Perineva pills 4mg №30

Packaging

Indications and usage

- Arterial hypertension.
- Chronic heart failure.
- Prevention of recurrent stroke (as part of complex therapy with indapamide) in patients with a history of cerebrovascular diseases (stroke or transient cerebral ischemic attack).
- Stable coronary artery disease: reducing the risk of cardiovascular complications in patients who have previously had myocardial infarction and / or coronary revascularization.

Contraindications

- Angioedema in history (hereditary, idiopathic or angioedema due to the use of ACE inhibitors).
- Age up to 18 years (efficacy and safety have not been established).
- Hereditary intolerance to galactose, lactase deficiency lapp or malabsorption syndrome glucose-galactose.
- Hypersensitivity to the drug.
- Hypersensitivity to other ACE inhibitors.

Caution should be used when:

- Renovascular hypertension.
- In patients with bilateral renal artery stenosis.
- Stenosis of the artery of a single kidney - the risk of severe arterial hypotension and renal failure.
- With chronic heart failure in the stage of decompensation.
- Arterial hypotension.
- Chronic renal failure (CC less than 60 ml / min).
- Significant hilovolemia and hyponatremia (salt-free diet and / or previous diuretic therapy, dialysis, vomiting, diarrhea).
- Cerebrovascular diseases (including cerebrovascular insufficiency, coronary artery disease, coronary insufficiency) - the risk of an excessive decrease in blood pressure.
- Aortic stenosis or mitral valve.
- Hypertrophic obstructive cardiomyopathy.
- Hemodialysis using high-flow polyacrylonitrile membranes - the risk of anaphylactoid reactions.
- In patients after kidney transplantation - there is no experience of clinical use.
- Before the procedure for apheresis LDL.
- Simultaneously with the conduct of desensitizing therapy with allergens (for example, hymenoptera poison) - the risk of anaphylactoid reactions.
- Diseases of the connective tissue (including SLE, scleroderma).
- Oppression of bone marrow hematopoiesis on the background of taking immunosuppressants, Allopurinol or procainamide - the risk of developing agranulocytosis and neutropenia.
- Congenital deficiency of glucose-6-phosphate dehydrogenase - isolated cases of hemolytic anemia.
- The representatives of the Negroid race - the risk of anaphylactoid reactions.
- Surgical intervention (the need for general anesthesia) - the risk of excessive blood pressure reduction.
- Diabetes mellitus (requires control of glucose concentration in the blood).
- Hyperkalemia.
- In elderly patients.

Pregnancy and Breastfeeding

In pregnancy, the use of the drug is contraindicated. When pregnancy is confirmed, Perineva should be discontinued as soon as possible. Use in the II and III trimesters of pregnancy can cause fetotoksicheskie effects (reduced kidney function, oligohydramnios, delayed ossification of the fetal bones of the skull) and neonatal toxic effects (renal failure, arterial hypotension, hyperkalemia). In the case of the drug in the II and III trimesters of pregnancy, an ultrasound examination of the kidneys and bones of the fetal skull is necessary.

The use of the drug Perineva during lactation is not recommended, due to the lack of data on the possibility of penetration of Perindopril into breast milk. If necessary, the use of the drug during lactation breastfeeding should be discontinued.

Dosage and administration

The drug is administered orally 1 time / day, before meals, preferably in the morning. The dose is selected individually for each patient, depending on the severity of the disease and the individual response to treatment.

