effect of Quadropril is due to the suppression of the renin-angiotensin-aldosterone system, which leads to a decrease in the concentration of angiotensin II and aldosterone, and increases the activity of renin in the blood plasma. The drug also inhibits the metabolism of bradykinin (vasopressor peptide). Quadropril reduces peripheral vascular resistance without causing clinically significant changes in renal plasma flow and glomerular filtration rate. The drug causes a decrease in blood pressure in the supine and standing positions without causing compensatory tachycardia. The hypotensive effect of the drug lasts more than 24 hours, which makes it possible to take Quadropril once a day.

Pharmacokinetics

Suction

After oral administration, approximately 45% of spirapril is absorbed from the gastrointestinal tract.
Cmax of spirapril in blood plasma is achieved after 45-90 minutes, and spiraprilat - 2-3 hours after taking Quadropril. The absolute bioavailability of spirapril is approximately 50%, and that of spiraprilat is approximately 70%. Distribution
About 90% of spirapril and spiraprilat are bound to plasma proteins.
The apparent Vd of spirapril averages 25 l. Metabolism
Spirapril is almost completely hydrolyzed in the liver to spiraprilat.
Excretion
The removal of spirapril from the body occurs in two phases, the first phase lasts 2 hours, the second - 40 hours. Spirapril and its active metabolite spiraprilat are excreted from the body in approximately equal parts with urine and feces. In healthy volunteers under Css conditions, about 44% of the dose is found in urine and about 51% in feces.

Indications

- arterial hypertension.

Dosage regimen

The initial daily dose of the drug is 3 mg (1/2 tablet), which is taken 1 time per day, in the morning. If necessary, the daily dose can be increased to 6 mg (1 tablet). The dose of the drug can be increased only after 3 weeks of treatment. The maintenance dose is, on average, 6 mg (1 tablet) per day. The duration of the course of treatment is determined by the doctor individually. For patients with impaired renal function

The dosage regimen is set depending on the creatinine clearance values: with a
clearance of 30-60 ml/min,
the drug is prescribed in average therapeutic doses, with
a clearance of 10-30 ml/min,
the recommended daily dose is 3 mg.
Treatment with the drug is started only under the condition of careful medical supervision of the patient. Depending on the indicators of kidney function, the daily dose of the drug can be increased to a maximum of 6 mg. If CC values ​​are less than 10 ml/min,
treatment with Quadropril is not carried out. Patients with impaired liver function, as well as elderly patients, do not require dose reduction. Quadropril can be taken before, during and after meals; The tablets should be taken without chewing, with a sufficient amount of liquid.

Side effect

From the cardiovascular system:

possible (mainly at the beginning of treatment, as well as in patients with a deficiency of mineral salts and fluid, weakened myocardial contractility, very high blood pressure) arterial hypotension (including orthostatic), accompanied by symptoms such as dizziness, weakness, visual disturbances;
rarely - fainting. Isolated cases of the following side effects occurring in connection with severe arterial hypotension when taking ACE inhibitors have been reported: tachycardia, cardiac arrhythmias, chest pain, myocardial infarction, transient cerebrovascular accident, stroke. From the urinary system:
possible occurrence or intensification of renal dysfunction, in isolated cases - up to acute renal failure;
rarely - proteinuria, partially with a simultaneous deterioration in renal function, increased concentrations of urea and creatinine in the blood plasma. From the respiratory system:
dry cough, bronchitis are possible;
in some cases - shortness of breath, sinusitis, rhinitis, bronchospasm. From the digestive system:
possible nausea, digestive disorders;
rarely - vomiting, diarrhea, constipation, lack of appetite, glossitis, dry mouth, cholestatic jaundice; in isolated cases - increased concentrations of bilirubin and liver enzymes in the blood, hepatitis, pancreatitis, intestinal obstruction. From the central nervous system and peripheral nervous system:
possible headache, feeling of fatigue;
rarely - confusion, depression, sleep disturbances, paresthesia, imbalance, tinnitus, visual disturbances, changes in taste or temporary loss of taste. From the hematopoietic system:
possible decrease in hemoglobin levels, hematocrit, leukopenia, thrombocytopenia;
rarely (mainly in predisposed patients) - anemia, eosinophilia; in isolated cases - agranulocytosis or pancytopenia. Dermatological reactions:
in some cases - psoriatic skin rashes, itching, photosensitivity, alopecia, onycholysis.
Allergic reactions:
skin reactions such as exanthema are possible;
rarely - urticaria, angioedema involving the lips, face and/or limbs (in isolated cases - involving the larynx, pharynx and/or tongue); severe skin reactions, such as exudative erythema multiforme, accompanied by fever, myalgia, arthralgia, vasculitis, eosinophilia and/or increased titer of antinuclear antibodies. Other:
impotence, increased potassium concentration and decreased sodium concentration in blood plasma.

