Pharmacodynamics and pharmacokinetics
Co-Perineva is a combination drug containing perindopril and indapamide .
The drug has an antihypertensive effect, the effectiveness of which does not depend on the patient’s age, body position, and is not accompanied by tachycardia. Does not affect lipid metabolism, including in patients with diabetes . When taking the drug, the risk of hypokalemia .
The antihypertensive effect persists throughout the day.
After just a month of taking the drug, a decrease in blood pressure is achieved. If treatment is stopped, there is no risk of withdrawal syndrome .
Perindopril is extremely effective in the fight against arterial hypertension (all forms of severity). 4-6 hours after taking the medicine, the maximum antihypertensive effect develops, which lasts throughout the day.
Perindopril after administration is quickly absorbed from the gastrointestinal tract. Bioavailability is 65-70%. 3-4 hours after administration, the maximum level of the drug in the blood plasma is reached. It is metabolized in the liver, forming an active (perindoprilat) and five inactive metabolites. A small amount of perindoprilate passes into breast milk and through the placenta. Excreted through the kidneys.
The elimination of perindoprilate is slowed down in patients with heart and renal failure and patients over 65 years of age. In patients suffering from liver cirrhosis, hepatic clearance is reduced by half, however, the level of perindoprilate is not reduced.
Indapamide is almost completely absorbed from the gastrointestinal tract; simultaneous intake of food can slow down this process. After an hour, the maximum level in the blood is reached. Metabolized in the liver. Excreted through the kidneys and intestines.
Pharmacokinetics
The combined use of perindopril and indapamide does not change their pharmacokinetic parameters compared to the separate administration of these drugs.
Perindopril after oral administration is rapidly absorbed from the gastrointestinal tract. Bioavailability is 65–70%. Eating reduces the conversion of perindopril to perindoprilat. T1/2 of perindopril from blood plasma is 1 hour.
Cmax in blood plasma is achieved 3–4 hours after oral administration. Since taking with food reduces the conversion of perindopril to perindoprilat and the bioavailability of the drug, perindopril should be taken once a day in the morning, before breakfast. Taking perindopril once a day, equilibrium concentration is achieved within 4 days.
It is metabolized in the liver to form an active metabolite - perindoprilate. In addition to the active metabolite perindoprilate, perindopril forms 5 more inactive metabolites. The binding of perindoprilate to plasma proteins is dose-dependent and amounts to 20%. Perindoprilat easily passes through histohematic barriers, excluding the blood-brain barrier; a small amount penetrates the placenta and into breast milk. Excreted by the kidneys, T1/2 of perindoprilate is about 17 hours. It does not accumulate.
In elderly patients and in patients with renal and heart failure, the elimination of perindoprilate is slowed down.
In case of renal failure, it is recommended to reduce the dose of perindopril depending on the severity of renal failure (creatinine clearance). The dialysis Cl of perindoprilate is 70 ml/min.
The kinetics of perindopril is altered in patients with liver cirrhosis: hepatic clearance is reduced by half. However, the amount of perindoprilate formed does not decrease, which does not require dose adjustment.
Indapamide. Quickly and almost completely absorbed into the gastrointestinal tract. Eating slightly slows down absorption, but does not significantly affect the amount of indapamide absorbed. Cmax in blood plasma is achieved 1 hour after oral administration of a single dose. Binds to plasma proteins by 79%. T1/2 ranges from 14 to 24 hours (average 18 hours). Does not accumulate.
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 intestines with bile in the form of inactive metabolites (22%). In patients with renal failure, the pharmacokinetic parameters of indapamide do not change significantly.
Contraindications
The drug Co-Perineva is contraindicated in the following cases:
- sensitivity to any element of the drug;
- lactose intolerance;
- refractory hyperkalemia;
- angioedema;
- bilateral renal artery stenosis;
- lactase deficiency;
- liver failure;
- glucose-galactose malabsorption;
- renal failure;
- renal artery stenosis;
- pregnancy, lactation, children under 18 years of age.
You should take the drug with caution in the following cases:
- connective tissue diseases ( scleroderma , SLE );
- immunosuppressant therapy;
- inhibition of bone marrow hematopoiesis;
- angina pectoris;
- renovascular hypertension;
- decrease in blood volume;
- hyperuricemia;
- diabetes;
- cerebrovascular diseases.
Side effects
The use of the drug may cause the following side effects:
- thrombocytopenia , agranulocytosis , hemolytic anemia , leukopenia , aplastic anemia ;
- vertigo , paresthesia , dizziness , headache , unstable mood, sleep disturbance, in rare cases - confusion ;
- tinnitus, blurred vision;
- orthostatic hypotension , arrhythmias ( bradycardia , atrial fibrillation , ventricular tachycardia ), myocardial infarction , angina pectoris ;
- dry cough , shortness of breath , bronchospasm , rhinitis , eosinophilic pneumonia ;
- dry mouth, constipation , nausea, abdominal pain, loss of appetite, epigastric pain, vomiting , diarrhea , dyspepsia , pancreatitis , jaundice ;
- angioedema (face, lips, limbs, here, tongue, larynx), rash, urticaria , itching ;
- muscle spasms;
- renal failure;
- impotence;
- asthenia , increased sweating.
Instructions for use (Method and dosage)
The medicine Co-Perineva is taken 1 time per day, orally, in the morning before breakfast, with water.
Doses are listed in the indapamine/perindopril ratio.
To begin with, you should take one tablet (0.625/2 mg) per day. If it is not possible to achieve blood pressure control within a month, the dose is increased to one tablet (1.25/4 mg). To achieve the most pronounced effect, you should increase the daily dose to the limit - one tablet (2.5/8 mg).
For elderly patients, the initial dose is one tablet (0.625/2 mg). Treatment with the drug can be prescribed in case of control of blood pressure and kidney function.
Patients with moderate renal impairment are started on the lowest dose, with the maximum allowed dose being 1.25/4 mg.
Instructions for use CO-PRENESSA® (CO-PRENESSA®)
Common to perindopril and indapamide
For the low-dose combination (2 mg/0.625 mg tablets), there was no significant reduction in adverse reactions to the drug, with the exception of hypokalemia, compared with the lowest approved dosages of the individual components. If a patient simultaneously starts taking two new antihypertensive drugs, an increase in the frequency of idiosyncratic reactions cannot be excluded. To minimize this risk, careful monitoring of the patient's condition should be carried out.
Typically, the combination of lithium and the combination of perindopril and indapamide is not recommended.