Arterial hypertension: Perineva can be used as monotherapy or in combination with other antihypertensive drugs. The recommended initial dose is 4 mg / day. For patients with marked activation of the RAAS (for example, in renovascular hypertension,hypovolemia and / or hyponatremia, chronic heart failure in the stage of decompensation or severe hypertension), the recommended initial dose is 2 mg / day. With the ineffectiveness of therapy during the month, the dose can be increased to 8 mg / day in 1 dose with good tolerability of the previous dose. The addition of ACE inhibitors to patients taking diuretics may cause arterial hypotension. In this regard, it is recommended to carry out therapy with caution, stop taking diuretics 2-3 days before starting treatment with Perineva or start treatment with Perineva with an initial dose of 2 mg / day. The control of blood pressure, kidney function and the concentration of potassium ions in the serum. In the future, the dose of the drug may be increased depending on the dynamics of blood pressure levels. If necessary, diuretic therapy can be resumed. In elderly patients, the recommended initial dose is 2 mg / day. In the future, the dose can be gradually increased to 4 mg and, if necessary, up to a maximum of 8 mg / day, provided that the lower dose is well tolerated.

Chronic heart failure: The recommended starting dose is 2 mg / day in the morning, under medical supervision. After 2 weeks, the dose may be increased to 4 mg / day in 1 dose, under the control of blood pressure. Treatment of chronic heart failure with clinical manifestations is usually combined with potassium-sparing diuretics,beta-blockers and / or Digoxin. In patients with chronic heart failure, with renal insufficiency and with a tendency to electrolyte disturbances (hyponatremia), as well as in patients taking diuretics and / or vasodilators at the same time, the drug treatment is started under strict medical supervision. In patients with a high risk of developing clinically severe arterial hypotension (for example, when taking high doses of diuretics), if possible, before starting the drug Perineva, it is necessary to eliminate hypovolemia and electrolyte disturbances. It is recommended that before starting therapy and during it, carefully monitor the level of blood pressure, the state of kidney function and the concentration of potassium ions in serum.

Prevention of recurrent stroke in patients with cerebrovascular diseases in history: treatment with Perineva should be started with 2 mg for the first 2 weeks before taking Indapamide. Treatment should begin at any time (from 2 weeks to several years) after a stroke.

Stable IHD: in patients with stable ischemic heart disease, the recommended initial dose of Perineva is 4 mg / day. After 2 weeks, the dose is increased to 8 mg / day, provided that the dose of 4 mg / day is well tolerated and the kidney function is monitored.

Treatment of Elderly Patients should start with a dose of 2 mg, which in a week can be increased to 4 mg / day. In the future, if necessary, a week later, the dose can be increased to 8 mg / day with the obligatory preliminary control of renal function.In elderly patients, the dose of the drug can be increased only with good tolerability of the previous, lower dose.

In patients with kidney disease The dose of Perineva is determined depending on the degree of renal dysfunction. During treatment should regularly monitor the content of potassium ions and creatinine in the serum. Recommended doses are presented in the table.

The dialysis clearance of perindoprilat is 70 ml / min. The drug Perineva must be taken after a session of dialysis.

Patients with liver disease dose adjustment is not required.

Adverse Effects

Nervous system: often - headache, dizziness, paresthesia; sometimes - sleep or mood disorders; very rarely - confusion.

Special senses: often - visual disturbances, tinnitus.

Cardiovascular: often - a pronounced decrease in blood pressure; very rarely - arrhythmias, stenocardia, myocardial infarction or stroke, possibly secondary, due to severe arterial hypotension in high-risk patients; vasculitis (frequency unknown).

On the part of the respiratory system: often - cough, shortness of breath; sometimes bronchospasm; very rarely - eosinophilic pneumonia, rhinitis.

From the digestive system: often - nausea, vomiting, abdominal pain, dysgeusia, dyspepsia , diarrhea, constipation; sometimes dryness of the oral mucosa; rarely - pancreatitis; very rarely - cytolytic or cholestatic hepatitis.

From the genitourinary system: sometimes - renal failure, impotence; very rarely, acute renal failure.

From the hematopoietic system and lymphatic system: very rarely - with prolonged use in high doses, hemoglobin and hematocrit may decrease, thrombocytopenia, leukopenia / neutropenia, agranulocytosis, pancytopenia; very rarely, hemolytic anemia (in patients with congenital glucose-6-phosphate dehydrogenase deficiency).

