Dosage form and composition
Prestarium is produced in the form of tablets for oral use. The active ingredient of the product is perindopril salt. The substance blocks the activity of the enzyme hormone angiotensin, which provokes an increase in blood pressure. The drug has several varieties, differing in dosage and content of auxiliary compounds:
- Prestarium tablets: containing 2, 4 and 8 mg. perindopril;
- Prestarium A: with an increased dosage: 2.5, as well as 5 and 10 mg;
- Bi-Prestarium: tablets in double dosage containing amlodipine, a calcium channel blocker.
All types of Prestarium have a similar effect, but they are prescribed for varying severity of hypertension.
How does Prestarium work?
The drug reduces the production of the hormone aldosterone, the breakdown of bradykinin and renin activity. The decrease in blood pressure as a result of taking it is not accompanied by a disturbance in heart rate. The use of Prestarium has a beneficial effect on renal blood flow. In this case, the main functions of the organs are not affected. During treatment, the size of the enlarged left ventricle is normalized, and the elasticity of the coronary and other large vessels improves. Prestarium containing amlodipine has a complex effect:
- dilates blood vessels;
- normalizes blood flow in the heart vessels and capillaries;
- reduces the load on the myocardium, improves its blood supply.
The medicine does not affect cholesterol metabolism and does not lead to metabolic disorders. The therapeutic effect develops within 1 hour after taking the tablets. It has a cumulative mechanism of action, the maximum is observed on days 4–5 from the start of the course and persists throughout its entire duration. Metabolites of the drug are excreted in the urine. Its remains do not accumulate inside the body. After withdrawal, patients do not exhibit addiction syndrome.
Interactions of the drug Bi-prestarium
All warnings associated with each of the components of the drug apply to the drug Bi-Prestarium. For perindopril, simultaneous use with:
- potassium-sparing diuretics, potassium supplements, or potassium salt substitutes, as these may significantly increase serum potassium levels. Their simultaneous use with Bi-Prestarium is not recommended. If concomitant use is indicated due to the presence of documented hypokalemia, they should be used with caution. It is necessary to monitor blood plasma potassium levels;
- lithium Concomitant use of lithium and ACE inhibitors is not recommended due to the possible occurrence of a reverse increase in the concentration of lithium in the blood serum and, accordingly, an increase in its toxicity (severe neurotoxicity). However, if this is truly necessary, serum lithium concentrations should be carefully monitored;
- estramustine - increased risk of angioedema.
Drugs that require monitoring when co-administered: NSAIDs, including acetylsalicylic acid at a dose of ≥3 g/day, may increase the risk of renal impairment, including acute renal failure, and increased serum potassium levels, especially in patients with existing impairment kidney function. Prescribe with caution, especially for elderly patients. Periodic monitoring of renal function is necessary. Antidiabetic agents (insulin, hypoglycemic sulfonamides): when used simultaneously with ACE inhibitors, the hypoglycemic effect may be enhanced (possibly due to increased glucose tolerance). Diuretics: to reduce the risk of arterial hypotension, it is recommended to stop taking diuretics and restore water and electrolyte balance before starting treatment with ACE inhibitors. Sympathomimetics may reduce the antihypertensive effects of ACE inhibitors. Gold : with the simultaneous use of ACE inhibitors, including perindopril, and injectable gold preparations (sodium aurothiomalate), reactions similar to those with the use of nitrates (facial redness, hot flushes, nausea, vomiting and hypotension) may rarely occur. For amlodipine, simultaneous administration of: Dantrolene (infusion): simultaneous administration of dantrolene and calcium antagonists is not recommended due to the