Related to perindopril
Neutropenia/agranulocytosis
Patients receiving ACE inhibitors may develop neutropenia/agranulocytosis, thrombocytopenia and anemia. In patients with normal renal function in the absence of other complications, neutropenia is rare. Perindopril should be prescribed with extreme caution to patients with collagen diseases receiving immunosuppressive treatment, treatment with allopurinol or procainamide, especially with pre-existing impairment of renal function. These patients may develop serious infections that, in some cases, do not respond to intensive antibiotic therapy. If perindopril is prescribed, it is recommended to periodically monitor the white blood cell count; patients should be informed that if any signs of an infectious disease appear (sore throat, fever), they should immediately consult a doctor.
Hypersensitivity/angioedema
There are known cases of angioedema of the face, extremities, lips, tongue, pharynx and/or larynx in patients treated with ACE inhibitors, including perindopril. These reactions may develop at any time during therapy. In such cases, you should immediately stop taking the drug and establish appropriate monitoring of the patient's condition until the complete disappearance of symptoms is confirmed. In cases where swelling affects only the face and lips, its symptoms usually resolve without special treatment, but antihistamines can be used to relieve symptoms.
Angioedema, accompanied by swelling of the larynx, can be fatal. Swelling of the tongue, pharynx, or larynx can lead to airway obstruction. In this case, appropriate therapy should be immediately prescribed, which may include subcutaneous administration of epinephrine solution 1:
- 1000 (0.3-0.5 ml) and/or measures to ensure airway patency.
A higher incidence of angioedema has been established in black patients receiving ACE inhibitors.
Patients with a history of angioedema that is not associated with ACE inhibitor therapy may be at increased risk of developing angioedema while taking drugs of this class.
There are rare cases of the development of angioedema of the intestine during therapy with ACE inhibitors, which should be taken into account when carrying out the differential diagnosis of patients receiving ACE inhibitors and admitted with abdominal pain. Patients experienced abdominal pain (with or without nausea or vomiting); in some cases this was not preceded by angioedema of the face, C1-esterase activity was within normal limits. Angioedema was diagnosed through procedures including abdominal CT or ultrasound or during surgery; resolution of symptoms occurred after discontinuation of the ACE inhibitor.
Concomitant use of mTOR inhibitors
Patients receiving mTOR inhibitors (for example, sirolimus, everolimus, temsirolimus) concomitantly with Co-Prenessa® have a higher risk of developing angioedema.
Anaphylactoid reactions during desensitization
There are isolated reports of the development of a persistent, life-threatening anaphylactoid reaction in patients taking ACE inhibitors during desensitizing therapy with hymenoptera venom (bees, wasps). ACE inhibitors should be prescribed with caution to patients prone to allergic reactions and undergoing desensitization; Prescribing the drug to patients undergoing immunotherapy with hymenoptera venoms should be avoided. In cases where a patient requires both treatment with ACE inhibitors and desensitization, the onset of such reactions can be prevented by temporarily discontinuing the ACE inhibitor at least 24 hours before starting the course of desensitization therapy.
Anaphylactoid reactions during LDL apheresis
Rare cases of life-threatening anaphylactoid reactions have been reported in patients receiving ACE inhibitors during LDL apheresis using dextran sulfate. The occurrence of such reactions can be prevented by temporarily stopping the use of ACE inhibitors before each LDL apheresis procedure.
Hemodialysis
Cases of anaphylactoid reactions have been reported in patients undergoing hemodialysis using high-flux density membranes (for example, AN69®) and simultaneously receiving treatment with ACE inhibitors. Such patients should be prescribed either a different type of dialysis membrane or a different class of antihypertensive drugs.
Potassium-sparing diuretics, potassium salts
The combined use of perindopril and potassium-sparing diuretics, as well as potassium salts, is not recommended.
Indapamide related
If liver function is impaired, taking thiazide and thiazide-like diuretics can cause encephalopathy. In this case, taking the drug should be stopped immediately.
Photosensitivity
There are known cases of photosensitivity reactions occurring while taking thiazide and thiazide-like diuretics. If such reactions develop, it is recommended to stop taking the drug. When re-prescribing diuretics, exposed skin should be protected from direct exposure to sunlight or artificial UV radiation.
Precautions for use
Common to perindopril and indapamide
Renal dysfunction
Treatment with the drug in doses of 2 mg/0.625 mg and 4 mg/1.25 mg is contraindicated in patients with severe renal failure (creatinine clearance <30 ml/min), in a dose of 8 mg/2.5 mg - with creatinine clearance <60 ml/min. Treatment should also be discontinued if a blood test reveals functional renal failure in a hypertensive patient without previous significant renal impairment. Therapy can be resumed either at a lower dose or with only one of the components.
Routine medical examination of such patients should include frequent monitoring of potassium and creatinine levels according to the following schedule:
- the first time - after 2 weeks of treatment, then - every 2 months during the period of therapeutic stability. Renal failure has been reported primarily in patients with acute heart failure or occult renal failure, including renal artery stenosis.
This drug is generally not recommended for patients with bilateral renal artery stenosis or patients with one functioning kidney.
Hypotension and water-electrolyte imbalance
With low sodium levels, especially in patients with renal artery stenosis, there is a risk of a sudden drop in blood pressure. Therefore, systematic analysis should be carried out to identify clinical signs of water and electrolyte deficiency in the body, for example, after diarrhea or vomiting. In such patients, it is necessary to regularly monitor plasma electrolytes.
In case of severe arterial hypotension, intravenous administration of an isotonic solution may be necessary. Transient hypotension is not a contraindication to continued treatment. After restoration of satisfactory blood volume and blood pressure, treatment can be resumed either with a lower dose of the drug or with only one of its components.
Potassium content
The combination of perindopril and indapamide does not prevent the development of hypokalemia, especially in patients with diabetes mellitus or renal failure. As with other antihypertensive drugs containing a diuretic, regular monitoring of plasma potassium levels should be carried out.
Excipients
The drug contains lactose, so it should not be prescribed to patients with rare hereditary galactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome.
Preclinical Safety Data
The combination of perindopril and indapamide slightly increased toxicity compared to the individual components. There was no increase in renal toxicity in rats, but the combination caused gastrointestinal toxicity in dogs. Maternal toxicity appears to be increased in rats (compared to perindopril alone). However, these adverse effects occurred when the drug was administered at doses with a very high margin of safety compared to the therapeutic doses used.
Associated with perindopril.
