Pharmacological properties of the drug Valsacor
The active hormone of the renin-angiotensin-aldosterone system is angiotensin II, which is formed from angiotensin I with the participation of ACE. Angiotensin II binds to specific receptors that are located on the cell membranes of various tissues. It has a whole range of physiological effects, exhibiting both direct and indirect effects on the regulation of blood pressure. As a powerful vasoconstrictor, angiotensin II has a direct pressor effect. In addition, it promotes sodium retention and aldosterone secretion. Valsartan is an oral, potent and specific angiotensin II receptor antagonist. Selectively acts on receptors of the AT1 subtype, which are responsible for the action of angiotensin II. When the concentration of angiotensin II in the blood plasma increases after blockade of AT1 receptors by valsartan, stimulation of unblocked AT2 receptors occurs, which regulate the action of AT1 receptors. Valsartan does not exhibit any agonistic activity towards AT1 receptors and has a significantly greater affinity (approximately 20,000 times) for AT1 receptors than for AT2 receptors. Valsartan does not inhibit the activity of ACE, also known as kininase II, an enzyme that converts angiotensin I into angiotensin II and catalyzes the breakdown of bradykinin. Angiotensin II antagonists do not cause cough because they do not affect the activity of ACE and do not increase the production of bradykinin and substance P. In clinical studies in which valsartan was compared with other ACE inhibitors, the incidence of dry cough in patients taking valsartan was significantly lower (P ≤0.05) than in patients using an ACE inhibitor (2.6% compared with 7.9%). In a clinical trial, dry cough was reported in 19.5% of patients taking valsartan, 19.0% of patients taking a thiazide diuretic, compared with 68.5% of patients taking an ACE inhibitor (P≤0.05). Valsartan does not bind to or block other hormonal receptors or ion channels important for the regulation of the cardiovascular system. Treatment of patients with hypertension (arterial hypertension) with valsartan helped reduce blood pressure without affecting heart rate. In most patients, the hypotensive effect develops within 2 hours after a single oral dose, and the maximum effect on blood pressure is observed after 4–6 hours and lasts 24 hours. With repeated administration of the drug at any dose, the maximum reduction in blood pressure is achieved after 2–4 weeks and persists throughout the entire treatment period. With the combined use of hydrochlorothiazide, a significant additional reduction in blood pressure occurs. Discontinuation of valsartan does not cause a sudden increase in blood pressure and other undesirable clinical events in patients. In a long-term study of the use of valsartan in patients with heart failure, it was noted that in patients taking valsartan, there was a decrease in plasma norepinephrine and brain natriuretic peptide levels compared to the initial level. Valsartan produced significant improvements in pulmonary capillary wedge pressure, systemic vascular resistance, cardiac output, and systolic blood pressure. Patients using valsartan experience a significant increase in ejection fraction and a decrease in the internal diameter of the left ventricle compared to the initial state, and a significant decrease in the severity of symptoms of heart failure, including shortness of breath, fatigue, swelling and breath sounds. Valsartan is rapidly absorbed after oral administration, but the amount absorbed varies significantly. The average absolute bioavailability of valsartan is 23%. Valsartan is characterized by multi-exponential elimination kinetics (half-life in the α phase ≤1 hour and half-life in the β phase ≈9 hours). The pharmacokinetics of valsartan in the studied dose range is linear. With repeated administration of the drug, the pharmacokinetic parameters do not change; When the drug is administered once a day, only a slight accumulation of valsartan is observed. Valsartan binds well to serum proteins (94–97%), mostly to albumin. The volume of distribution at steady state is low (≈17 l). Plasma clearance occurs relatively slowly (≈2 L/h) compared to hepatic blood flow (≈30 L/h). The drug is excreted mainly unchanged: 70% of the absorbed amount is in feces, 30% in urine. When valsartan is taken with food, AUC decreases by 48%; however, after 8 hours, the concentration of valsartan in the blood plasma is the same both when taken on an empty stomach and when taken with food. This indicates the possibility of using valsartan regardless of food intake.
Use of the drug Valsacor
AH (arterial hypertension) The recommended dose of Valsacor is 80 mg 1 time per day, regardless of the patient’s age, gender or race. The hypotensive effect is achieved after 2 weeks, and the maximum antihypertensive effect is achieved after 4 weeks of treatment. For patients who do not achieve an adequate reduction in blood pressure, the daily dose can be increased to 160 mg or supplemented with diuretic therapy. There is no need to change the dose in patients with impaired renal or hepatic function of non-biliary origin in the absence of cholestasis. Valsacor can also be taken in combination with other antihypertensive drugs. Heart failure The recommended initial dose is 40 mg 2 times a day. This dose is gradually increased to 80 mg twice daily and then to 160 mg twice daily, the highest dose the patient can tolerate. The maximum daily dose of valsartan is 320 mg. For patients who are simultaneously treated with a diuretic, it is recommended to reduce the dose of Valsacor. Post-myocardial infarction Treatment with the drug can begin 12 hours after myocardial infarction. The initial dose of Valsacor is 20 mg 2 times a day. At the beginning of treatment, it is recommended to use Valsacor 40 mg tablets with a notch on one side. After a few weeks, the dose should be gradually increased to 40, 80 and 160 mg 2 times a day, depending on the patient’s tolerance to treatment. If symptomatic hypotension or renal failure occurs, the dose should be reduced.
