Valsartan Zentiva
Valsartan Zentiva: instructions for use and reviews
- 1. Release form and composition
- 2. Pharmacological properties
- 3. Indications for use
- 4. Contraindications
- 5. Method of application and dosage
- 6. Side effects
- 7. Overdose
- 8. Special instructions
- 9. Application during pregnancy and lactation
- 10. Use in childhood
- 11. In case of impaired renal function
- 12. For violations of liver function
- 13. Use in the elderly
- 14. Drug interactions
- 15. Analogs
- 16. Terms and conditions of storage
- 17. Terms of dispensing from pharmacies
- 18. Reviews
- 19. Price in pharmacies
Latin name: Valsartan Zentiva
ATX code: C09CA03
Active ingredient: valsartan (Valsartan)
Manufacturer: Zentiva k.s. (Zentiva, ks) (Czech Republic)
Description and photo update: 2019-05-07
Valsartan Zentiva is an angiotensin II receptor antagonist.
Release form and composition
Dosage form - film-coated tablets: round, biconvex, dark pink (dosage 80 mg) or brownish yellow (dosage 160 mg) color, with a line on one side; on a cross-section almost white or white (14 and 15 pcs. in blisters, in a cardboard box 2 or 6 blisters and instructions for use of Valsartan Zentiva).
Composition of 1 tablet:
- active substance: valsartan - 80 or 160 mg;
- auxiliary components: sorbitol, povidone K25, pregelatinized corn starch, sodium lauryl sulfate, sodium stearyl fumarate, destab magnesium carbonate 90 (magnesium carbonate, water, pregelatinized starch), silicified microcrystalline cellulose SMCC 90 (silicon dioxide colloidal silicon dioxide) colloidal silicon dioxide (Aerosil 200 Pharma) crospovidone Type A;
- film shell: macrogol / PEG 6000, hypromellose, talc, lactose monohydrate; 80 mg tablets also contain iron oxide red dye, 160 mg tablets contain indigo carmine aluminum varnish and iron oxide brown dyes.
Pharmacological properties
Pharmacodynamics
Valsartan is a specific angiotensin II receptor antagonist. It has the ability to selectively block the AT1 subtype receptors responsible for the known effects of angiotensin II. Due to the blockade of AT1 receptors, the concentration of angiotensin II in plasma increases, which can stimulate unblocked AT2 receptors.
The drug has no AT1 receptor agonist activity. The affinity for the AT1 subtype receptors is approximately 20,000 times higher than for the AT2 subtype receptors.
Valsartan has practically no effect on kininase II, an angiotensin-converting enzyme (ACE), which is responsible for the degradation of bradykinin, so when it is used, the likelihood of a cough is very low.
In patients with arterial hypertension, Valsartan Zentiva helps to lower blood pressure, but does not change the heart rate (HR).
After taking a single dose, in most cases, the hypotensive effect begins to develop within 2 hours, reaches a maximum after 4-6 hours and lasts for 24 hours. As a result of repeated applications of Valsartan Zentiv, regardless of the dose, a pronounced therapeutic effect is usually achieved within 2-4 weeks and with prolonged use of the drug is maintained at the achieved level. The simultaneous appointment of hydrochlorothiazide significantly contributes to an additional decrease in blood pressure. Sudden withdrawal of valsartan does not cause a sharp increase in blood pressure and the development of other undesirable reactions.
The mechanism of action of Valsartan Zentiva in chronic heart failure (CHF) is explained by the elimination of the negative consequences of chronic hyperactivation of the renin-angiotensin-aldosterone system (RAAS) and its main effector angiotensin II, such as:
- fluid retention in the body;
- vasoconstriction;
- cell proliferation leading to remodeling of target organs (kidney, blood vessels, heart);
- stimulation of excessive synthesis of hormones acting synergistically with the RAAS: vasopressin, aldosterone, endothelin, catecholamines.
In CHF, valsartan reduces the preload, reduces the diastolic pressure in the pulmonary artery and the pressure of wedging in the pulmonary capillaries, and increases cardiac output. In addition to hemodynamic effects, Valsartan Zentiva reduces water and sodium retention in the body (due to an indirect blockade of aldosterone synthesis).
It is reliably known that Valsartan Zentiva does not have a significant effect on the level of total cholesterol, the concentration of uric acid, as well as on the content of glucose and triglycerides in the blood serum when examined on an empty stomach.
Pharmacokinetics
Valsartan is rapidly absorbed after oral administration, but the degree of absorption varies over a wide range. The absolute bioavailability averages 23%. The substance is characterized by linear kinetics, with repeated use, no changes in indicators are noted.
Simultaneous food intake reduces the effect of valsartan by about 40% and the equilibrium concentration (Css) by about 50%. However, these changes are not accompanied by a significant decrease in the therapeutic effect. After 8 hours after taking the drug, the plasma concentration was approximately comparable in the group receiving Valsartan Zentiva on an empty stomach and the group taking the tablets with food. In this regard, there is no strict need to separate the time of taking the drug and food.
After intravenous administration of valsartan, its volume of distribution (Vd) in the equilibrium state is ~ 17 liters, which demonstrates a weak intensity of distribution of the drug in the tissues. Plasma proteins (mainly albumin) bind 94–97% of the dose.
Valsartan undergoes minor metabolism. In the form of metabolites, about 20% of the dose received is recorded. In the blood plasma, a hydroxymetabolite is found, which does not have pharmacological activity.