In chronic toxicity studies conducted in rats and monkeys, the kidney was the target organ with reversible damage when administered orally. Mutagenicity was not observed in in vitro or in vivo studies. Reproductive toxicity studies in rats, mice, rabbits and monkeys showed no evidence of embryotoxicity or teratogenicity. However, ACE inhibitors as a class cause side effects late in fetal development. In rodents and rabbits, these effects have resulted in fetal death or congenital anomalies:
- Kidney damage and increased peri- and postnatal mortality were observed. No carcinogenicity was reported in long-term studies conducted in rats and mice.
Related to indapamide.
The highest doses administered orally to various animal species (from 40 to 8000 therapeutic doses) have shown an increase in the diuretic properties of indapamide. The main symptoms of toxicity in acute toxicity studies with indapamide administered IV or intraperitoneally were related to the pharmacological action of indapamide, that is, bradypnea and peripheral vasodilation. No mutagenic or carcinogenic effects were observed during studies.
Related to perindopril
Cough
Taking ACE inhibitors can cause a dry cough, which is persistent and disappears after discontinuation of the drug. This symptom may have an iatrogenic etiology. If an ACE inhibitor is preferred, continued treatment should be considered.
Children and teenagers
The effectiveness and tolerability of perindopril and its combinations in children and adolescents has not been established.
Double blockade of the RAAS
There is evidence that concomitant use of ACE inhibitors, angiotensin II receptor antagonists or aliskiren increases the risk of hypotension, hyperkalemia and decreased renal function (including acute renal failure). Therefore, double blockade of the RAAS by combined use of ACE inhibitors, angiotensin II receptor antagonists or aliskiren is not recommended. If dual blockade therapy is considered absolutely necessary, it should only be undertaken with close observation and frequent monitoring of renal function, electrolytes and blood pressure. ACE inhibitors and angiotensin II receptor antagonists should not be used concomitantly in patients with diabetic nephropathy.
Risk of arterial hypotension and/or renal failure (in case of heart failure, fluid and electrolyte imbalance)
With significant loss of water and electrolytes (salt diet or long-term treatment with diuretics), especially in patients with initially low blood pressure, with renal artery stenosis, congestive heart failure or cirrhosis of the liver, accompanied by edema and ascites, pronounced stimulation of the RAAS occurs. Consequently, inhibition of this system when taking ACE inhibitors can cause (most likely when the drug is first taken or during the first two weeks of treatment) a sharp drop in blood pressure or an increase in plasma creatinine, indicating functional renal failure. In some, although rare, cases, these symptoms may develop acutely and with varying time before their onset. In such cases, treatment can be resumed with a lower dose, gradually increasing it.
Elderly patients
Renal function and potassium concentrations should be assessed before starting treatment. To avoid a sharp decrease in blood pressure, the initial dose of the drug is selected depending on the degree of blood pressure reduction, especially in case of water-electrolyte imbalance.
Patients with established atherosclerosis
The risk of hypotension exists in all patients, but special care must be taken in patients with coronary artery disease or cerebrovascular insufficiency. Treatment should begin with low doses.
Renovascular hypertension
Renovascular hypertension is treated by revascularization. However, the use of ACE inhibitors may be beneficial in patients with renovascular hypertension awaiting surgical intervention or in the absence of such treatment.
When prescribing Co-Prenessa® to patients with established or suspected renal artery stenosis, treatment should begin in a hospital setting with a low dose, and monitoring of renal function and potassium levels is necessary, since Some patients developed functional renal failure, which was reversible when the drug was discontinued.
Co-Prenessa® 8 mg/2.5 mg is not prescribed to patients with known or suspected renal artery stenosis, because in this case, treatment should begin in a hospital setting with lower doses.
Patients with diabetes mellitus
When prescribing ACE inhibitors to patients with diabetes mellitus receiving oral hypoglycemic agents or insulin, blood glucose concentrations should be regularly monitored during the first month of therapy.
Other risk groups
In patients with severe heart failure (grade IV) or in patients with insulin-dependent diabetes mellitus (risk of spontaneous increase in potassium concentration), treatment should be started with low doses and under medical supervision, therefore Co-Prenessa® 8 mg/2.5 mg is not suitable for initiation therapy. Patients with arterial hypertension and coronary insufficiency should not stop treatment with beta-blockers:
- An ACE inhibitor should be taken together with beta-blockers.
Surgical interventions/Anesthesia
ACE inhibitors may cause a drop in blood pressure during anesthesia, especially if the anesthetic used has a hypotensive effect. Therefore, treatment with long-acting ACE inhibitors such as perindopril is recommended to be discontinued, if possible, one day before surgery.
Aortic or mitral valve stenosis/hypertrophic cardiomyopathy
Caution should be exercised when using ACE inhibitors in patients with left ventricular outflow tract obstruction.
Liver failure
In rare cases, ACE inhibitor therapy has been associated with a syndrome that begins with cholestatic jaundice, progresses to fulminant hepatic necrosis, and (sometimes) ends in death. The mechanism of this syndrome is unknown. Patients receiving ACE inhibitors who develop jaundice or significantly elevated liver enzymes should stop taking the ACE inhibitor and undergo careful medical evaluation.
Hyperkalemia
In some patients treated with ACE inhibitors, including perindopril, cases of increased serum potassium levels have been reported. Risk factors for hyperkalemia include renal failure, age over 70 years, diabetes mellitus, certain concomitant conditions (decreased blood volume, acute decompensated heart failure, metabolic acidosis), concomitant use of potassium-sparing diuretics (for example, spironolactone, eplerenone, triamterene or amiloride), and also potassium preparations or potassium-containing salt substitutes. Patients at risk also include patients taking other drugs that increase serum potassium levels (for example, heparin). Hyperkalemia can cause serious heart rhythm problems, sometimes fatal. If the concomitant administration of the above-mentioned drugs is considered necessary, then their use should be carried out with regular monitoring of potassium concentration in the blood serum.
Ethnic characteristics
Perindopril (like other ACE inhibitors) has a less pronounced hypotensive effect in patients of the Black race compared to representatives of other races, possibly due to the higher prevalence of low-renin conditions in this category of patients.
Indapamide related
Sodium content
Before starting treatment, sodium levels should be assessed; In the future, such examinations should be carried out regularly. Taking any diuretic drugs can lead to a decrease in sodium levels in the blood plasma, which, in turn, contributes to the development of a number of serious complications. Initially, a decrease in sodium concentration may be asymptomatic, which is why regular monitoring is necessary. In elderly patients and patients with cirrhosis, monitoring should be performed even more frequently.
