Description
Release form
Tablets, film-coated green, round, biconvex, engraved on one side 10, on the other side T on the transverse section – the core is white or almost white.
Pharmacological action
ACE inhibitor. It is a prodrug from which the active metabolite perindoprilat is formed in the body. It is believed that the mechanism of antihypertensive action is associated with competitive inhibition of ACE activity, which leads to a decrease in the rate of conversion of angiotensin I to angiotensin II, which is a powerful vasoconstrictor. As a result of a decrease in the concentration of angiotensin II, a secondary increase in plasma renin activity occurs due to the elimination of negative feedback during renin release and a direct decrease in aldosterone secretion. Due to its vasodilating effect, it reduces the OPSS (afterload), jamming pressure in the pulmonary capillaries (preload) and resistance in the pulmonary vessels increases cardiac output and exercise tolerance.
The antihypertensive effect develops within the first hour after taking perindopril, reaches a maximum after 4-8 hours and lasts for 24 hours.
In clinical studies with perindopril (monotherapy or in combination with a diuretic), a significant reduction in the risk of recurrent stroke (as ischemic and hemorrhagic), as well as the risk of fatal or disability-related strokes of the main cardiovascular complications, including myocardial infarction, including fatal dementia associated with stroke severe deterioration in cognitive function. These therapeutic benefits were noted both in patients with arterial hypertension and in normal blood pressure, regardless of age, gender, presence or absence of diabetes mellitus, and the type of stroke.
It has been shown that with the use of perindopril tertbutylamine at a dose of 8 mg / day (equivalent to 10 mg of perindopril arginine) in patients with stable coronary artery disease, there is a significant decrease in the absolute risk of complications stipulated by the main criterion of effectiveness (mortality from cardiovascular diseases, the frequency of non-fatal myocardial infarction and / or cardiac arrest followed by successful resuscitation) by 1.9%. In patients who had previously undergone myocardial infarction or coronary revascularization, the reduction in absolute risk was 2.2% compared with the placebo group.
Perindopril is used both as monotherapy and in the form of fixed combinations with indapamide, with amlodipine.
Pharmacokinetics of
After oral administration, perindopril is rapidly absorbed from the gastrointestinal tract. Cmax is reached after 1 h. Bioavailability is 65-70%.
In the process of metabolism, perindopril is biotransformed with the formation of an active metabolite – perindoprilat (about 20%) and 5 inactive compounds. Cmax of perindoprilat in plasma is reached between 3 and 5 hours after administration. The binding of perindoprilat to plasma proteins is insignificant (less than 30%) and depends on the concentration of the active substance. Vd of free perindoprilat is close to 0.2 l / kg.
Does not cumulate. Repeated administration does not lead to cumulation and T1 / 2 corresponds to the period of its activity.
When taken with food, perindopril metabolism slows down.
T1 / 2 of perindopril is 1 hour.
Perindoprilat is excreted by the kidneys of T1 / 2 of its free fraction is 3-5 hours.
In elderly patients, as well as in renal and heart failure, perindoprilat excretion is slowed down.
Indications
Chronic heart failure.
Prevention of re-stroke (combination therapy with indapamide) in patients who have had a stroke or transient ischemic type of cerebrovascular accident.
Stable coronary artery disease: reducing the risk of cardiovascular complications in patients with stable coronary artery disease.
Contraindications
History of angioedema, simultaneous use with aliskiren and aliskiren-containing drugs in patients with diabetes mellitus or impaired renal function (GFR
Use during pregnancy and lactation
Perindopril is contraindicated in pregnancy and lactation (breastfeeding).
Special instructions
Caution is advised to use perindopril in case of bilateral renal artery stenosis or renal artery stenosis of a single kidney renal failure systemic connective tissue therapy with immunosuppressive drugs, allopurinol, procainamide (risk of neutropenia, reduced agranulocytosis with diuretic diuretic) , vomiting, diarrhea) angina pectoris cerebrovascular diseases of renovascular hypertension diabetes mellitus chronic heart failure ochnosti IV NYHA functional class classification simultaneously with potassium-sparing diuretics, potassium supplements, potassium-containing salt substitutes food, with lithium preparations for hyperkalemia, surgical intervention / general anesthesia of hemodialysis using high-flow membranes of desensitizing therapy for LDL apheresis after kidney transplantation, aortic stenosis / mitral stenosis / hypertrophic obstructive cardiomyopathy in patients of the Negroid race.
