Composition, form of production and packaging
Tablets are white or almost white, round, biconvex, with a facet, on one side a short line is engraved.
Perindopril erbumin To semi-finished granules 37.515 mg,
which corresponds to the content of perindopril erbumine 2 mg
indapamide 0.625 mg
Excipients of semi-finished granules: calcium chloride hexahydrate - 0.6 mg, lactose monohydrate - 30.915 mg, crospovidone - 4 mg.
Excipients: microcrystalline cellulose - 11.25 mg, sodium hydrogen carbonate - 0.25 mg, silicon dioxide colloid - 0.135 mg, magnesium stearate - 0.225 mg.
10 pieces. - packings cellular planimetric (3) - packs cardboard.
Tablets are white or almost white in color, round, biconvex, with a risk on one side and with a facet.
Perindopril erbumin To semi-finished granules 75.03 mg,
which corresponds to the content of perindopril erbumine 4 mg
indapamide 1.25 mg
Excipients of semi-finished granules: calcium chloride hexahydrate - 1.2 mg, lactose monohydrate - 61.83 mg, crospovidone - 8 mg.
Excipients: microcrystalline cellulose - 22.5 mg, sodium hydrogen carbonate - 0.5 mg, silicon dioxide colloid - 0.27 mg, magnesium stearate - 0.45 mg.
10 pieces. - packings cellular planimetric (3) - packs cardboard.
10 pieces. - packings cellular planimetric (9) - packs cardboard.
Tablets are white or almost white in color, round, biconvex, with a risk on one side.
perindoprila erbumin To semi-finished granules 150.06 mg,
which corresponds to the content of perindopril erbumine 8 mg
indapamide 2.5 mg
Excipients of semi-finished granules: calcium chloride hexahydrate - 2.4 mg, lactose monohydrate - 123.66 mg, crospovidone - 16 mg.
Excipients: microcrystalline cellulose - 45 mg, sodium hydrogencarbonate - 1 mg, silicon dioxide colloid - 0.54 mg, magnesium stearate - 0.9 mg.
10 pieces. - packings cellular planimetric (3) - packs cardboard.
10 pieces. - packings cellular planimetric (9) - packs cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2015.
Combined antihypertensive drug containing ACE inhibitor - perindopril and thiazide-like diuretic - indapamide. The drug has antihypertensive, diuretic and vasodilating effect.
Ko-Perineva В® has a pronounced dose-dependent antihypertensive effect, independent of the age and position of the patient's body and not accompanied by reflex tachycardia. Does not affect the metabolism of lipids (total cholesterol, LDL, VLDL, HDL, triglycerides and carbohydrates), incl. in patients with diabetes mellitus.Reduces the risk of hypokalemia due to monotherapy with a diuretic.
The antihypertensive effect persists for 24 hours.
A stable decrease in blood pressure is achieved within 1 month against the background of the use of Ko-Perineva В® without increasing the heart rate. Termination of treatment does not lead to the development of withdrawal syndrome.
Perindopril - ACE inhibitor, whose mechanism of action is associated with inhibition of ACE activity, leading to a decrease in the formation of angiotensin II, eliminates the vasoconstrictive effect of angiotensin II, reduces the secretion of aldosterone. The use of perindopril does not lead to the retention of sodium and liquid, does not cause reflex tachycardia in long-term treatment. The antihypertensive effect of perindopril is developed in patients with low or normal renin activity of blood plasma.
Perindopril acts via its main active metabolite, perindoprilat. Its other metabolites are inactive.
The effect of Ko-Perineva В® leads to the expansion of veins (decrease in preload on the heart), caused by a change in the metabolism of prostaglandins; decrease in OPSS (decrease in postload on the heart).
In patients with heart failure, perindopril helps to lower the filling pressure of the left and right ventricles, increase cardiac output and cardiac index, and increase regional blood flow in the muscles.
Perindopril is effective in arterial hypertension of any severity: mild, moderate and severe.
The maximum antihypertensive effect develops 4-6 hours after a single oral intake and persists throughout the day.