Metabolism: increased serum urea and plasma creatinine levels, hyperkalemia, reversible after discontinuation of the drug (especially in patients with renal failure, severe chronic heart failure and renovascular hypertension); rarely - increased activity of liver enzymes and serum bilirubin; hypoglycemia.

From the skin: often - skin rash, itching; sometimes - increased sweating, angioedema of the face, extremities, urticaria; very rarely - erythema multiforme.

Other: often - asthenia, muscle cramps.

Influence on ability to drive motor transport and control mechanisms: it is necessary to consider the possibility of arterial hypotension or dizziness, which may affect the management of vehicles and work with technical means.

In patients with coronary artery disease with the development of an episode of unstable angina (significant or not) during the first month of treatment with Perineva, it is necessary to estimate the benefit / risk ratio.

In the treatment of hypertension, ACE inhibitors can cause a sharp decrease in blood pressure. In patients with uncomplicated arterial hypertension, symptomatic hypotension rarely occurs after taking the first dose. The risk of excessive blood pressure reduction is increased in patients with reduced BCC during diuretic therapy, with a strict salt-free diet, hemodialysis, as well as with diarrhea or vomiting, or in patients with severe renin-dependent arterial hypertension. Severe arterial hypotension was observed in patients with severe chronic heart failure, both in the presence of concomitant renal failure and in its absence. The most frequently pronounced arterial hypotension can develop in patients with more severe chronic heart failure, receiving “loop” diuretics in high doses, and also against the background of hyponatremia or renal failure. Such patients are advised to have a thorough medical observation at the beginning of therapy and when titrating doses of the drug. The same applies to patients with coronary artery disease or cerebrovascular diseases in which an excessive decrease in blood pressure can lead to myocardial infarction or cerebrovascular complications. In the event of arterial hypotension, it is necessary to give the patient a horizontal position with the legs elevated, and, if necessary, in / into the sodium chloride solution to increase the BCC.Transient arterial hypotension is not a contraindication for further therapy. After the restoration of BCC and blood pressure treatment can be continued, provided that the dose of the drug is carefully selected.

In some patients with chronic heart failure and normal or low blood pressure during therapy with Perineva, an additional decrease in blood pressure may occur. This effect is expected and usually is not a reason to discontinue the drug. If arterial hypotension is accompanied by clinical manifestations, it may be necessary to reduce the dose or cancel the drug Perineva.

ACE inhibitors, incl. perindopril, should be used with caution in patients with mitral valve stenosis and obstruction of the outflow tract of the left ventricle.

In patients with symptomatic heart failure, hypotension that develops during the initial period of therapy with ACE inhibitors can lead to a deterioration in renal function. In these patients, there have sometimes been cases of acute renal failure, usually reversible.

Some patients with bilateral renal artery stenosis or renal artery stenosis of a single kidney (especially in the presence of renal failure) during therapy with ACE inhibitors showed an increase in serum concentrations of urea and creatinine, reversible after discontinuation of therapy. In patients with renovascular hypertension during therapy with ACE inhibitors, there is an increased risk of developing severe arterial hypotension and renal failure.Treatment of such patients should begin under close medical supervision, with small doses of the drug and with further adequate dose selection. During the first weeks of treatment with Perineva, diuretics should be discontinued and kidney function should be regularly monitored. In some patients with arterial hypertension in the presence of previously undetected renal failure, especially with concomitant diuretic therapy, there was a slight and temporary increase in the concentration of urea and creatinine in the blood serum. In this case, it is recommended to reduce the dose of the drug Perineva and / or cancel diuretic drugs.

In patients on dialysis using high-flow membranes, and taking both ACE inhibitors, there have been several cases of persistent, life-threatening Anaphylactic reactions. If hemodialysis is needed, a different type of membrane must be used.