risk of ventricular fibrillation. Drugs for which simultaneous use requires caution Inducers of CYP 3A4 (rifampicin, hypericum perforatum, anticonvulsants such as carbamazepine, phenobarbital, fosphenytoin, phenytoin, primidone): simultaneous use may lead to a decrease in the concentration of amlodipine in the blood plasma. Amlodipine should be prescribed in combination with CYP3A4 inducers with caution; if necessary, the dose of amlodipine can be adjusted. CYP3A4 inhibitors (itraconazole, ketoconazole): simultaneous use may increase the plasma concentration of amlodipine and the incidence of its side effects. Amlodipine should be prescribed in combination with these drugs with caution; if necessary, the dosage of amlodipine can be changed. β-receptor blockers used for heart failure (bisoprolol, carvedilol, metoprolol): risk of arterial hypotension, cardiac weakness in patients with heart failure (both latent and uncontrolled). Co-administration of amlodipine is safe with thiazide diuretics, ACE inhibitors, β-receptor blockers, long-acting nitrates, sublingual nitroglycerin, digoxin, warfarin, atorvastatin, sildenafil, drugs to reduce gastric acidity (aluminum hydroxide gel, magnesium hydroxide, simethicone), cimetidine, NSAIDs , antibiotics and oral hypoglycemic drugs. Consuming grapefruit juice does not significantly affect the pharmacokinetics of amlodipine. General properties of perindopril and amlodipine Drugs whose simultaneous administration requires monitoring: baclofen - may enhance the antihypertensive effect; antihypertensive drugs (such as beta-receptor blockers) and vasodilators : the simultaneous use of these drugs may enhance the hypotensive effect of perindopril and amlodipine; α-receptor blockers (prazosin, alfuzosin, doxazosin, tamsulosin, terazosin): enhance the antihypertensive effect and increase the risk of orthostatic hypotension; GCS, tetracosactide : weakening of the antihypertensive effect (through the retention of water and salts of GCS); amifostine : may enhance the hypotensive effect; tricyclic antidepressants/antipsychotics/anesthetics : increased antihypertensive effect and increased risk of orthostatic hypotension.
When is Prestarium shown?
The drug alleviates the physical condition of various cardiovascular pathologies:
- hypertension;
- chronic heart failure;
- for coronary heart disease: in stable condition;
- after a transient ischemic attack;
Prestarium can also be prescribed as a prevention of heart attack as part of complex treatment: in combination with other drugs.
Contraindications to the use of the drug Bi-prestarium
Hypersensitivity to perindopril (or any other ACE inhibitors), amlodipine (or other dihydropyridines) or to any excipient; history of angioedema associated with previous treatment with ACE inhibitors; congenital or idiopathic angioedema; During pregnancy and breastfeeding; severe arterial hypotension; shock, including cardiogenic; obstruction of the exit from the left ventricle (for example, clinically significant aortic stenosis); unstable angina (with the exception of Prinzmetal angina); heart failure after acute myocardial infarction (during the first 28 days).
Contraindications
Prestarium is prohibited for use in the following pathologies:
- angioedema;
- intolerance to ACE inhibitors;
- galactosemia.
Breastfeeding and pregnancy at all stages are also reasons to exclude the drug from the treatment regimen. The drug should be used with caution in cases of electrolyte imbalance, after internal organ transplantation, aortic valve stenosis, and systemic connective tissue pathologies. Patients on hemodialysis or taking antidepressants should carefully select the dosage and monitor their well-being. Conditions accompanied by excessive vomiting, diarrhea, dehydration, and renal failure also require special attention.
Instructions for use PRESTARIUM®
Stable ischemic heart disease
If episodes of unstable angina (severe or not) occur during the first month of taking perindopril, it is recommended that a careful assessment of the risk/benefit ratio be carried out before continuing treatment.