Termination of therapy does not lead to the development of withdrawal syndrome.
Has vasodilating properties and restores the elasticity of large arteries. The addition of a thiazide-like diuretic enhances the antihypertensive (additive) effect of perindopril.
Indapamide refers to derivatives of sulfonamide, is a diuretic. 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 increases the excretion of potassium and magnesium. Possessing the ability to selectively block slow calcium channels, indapamide increases the elasticity of the walls of the arteries and reduces the OPSS. Has hypotensive effect in doses that do not have a pronounced diuretic effect. An increase in the dose of indapamide does not entail an increase in the antihypertensive effect, but increases the risk of developing undesirable phenomena.
Indapamide in patients with hypertension has no effect on the metabolism of lipids - TG, LDL and HDL; on the metabolism of carbohydrates, even in patients with diabetes mellitus and hypertension.
The combined use of perindopril and indapamide does not alter their pharmacokinetic parameters, as compared to the separate administration of these drugs.
After oral administration, perindopril is rapidly absorbed from the digestive tract. Bioavailability is 65-70%. C max in the blood plasma is achieved 3-4 hours after ingestion.
Eating a meal reduces the conversion of perindopril to perindoprilat and the bioavailability of perindopril, so it should be taken 1 time / day in the morning, before breakfast. When taking perindopril 1 time / day C ss is reached within 4 days.
Binding to blood plasma proteins perindoprilata has a dose-dependent character and is 20%. Perindoprilat easily passes through the histohematological barriers, excluding the BBB. In small amounts, it penetrates the placental barrier and is excreted in breast milk. Do not cumulate.
In the liver is metabolized with the formation of an active metabolite perindoprilata. In addition, 5 more inactive metabolites are formed.
T 1/2 perindopril from blood plasma is 1 hour. T 1/2 perindoprilata is about 17 hours. It is excreted by the kidneys.
Pharmacokinetics in special clinical cases
In patients of advanced age, in patients with renal and cardiac failure, excretion of perindoprilate is slowed.
The dialytic clearance of perindoprilat is 70 ml / min.
The kinetics of perindopril has been altered in patients with cirrhosis: the liver clearance is reduced by half. Nevertheless, the amount of perindoprilate formed does not decrease, which does not require correction of the dose.
After oral administration, it is quickly and almost completely absorbed from the digestive tract. Eating somewhat slows down absorption, but does not significantly affect the amount of absorbed indapamide. After oral administration in a single dose of C max in blood plasma is achieved after 1 hour.
The binding with plasma proteins is 79%. Do not cumulate.
Metabolised in the liver.
T 1/2 is from 14 to 24 hours (an average of 18 hours). It is excreted by the kidneys (70%) mainly in the form of metabolites (the fraction of the unchanged drug is about 5%) and the intestine with bile in the form of inactive metabolites (22%).
Pharmacokinetics in special clinical cases
In patients with renal insufficiency, the pharmacokinetic parameters of indapamide do not change significantly.
The drug is taken orally 1 time / day, preferably in the morning before breakfast, with plenty of liquid.
If possible, the drug should be started with the selection of doses of perindopril and indapamide separately. In case of clinical necessity, it is possible to prescribe a combined therapy with Ko-Perineva В® immediately after monotherapy.
Doses are given for the ratio of perindopril / indapamide.
The initial dose of the preparation Ko-Perineva В® - 2 mg / 0.625 mg (1 tab.) 1 time / day. If after 1 month of using the drug fails to achieve adequate control of blood pressure, the dose should be increased to 4 mg / 1.25 mg (1 tab.) 1 time / day.
If necessary, in order to achieve a more pronounced hypotensive effect, it is possible to increase to a maximum daily dose of Ko-Perineva В® - 1 tablet. (8 mg / 2.5 mg) 1 time / day.
For elderly patients, the initial dose of Ko-Perineva В® is 2 mg / 0.625 mg (1 tab.) 1 time / day. It should be prescribed treatment with the drug after monitoring the function of the kidneys and blood pressure.