Contraindications

– history of angioedema; – stenosis of the renal arteries (both or one kidney); – severe renal dysfunction (creatinine clearance less than 10 ml/min); – condition after kidney transplantation; – stenosis of the aortic or mitral valve (with hemodynamic disturbances); – hypertrophic cardiomyopathy (with hemodynamic disturbances); – primary hyperaldosteronism; – pregnancy; – lactation (breastfeeding); – hypersensitivity to the components of the drug.

Pregnancy and lactation

Quadropril is contraindicated for use during pregnancy. If it is necessary to use Quadropril during lactation, the issue of stopping breastfeeding should be decided. Use of Quadropril in women of childbearing age

begin after excluding pregnancy. During treatment with Quadropril, effective methods of contraception should be used. If pregnancy occurs during treatment with Quadropril, therapy should be changed, because When taking Quadropril, especially in the second and third trimesters of pregnancy, intrauterine damage to the fetus may occur.

special instructions

With extreme caution, subject to regular medical monitoring, the drug is prescribed to patients with chronic heart failure in the decompensation phase, severe arterial hypertension, water and electrolyte imbalances, systemic connective tissue diseases, severe renal dysfunction (creatinine clearance 10 ml/min) and proteinuria ( more than 1 g/day), as well as in elderly patients. These categories of patients have an increased risk of developing side effects (including those from the hematopoietic system), and a sharp drop in blood pressure is also possible at the beginning of therapy. Patients with water-electrolyte imbalances, severe arterial hypertension and chronic heart failure should, before starting therapy, replenish the deficiency of mineral salts and/or fluids and carry out therapy correction. In such cases, it is preferable to select the dose of Quadropril in a hospital, subject to constant medical supervision for 6 hours after taking the drug. If fever, swollen lymph nodes and/or sore throat occur during treatment with Quadropril, the leukocyte count should be immediately determined. Rarely, during treatment with ACE inhibitors, a syndrome has been observed that begins with cholestatic jaundice and progresses to liver necrosis (sometimes with death). The cause of this syndrome is unknown. In this regard, if jaundice appears or if there is a clear increase in the level of liver enzymes in the blood, treatment with ACE inhibitors should be discontinued; Careful medical supervision of the patient is necessary. With long-term use of the drug in the recommended daily dose, addiction to it does not develop. Short-term withdrawal of Quadropril does not lead to a rapid, sharp increase in blood pressure (withdrawal phenomenon). In patients with diabetes mellitus, while taking Quadropril, an increase in potassium levels in the blood plasma and an increase in proteinuria were observed. Isolated cases of hemolysis and/or hemolytic anemia have been reported (especially in patients with glucose-6-phosphate dehydrogenase deficiency), but a clear cause-and-effect relationship with the prescription of ACE inhibitors has not been established. During treatment with Quadropril, hemofiltration or plasmapheresis should not be performed using a polyacrylonitrile metallyl sulfonate high-flux membrane, because During the procedure, there is a risk of hypersensitivity reactions, including the development of anaphylactic shock. Therefore, if emergency dialysis or hemofiltration is necessary, the patient should be prescribed an antihypertensive drug of a different group (not an ACE inhibitor) or use a different dialysis membrane. When using ACE inhibitors during desensitizing therapy against insect venom (for example, bee or wasp stings), anaphylactoid reactions may develop, sometimes life-threatening to the patient (for example, a drop in blood pressure, shortness of breath, vomiting, skin rash). For patients receiving cytostatics, antimetabolites, allopurinol, procainamide, lithium preparations, Quadropril should be prescribed with caution, under constant monitoring of laboratory parameters, due to the increased risk of side effects (including from the hematopoietic system). Drinking alcohol while using Quadropril causes a sharper decrease in blood pressure and an increase in the effect of alcohol. Control of laboratory parameters

Before starting therapy with Quadropril and systematically during treatment, it is necessary to conduct a general blood test and monitor the content of electrolytes, urea and creatinine, as well as bilirubin and liver enzymes in the blood plasma.
Use in pediatrics
The safety and effectiveness of the drug in children have not been established.
Results of experimental studies
Carcinogenicity studies of spirapril in rats and mice did not provide data of relevance to humans.
In studies of spirapril for gene mutations conducted in vitro and for chromosomal aberrations performed in vivo, negative results were obtained. On the contrary, spirapril in very high toxic doses causes chromosomal aberrations in vitro. This effect is probably not due to direct interaction of spirapril with DNA. Therefore, when used therapeutically, the mutagenic effect of spirapril on humans can be excluded with complete certainty. Effect on the ability to drive vehicles and operate machinery
Since the drug can (especially at the beginning of treatment, when increasing the dose and replacing one drug with another, as well as while drinking alcohol) cause a decrease in the ability to concentrate, outpatients should be careful when participating in street activities. movement, maintenance of machines and mechanisms.