Arterial hypotension
ACE inhibitors may cause a decrease in blood pressure. Arterial hypotension with clinical manifestations rarely develops in patients with arterial hypertension without concomitant diseases, more often it occurs in patients with reduced blood volume (taking diuretics, on a diet with limited salt intake, patients on dialysis, patients with diarrhea or vomiting) or in patients with severe renin-dependent hypertension. Symptomatic hypotension has been reported in patients with symptomatic severe heart failure with or without concomitant renal failure. Arterial hypotension may more often develop in patients with more severe heart failure, as a result of taking high-dose loop diuretics, hyponatremia, or functional renal failure. Patients at increased risk of developing symptomatic hypotension should be closely monitored during initiation of therapy and during dose adjustments. A similar approach should also be followed when treating patients with ischemia and/or cerebrovascular disease, in whom severe hypotension can lead to myocardial infarction or stroke.
If arterial hypotension develops, it is necessary to place the patient on his back and, if necessary, replenish the blood volume by intravenous administration of 0.9% sodium chloride solution. Transient arterial hypotension is not a contraindication for further use of the drug, which can be continued after blood pressure has increased again after an increase in blood volume.
In some patients with congestive heart failure with normal or low blood pressure, taking Prestarium® may lead to an additional decrease in systemic blood pressure (usually does not require discontinuation of the drug). If clinical manifestations of arterial hypotension develop, it may be necessary to reduce the dose or discontinue taking Prestarium®.
Aortic stenosis, mitral stenosis, hypertrophic cardiomyopathy
Like other ACE inhibitors, Prestarium should be administered with extreme caution to patients with mitral valve stenosis and left ventricular outflow obstruction, for example, aortic stenosis or hypertrophic cardiomyopathy.
Renal dysfunction
In case of impaired renal function (creatinine clearance < 60 ml/min), the initial dose should be adjusted according to the patient's creatinine clearance and then depending on the patient's response to treatment. Potassium and creatinine levels need to be monitored.
If arterial hypotension develops at the beginning of therapy with ACE inhibitors in patients with heart failure with clinical manifestations, further deterioration of renal function is possible. There are reports of the development of acute renal failure, which is usually reversible.
In some patients with bilateral renal artery stenosis or solitary renal artery stenosis taking ACE inhibitors, there have been cases of increases in blood urea and serum creatinine, reversible after discontinuation of therapy (more common in patients with renal failure). With renovascular hypertension there is also an increased risk of severe hypotension and renal failure. Treatment of such patients should be initiated under close medical supervision, with low doses and careful dose titration. Since diuretics may be a factor contributing to the development of the conditions described above, in the first weeks of treatment with Prestarium®, diuretics should be discontinued and renal function should be constantly monitored.
In some patients with arterial hypertension without visible renal vascular impairment, an increase in blood urea and serum creatinine concentrations was observed, usually slight and transient, especially in the case of concomitant use of Prestarium® and diuretics. These changes are most likely in patients with existing renal impairment. In this case, it may be necessary to reduce the dose and/or stop taking the diuretic and/or Prestarium.
Patients on hemodialysis
In some patients undergoing hemodialysis using high-flux membranes and simultaneously receiving ACE inhibitors, cases of anaphylactoid reactions have been reported. For such patients, the use of a different type of membrane or a different class of antihypertensive drug should be considered.
Kidney transplant
There is no experience with the use of Prestarium® in patients with recent kidney transplantation.
Hypersensitivity/angioedema
Rarely, angioedema of the face, extremities, lips, mucous membranes, tongue, vocal cords and/or larynx has been reported. These reactions may occur at any time during therapy. In such cases, Prestarium should be stopped immediately and appropriate monitoring should be carried out until symptoms disappear completely. Typically, when swelling affected only the face and lips, it resolved without any treatment, although antihistamines helped relieve symptoms.
Angioedema that extends to the larynx can be fatal. If there is swelling of the tongue, vocal cords or larynx, which may lead to airway obstruction, appropriate measures should be taken immediately. Emergency care may include giving epinephrine (adrenaline) and/or maintaining an airway. The patient should be under medical supervision until symptoms disappear completely and permanently.
An increased risk of developing angioedema while taking ACE inhibitors exists for patients who have had angioedema not associated with taking ACE inhibitors.
