Perindopril
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Clinical Pharmacology
ACE inhibitor. It is a prodrug from which the active metabolite of perindoprilat is formed in the body. It is believed that the mechanism of antihypertensive action is associated with competitive inhibition of ACE activity, which leads to a decrease in the rate of angiotensin I conversion to angiotensin II, which is a potent vasoconstrictor. As a result of reducing the concentration of angiotensin II, a secondary increase in plasma renin activity occurs due to the elimination of negative feedback during renin release and a direct decrease in aldosterone secretion. Due to the vasodilating action, it reduces the round fissure (afterload), the jamming pressure in the pulmonary capillaries (preload) and the resistance in the pulmonary vessels; increases heart volume and load tolerance.
The antihypertensive effect develops within the first hour after taking perindopril, reaches a maximum by 4-8 hours and lasts for 24 hours.
Indications
Arterial hypertension, chronic heart failure.
Composition
perindopril 8 mg.
Perindopril is marketed under different brands and generic names, and comes in different dosage forms:
Brand name | Manufacturer | Country | Dosage form |
---|---|---|---|
Perindopril | Izvarino Pharma | Russia | pills |
Perindopril-SZ | North Star | Russia | pills |
Perindopril-Teva | Teva | Israel | pills |
Prestarium A | Servier | Ireland, Ireland, Russia | pills |
Perineva | Krka dd Novo mesto AO | Slovenia | pills |
Prestarium A | Servier | France, France, Russia | pills |
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Dosage and Administration
Orally, in the morning, before eating. The initial dose for the treatment of hypertension is 4 mg / day, if necessary (after 1 month), the dose can be increased to 8 mg / day in a single dose. When prescribing ACE inhibitors to patients receiving diuretic therapy, there may be a sharp decrease in blood pressure, for the prevention of which it is recommended to stop taking diuretics 2-3 days before the expected start of therapy with Perindopril or prescribe the drug in lower doses - 2 mg 1 time per day.
In patients with renovascular hypertension, the initial dose is 2 mg 1 time per day. If necessary, the subsequent dose may be increased.
In elderly patients, therapy should begin with a dose of 2 mg per day, and subsequently, if necessary, gradually increase it up to a maximum dose of 8 mg per day.
It is recommended to start treatment of patients with heart failure in combination with non-Palli-preserving diuretic and / or digoxin under close medical supervision. Perindopril should be administered in an initial dose of 2 mg 1 time per day, in the morning. In the future, after 1-2 weeks of therapy, the dose of the drug can be increased to 4 mg 1 time per day.
In patients with impaired renal function, the dose of the drug should be selected based on the degree of renal failure: depending on creatinine clearance (CK). With CC 30-60 ml / min - 2 mg once a day; with CC 15-30 ml / min - 2 mg every other day; patients on hemodialysis (CC less than 15 ml / min) - 2 mg per day dialysis. When QA more than 60 ml / min, 4 mg per day. Patients with impaired liver function, changes in the dose of Perindopril is not required.
Adverse reactions
- From the side of the cardiovascular system: often - excessive reduction of arterial pressure, pressure and associated symptoms, rarely - arrhythmia, angina pectoris, myocardial infarction and stroke.
- From the urinary system: reduced kidney function, acute renal failure.
- On the part of the respiratory system: often - "dry" cough, difficulty breathing; rarely - bronchospasm, rhinorrhea.
- On the part of the digestive system: often - nausea, vomiting, abdominal pain, change in taste, diarrhea or constipation, dry mouth, decreased appetite, cholestatic jaundice, pancreatitis, intestinal edema.
- From the side of the central nervous system: often - headache, asthenia, fatigue, dizziness, tinnitus, visual disturbances, muscle cramps, paresthesias; rarely - lowering mood, insomnia; extremely rare - confusion.