The drug Ko-Perineva В® is contraindicated in patients with severe renal failure (CC less than 30 ml / min). Patients with moderate renal insufficiency (CK 30-60 ml / min) are advised to start therapy with the necessary doses of drugs (in monotherapy) included in the preparation of Ko-Perineva В® ; the maximum daily dose of Ko-Perineva В® 4 mg / 1.25 mg. Patients with QC? 60 mL / min dosage adjustment is not required. On the background of therapy, it is necessary to regularly monitor the concentration of creatinine and the content of potassium in the blood serum.
The drug is contraindicated in patients with severe hepatic impairment. With moderate hepatic insufficiency, dose adjustment is not required.
The preparation of Ko-Perineva В® should not be used in children and adolescents under the age of 18 , There is insufficient data on efficiency and safety.
Perindopril has an inhibitory effect on RAAS and reduces the excretion of potassium ions by the kidneys while taking indapamide. The risk of hypokalemia (the serum potassium content in the serum is less than 3.4 mmol / l) is 2%, 4 mg / 1.25 mg - 4% and 8 mg / 2.5 in patients with the use of the preparation Ko-Perineva В® at a daily dose of 2 mg / 0.625 mg mg - 6%.
Classification of the incidence of adverse events (WHO): very often (? 1/10), often (from? 1/100 to <1/10), infrequently (from? 1/1000 to <1/100), rarely (from? 1/10 000 to <1/1000), very rarely (from <1/10 000), the frequency is unknown - can not be estimated from the available data.
In each group, undesirable effects are presented in order of decreasing severity.
On the part of the hematopoiesis system: very rarely - thrombocytopenia, leukopenia / neutropenia, agranulocytosis, aplastic anemia, hemolytic anemia (there are reports using ACE inhibitors). In certain clinical situations (conditions after kidney transplantation or patients on hemodialysis or peritoneal dialysis), ACE inhibitors can cause anemia.
From the nervous system: often - paresthesia, headache, dizziness, vertigo; infrequent - lability of mood, sleep disturbance; very rarely confusion; frequency unknown - faint.
From the sense organs: often - visual disturbances, noise in the ears.
From the side of the cardiovascular system: often - marked decrease in blood pressure, incl. orthostatic hypotension; very rarely - arrhythmias, incl. bradycardia, ventricular tachycardia, atrial fibrillation, as well as angina pectoris, myocardial infarction, possibly secondary, due to lowering blood pressure in patients at high risk;frequency unknown - ventricular tachycardia of the "pirouette" type (possibly fatal).
On the part of the respiratory system: often - a dry cough that persists long after the use of ACE inhibitors and disappears after their withdrawal, dyspnea; infrequently bronchospasm; very rarely - eosinophilic pneumonia, rhinitis.
On the part of the digestive system: often - constipation, dryness of the oral mucosa, decreased appetite, nausea, epigastric pain, abdominal pain, eating disorders, vomiting, dyspepsia, diarrhea; very rarely - pancreatitis, angioedema, intestinal edema, cholestatic jaundice; the frequency is unknown - with hepatic insufficiency, there is a chance of developing hepatic encephalopathy.
From the skin and subcutaneous fat: often - skin itching, skin rash, maculopapular rashes; possibly worsening of the systemic lupus erythematosus; very rarely erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome; in isolated cases - photosensitivity reactions.
Allergic reactions: infrequently - angioedema, swelling of the face, extremities, lips, mucous membranes of the mouth, tongue, vocal cords and / or larynx, urticaria;in patients with a history of allergic anamnesis - mainly dermatological reactions of hypersensitivity.
From the musculoskeletal system: often - muscle spasms.
From the side of the urinary system: infrequently - kidney failure; very rarely acute renal failure.
From the side of the reproductive system: infrequently - impotence.
Other: often - asthenia; infrequently - increased sweating.