Cases of arterial hypotension, syncope, stroke, hyperkalemia, and impaired renal function (including acute renal failure) have been reported in predisposed patients, especially when used concomitantly with drugs that affect RAAS. Therefore, the double blockade of RAAS as a result of the combination of an ACE inhibitor with an angiotensin II receptor antagonist or aliskiren is not recommended.
Before starting treatment with perindopril, a study of renal function is recommended for all patients.
During treatment with perindopril, renal function, liver enzyme activity in the blood should be regularly monitored, peripheral blood tests should be performed (especially in patients with diffuse connective tissue diseases, in patients who receive immunosuppressive drugs, allopurinol). Before starting treatment, patients with sodium and fluid deficiency should be corrected for water-electrolyte disturbances.
Composition
1 tab. perindopril
(in the form of tosylate) 10 mg
Excipients: lactose monohydrate – 143.924 mg, corn starch – 5.4 mg, sodium bicarbonate – 3.172 mg, pregelatinized corn starch – 14.4 mg, povidone K30 – 3.6 mg, magnesium stearate – 1.8 mg.
Shell composition: Opabrai II green 85F210013 (partially hydrolyzed polyvinyl alcohol 3.6 mg, titanium dioxide (E171) 2.133 mg, macrogol-3350 1.818 mg, talc 1.332 mg, indigo carmine (E132) 0.0495 mg, brilliant blue dye ( E133) – 0.0315 mg, iron dye oxide yellow (E172) – 0.018 mg, quinoline yellow dye (E104) – 0.018 mg).
Dosage and administration
Initial dose – 1-2 mg / day in 1 dose. Maintenance doses – 2-4 mg / day for congestive heart failure, 4 mg (less often – 8 mg) – for arterial hypertension in 1 dose.
In case of impaired renal function, a correction of the dosage regimen is required depending on the QC values.
Side effects of
From the hematopoietic system: eosinophilia, decreased hemoglobin and hematocrit, thrombocytopenia, leukopenia / neutropenia, agranulocytosis, pancytopenia, hemolytic anemia in patients with congenital glucose-phosphate deficiency.
From the side of metabolism: hypoglycemia, hyperkalemia, reversible after drug withdrawal, hyponatremia.
From the nervous system: paresthesia, headache, dizziness, vertigo, sleep disturbances, lability of mood, drowsiness, fainting, confusion.
From the sensory organs: visual impairment, tinnitus.
From the cardiovascular system: excessive decrease in blood pressure and related symptoms, vasculitis, tachycardia, palpitations, heart rhythm disturbances, angina pectoris, myocardial infarction and stroke, possibly due to an excessive decrease in blood pressure in high-risk patients.
From the respiratory system: cough, shortness of breath, bronchospasm, eosinophilic pneumonia, rhinitis.
From the digestive system: constipation, nausea, vomiting, abdominal pain, taste disorder, dyspepsia, diarrhea, dry oral mucosa, pancreatitis, hepatitis (cholestatic or cytolytic).
From the skin and subcutaneous fat: itching, rash, photosensitivity, pemphigus, increased sweating.
Allergic reactions: angioedema, urticaria, erythema multiforme.
From the musculoskeletal system: muscle spasms, arthralgia, myalgia.
From the urinary system: renal failure, acute renal failure.
From the reproductive system: erectile dysfunction.
General reactions: asthenia, chest pain, peripheral edema, weakness, fever, falls.
On the part of laboratory parameters: increased activity of hepatic transaminases and bilirubin in blood serum, increased concentration of urea and creatinine in blood plasma.