Experience with perindopril in patients with recent kidney transplantation is absent.

Rarely in patients who have taken ACE inhibitors, incl. perindopril, developed angioedema of the face, extremities, lips, mucous membranes, tongue, glottis and / or larynx. This condition can develop at any time of treatment. With the development of angioedema, treatment should be immediately stopped, the patient should be under medical supervision until the symptoms disappear.Angioedema of the lips and face usually does not require treatment; antihistamines can be used to reduce the severity of symptoms. Angioedema of the tongue, glottis, or larynx can be fatal. With the development of angioneurotic edema , epinephrine (adrenaline) should be immediately subcutaneously injected and the airways passable. Patients with a history of angioedema, not associated with the use of ACE inhibitors, have a higher risk of developing angioedema when taking an ACE inhibitor.

In patients with the appointment of ACE inhibitors against the background of the procedure for the apheresis of LDL using dextran-sulfate absorption, in rare cases it is possible the development of an anaphylactic reaction. The temporary cancellation of an ACE inhibitor is recommended before each apheresis procedure.

Patients receiving ACE inhibitors during a course of desensitization (for example, hymenoptera poison), in very rare cases, may develop life-threatening anaphylactic reactions. It is recommended that the ACF inhibitor be temporarily canceled prior to each desensitization procedure.

During therapy with ACE inhibitors, it is sometimes possible to develop a syndrome that begins with cholestatic jaundice and then progresses to fulminant hepatic necrosis, sometimes with a fatal outcome. The mechanism for the development of this syndrome is unclear. If while taking an ACE inhibitor jaundice appears or an increase in liver enzyme activity is observed, the ACE inhibitor should be immediately discontinued, and the patient should be under close supervision.It is also necessary to conduct an appropriate survey.

Cases of the development of neutropenia / agranulocytosis, thrombocytopenia and anemia were noted in patients on the background of therapy with ACE inhibitors. With normal kidney function in the absence of other complications, neutropenia rarely develops. Perineva should be used with great caution in patients with systemic connective tissue diseases (for example, SLE, scleroderma) who are simultaneously receiving immunosuppressive therapy, allopurinol or procainamide, as well as when combining all these factors, especially if there is an impaired renal function. Such patients may develop severe infections that are not susceptible to intensive antibiotic therapy. When conducting treatment with Perinev's drug in patients with the above factors, it is recommended to periodically monitor the number of leukocytes in the blood and warn the patient about the need to inform the doctor about the appearance of any symptoms of infection.

In patients with congenital glucose-6-phosphate dehydrogenase deficiency, isolated cases of hemolytic anemia were observed.

The risk of developing angioedema in patients of the Negroid race is higher. Like other ACE inhibitors, perindopril is less effective in reducing blood pressure in patients of the Negroid race, possibly because of the higher prevalence of low-Robin conditions in the population of this group of patients with arterial hypertension.

During therapy with ACE inhibitors, a persistent, unproductive cough may develop, which stops after discontinuation of the drug. This should be considered in the differential diagnosis of cough.

In patients whose condition requires extensive surgical intervention or anesthesia with drugs that cause arterial hypotension, ACE inhibitors, including perindopril, can block the formation of angiotensin II during compensatory renin release. The day before surgery, ACE inhibitor therapy should be canceled. If the ACE inhibitor cannot be canceled, then the hypotension that develops according to the described mechanism can be corrected by an increase in the BCC.

During therapy with ACE inhibitors, including perindopril, some patients may increase the concentration of potassium ions in the blood. The risk of hyperkalemia is increased in patients with renal and / or heart failure, decompensated diabetes mellitus, and in patients using potassium-sparing diuretics, potassium preparations, or other drugs that cause hyperkalemia (for example, heparin). If necessary, the simultaneous appointment of these drugs, it is recommended to regularly monitor the content of potassium in the serum.