In rare cases, angioedema of the intestine has been reported in patients treated with ACE inhibitors. These patients experienced abdominal pain (with or without nausea and vomiting); in several cases there was no previous facial edema and C-1 esterase levels were normal. Angioedema was diagnosed by abdominal CT, ultrasound, or surgery; symptoms resolved after discontinuation of ACE inhibitors. The development of angioedema of the intestine should be taken into account in the differential diagnosis of patients with abdominal pain during treatment with ACE inhibitors.
Anaphylactoid reactions during hemodialysis or LDL apheresis procedures
Rare cases of life-threatening anaphylactoid reactions have been reported in some patients undergoing hemodialysis using high-flux membranes or receiving LDL apheresis using dextran sulfate absorption when prescribed ACE inhibitors. These reactions can be avoided by temporarily discontinuing the ACE inhibitor each time before apheresis.
Anaphylactoid reactions during desensitization
Anaphylactoid reactions have occurred in some patients receiving ACE inhibitors during desensitization therapy (eg, hymenopteric venom). In some patients, these reactions were avoided by temporarily discontinuing the ACE inhibitor, but they occurred again if the drug was taken carelessly.
Liver dysfunction
In rare cases, ACE inhibitors have been associated with a syndrome that begins with cholestatic jaundice and progresses to fulminant hepatic necrosis and (sometimes) death. The mechanism of this syndrome is not yet clear. In patients receiving ACE inhibitors, if jaundice or a marked increase in liver enzyme activity develops, the ACE inhibitor should be discontinued and a thorough medical examination should be performed.
Neutropenia, agranulocytosis, thrombocytopenia, anemia
Neutropenia/agranulocytosis, thrombocytopenia and anemia were observed while taking ACE inhibitors. In patients with normal liver function and in the absence of other complicating factors, neutropenia rarely develops. Perindopril should be used with extreme caution in patients with diffuse connective tissue diseases, while taking immunosuppressants, allopurinol or procainamide, especially in patients with pre-existing liver dysfunction. Some of these patients developed severe infections, in some cases resistant to intensive antibiotic therapy. When prescribing perindopril to such patients, it is recommended to periodically monitor the number of leukocytes in the blood. Patients should report any signs of infectious diseases (eg, sore throat, fever) to their doctor.
Cough
Taking an ACE inhibitor may cause a dry cough. The cough is non-productive and persists while taking the drug, but disappears when it is discontinued. This symptom may have an iatrogenic etiology. Cough caused by taking an ACE inhibitor should be considered in the differential diagnosis of cough.
Surgery, anesthesia
During surgery or during anesthesia with drugs that cause arterial hypotension, Prestarium® can block the formation of angiotensin II, as a result of compensatory release of renin. It is recommended to stop treatment the day before surgery. When arterial hypotension occurs, which is presumably associated with this mechanism of action, the blood volume should be increased.
Hyperkalemia
In some patients treated with ACE inhibitors, incl. perindopril, cases of elevated serum potassium levels have been reported. Risk factors for the development of hyperkalemia include renal failure, deterioration of renal function, age (>70 years), diabetes mellitus, intercurrent events such as dehydration, acute heart failure, metabolic acidosis, concomitant use of potassium-sparing diuretics (eg, spironolactone, eplerenone, triamterene or amiloride), potassium supplements or potassium-containing salt substitutes, or taking other drugs that cause increases in serum potassium (eg, heparin). Taking potassium supplements, potassium-sparing diuretics, or potassium-containing salt substitutes, especially in patients with impaired renal function, may result in significant increases in serum potassium levels. Hyperkalemia can cause serious arrhythmias, sometimes fatal. If concomitant administration of perindopril or the above drugs is considered necessary, they should be taken with caution and with regular monitoring of serum potassium levels.
Diabetes
In diabetic patients already taking oral hypoglycemic agents or insulin, glycemic levels should be carefully monitored, especially during the first month of taking an ACE inhibitor.