- Allergic reactions: often - skin rash, itching; rarely - urticaria, angioedema; extremely rare - erythema multiforme exudative. -
Laboratory indicators: often - hypercreatininemia, proteinuria, hyperkalemia; hyperuricemia; rarely (with prolonged use in high doses) - neutropenia, leukopenia, hypohemoglobinemia, thrombocytopenia, decrease in hematocrit; extremely rarely - agranulocytosis, pancytopenia, increased activity of "liver" enzymes, hyperbilirubinemia, hemolytic anemia (against the background of a deficiency of glucose-6-phosphate dehydrogenase).
- Other: increased sweating, impaired sexual function.
Contraindications
Hypersensitivity to perindopril and other components of the drug or other ACE inhibitors, angioedema in the history of the background, therapy with inhibitors. ACE, hereditary or idiopathic angioedema, pregnancy, lactation, age 18 years (efficacy and safety have not been established).
With caution: Aortic stenosis, hypertrophic obstructive cardiomyopathy, cerebrovascular diseases (including cerebrovascular insufficiency, coronary heart disease, coronary insufficiency - the risk of excessive blood pressure reduction and concomitant ischemia). Severe autoimmune systemic diseases of the connective tissue (incl.systemic lupus erythematosus, scleroderma), inhibition of bone marrow hematopoiesis in patients receiving immunosuppressants (increased likelihood of developing neutropenia). Renovascular hypertension, bilateral renal artery stenosis, single kidney artery stenosis, a condition after kidney transplantation (risk of developing renal dysfunction and agranulocytosis), chronic renal failure (especially accompanied by hyperkalemia), hyperkalemia, sodium-restricted diet, conditions accompanied by a decrease in circulating blood volume (including diarrhea, vomiting, diuretic intake), diabetes mellitus, advanced age, surgery (general anesthesia).
Drug interactions
Increases the severity of the hypoglycemic effect of insulin and sulfonylurea derivatives. Baclofen, tricyclic antidepressants, antipsychotic drugs (neuroleptics), saluretics enhance the hypotensive effect and increase the risk of orthostatic hypotension (additive effect), antacids reduce the bioavailability of ACE inhibitors. Glucocorticosteroids, nonsteroidal anti-inflammatory drugs reduce the severity of the hypotensive effect (fluid and electrolyte retention). Potassium-sparing diuretics (spironolactone, triamterene, amiloride), potassium preparations increase the risk of hyperkalemia. The simultaneous use of drugs that can cause hyperkalemia and ACE inhibitors is not recommended, except in cases of severe hypokalemia (control of serum potassium). With simultaneous use with lithium preparations it is possible to slow its elimination from the body (regular monitoring of the lithium content in the blood is necessary). Diuretics, general anesthetic drugs and muscle relaxants, ethanol increase the risk of excessive blood pressure reduction. The risk of developing clinically significant arterial hypotension can be reduced by stopping diuretic administration several days before starting treatment with Perindopril.
Special instructions
The risk of arterial hypotension and / or renal insufficiency while taking the drug increases with significant loss of sodium and water (strict salt-free diet and / or diuretic administration, diarrhea, vomiting) or stenosis of the renal arteries (blockade of the renin-angiotensin system in these situations may result , especially with the first dose of the drug and during the first 2 weeks of treatment, to a sudden decrease in blood pressure and the development of chronic renal failure). Before and during therapy, it is recommended to determine the concentration of creatinine, electrolytes and urea (for 1 month). In patients with arterial hypertension who are already receiving diuretic therapy, they should be discontinued (3 days before the initiation of perindopril) and, if necessary, be added to the treatment again. In patients with chronic heart failure receiving diuretic therapy, if possible, their dose should also be reduced several days before the start of treatment. In patients at risk, especially with chronic heart failure in the stage of decompensation, elderly patients, as well as patients with initially low blood pressure, impaired renal function or receiving large doses of diuretics, the drug should be started under control. In patients on hemodialysis, the use of polyacrylonitrile membranes should be avoided (anaphylactoid reactions may develop). It is necessary to stop taking before the upcoming surgery for 12 hours and warn the anesthesiologist about taking the drug.