From laboratory indicators: rarely - hypercalcemia; the frequency is unknown - an increase in QT on the ECG, an increase in the concentration of uric acid and glucose in the blood serum during the drug intake, increased activity of liver enzymes, a slight increase in serum creatinine, reversible after discontinuation of therapy, which often develops against the background of stenosis of the renal arteries or stenosis arteries of a single kidney, arterial hypertension on the background of diuretic therapy, with renal failure; hypokalemia, especially significant for patients at risk; hypochloremia can lead to compensatory metabolic alkalosis (the probability and severity of the effect are low); hyperkalaemia is more often reversible; hyponatremia with hypovolemia, leading to a decrease in bcc and orthostatic hypotension.
Side effects from clinical trials
According to clinical studies, side effects correspond to the previously established safety profile of the combination of perindopril and indapamide. In rare cases, the following serious adverse reactions developed: hyperkalemia, acute renal failure, arterial hypotension and cough, possibly angioedema development.
- angioedema in the anamnesis (hereditary / idiopathic or angioedema due to the administration of other ACE inhibitors in the history);
- marked renal failure (CC less than 30 ml / min);
- bilateral stenosis of the renal arteries, stenosis of the artery of a single kidney;
- refractory hyperkalemia;
- severe hepatic insufficiency (including with encephalopathy);
- lactose intolerance, lactase deficiency or glucose-galactose malabsorption;
- simultaneous use of drugs that extend the QT interval on the ECG;
- simultaneous use with antiarrhythmic drugs that can cause ventricular tachycardia as pirouette;
- the period of breastfeeding;
- age under 18 years (efficiency and safety not established);
- Hypersensitivity to active substances, any ACE inhibitor, sulfonamide derivative or any auxiliary components of the drug.
Given the lack of sufficient clinical experience, Co-Perineva В® should not be used in dialysis patients and in patients with untreated decompensated heart failure.
With caution should apply the drug in systemic diseases of connective tissue (including systemic lupus erythematosus, scleroderma); on the background of immunosuppressant therapy (risk of neutropenia, agranulocytosis); when oppression of bone marrow hematopoiesis; decrease in BCC (diuretic intake, salt-free diet, vomiting, diarrhea); with angina pectoris; cerebrovascular diseases; Renovascular hypertension; diabetes mellitus; chronic heart failure (NYHA functional class IV); with hyperuricemia (especially accompanied by gout and urate nephrolithiasis); lability of blood pressure; when hemodialysis using high-flow polyacrylonitrile membranes;before the procedure for apheresis of LDL; simultaneously with the conduct of desensitizing therapy with allergens (for example, Hymenoptera venom); after renal transplantation; stenosis of the aortic and / or mitral valve; hypertrophic obstructive cardiomyopathy; in elderly patients.
PREGNANCY AND LACTATION
The use of Ko-Perineva В® is contraindicated in pregnancy.
When planning pregnancy or when it comes on the background of taking the drug Ko-Perineva В® should immediately stop taking the drug and prescribe another antihypertensive therapy. Do not use Ko-Perineva В® in the first trimester of pregnancy.
Controlled clinical studies on the use of ACE inhibitors in pregnant women have not been conducted. Limited data suggest that the use of ACE inhibitors in the I trimester did not lead to fetal malformations associated with fetotoxicity, but the fetotoxic effect of ACE inhibitors can not be completely ruled out.
The preparation of Ko-Perineva В® is contraindicated in II and III trimester of pregnancy. Long-term use of ACE inhibitors in the II and III trimesters of pregnancy can lead to impaired fetal development (decreased kidney function, oligohydramnion, slowing ossification of the skull bones) and development of complications in the newborn (kidney failure, arterial hypotension, hyperkalemia).
Prolonged use of thiazide diuretics in the III trimester of pregnancy can cause hypovolemia in the mother and decrease utero-placental blood flow, which leads to fetoplacental ischemia and delayed development of the fetus. In rare cases, the development of fetal / newborn hypoglycemia and thrombocytopenia is possible on the background of taking diuretics.
If a woman is taking an ACE inhibitor in the II and III trimester of pregnancy, it is recommended to conduct ultrasound of the kidneys and the skull of the fetus / newborn.