Potassium content
Therapy with thiazide and thiazide-like diuretics is associated with a risk of hypokalemia. It is necessary to take into account the risk of a decrease in potassium levels below the permissible level (<3.4 mmol/l) in persons included in high-risk groups:
- elderly and/or malnourished patients, regardless of whether they are taking other medications;
- patients with liver cirrhosis, which is accompanied by edema and ascites;
- patients with coronary heart disease and heart failure. In such cases, hypokalemia increases the toxicity of cardiac glycosides and increases the risk of arrhythmia.
Patients with an increased QT interval are also at increased risk. Hypokalemia, like bradycardia, is a risk factor for the development of serious cardiac arrhythmias, especially torsade de pointes (TdP), which can be fatal. In all of the described cases, potassium concentrations should be regularly monitored. The first determination of plasma potassium should be carried out within the first week after the start of treatment. If potassium concentration decreases, correction is necessary.
Calcium content
Thiazide and thiazide-like diuretics may reduce urinary calcium excretion, leading to a slight and temporary increase in plasma calcium levels. A significant increase in calcium levels may be a consequence of latent hyperparathyroidism. In this case, treatment should be stopped until the function of the parathyroid glands is examined.
Blood glucose level
In patients with diabetes mellitus, it is necessary to constantly monitor the concentration of glucose in the blood, especially in cases where potassium levels are simultaneously reduced.
Uric acid
In patients with hyperuricemia, the frequency of exacerbation of gout attacks may increase during drug therapy.
Kidney function and diuretics
Thiazide and thiazide-like diuretics are most effective in cases where renal function is normal or slightly impaired (for adult patients, creatinine levels are below 25 mg/l, i.e. 220 µmol/l). In elderly patients, plasma creatinine levels should be adjusted taking into account the age, body weight and gender of the patient using the Cockroft formula:
- For men:
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For women:
the calculation result should be multiplied by 0.85.
At the beginning of treatment, hypovolemia caused by loss of water and sodium while taking diuretics may lead to a decrease in GFR and be accompanied by an increase in plasma creatinine and urea concentrations. This transient functional renal failure does not lead to undesirable consequences in patients with unchanged renal function, but may cause deterioration in patients with renal failure.
Visual impairment
Drugs based on sulfonamide derivatives can cause an idiosyncratic reaction, leading to short-term myopia and acute angle-closure glaucoma. Acute glaucoma can cause permanent vision loss. The first step is to stop treatment as soon as possible. If intraocular pressure remains uncontrolled, appropriate drug therapy or surgery may be required. A risk factor for the development of acute closed glaucoma is a history of hypersensitivity to sulfonamides or penicillins.
Athletes
The drug contains an active substance that can give a positive reaction during doping control.
Impact on the ability to drive vehicles and operate machinery
None of the active ingredients, either individually or in combination as part of the Co-Prenessa® drug, has a direct effect on the ability to drive a car or operate potentially dangerous machinery. However, in some patients, especially at the beginning of treatment or when combined with other antihypertensive drugs, the drug may cause individual reactions associated with a decrease in blood pressure, and thus indirectly affect their psychophysical state. As a result, the ability to drive vehicles and operate machinery may be impaired.
Overdose
Symptoms of overdose: vomiting , nausea , muscle cramps , drowsiness , dizziness , confusion , decreased water and electrolyte balance, oliguria , significant decrease in blood pressure.
If the above symptoms appear, you should rinse your stomach, then take activated charcoal to restore the water and electrolyte balance. If the pressure decreases significantly, the patient should lie on his back and raise his legs, then inject a 0.9% sodium chloride solution.
Interaction
You should not combine Co-Perineva with ACE inhibitors and lithium preparations, as the level of lithium in the blood may increase. If co-administration is necessary, lithium levels should be monitored.
Baclofen with extreme caution , as it may increase the hypotensive effect. Blood pressure and kidney function should be monitored and the dose adjusted if necessary.
Neuroleptics and tricyclic antidepressants enhance the effect of hypotension and increase the likelihood of orthostatic hypotension.
Tetracosactide and GCS help reduce the hypotensive effect.
When taken simultaneously with any other antihypertensive drugs, there is a possibility of a stronger manifestation of the hypotensive effect.
Perindopril
At the same time, it is not recommended to use it with potassium-sparing diuretics ( Spironolactone , Amiloride , Eplerenone , Triamterene ) and potassium supplements. When used in parallel, the level of potassium in the blood may increase, which can lead to death. If joint therapy is necessary (for hypokalemia), it is necessary to monitor potassium levels and ECG parameters.
It is recommended to take Co-Perineva together with insulin and hypoglycemic agents with extreme caution. leukopenia increases when used with cytostatic immunosuppressants, Allopurinol , GCS and procainamide . When used with general anesthesia agents, their hypotensive effect may increase. When used in high doses, thiazide and loop diuretics can lead to hypovolemia .
Indapamide
Drugs that cause ari must be taken with caution, since there is a possibility of developing hypokalemia . It is recommended to take Indapamide with caution with medications such as antipsychotics ( cyamemazine , trifluoperazine , chlorpromazine , etc.), antiarrhythmic drugs ( Amiodarone , hydroquinidine , ibutilide , tosylate etc.), benzamides ( sultopride , Tiapride , Sulpiride , Amisulpride ), butyrophenones ( Haloperidol , Droperidol ), other drugs ( Astemizole , mizolastine , sparfloxacin , methadone , bepridil , halofantrine , terfenadine , cisapride ).
Medicines that can cause hypokalemia : tetracosactide , laxatives that stimulate intestinal motility, Amphotericin B , glucocorticoids, mineralocorticoids, cardiac glycosides.
lactic acidosis increases when used with Metformin .
Patients taking high-dose iodine contrast agents are at risk of kidney failure. Hypercalcemia can develop when taking medications containing calcium salts.
KO-PERINEVA
special instructions
Co-Perineva®
Lithium preparations:
The simultaneous use of Co-Perineva® with lithium preparations is not recommended.
Renal dysfunction
| Therapy with Co-Perineva® is contraindicated in patients with severe renal failure (creatinine clearance less than 30 ml/min). In some patients with arterial hypertension without previous renal impairment, signs of acute renal failure may appear during therapy with Co-Perineva®. |In this case, treatment with Co-Perineva® should be discontinued. In the future, you can resume combination therapy using low doses of Co-Perineva®, or use perindopril and indapamide in monotherapy.
Such patients require regular monitoring of potassium and creatinine levels in the blood serum every 2 weeks after the start of therapy and every subsequent 2 months of therapy with Co-Perineva®.