Lithium preparations
The combined use of perindopril and lithium is usually not recommended.
Potassium-sparing diuretics, potassium supplements, and potassium-containing salt substitutes
The combination of perindopril with potassium-sparing diuretics, potassium supplements, and potassium-containing salt substitutes is generally not recommended.
Double blockade of the RAAS
Cases of hypotension, syncope, stroke, hyperkalemia, and impaired renal function (including acute renal failure) have been reported in susceptible patients, particularly when receiving combined medications that affect this system. In this regard, double blockade of the RAAS by combined administration of an ACE inhibitor and an angiotensin II receptor antagonist or aliskiren is not recommended.
Combined use with aliskiren in patients with diabetes mellitus or renal failure (GFR < 60 ml/min/1.73 m2) is contraindicated.
Race
When treated with ACE inhibitors, angioedema develops more often in patients of the Black race than in patients of other races.
Like other ACE inhibitors, the effectiveness of perindopril in lowering blood pressure may be lower in patients of the black race than in patients of other races, perhaps the reason for this is that hypertension in black patients very often resolves against the background of low renin levels.
Excipients
Prestarium® tablets contain lactose, so the drug should not be prescribed to patients with rare problems of hereditary lactose intolerance, glucose-galactose malabsorption or lapp lactase deficiency.
Use in pediatrics
Safety and effectiveness of Prestarium in children and adolescents under 18 years of age
have not been established, so prescribing the drug to this category of patients is not recommended.
Impact on the ability to drive vehicles and operate machinery
Prestarium® does not affect the ability to concentrate and the speed of psychomotor reactions. However, in some patients, especially at the beginning of treatment or when combined with other antihypertensive drugs, individual reactions may develop with a decrease in blood pressure. This leads to a deterioration in the ability to drive vehicles and operate machinery.
Preclinical safety data
Reversible renal impairment was observed in oral chronic toxicity studies in rats and monkeys. No mutagenicity was observed in in vivo or in vitro studies. No carcinogenicity was observed in rats or mice with long-term administration.
Reproductive toxicity studies (in rats, mice, rabbits and monkeys) showed no evidence of embryotoxicity or teratogenicity. However, ACE inhibitors as a class have been shown to have adverse effects on late fetal development, resulting in fetal death and congenital disorders in rodents and rabbits; kidney damage and an increase in perinatal and postnatal mortality were observed. No effects on fertility were observed in male or female rats.
Side effects
Prestarium can cause the following undesirable reactions from the body:
- nausea, dry mouth, loss of appetite;
- dry cough;
- increased uric acid levels;
- dizziness, headaches;
- physical weakness, apathy, increased drowsiness;
- depression;
- swelling of the ankles;
- thrombocytopenia, decreased hemoglobin, red blood cells and other blood count disorders.
Allergic reactions may cause skin itching, rashes, swelling of the mucous membranes and skin, and respiratory problems. Men may experience decreased libido. In case of overdose, vascular collapse, bradycardia, and impaired coordination of movements are likely.
How to use Prestarium: instructions
The doctor prescribes the exact treatment regimen depending on the type of disease and the age of the patient. General recommendations:
- The tablets must be taken on an empty stomach, in the morning, with plenty of water; there is no need to chew the drug;
- the prescribed dose is taken once: it can range from 2 to 8 mg per day;
- in acute conditions, the drug is taken no earlier than complete normalization and remission.
For elderly people and other risk groups, the dosage is adjusted downwards. It is prohibited to change the number of tablets on your own. The course of treatment is continued until the physical condition is stabilized and the existing pathologies are normalized. If necessary, Prestarium is taken for several months in a row or continuously. It is allowed to combine it with diuretic medications.
The drug is incompatible with narcotic analgesics, corticosteroid hormones, immunosuppressants, cytostatics, diabetes treatments, antipsychotics, since when taken simultaneously, the risk of side effects mutually increases.