Neonates whose mothers were treated with ACE inhibitors, there may be hypotension, so babies should be kept under close medical supervision.
Preparation Ko Perineva В® is contraindicated during breastfeeding.
It is not known whether perindopril is allocated to breast milk.
Indapamide is excreted in breast milk. It causes a decrease in the volume of breast milk or suppression of lactation. A newborn may develop hypersensitivity to sulfonamide derivatives, hypokalaemia and nuclear jaundice.
It is necessary to evaluate the significance of therapy to the mother and to decide on the termination of breastfeeding or stopping treatment.
APPLICATION FOR FUNCTIONS OF THE LIVER
Patients with renal failure (creatinine clearance of 60 ml / min or more) dose adjustment is required. For patients with CC 30-60 ml / min maximum dose Ko Perineva В® is 2 mg / 625 mg (1 tab.) 1 time / day. When CC less than 30 ml / min formulation Ko Perineva В® is contraindicated.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Contraindicated: severe liver failure (including encephalopathy).
APPLICATION FOR CHILDREN
Contraindication: age under 18 years (efficacy and safety not established).
APPLICATION IN ELDERLY PATIENTS
For elderly patients, the initial dose Ko Perineva В® is 2 mg / 625 mg (1 tab.) 1 time / day.
Ko Perineva В®
Not recommended simultaneous use of co-drug Perineva В® with lithium therapy.
Co-therapy with Perineva В® is contraindicated in patients with severe renal impairment (creatinine clearance less than 30 mL / min). Some hypertensive patients with no prior renal dysfunction on the background of therapy with Co-Perineva В® may cause symptoms of acute renal failure. In this case, treatment with Ko Perineva В®should be discontinued. Further it is possible to resume the combination therapy using low dose Ko Perineva В®Or use drugs perindopril and indapamide monotherapy. Such patients requires regular monitoring the potassium content and serum creatinine every 2 weeks after initiation of therapy, and every subsequent two months therapy with Ko Perineva В® .
Acute renal failure often develops in patients with severe congestive heart failure or renal dysfunction source, including with bilateral renal artery stenosis or stenosis of the artery only functioning kidney. The drug Ko Perineva В® not recommended for patients with bilateral renal artery stenosis or artery stenosis only functioning kidneys.
Hyponatremia associated with the risk of a sudden drop in blood pressure (especially in patients with bilateral renal artery stenosis or stenosis of the artery only functioning kidney). Therefore, in the follow-up of patients should pay attention to possible symptoms of dehydration and reduction of electrolytes in the blood plasma, for example, after prolonged diarrhea or vomiting. Such patients requires regular monitoring of electrolytes in the blood plasma. In marked decrease in blood pressure may be required in / in a 0.9% sodium chloride solution.
Transient hypotension is not a contraindication to further continuation of therapy. After restoration of blood pressure and BCC can resume therapy with Ko PerinevaВ®Using low doses of the drug, or using drugs perindopril and indapamide monotherapy.
Combined use of perindopril and indapamide does not prevent the development of hypokalemia, especially in patients with diabetes or renal failure. As in the case of combined use of antihypertensive and diuretic agents requires regular monitoring the potassium content in the blood plasma.
Note that in the formulation auxiliaries Ko Perineva В® includes lactose monohydrate, and the drug is contraindicated in patients with hereditary galactosemia, lactase deficiency, glucose-galactose malabsorption.
Patients taking ACE inhibitors, there may be cases of neutropenia / agranulocytosis, thrombocytopenia and anemia. In patients with normal renal function, in the absence of other complications of neutropenia is rare and takes place spontaneously after discontinuation of ACE inhibitors.
Perindopril is necessary with great caution in patients with connective tissue diseases and at the same time receiving immunosuppressive therapy, allopurinol or procainamide, especially when existing renal impairment. These patients may develop severe infections refractory to intensive antibiotic therapy. In the case of perindopril recommended destination periodically monitor the number of leukocytes in blood. Patients should be warned that in case of any signs of infection (sore throat, fever), you should immediately consult a doctor.