Influence on ability to driving of the car and performance of the works demanding special attention.
Due to the risk of arterial hypotension and dizziness, ACE inhibitors should be carefully prescribed to those who drive vehicles and engage in activities requiring increased attention and quick motor response.
Overdosage
Symptoms: marked reduction in blood pressure, shock, stupor, bradycardia, electrolyte disturbances (hyperkalemia, hyponatremia), renal failure.
Treatment: gastric lavage, restoration of the water-electrolyte state, intravenous administration of a 0.9% sodium chloride solution. In the case of a pronounced decrease in the blood pressure of the patient, it is necessary to lay horizontally, raising the legs up. Hemodialysis is effective (do not use highly permeable polyacrylonitrile membranes). With the development of bradycardia - atropine, may require staging of an artificial pacemaker.
- Brand name: Perindopril
- Active ingredient: Perindopril
- Manufacturer: Izvarino Pharma
- Country of Origin: Russia
Studies and clinical trials of Perindopril (Click to expand)
- Structural and conformational analysis by 1H NMR and 13C NMR of a new angiotensin I converting enzyme inhibitor, the tert-butylamine salt of (2S)-2-[(1S)-1-carbethoxybutylamino]-1-oxopropyl-(2S, 3aS, 7aS) perhydroindole-2-carboxylic acid (perindopril)
- The use of microcalorimetry and HPLC for the determination of degradation kinetics and thermodynamic parameters of Perindopril Erbumine in aqueous solutions
- Crystal and molecular structure of perindopril erbumine salt
- A new radioimmunoassay for the determination of the angiotensin-converting enzyme inhibitor Perindopril and its active metabolite in plasma and urine: Advantages of a lysine derivative as immunogen to improve the assay specificity
- Molecular structure and stability of perindopril erbumine and perindopril l-arginine complexes
- First LC–MS/MS electrospray ionization validated method for the quantification of perindopril and its metabolite perindoprilat in human plasma and its application to bioequivalence study
- Evaluation of impurities level of perindopril tert-butylamine in tablets
- On-line simultaneous determination of S- and R-perindopril using amperometric biosensors as detectors in flow systems
- Gas chromatography—mass spectrometry of perindopril and its active free metabolite, an angiotensin convertase inhibitor: choice of derivatives and ionization modes
- Comparison of spectrophotometric and an LC method for the determination perindopril and indapamide in pharmaceutical formulations
- Utility of certain π-acceptors for the spectrophotometric determination of perindopril
- Spectrophotometric and atomic absorption spectrometric determination of ramipril and perindopril through ternary complex formation with eosin and Cu(II)
- Further evidence that chronic perindopril treatment maintains neurohormonal suppression but does not lower blood pressure in chronic cardiac failure
- Perindopril postmarketing surveillance: a 12 month study in 47 351 hypertensive patients
- Persistence of anti-hypertensive effect after missed dose of perindopril
- LOW DOSE INDAPAMIDE PLUS PERINDOPRIL COMBINATION EFFECTS ON CARDIOVASCULAR STRUCTURE AND FUNCTION IN GENETIC HYPERTENSION
- The albuminuric action of atrial natriuretic peptide is not modified by ACE-inhibition with perindopril in Type 2 diabetes
- Blood Pressure Reduction After the First Dose of Captopril and Perindopril
- Influence of Perindopril on Left Ventricular Global Performance During the Early Phase of Inferior Acute Myocardial Infarction: Assessment by Tei Index
- Fracture risk and the use of a diuretic (indapamide sr) ± perindopril: a substudy of the Hypertension in the Very Elderly Trial (HYVET)
- High-throughput quantification of perindopril in human plasma by liquid chromatography/tandem mass spectrometry: application to a bioequivalence study
- Humoral effects of perindopril in essential hypertension
- The effect of perindopril and hydrochlorothiazide alone and in combination on blood pressure and on the renin-angiotensin system in hypertensive subjects