Acute renal failure often develops in patients with severe CHF or underlying renal impairment, including bilateral renal artery stenosis or arterial stenosis of a single functioning kidney.
Taking Co-Perineva® is not recommended for patients with bilateral renal artery stenosis or stenosis of the artery of a single functioning kidney.
Decreased blood pressure and water-electrolyte imbalance
Hyponatremia is associated with a risk of a sudden decrease in blood pressure (especially in patients with bilateral renal artery stenosis or arterial stenosis of a single functioning kidney). Therefore, during dynamic monitoring of patients, attention should be paid to possible symptoms of dehydration and a decrease in the content of electrolytes in the blood plasma, for example, after prolonged diarrhea or vomiting. Such patients require regular monitoring of plasma electrolytes. With a pronounced decrease in blood pressure, intravenous administration of 0.9% sodium chloride solution may be required.
Transient arterial hypotension is not a contraindication for further continuation of therapy. After restoration of blood volume and blood pressure, you can resume therapy with Co-Perineva®, using low doses of the drug, or using the drugs perindopril and indapamide in monotherapy.
Potassium content
The combined use of perindopril and indapamide does not prevent the development of hypokalemia, especially in patients with diabetes mellitus or renal failure. As in the case of the combined use of antihypertensive drugs and a diuretic, regular monitoring of potassium levels in the blood plasma is necessary.
Excipients
It should be taken into account that the excipients of the drug Co-Perineva® include lactose monohydrate, therefore the drug is contraindicated in patients with hereditary galactosemia, lactase deficiency, and glucose-galactose malabsorption. (see section "Contraindications")
Perindopril
Neutropenia/agranulocytosis
In patients taking ACE inhibitors, cases of neutropenia/agranulocytosis, thrombocytopenia and anemia may develop. In patients with normal renal function in the absence of other complications, neutropenia rarely develops and resolves spontaneously after discontinuation of ACE inhibitors.
Perindopril should be used with great caution in patients with connective tissue diseases and simultaneously receiving immunosuppressive therapy, allopurinol or procainamide, especially with existing renal impairment. These patients may develop severe infections that do not respond to intensive antibiotic therapy. If perindopril is prescribed, it is recommended to periodically monitor the number of leukocytes in the blood. The patient should be warned that if any signs of an infectious disease appear (sore throat, fever), consult a doctor immediately.
Hypersensitivity/angioedema (Quincke's edema)
When taking ACE inhibitors, including perindopril, in rare cases, the development of angioedema of the face, lips, tongue, uvula, and/or larynx may occur. If these symptoms appear, the drug should be stopped immediately, and the patient should be observed until the signs of edema disappear completely.
If angioedema affects only the face and lips, its symptoms usually resolve on their own, or antihistamines can be used to treat the symptoms. Angioedema, accompanied by swelling of the tongue or larynx, can lead to airway obstruction and death.
If such symptoms appear, epinephrine (adrenaline) should be immediately administered subcutaneously (diluted 1:1000 (0.3 or 0.5 ml) and/or the airway should be secured.
Patients with a history of angioedema not associated with taking ACE inhibitors may have an increased risk of developing it when taking drugs of this group.
In rare cases, angioedema of the intestine develops during ACE inhibitor therapy. In this case, patients experience abdominal pain as an isolated symptom or in combination with nausea and vomiting, in some cases without previous angioedema of the face and with a normal level of C1-esterase. The diagnosis is made using computed tomography of the abdominal cavity, ultrasound, or at the time of surgery. Symptoms disappear after stopping ACE inhibitors. In patients with abdominal pain receiving ACE inhibitors, the possibility of developing angioedema of the intestine must be taken into account when making a differential diagnosis.
Anaphylactoid reactions during desensitization procedures
There are isolated reports of the development of long-term, life-threatening anaphylactoid reactions in patients receiving ACE inhibitors during desensitizing therapy with the venom of hymenoptera insects (bees, wasps). ACE inhibitors should be used with caution in patients prone to allergic reactions undergoing desensitization procedures. Prescription of an ACE inhibitor should be avoided in patients receiving immunotherapy with hymenoptera venom. However, the development of anaphylactoid reactions can be avoided by temporarily discontinuing the ACE inhibitor at least 24 hours before the start of the desensitization procedure.
Anaphylactoid reactions during LDL apheresis
In rare cases, life-threatening anaphylactoid reactions may occur in patients receiving ACE inhibitors during LDL apheresis using dextran sulfate. To prevent an anaphylactoid reaction, ACE inhibitor therapy should be discontinued before each LDL apheresis procedure using high-flux membranes.
Hemodialysis
Anaphylactoid reactions have been reported in patients receiving ACE inhibitors during hemodialysis using high-flux membranes (eg, AN69®). Therefore, it is advisable to use a different type of membrane or use an antihypertensive drug of a different pharmacotherapeutic group (see section “With caution”).
Potassium-sparing diuretics and potassium supplements
The combined use of perindopril and potassium-sparing diuretics, as well as potassium preparations and potassium-containing table salt substitutes is not recommended.
Cough
During therapy with an ACE inhibitor, a dry cough may occur, which disappears after discontinuation of drugs in this group. If a dry cough appears, you should be aware of the possible connection of this symptom with taking an ACE inhibitor. If the doctor believes that ACE inhibitor therapy is necessary for the patient, taking Co-Perineva® can be continued.
Children and adolescents under 18 years of age
The drug Co-Perineva® is contraindicated in children and adolescents under 18 years of age due to the lack of data on the effectiveness and safety of use.
Risk of arterial hypotension and/or renal failure in patients with CHF, water and electrolyte imbalance, etc.)
In liver cirrhosis, accompanied by edema and ascites, arterial hypotension, and CHF, significant activation of the renin-angiotensin-aldosterone system (RAAS) may be observed, especially with severe hypovolemia and a decrease in the content of electrolytes in the blood plasma (against the background of a salt-free diet or long-term use of diuretics).
The use of an ACE inhibitor causes blockade of the RAAS, and therefore a sharp decrease in blood pressure and/or an increase in the concentration of creatinine in the blood plasma is possible, indicating the development of acute renal failure, which is more often observed when taking the first dose of Co-Perineva® or during the first two weeks of therapy .
Elderly patients
Before starting to take Co-Perineva®, renal function and potassium levels in the blood plasma should be assessed. The initial dose of Co-Perineva® is selected depending on the degree of reduction in blood pressure, especially with a decrease in blood volume and heart failure (functional class IV according to the NYHA classification). Such measures help to avoid a sharp decrease in blood pressure.