Drug interactions
The risk of developing hyperkalemia increases with the simultaneous use of perindopril with other drugs that can cause hyperkalemia: aliskiren and aliskiren containing drugs, potassium salts, potassium-sparing diuretics, ACE inhibitors, antagonists of heparin receptors, antipsychotens, or tacrolimus, trimethoprim.
With simultaneous use with aliskiren in patients with diabetes mellitus or impaired renal function (GFR
, simultaneous use with aliskiren in patients without diabetes mellitus or impaired renal function is not recommended, since the risk of hyperkalemia may increase, impaired renal function and increased incidence of cardiovascular morbidity and mortality.
It has been reported in the literature that in patients with established atherosclerotic disease, heart failure, or diabetes mellitus with target organ damage, concomitant therapy with an ACE inhibitor and an angiotensin II receptor antagonist is associated with a higher incidence of hypotension, syncope, hyperkalemia, and impaired renal function (including acute renal failure) compared with the use of only one drug that affects RAAS. Double blockade (for example, when combining an ACE inhibitor with an angiotensin II receptor antagonist) should be limited to individual cases with careful monitoring of renal function, potassium content and blood pressure.
Concomitant use with estramustine may increase the risk of side effects, such as angioedema.
With the simultaneous use of lithium and perindopril preparations, a reversible increase in serum lithium concentration and the associated toxic effects are possible (this combination is not recommended).
Concomitant use with hypoglycemic drugs (insulin, hypoglycemic agents for oral administration) requires special care, as ACE inhibitors, including perindopril, may enhance the hypoglycemic effect of these drugs up to the development of hypoglycemia. As a rule, this is observed in the first weeks of concurrent therapy and in patients with impaired renal function.
Baclofen enhances the antihypertensive effect of perindopril, with simultaneous use, dose adjustment of the latter may be required.
In patients receiving diuretics, especially excreting liquid and / or salts, an excessive decrease in blood pressure may be observed at the beginning of perindopril therapy, the risk of which can be reduced by discontinuing the diuretic, replenishing the loss of fluid or salts before starting perindopril therapy, as well as using perindopril in low initial dose with a further gradual increase.
In case of chronic heart failure, when using diuretics, perindopril should be used in a low dose, possibly after reducing the dose of a potassium-sparing diuretic used simultaneously. In all cases, renal function (creatinine concentration) should be monitored in the first weeks of ACE inhibitors.
Use of eplerenone or spironolactone in doses of 12.5 mg to 50 mg / day and ACE inhibitors (including perindopril) in low doses: in the treatment of heart failure II-IV functional class according to NYHA classification with left ventricular ejection fraction
perindopril with NSAIDs (acetylsalicylic acid in a dose that has anti-inflammatory effects, COX-2 inhibitors and non-selective NSAIDs) can lead to a decrease in the antihypertensive effect of ACE inhibitors. The simultaneous use of ACE inhibitors and NSAIDs can lead to impaired renal function, including the development of acute renal failure, and an increase in serum potassium, especially in patients with reduced renal function. Use this combination with caution in elderly patients. Patients should receive an adequate amount of fluid, it is recommended to carefully monitor renal function, both at the beginning and during treatment.
The antihypertensive effect of perindopril may be enhanced while it is used with other antihypertensive drugs, vasodilators, including short and prolonged nitrates.
The concomitant use of gliptins (linagliptin, saxagliptin, sitagliptin, vitagliptin) with ACE inhibitors (including perindopril) may increase the risk of angioedema due to the suppression of the activity of dipeptidyl peptidase IV glptin.
The simultaneous use of perindopril with tricyclic antidepressants, antipsychotic drugs and general anesthesia can lead to increased antihypertensive action.
Sympathomimetics may attenuate the antihypertensive effect of perindopril.
When using ACE inhibitors, incl. perindopril, in patients receiving an iv gold preparation (sodium aurothiomalate), a symptom complex was described in which hyperemia of the skin of the face, nausea, vomiting, and arterial hypotension were observed.
Terms and conditions
prescription
lekarstvennaja form
tablets
Teva Pharmaceutical Enterprises Ltd. td, Israel