When receiving ACE inhibitors, including perindopril, in rare cases, can be observed the development of facial angioedema, lips, tongue, uvula upper palate, and / or the larynx. When these symptoms the drug should be discontinued immediately. The patient should be monitored for as long as edema symptoms do not disappear completely.
If angioedema affects only the face and lips, his symptoms usually disappear on their own, or to treat the symptoms can be used antihistamines. Angioneurotic edema, accompanied by edema of the larynx or tongue may cause airway obstruction and death.
When angioedema symptoms should immediately enter p / epinephrine (adrenaline), diluted 1: 1000 (0.3 or 0.5 ml) and / or to ensure airway patency.
Patients with a history of observed angioedema not associated with ACE inhibitors, the risk of development can be enhanced when receiving the drugs in this group.
In rare cases during treatment with ACE inhibitors develop angioedema bowel edema. Thus, patients have a pain in the abdomen as an isolated symptom or in combination with nausea and vomiting in some cases without prior angioneurotic edema of the face and under the normal C-1 esterase. Diagnosis is established via CT abdomen, ultrasound or during surgery. Symptoms disappear after discontinuation of ACE inhibitors. In patients with abdominal pain who receive ACE inhibitors in the differential diagnosis should consider the possibility of angioneurotic edema of the intestine.
There are some reports about the development of long-term, life-threatening anaphylactoid reactions in patients receiving ACE inhibitors during desensitizing treatment with poison Hymenoptera (bees, wasps). ACE inhibitors should be used with caution in patients prone to allergic reactions, undergoing desensitization procedure. Avoid destination ACE inhibitor to patients receiving immunotherapy Hymenoptera venom. Nevertheless, development of anaphylactoid reactions can be avoided by temporary discontinuation of ACE inhibitor at least 24 hours prior to the desensitization treatment.
In rare cases, patients treated with ACE inhibitors, life-threatening anaphylactoid reactions may develop during LDL apheresis using a dextran sulfate. To prevent anaphylactoid reactions should discontinue therapy with an ACE inhibitor before every LDL apheresis procedure using vysokoprotochnyh membranes.
Patients receiving ACE inhibitors during hemodialysis using vysokoprotochnyh membranes (e.g., AN69 В® ) anaphylactoid reactions have been observed. It is therefore desirable to use a diaphragm or other type use an antihypertensive drug other pharmacotherapeutic group.
The combined use of perindopril and potassium-sparing diuretics, potassium and potassium-containing preparations substitutes edible salt is not recommended.
The therapy of ACE inhibitor, dry cough can occur which disappears after drug withdrawal in this group. When dry cough should be mindful of possible connection with this symptom receiving ACE inhibitor. If the doctor believes that ACE inhibitor therapy requires the patient receiving the drug Co-Perineva В® can be continued.
In liver cirrhosis, accompanied by edema and ascites, hypotension, congestive heart failure can be significant RAAS activation, especially in severe hypovolemia and reducing the content of electrolytes in plasma (compared to a low-salt diet or prolonged use of diuretics).
ACE inhibitors cause a blockade of the RAAS, in connection with the possible sharp decline in blood pressure and / or elevated levels of serum creatinine, indicative of the development of acute renal failure that often occurs when taking the first dose of the drug Co-Perineva В® or within the first 2 weeks of therapy.
Elderly patients before the administration of the drug Co-Perineva В®should assess renal function and potassium content in the blood plasma. The initial dose Ko Perineva В® selected depending on the degree of decrease in blood pressure, particularly when reducing the bcc and chronic heart failure (IV NYHA functional class classification). Such measures make it possible to avoid a sharp decrease in blood pressure.
The risk of hypotension exists in all patients but particular care should be observed when using the drug Co-Perineva В® in patients with ischemic heart disease and cerebrovascular insufficiency. In such patients, the drug treatment should begin with a dose of 2 mg / mg 0.625 (initial dose).