Atherosclerosis
The risk of arterial hypotension exists in all patients, however, special caution should be observed when using the drug Co-Perineva® in patients with coronary heart disease and cerebrovascular insufficiency. In such patients, treatment should begin with a dose of 0.625 mg/2 mg of Co-Perineva® (initial dose).
Patients with renovascular hypertension
Treatment with Co-Perineva in patients with diagnosed or suspected renal artery stenosis should begin in a hospital setting with a dose of Co-Perineva® 0.625 mg/2 mg, monitoring renal function and potassium levels in the blood plasma. Some patients may develop acute renal failure, which is reversible after discontinuation of the drug.
Other risk groups
In patients with CHF (functional class IV according to the NYHA classification) and patients with type 1 diabetes mellitus (risk of spontaneous increase in potassium levels), treatment should begin with an initial dose of 0.625 mg/2 mg of Co-Perineva® and under medical supervision.
Patients with diabetes mellitus
When prescribing Co-Perineva® to patients with diabetes mellitus receiving oral hypoglycemic agents or insulin, blood glucose concentrations should be regularly monitored during the first month of therapy.
Ethnic characteristics
Perindopril (like other ACE inhibitors) has a less pronounced hypotensive effect in patients of the Negroid race compared to representatives of other races.
Surgical interventions/General anesthesia
The use of ACE inhibitors in patients undergoing surgery using general anesthesia may lead to a significant decrease in blood pressure, especially when using general anesthesia agents that have a hypotensive effect.
It is recommended to stop taking ACE inhibitors, including perindopril, 12 hours before surgery, warning the anesthesiologist about the use of ACE inhibitors.
Aortic stenosis/Mitral stenosis/Hypertrophic obstructive cardiomyopathy
ACE inhibitors should be used with caution in patients with left ventricular outflow tract obstruction and aortic and/or mitral stenosis.
Liver failure
In rare cases, cholestatic jaundice occurs while taking ACE inhibitors, and as it progresses, fulminant liver necrosis develops, sometimes with death. If jaundice or a significant increase in the activity of “liver” transaminases occurs while taking ACE inhibitors, taking Co-Perineva® should be discontinued.
Anemia
Anemia can develop in patients after kidney transplantation or in patients on hemodialysis.
Hyperkalemia
May develop during treatment with ACE inhibitors, including perindopril. Risk factors for hyperkalemia are renal failure, old age, diabetes mellitus, some concomitant conditions (decrease in blood volume, acute heart failure in the stage of decompensation, metabolic acidosis), simultaneous use of potassium-sparing diuretics (such as spironolactone, eplerenone, triamterene, amiloride), as well as drugs potassium or potassium-containing substitutes for table salt and the use of other drugs that increase the content of potassium in the blood plasma (for example, heparin). Hyperkalemia can cause serious heart rhythm problems, sometimes fatal. The combined use of the drugs listed above must be carried out with caution.
Indapamide
Photosensitivity
There are reports of cases of increased photosensitivity while taking thiazide and thiazide-like diuretics. If a photosensitivity reaction develops while taking Co-Perineva®, treatment should be discontinued. If there is a need to resume use of the drug Co-Perineva®, you should protect exposed skin from direct exposure to sunlight and artificial ultraviolet rays.
Water and electrolyte balance
Sodium content in blood plasma
|Before starting treatment with Co-Perineva®, it is necessary to determine the sodium content in the blood plasma and, while taking the drug, regularly monitor electrolytes in the blood plasma. All diuretics can cause hyponatremia, leading to serious complications.
Potassium content in blood plasma
Therapy with thiazide and thiazide-like diuretics is associated with a risk of developing hypokalemia (less than 3.4 mmol/l) in the following patients: elderly, malnourished patients, patients with liver cirrhosis, patients with peripheral edema, ascites, coronary heart disease, CHF. Hypokalemia in these patients enhances the toxic effect of cardiac glycosides and increases the risk of developing arrhythmia.
The high-risk group includes patients with an increased QT interval on the ECG.
Hypokalemia, like bradycardia, contributes to the development of severe heart rhythm disturbances, especially arrhythmias, which can be fatal. In all the described cases, regular monitoring of potassium levels in the blood plasma is necessary. The first determination of potassium content in the blood plasma should be carried out within the first week from the start of therapy with Co-Perineva®.
Calcium content in blood plasma
Thiazide and thiazide-like diuretics reduce the excretion of calcium by the kidneys, leading to a slight and temporary increase in calcium levels in the blood plasma. Severe hypercalcemia may be a consequence of latent hyperparathyroidism. Before studying the function of the parathyroid glands, you should stop taking Co-Perineva®.
Plasma glucose concentration
Glucose concentrations should be monitored in patients with diabetes mellitus.
Uric acid
In patients with increased concentrations of uric acid in the blood plasma during therapy with Co-Perineva®, the frequency of exacerbations of gout may increase.
Diuretics and kidney function
Hypovolemia as a result of a decrease in blood volume or hyponatremia caused by taking diuretics at the beginning of treatment with Co-Perineva® can lead to a decrease in glomerular filtration rate I and be accompanied by an increase in concentration; creatinine and urea in blood plasma.
Athletes
Indapamide may give a false-positive reaction during doping control.
Analogs
Level 4 ATX code matches:
Akkuzid
Enap-N
Iruzid
Co-Diroton
Enalozide
Enap NL
Enapril-N
Capozide
Tritace Plus
Enzix
Liprazid
Co-Renitec
Hartil N
Hartil D
Noliprel
Kaptopres
special instructions
It is not recommended to take it in parallel with lithium preparations.
Therapy is strictly contraindicated in patients with impaired renal function. Patients suffering from hypertension may experience symptoms of renal failure . In this case, you should stop treatment with Co-Perineva. Later, therapy can be repeated, prescribing minimal doses, or indapamide and perindopril can be used in monotherapy. These patients should have their blood creatinine and potassium levels checked every two weeks.
The combination of indapamide and perindopril cannot prevent the development of hypokalemia , especially in cases where the patient has diabetes mellitus or renal failure. In this case, the level of potassium in the blood must be monitored regularly.
Co-Prenessa®
With the simultaneous use of
lithium
and indapamide, careful monitoring of the concentration of lithium in the blood plasma and dosage adjustment are necessary; it is possible to increase the concentration of lithium in the blood plasma with symptoms of overdose, as well as with a salt-free diet (decreased lithium excretion in the urine).