In patients with diabetes who are taking hypoglycemic agents for oral administration or insulin , in the first few months of therapy with ACE inhibitors, it is necessary to carefully monitor the concentration of glucose in the blood.

Joint administration of lithium and perindopril is not recommended. Not recommended for combined use with ACE inhibitors.Perinev tablets contain lactose. Therefore, patients with hereditary intolerance to galactose, lactase-deficient lapp or glucose-galactose malabsorption syndrome should not take this drug.

In patients taking diuretics, especially with excessive removal of fluid and / or sodium, at the beginning of therapy with ACE inhibitors, excessive arterial hypotension may develop. The risk of excessive arterial hypotension can be reduced by discontinuing the diuretic, intravenous administration of a 0.9% sodium chloride solution, and also prescribing an ACE inhibitor in lower doses. A further increase in the dose of perindopril should be carried out with caution.

Usually, during therapy with ACE inhibitors, the concentration of potassium in the blood serum remains within the normal range, but in some patients hyperkalemia may develop. Combined use of ACE inhibitors and potassium-sparing diuretics (for example, spironolactone, triamterene, or amiloride), potassium or potassium supplements, and nutritional supplements can cause hyperkalemia. Therefore, it is not recommended to combine perindopril with these drugs. These combinations should be prescribed only in the case of hypokalemia, observing precautions and regularly monitoring the concentration of potassium ions in the blood serum.

With the simultaneous use of lithium preparations and ACE inhibitors, a reversible increase in serum lithium concentrations and lithium toxicity may develop.With simultaneous use of ACE inhibitors with thiazide diuretics, it is possible to further increase the concentration of lithium in the blood serum and increase the risk of developing its toxic effects. Simultaneous use of perindopril and lithium is not recommended. If necessary, such a combination therapy, it is carried out under regular control of the concentration of lithium in the serum.

NSAID therapy may weaken the antihypertensive effect of ACE inhibitors. In addition, NSAIDs and ACE inhibitors have an additive effect on increasing the concentration of potassium ions in the serum, which can cause deterioration of renal function. This effect is usually reversible. In rare cases, acute renal failure may develop, especially in patients with an existing renal dysfunction, for example, in elderly patients or against the background of dehydration.

With simultaneous use of perindopril with other antihypertensive agents, it is possible to enhance the antihypertensive effect of perindopril. The simultaneous use of Nitroglycerin , other nitrates or vasodilators can lead to an additional hypotensive effect.

The simultaneous use of ACE inhibitors and hypoglycemic agents (insulin or hypoglycemic agents for oral administration) can enhance the hypoglycemic effect, up to the development of hypoglycemia. As a rule, this phenomenon occurs in the first weeks of combination therapy in patients with renal insufficiency.

Perindopril can be combined with Acetylsalicylic acid (as an antiplatelet agent), thrombolytic agents and beta-blockers and / or nitrates.

Combined use with ACE inhibitors can lead to increased hypotensive effect.

Sympathomimetics can weaken the antihypertensive effect of ACE inhibitors. In the appointment of such a combination should regularly evaluate the effectiveness of ACE inhibitors.

Symptoms: pronounced decrease in blood pressure, shock, impaired water and electrolyte balance (hyperkalemia, hyponatremia), renal failure, hyperventilation, tachycardia, palpitations, bradycardia, dizziness, anxiety, cough.
Treatment: with a pronounced decrease in blood pressure - give the patient a horizontal position with raised legs and take measures to replenish the BCC, if possible in / in the introduction of angiotensin II and / or in / in the introduction of catecholamines. With the development of severe bradycardia, which is not amenable to drug therapy (including atropine), the installation of an artificial pacemaker (pacemaker) is shown. It is necessary to monitor the vital functions and the content of creatinine and electrolytes in the serum. Perindopril can be removed from the systemic circulation by hemodialysis. The use of high-flow polyacrylonitrile membranes should be avoided.

Store at a temperature not higher than 30 ° C.