pronounced decrease in blood pressure, nausea, vomiting, muscle cramps, dizziness, drowsiness, confusion, oliguria up to anuria (due to a decrease in BCC), possible violations of the water-electrolyte balance (low content of sodium and potassium in blood plasma).
gastric lavage and / or administration of activated carbon, restoration of water-electrolyte balance in a hospital setting. With a pronounced decrease in blood pressure, it is necessary to transfer the patient to a lying position on his back with his legs raised upside down, then measures should be taken to increase the BCC (introduction of 0.9% sodium chloride solution in/in). Perindoprilate, the active metabolite of perindopril, can be eliminated from the body by dialysis.
hypersensitivity to the active substance, any ACE inhibitor, sulfonamide derivatives, or any excipients of the drug,
severe renal failure,
bilateral renal artery stenosis, single kidney artery stenosis,
severe hepatic insufficiency (including encephalopathy),
given the lack of sufficient experience of use, the drug Co-Parnavel®
systemic diseases of the connective tissue (in t.tsch.
Simultaneous use of the drug Co-Parnavel
Simultaneous use, requiring special care
Baclofen - potentiation of the hypotensive effect. It is necessary to monitor blood pressure, kidney function and, if necessary, adjust the dose of antihypertensive agents.
They increase the hypotensive effect and increase the risk of developing orthostatic hypotension (additive effect).
. Reduction of the hypotensive effect (retention of fluid and sodium ions as a result of the action of GCS).
it is possible to increase the hypotensive effect of the drug Co-Parnavel®.
Potassium-sparing diuretics (spironolactone, triamterene, amiloride, eplerenone) and potassium preparations:
and : the use of ACE inhibitors (described for captopril and enalapril) in very rare cases may increase the hypoglycemic effect of sulfonylureas and insulin derivatives in patients with diabetes mellitus, with their simultaneous use, it is possible to increase glucose tolerance and reduce the need for insulin, which may require correction of doses of hypoglycemic agents for oral administration and insulin.
Simultaneous use requiring caution
: concomitant use of these drugs with ACE inhibitors may increase the risk of developing leukopenia.
Means for general anesthesia: ACE inhibitors may increase the hypotensive effect of some general anesthesia agents.
Diuretics (thiazide and loop):
Indapamide
Simultaneous use, requiring special care
t.to.. Concomitant use with the above drugs should be avoided. It is necessary to monitor the content of potassium in the blood serum in order to avoid hypokalemia, with the development of which it is necessary to correct it, to monitor the QT interval on the ECG
hypokalemia increases the toxic effect of cardiac glycosides. With the simultaneous use of indapamide and cardiac glycosides, the content of potassium in the blood plasma, ECG indicators should be monitored and, if necessary, the dose of cardiac glycosides should be adjusted.
in patients with hypovolemia on the background of the use of diuretics, there is an increased risk of acute renal failure, especially when using contrast agents containing high doses of iodine. Before using iodine-containing contrast agents, the BCC should be replenished.
with simultaneous use, hypercalcemia may develop due to a decrease in the excretion of calcium by the kidneys.
Cyclosporine:
Perindopril has an inhibitory effect on the RAAS and reduces the excretion of potassium ions by the kidneys while taking indapamide. Risk of hypokalemia (serum potassium content less than 3.4 mmol/l) in patients with the use of the drug Co-Parnavel®
very rarely — thrombocytopenia, leukopenia/neutropenia, agranulocytosis, aplastic anemia, hemolytic anemia (there are reports of the use of ACE inhibitors). In certain clinical situations (conditions after kidney transplantation or in patients undergoing hemodialysis or peritoneal dialysis), ACE inhibitors can cause anemia.
On the part of the senses:
often-a marked decrease in blood pressure, including orthostatic hypotension, very rarely-arrhythmias, including bradycardia, ventricular tachycardia, atrial fibrillation, as well as angina, myocardial infarction, possibly secondary, due to a decrease in blood pressure in high — risk patients, the frequency is unknown-ventricular tachycardia of the "pirouette" type (possibly fatal).
often-dry, long-lasting against the background of the use of ACE inhibitors and disappearing after their withdrawal cough, shortness of breath, infrequently — bronchospasm, very rarely — eosinophilic pneumonia, rhinitis.
From the digestive system:
often — skin itching, skin rash, maculopapular rashes, infrequently — angioedema of the face, limbs, lips, oral mucosa, tongue, vocal folds and/or larynx, urticaria, hypersensitivity reactions, mainly dermatological, in patients with a burdened allergic history, worsening of SLE, very rarely — erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome, isolated cases of photosensitivity reactions.
From the musculoskeletal system: often-muscle spasms.
On the part of the reproductive system: infrequently-impotence.
Other: often-asthenia, infrequently-increased sweating.
Laboratory parameters:
Ko-Parnavel®
Ko-Parnavel It has a pronounced dose-dependent antihypertensive effect, which does not depend on the age and body position of the patient and is not accompanied by reflex tachycardia. It does not affect the metabolism of lipids (total cholesterol, LDL, VLDL, HDL, triglycerides (TG) and carbohydrates), including in patients with diabetes mellitus. Reduces the risk of hypokalemia due to diuretic monotherapy.
The antihypertensive effect persists for 24 hours.