With astemizole, bepridine, erythromycin (with intravenous administration), halofantrine, pentamidine, sultopride, terfenadine and vincamine, class IA antiarrhythmic drugs (quinidine, disopyramide, amiodarone, bretylium, sotalol)
- the likelihood of cardiac dysfunction increases. Risk factors include hypokalemia, bradycardia, and previous prolongation of the QT interval.
With non-steroidal anti-inflammatory drugs
(when administered systemically), high doses of salicylates - there is a risk of acute renal failure in dehydrated patients (decreased glomerular filtration rate). It is necessary to compensate for fluid loss and monitor renal function at the beginning of treatment.
With amphotericin B (iv), gluco- and mineralocorticosteroids (if administered systemically), tetracosactide, laxatives that stimulate intestinal motility, cardiac glycosides
- the risk of hypokalemia increases (additive effect). It is necessary to monitor the level of potassium in the blood plasma, an ECG, and, if necessary, prescribe appropriate treatment.
With baclofen
- increased hypotensive effect.
With cyclosporine
- an increase in the concentration of creatinine in the blood plasma, with an unchanged concentration of circulating cyclosporine.
With tricyclic antidepressants, antipsychotics
- the hypotensive effect of indapamide is enhanced and the risk of developing orthostatic hypotension increases (additive effect).
With antihypertensive drugs
- increased risk of severe arterial hypotension.
With iodine-containing radiocontrast agents
(in high doses) - dehydration and increased risk of developing acute renal failure. Before using iodine-containing contrast agents, patients must compensate for fluid loss.
With calcium salts
- an increase in the concentration of calcium ions in the blood plasma due to a decrease in their excretion in the urine.
With potassium-sparing diuretics (amiloride, spironolactone, triamterene)
- the risk of developing hypokalemia or hyperkalemia, especially in patients with diabetes mellitus and patients with impaired renal function.
With hypoglycemic drugs
(insulin, sulfonamides)
- ACE inhibitors can enhance the hypoglycemic effect in patients with diabetes.
With painkillers
- enhancing the hypotensive effect of angiotensin-converting enzyme (ACE) inhibitors.
With allopurinol, cytotoxic or immunosuppressive drugs, systemically administered corticosteroids, or procainamide
- risk of developing leukopenia.
Ko-Perineva price, where to buy
The cost of the drug in Russia on average is about 500 rubles per package of 1.25 mg + 4 mg 30 pcs. and 900 rubles for 1.25 mg + 4 mg 90 pcs. packaged.
- Online pharmacies in RussiaRussia
ZdravCity
- KO-Perineva tablets 4mg+1.25mg 30 pcs. Krka-Rus LLC
502 rub. order - KO-Perineva tablets 8mg+2.5mg 90 pcs. Krka-Rus LLC
RUB 1,141 order
- KO-Perineva tablets 8mg+2.5mg 30 pcs. Krka-Rus LLC
RUR 617 order
- KO-Perineva tablets 2mg+0.625mg 30 pcs. Krka-Rus LLC
RUB 344 order
- KO-Perineva tablets 4mg+1.25mg 90 pcs. Krka-Rus LLC
RUR 978 order
Co-Prenessa tablets 4mg/1.25mg No. 10x3
Name
Co-Prenessa.
Release forms
Pills.
INN
Perindopril + indapamide.
FTG
Combination antihypertensive agent (ACE blocker + diuretic).
Compound
Co-Prenessa 2 mg/0.625 mg tablets Each tablet contains 2 mg perindopril erbumine and 0.625 mg indapamide. Co-Prenessa 4 mg/1.25 mg tablets Each tablet contains 4 mg perindopril erbumine and 1.250 mg indapamide. Excipients: calcium chloride hexahydrate, lactose monohydrate, crospovidone, microcrystalline cellulose, sodium bicarbonate, hydrated colloidal silicon dioxide, magnesium stearate.
Description
Co-Prenessa 2 mg/0.625 mg tablets Round, slightly biconvex, white or off-white tablets with beveled edges and a short line engraved on one side. Co-Prenessa 4 mg/1.25 mg tablets Round, slightly biconvex tablets of white or almost white color with beveled edges and a score on one side.
Pharmacotherapeutic group
Drugs that affect the renin-angiotensin system. ACE inhibitors in combination with diuretics. ATX code: C09BA04.
Pharmacological properties
Pharmacodynamics
Co-Prenessa is a complex drug containing an angiotensin-converting enzyme (ACE) inhibitor - perindopril erbumine and a chlorosulfamoyl (thiazide-like) diuretic - indapamide. The pharmacological effect of the drug is due to the properties of each of these components, taken separately, as well as the additive synergistic effect of both components when combined.
Pharmacodynamic properties
Related to perindopril Perindopril is an angiotensin converting enzyme inhibitor (ACE inhibitor), which converts angiotensin I to angiotensin I, belongs to the class of vasoconstrictors; In addition, the enzyme stimulates the secretion of aldosterone by the adrenal cortex and stimulates the breakdown of bradykinin, a vasodilator, into inactive heptapeptides. This leads to: - a decrease in aldosterone secretion, - an increase in plasma renin activity due to a decrease in the effect of aldosterone on negative feedback, - a decrease in total peripheral resistance with a predominant effect on the vascular bed in the muscles and kidneys, without concomitant water and salt retention or reflex tachycardia with constant treatment. The antihypertensive effect of perindopril is also observed in patients with low or normal renin concentrations. Perindopril acts through its active metabolite, perindoprilate. Other metabolites are inactive. Perindopril reduces cardiac workload: by a vasodilatory effect on the veins, possibly caused by changes in prostaglandin metabolism: decreased preload, by reduced total peripheral resistance: decreased afterload. Studies conducted on patients with heart failure have revealed: a decrease in left and right ventricular filling pressure, a decrease in total peripheral vascular resistance, an increase in cardiac output and an improvement in cardiac performance index, and an increase in regional blood flow in the muscle. Exercise test results also showed improvement. Related to indapamide Indapamide is a sulfonamide derivative with an indole ring, pharmacologically belonging to the group of thiazide diuretics. Indapamide inhibits sodium reabsorption in the cortical segment. It increases the urinary excretion of sodium and chloride and at least the excretion of potassium and magnesium, thereby increasing diuresis and having an antihypertensive effect. Characteristics of the antihypertensive effect Associated with Co-Preness In patients with high blood pressure, regardless of age, the drug has a dose-dependent antihypertensive effect on diastolic and systolic blood pressure in both the supine and standing positions. The antihypertensive effect lasts for 24 hours. Blood pressure reduction is achieved in less than one month without tachyphylaxis. Stopping treatment does not cause withdrawal syndrome. During clinical studies, the simultaneous administration of perindopril and indapamide