Overdose

Symptoms:

severe arterial hypotension, bradycardia, collapse, water and electrolyte imbalance, renal failure.
Treatment:
along with general therapeutic measures aimed at removing spirapril from the body (gastric lavage, use of adsorbent substances and sodium sulfate in the first 30 minutes after taking the drug), monitoring of the vital functions of the body should be established in the intensive care unit and, if necessary, carried out correction. In case of severe arterial hypotension, first of all, the deficiency of mineral substances and the volume of circulating blood in the body should be compensated, then, if necessary, catecholamines can be additionally administered intravenously. For bradycardia that does not respond to drug therapy, an artificial pacemaker should be implanted. It is necessary to constantly monitor the concentration of electrolytes and creatinine in the blood plasma. Spirapril and spiraprilat are eliminated from the body by dialysis.

Drug interactions

With simultaneous use of Quadropril with other antihypertensive drugs (especially diuretics), an increase in the hypotensive effect of Quadropril is observed. With the simultaneous use of Quadropril and sodium chloride, NSAIDs (for example, acetylsalicylic acid, indomethacin), the hypotensive effect of Quadropril may be reduced. When using drugs for anesthesia and local anesthesia during therapy with Quadropril, the risk of a sharp drop in blood pressure increases. With simultaneous use, Quadropril enhances the hypoglycemic effect of insulin and oral antidiabetic agents (biguanides, sulfonylurea derivatives). When Quadropril is used together with allopurinol, cytostatics, immunosuppressants, systemic corticosteroids, procainamide, the risk of developing leukopenia increases. Pharmacokinetic interaction

With simultaneous use of Quadropril with potassium preparations, potassium-sparing diuretics (for example, spironolactone, amiloride, triamterene), as well as with other drugs that, in turn, can increase the concentration of potassium in the blood plasma (for example, heparin), a pronounced increase in potassium concentration may be observed in blood plasma. Quadropril, when used simultaneously with lithium, causes an increase in the concentration of lithium in the blood plasma.

Storage conditions and periods

The drug should be stored at a temperature not exceeding 25°C. Shelf life: 3 years. Conditions for dispensing from pharmacies

The drug is available with a prescription.

Interactions of the drug Quadropril

When prescribed simultaneously with antihypertensive drugs, the hypotensive effect may be enhanced; with analgesics and NSAIDs, the hypotensive effect of Quadropril may be weakened; with potassium, potassium-sparing diuretics (spironolactone, amiloride, triamterene), as well as with other drugs that can increase the concentration of potassium in the blood serum (for example, heparin) - severe hyperkalemia; with lithium compounds - an increase in the concentration of lithium in the blood serum (systematic monitoring of the level of lithium in the blood serum is necessary); with sleeping pills, narcotics - severe arterial hypotension (the anesthesiologist should be informed that the patient is taking an ACE inhibitor); with allopurinol, procainamide, cytostatic, immunosuppressive drugs, corticosteroids for systemic use - leukopenia; with insulin, oral hypoglycemic agents (biguanides, sulfonylureas, acarbose) - severe hypoglycemia. Abuse of table salt may reduce the hypotensive effect of Quadropril. Simultaneous intake of alcohol enhances the hypotensive effect.

Overdose of the drug Quadropril, symptoms and treatment

Depending on the degree of overdose, the following symptoms may be noted: severe arterial hypotension, bradycardia, collapse, electrolyte imbalance, and renal failure. Gastric lavage, the use of enterosorbents and sodium sulfate in the first 30 minutes after an overdose, monitoring and maintaining vital body functions (respiration, cardiac activity) are indicated. Quadropril can be removed from the body by hemodialysis. In case of severe arterial hypotension, restoration of bcc with the help of intravenous infusion of isotonic sodium chloride solution is indicated. If the effect is insufficient, catecholamines are administered intravenously. In case of severe bradycardia, which cannot be corrected with medication, a temporary cardiac pacemaker is installed. The level of electrolytes and creatinine in the blood serum is constantly monitored.