A stable decrease in blood pressure is achieved within 1 month on the background of the use of the drug Co-Parnavel
Perindopril-an ACE inhibitor, the mechanism of action of which is associated with the inhibition of ACE activity, leading to a decrease in the formation of angiotensin II, eliminates the vasoconstrictor effect of angiotensin II, reduces the secretion of aldosterone. The use of perindopril does not lead to sodium and fluid retention, does not cause reflex tachycardia with long-term treatment. The antihypertensive effect of perindopril develops in patients with low or normal plasma renin activity.
results in:
- venous dilation (reduction of preload on the heart), due to changes in the metabolism of PG,
In patients with heart failure, perindopril promotes:
- reducing the filling pressure of the left and right ventricles,
- increased cardiac output and cardiac index,
- increased regional blood flow in the muscles.
It has vasodilating properties and restores the elasticity of large arteries. The addition of a thiazide-like diuretic enhances the antihypertensive effect of perindopril.
Indapamide belongs to the derivatives of sulfonamide, is a diuretic. It inhibits the reabsorption of sodium in the cortical segment of the renal tubules, increasing the excretion of sodium and chlorine by the kidneys, thus leading to increased diuresis. To a lesser extent, it increases the excretion of potassium and magnesium. Having the ability to selectively block "slow" calcium channels, indapamide increases the elasticity of the arterial walls and reduces OPSS. It has a hypotensive effect in doses that do not have a pronounced diuretic effect. Increasing the dose of indapamide does not lead to an increase in the antihypertensive effect, but increases the risk of adverse events.
Indapamide in patients with arterial hypertension does not affect the metabolism of lipids: TG, LDL and HDL and carbohydrate metabolism, even in patients with diabetes mellitus and arterial hypertension.
The combined use of perindopril and indapamide does not change their pharmacokinetic parameters in comparison with the separate administration of these drugs.
Perindopril after oral administration, it is rapidly absorbed from the gastrointestinal tract. Bioavailability is 65-70%. Food intake reduces the conversion of perindopril to perindoprilate. T1/2 perindopril from the blood plasma is 1 h.
max in the blood plasma, it is reached in 3-4 hours after oral administration. Since food intake reduces the conversion of perindopril to perindoprilate and the bioavailability of the drug, perindopril should be taken 1 time a day in the morning, before breakfast. Taking perindopril 1 time a day, the equilibrium concentration is reached within 4 days.
In the liver, it is metabolized to form an active metabolite, perindoprilate. In addition to the active metabolite of perindoprilat, perindopril forms 5 more inactive metabolites. The binding to plasma proteins of perindoprilat is dose-dependent and is 20%. Perindoprilat easily passes through the histohematic barriers, excluding BBB, a small amount penetrates through the placenta and into breast milk. Excreted by the kidneys, T1/2 perindoprilate is about 17 hours. It does not accumulate.
In elderly patients, in patients with renal and heart failure, the elimination of perindoprilat is slowed down.
In case of renal insufficiency, it is recommended to reduce the dose of perindopril depending on the severity of renal insufficiency (creatinine clearance). The dialysis Cl of perindoprilate is 70 ml / min.
The kinetics of perindopril is changed in patients with cirrhosis of the liver: hepatic clearance is reduced by half. However, the amount of perindoprilate formed does not decrease, which does not require dose adjustment.
It is quickly and almost completely absorbed into the gastrointestinal tract. Food intake slows down the absorption somewhat, but does not significantly affect the amount of absorbed indapamide. Cmax in the blood plasma, it is reached 1 h after ingestion of a single dose. Binds to plasma proteins by 79%. T it is from 14 to 24 hours (on average-18 hours). It does not accumulate.
It is metabolized in the liver. It is excreted by the kidneys (70%) mainly in the form of metabolites (the fraction of the unchanged drug is about 5%) and by the intestine with bile in the form of inactive metabolites (22%). In patients with renal insufficiency, the pharmacokinetic parameters of indapamide do not significantly change.
Ko-Parnavel
1 time a day, preferably in the morning before breakfast, with a sufficient amount of liquid.
If possible, the drug should be started with the selection of doses of single-component drugs. In case of clinical necessity, it is possible to prescribe combination therapy with Co-Parnavel immediately after monotherapy.
Doses are given for the indapamide/perindopril ratio.
The initial dose is 1 tablet of the drug Co-Parnavel (0.625 mg/2 mg) 1 time per day. If after 1 month of taking the drug it is not possible to achieve adequate control of blood pressure, the dose of the drug should be increased to 1 table. of the drug Co-Parnavel
If necessary, to achieve a more pronounced antihypertensive effect, it is possible to increase the dose of the drug to the maximum daily dose of Co-Parnavel® — 1 table (2.5 mg/8 mg) 1 time per day.
The initial dose is 1 tab. of the drug Co-Parnavel®
Patients with impaired renal function. in patients with severe renal insufficiency, it is contraindicated (creatinine Cl less than 30 ml / min) (see "Contraindications").
Patients with moderate renal insufficiency (creatinine Cl 30-60 ml / min) are recommended to start therapy with the necessary doses of drugs (in monotherapy) that are part of the drug Co-Parnavel®, the maximum daily dose of the drug Co-Parnavel
The drug is contraindicated in patients with severe hepatic insufficiency (see "Contraindications"). In moderate hepatic insufficiency, dose adjustment is not required.
Children and teenagers.
C09BA04 Perindopril in combination with diuretics