caused a synergistic antihypertensive effect relative to each drug prescribed separately. Co-Prenessa tablets 2 mg/0.625 mg alone The effect of the combination with a low dose of Co-Prenessa 2 mg/0.625 mg on cardiovascular morbidity and mortality has not yet been studied. PICXEL, a multicenter, randomized, double-blind, active-controlled study, assessed the effect of perindopril/indapamide combination on LVH on echocardiography compared with enalapril monotherapy. In the PICXEL trial, patients with elevated blood pressure with LVH (defined as left ventricular mass index (LVMI) > 120 g/m2 in men and > 100 g/m2 in women) were randomized to either perindopril 2 mg/indapamide 0.625 mg. or enalapril 10 mg once daily for one year. The dosage was adjusted according to blood pressure control up to 8 mg perindopril and 2.5 mg indapamide or up to 40 mg enalapril once a day. Only 34% of patients continued treatment with perindopril 2 mg/indapamide 0.625 mg (compared to 20% with enalapril 10 mg). At the end of treatment, LVMI decreased significantly more in the perindopril/indapamide group (-10.1 g/m2) than in the enalapril group (-1.1 g/m2) in all randomized groups of patients. The difference in change in LVMI between groups was 8.3 (95% CI (-11.5-5.0), p
Pharmacokinetics
Related to Co-Preness The pharmacokinetic properties of perindopril and indapamide combination are not changed compared to their separate use. Associated with perindopril Following oral administration, perindopril is rapidly absorbed and reaches peak concentrations within 1 hour. The half-life is 1 hour. Perindopril is a prodrug. 27% of the administered dose of perindopril reaches the bloodstream in the form of the active metabolite perindoprilate. In addition to the active perindoprilate, perindopril forms five inactive metabolites. Peak plasma concentrations of perindoprilate are reached after 3-4 hours. Since food intake reduces the conversion of perindopril to perindoprilat, and, consequently, its bioavailability, perindopril tert-butylamine is recommended to be taken orally once a day in the morning before meals. It has been shown that the relationship between the dose of perindopril and its plasma levels is a linear function. The volume of distribution of unbound perindoprilate is approximately 0.2 l/kg. The binding of perindoprilate to plasma protein is 20%, mainly binding to the angiotensin converting enzyme and depends on the concentration of the drug. Perindoprilat is excreted in the urine. The terminal half-life of the unbound fraction is approximately 17 hours. The state of equilibrium is achieved within 4 days. The elimination of perindoprilate is reduced in the elderly and in patients with cardiac or renal failure. Dose selection for patients with renal failure depends on the degree of renal dysfunction (creatinine clearance). The dialysis clearance of perindoprilate is 70 ml/min. The kinetics of perindopril changes in patients with cirrhosis: the hepatic clearance of the parent molecule is reduced by half. However, the amount of perindoprilate formed is not reduced and, therefore, no dose adjustment is required. Bound to indapamide, indapamide is rapidly and completely absorbed from the digestive tract. Peak plasma concentrations in humans are achieved approximately one hour after oral administration of the drug. Plasma protein binding is 79%. The half-life period ranges from 14 to 24 hours (average 18 hours). Repeated administration of the drug does not lead to its accumulation in the body. It is excreted mainly in urine (70% of the dose) and feces (22%) in the form of inactive metabolites. Pharmacokinetics do not change in patients with renal failure.
Indications for use
Co-Prenessa 2 mg/0.625 mg and 4 mg/1.25 mg Primary arterial hypertension. Co-Prenessa 4 mg/1.25 mg Co-Prenessa tablets 4 mg/1.25 mg are prescribed to patients when blood pressure is not sufficiently controlled with perindopril monotherapy.
Contraindications
Perindopril-related Hypersensitivity to perindopril or any other ACE inhibitors. History of angioedema (Quincke's edema) associated with taking ACE inhibitors. Hereditary or idiopathic angioedema. Second and third trimesters of pregnancy. The simultaneous use of Co-Prnessa and aliskiren-containing drugs is contraindicated in patients with diabetes mellitus or renal failure (GFR
Directions for use and doses
For oral administration. Co-Prenessa 2 mg/0.625 mg The usual dose is 1 tablet 1 time per day, preferably in the morning before meals. If after one month of treatment the blood pressure is not controlled, the dosage may be doubled. Co-Prenessa 4 mg/1.25 mg Co-Prenessa tablets 4 mg/1.25 mg are prescribed in cases where blood pressure control cannot be achieved by taking Co-Prenessa tablets 2 mg/0.625 mg. The usual dose is 1 tablet 1 time per day, preferably in the morning before meals. Individual dose selection is carried out, if possible, by each component separately. If clinically necessary, it is possible to prescribe Co-Preness tablets 4 mg/1.25 mg if perindopril monotherapy is ineffective. Elderly patients Co-Press 2 mg/0.625 mg Initial dose - 1 tablet 1 time per day. Co-Prenessa 4 mg/1.25 mg Treatment should be initiated after assessing blood pressure response and renal function. Patients with impaired renal function Co-Press 2 mg/0.625 mg and 4 mg/1.25 mg In case of severe impaired renal function (creatinine clearance below 30 ml/min), treatment is contraindicated. For patients with moderate renal impairment (creatinine clearance 30-60 ml/min), the maximum dose of Co-Prenessa is 2 mg/0.625 mg - 1 tablet once a day. Co-Prenessa 4 mg/1.25 mg In patients with moderate renal impairment (creatinine clearance 30-60 ml/min), it is recommended to begin treatment with an adequate dose of the free combination. Patients with creatinine clearance greater than or equal to 60 ml/min do not require dose modification. Routine medical monitoring should include frequent monitoring of creatinine and potassium. Patients with impaired liver function Treatment is contraindicated in cases of severe hepatic impairment. No dose modification is required in patients with moderate hepatic impairment.
Children and teenagers
Co-Prenessa tablets 2 mg/0.625 mg and tablets 4 mg/1.25 mg should not be prescribed to children and adolescents, since the effectiveness and tolerability of perindopril in mono- or combination therapy in this category of patients have not been established. Co-Press tablets should be taken regularly, every day. If a drug dose is missed, the patient should continue treatment according to the prescribed regimen without doubling the dose.
Side effect
Taking perindopril inhibits the renin-angiotensin-aldosterone system and reduces potassium loss caused by indapamide. Hypokalemia (potassium level
Manufacturer
KRKA, d.d., Slovenia, Slovenia
Instructions
Instructions for the drug 737.33kB