Analogs
In cases of ineffectiveness of this drug or its individual intolerance, the doctor selects an analogue or substitute for further treatment. An alternative remedy differs in composition, but is identical in effect.
Identical in composition:
According to the mechanism of action:
The drug does not have hormonal substitutes.
The material was prepared specifically for the website venaprof.ru, edited by pharmacist M.N. Aleksandrova.
Side effects of the drug Valsacor
During treatment with the drug, viral infections, upper respiratory tract infections, rhinitis, sinusitis, and pharyngitis often occurred (≥1%). Nervous system and mental disorders; headache, dizziness; cough; nausea, diarrhea, abdominal pain; back pain and arthralgia; hyperkalemia; fatigue. Rarely (≤1%) rash, itching, insomnia, and swelling were noted; isolated cases of hypersensitivity reactions; very rarely - renal function disorders. The frequency of side effects does not depend on the dose and period of treatment, as well as the gender, race and age of the patient.
Overdose
If you independently increase the dose and frequency of use of the drug, an overdose occurs with subsequent negative manifestations:
In rare cases, collapse and shock with death.
The victim needs to undergo symptomatic therapy - rinse the stomach, induce vomiting, and administer saline intravenously to normalize the water-salt balance.
Special instructions for the use of the drug Valsacor
Caution should be exercised when starting treatment in patients with heart failure after myocardial infarction. They often initially experience a slight decrease in blood pressure, however, if dosing instructions are properly followed, such symptomatic hypotension for the most part does not cause discontinuation of treatment. During treatment with Valsacor, renal function should be regularly checked in patients with heart failure and special caution should be exercised with the combined use of ACE inhibitors, beta-adrenergic blockers and angiotensin II receptor antagonists (AT1 subtype). In debilitated patients and/or with significantly reduced sodium levels (for example, those taking high doses of diuretics), symptomatic hypotension may rarely occur when starting treatment with Valsacor. Before starting therapy, it is necessary to restore the amount of water and sodium in the body (for example, by reducing the dose of the diuretic). If arterial hypotension occurs, the patient should be placed in a horizontal position and, if necessary, given an intravenous infusion of 0.9% sodium chloride solution. After stabilization of blood pressure, treatment with Valsacor can be continued. During therapy, it is recommended to carefully evaluate patients with unilateral or bilateral renal artery stenosis, since drugs that affect the activity of the renin-angiotensin-aldosterone system can cause an increase in serum urea and creatinine levels. The drug should be used with caution in patients with impaired renal function and obstructive diseases of the biliary tract. In this case, the dose should not be reduced. Since Valsacor contains lactose, the drug is not recommended for use in patients with galactosemia, lactase deficiency or impaired glucose/galactose absorption. In patients with hypersensitivity, changes in the functional activity of the kidneys may occur, which are caused by inhibition of the activity of the renin-angiotensin system. Treatment with ACE inhibitors and angiotensin II receptor antagonists (AT1 subtype) should not be carried out in patients whose renal function depends on the activity of the renin-angiotensin-aldosterone system. This can cause oliguria, progressive azotemia, and sometimes acute renal failure or death. Children. The safety and effectiveness of the drug in treating children has not been established. Period of pregnancy or breastfeeding. Given the mechanism of action of angiotensin II receptor antagonists, a risk to the fetus cannot be excluded. It has been shown that the use of ACE inhibitors in the second and third trimester of pregnancy can cause damage and death of the fetus. Like other drugs that act directly on the renin-angiotensin-aldosterone system, Valsacor is not recommended for use during pregnancy. It is not known whether valsartan passes into breast milk, so Valsacor is not recommended for use during breastfeeding. The ability to influence reaction speed when driving vehicles or working with other mechanisms. As with the use of other antihypertensive drugs, during treatment with Valsacor it is recommended to exercise caution when driving vehicles and operating machinery.
Contraindications
The drug is not approved for use in patients:
- patients with diabetes mellitus;
- with cirrhosis of the liver;
- with impaired renal function;
- hypersensitivity to the components of the drug;
- during pregnancy and pregnancy;
- children under 16 years of age.
Use with caution in patients after a kidney transplant.
Interactions of the drug Valsacor
For patients after myocardial infarction, Valsacor can be taken in combination with other drugs, such as thrombolytics, acetylsalicylic acid, beta-adrenergic blockers or statins. When Valsacor is used in combination with potassium-sparing diuretics (such as spironolactone, triamterene, amiloride), potassium preparations or salt substitutes that contain potassium, an increase in the concentration of potassium in the blood serum may occur. There were no signs of clinically significant interaction between Valsacor and other drugs. In clinical studies, drugs such as cimetidine, warfarin, furosemide, digoxin, atenolol, indomethacin, hydrochlorothiazide, amlodipine, and glibenclamide were studied. Since Valsacor does not undergo significant metabolism, it is unlikely that clinically significant interactions in the form of metabolic induction or inhibition of the cytochrome P450 system will occur. Valsartan binds well to plasma proteins, but in vitro did not indicate any interactions at this level with molecules that are also highly protein bound (diclofenac, furosemide or warfarin).