In patients with diagnosed or suspected renal artery stenosis, treatment with Co-Perineva В®should start at a hospital with a dose of 2 mg / 0.625 mg under the control of renal function and potassium in the blood plasma. Some patients may develop acute renal failure, which is reversible after discontinuation of the drug.
Patients with chronic heart failure (IV NYHA functional class classification) Co-treatment with Perineva В® must begin with an initial dose of 2 mg / 0.625 mg under medical supervision.
When assigning Ko Perineva drug В® patients with diabetes receiving hypoglycemic agents for oral or insulin, for the first month of therapy is necessary to regularly monitor the concentration of glucose in the blood.
Perindopril (and other ACE inhibitors), has a less pronounced hypotensive effect in blacks compared to patients with other races.
The use of ACE inhibitors in patients undergoing surgery with general anesthesia can lead to a marked decrease in blood pressure, particularly when using tools for general anesthesia has a hypotensive effect.
It is recommended to stop taking ACE inhibitors, including perindopril, 12 hours before surgery, alerting the anesthetist the use of ACE inhibitors.
ACE inhibitors should be used with caution in patients with obstruction of the left ventricular outflow tract and the aortic and / or mitral stenosis.
In rare cases in patients receiving an ACE inhibitor arises cholestatic jaundice, which develops in the progression of fulminant hepatic necrosis, sometimes with fatal consequences. When jaundice or significant increase in liver transaminases in patients receiving an ACE inhibitor drug reception Ko Perineva В® should be discontinued.
In patients following kidney transplantation or in patients on hemodialysis, may develop anemia.
During treatment with ACE inhibitors, including and perindopril may develop hyperkalemia. Risk factors for hyperkalemia are renal failure, advanced age, diabetes, some comorbid conditions (reduction of BCC, acute heart failure decompensation, metabolic acidosis), simultaneous reception of potassium-sparing diuretics (such as spironolactone, eplerenone, triamterene, amiloride), as well as drugs potassium or potassium-containing salt and substitutes the use of other drugs that enhance the potassium content in the blood plasma (e.g., heparin). Hyperkalemia can cause serious heart rhythm abnormalities, sometimes with fatal consequences. Combined use of the above formulations must be done with caution.
There are reports of increased photosensitivity in patients receiving thiazide and thiazide diuretics. With the development of photosensitivity reactions in patients receiving the drug Ko Perineva В® treatment should cease. If necessary, to resume use of the drug Ko Perineva В® , should protect exposed skin from direct exposure to solar and artificial UV rays.
Prior to treatment Ko Perineva preparation В® necessary to determine sodium content in the blood plasma and on the background of the drug regularly monitor electrolytes in the blood plasma. All diuretics can cause hyponatremia, leading to serious complications.
Therapy thiazide and thiazide diuretics associated with the risk of hypokalemia (less than 3.4 mmol / l) in the elderly, malnourished patients, patients with liver cirrhosis, patients with peripheral edema, ascites, ischemic heart disease, chronic heart failure. Hypokalemia in these patients increases the toxic effects of cardiac glycosides and increased risk of arrhythmia. High-risk group includes patients with an increased QT interval on the electrocardiogram. Hypokalemia as bradycardia, promotes the development of severe cardiac arrhythmias, particularly ventricular arrhythmias such as "pirouette", which can be lethal. In each case, requires regular monitoring of potassium in the blood plasma.The first definition of the content of potassium in the blood plasma must be held during the first weeks of starting therapy with Co-PerinevaВ® .
Thiazide and thiazide diuretics reduce the renal excretion of calcium, leading to a slight and temporary increase in calcium in the blood plasma. Marked hypercalcemia may be the result of hidden hyperparathyroidism. Before examining the function of the parathyroid glands should stop taking the drug Co-Perineva В® .
It should monitor the concentration of glucose in patients with diabetes.
In patients with an increased concentration of uric acid in blood plasma on the background of therapy with Co-Perineva В® may increase the frequency of acute gout.
Hypovolemia resulting reduction bcc or hyponatremia caused by diuretics, early