Compared with the hepatic blood flow (~ 30 L / h), the plasma clearance of the drug is relatively small (~ 2 L / h). The half-life (T 1/2) is 9 hours. The drug is excreted mainly through the intestines - 70%. Approximately 30% of the dose is excreted by the kidneys, mainly unchanged.
Pharmacokinetics in special cases:
- old age: the systemic effect of the drug is more pronounced than in young patients, but this phenomenon has no clinical significance;
- renal function: there is no correlation between renal function and systemic action of valsartan, so there is no need to adjust the dose in case of renal impairment [creatinine clearance (CC)> 10 ml / min]. There is no experience with Valsartan Zentiva in patients with CC <10 ml / min and in patients on hemodialysis. The drug is largely bound to plasma proteins, so its elimination from the body during hemodialysis is unlikely;
- liver function: valsartan undergoes insignificant metabolism, most of the dose is excreted through the intestine mainly unchanged, therefore there is no correlation between hepatic function and the systemic effect of valsartan. In this regard, there is no need to adjust the dose of Valsartan Zentiv in patients with hepatic insufficiency of non-biliary origin without cholestasis. There is no experience of using the drug in severe liver functional disorders;
- CHF: the maximum plasma concentration (Cmax) and the area under the concentration-time curve (AUC) increase linearly and almost proportionally with increasing doses in the range from 40 to 160 mg 2 times a day. The average time to reach Cmax and T 1/2 are similar to those in healthy volunteers.
Indications for use
- arterial hypertension;
- chronic heart failure (II – IV functional class according to NYHA classification) in patients receiving standard therapy for this disease, including one of the following drugs: cardiac glycoside, diuretic, ACE inhibitor, beta-blocker;
- acute myocardial infarction and acute myocardial infarction, complicated by systolic dysfunction of the left ventricle and / or left ventricular failure, in the presence of stable hemodynamic parameters - to increase survival.
Contraindications
Absolute:
- cholestasis;
- severe liver dysfunction;
- biliary cirrhosis;
- lactose intolerance, lactase deficiency, glucose-galactose malabsorption;
- period of pregnancy and lactation;
- age up to 18 years;
- increased sensitivity to any component of the drug.
Valsartan Zentiva tablets should be used with caution in patients with bilateral renal artery stenosis or stenosis of a solitary kidney artery, primary hyperaldosteronism, mitral / aortic stenosis, hypertrophic obstructive cardiomyopathy, conditions accompanied by a decrease in circulating blood volume (including diarrhea)), mild and moderate impairment of the hepatic function of non-biliary origin without cholestasis, severe renal failure (CC <10 ml / min, including during hemodialysis or after kidney transplantation), as well as in patients on a diet with limited consumption salt.
Valsartan Zentiva, instructions for use: method and dosage
Valsartan Zentiva tablets must be taken orally. Meal timing doesn't matter.
In case of arterial hypertension, treatment begins with a dose of Valsartan Zentiva 80 mg 1 time per day, if necessary, then the dose is gradually increased. The maximum allowable daily dose is 320 mg. If necessary, diuretics are prescribed in addition.
In chronic heart failure, the recommended initial dose is 40 mg (½ tablet Valsartan Zentiva 80 mg) 2 times a day. The dose is gradually increased to 80 mg 2 times a day. If the effect is insufficient and the drug is well tolerated, the dose may be increased to a maximum of 160 mg 2 times a day.
After suffering myocardial infarction, it is optimal to start treatment before 12 noon. The initial dose is 20 mg 2 times a day. Gradually, over several weeks, the dose is increased. The recommended increase in single doses: by the end of the first week - 40 mg, by the end of the second week - 80 mg, by the end of the third month - the target dose of 160 mg. The frequency of admission is 2 times a day. Achieving the target dose depends on the tolerance of Valsartan Zentiv during the titration period.
For mild to moderate renal impairment without cholestasis, a daily dose of 80 mg should not be exceeded.
Side effects
The side effects described below are classified by frequency of development as follows: very often -> 10%, often - from> 1% to 0.1% to 0.01% to <0.1%, very rarely - <0.01% (including individual messages), unspecified frequency - it is not possible to accurately establish the frequency of development.
Possible negative reactions of Valsartan Zentiva in patients with arterial hypertension:
- allergic reactions: unspecified frequency - serum sickness, hypersensitivity reaction;
- laboratory parameters: unspecified frequency - increased serum potassium;
- on the part of the cardiovascular system: unspecified frequency - vasculitis;
- from the hematopoietic system: unspecified frequency - thrombocytopenia, neutropenia, decreased hemoglobin and hematocrit;
- from the respiratory system: infrequently - cough;
- on the part of the urinary system: unspecified frequency - increased serum creatinine concentration, functional renal impairment;
- from the digestive system: infrequently - abdominal pain; unspecified frequency - increased activity of hepatic transaminases, hyperbilirubinemia, abnormal liver function;
- from the musculoskeletal system: unspecified frequency - myalgia;
- on the part of the skin: very rarely - skin rash, itching, angioedema;
- from the senses: infrequently - vertigo;
- others: infrequently - increased fatigue.
Possible negative reactions of Valsartan Zentiva in patients with chronic heart failure and / or after a heart attack:
- allergic reactions: very rarely - angioedema; unspecified frequency - serum sickness, hypersensitivity reactions;
- on the part of the cardiovascular system: often - a marked decrease in blood pressure, orthostatic hypotension; infrequently - increased symptoms of CHF; unspecified frequency - vasculitis;
- from the urinary system: often - functional impairment of the kidneys; infrequently - acute renal failure; unspecified frequency - increased serum urea nitrogen, hypercreatininemia;
- from the respiratory system: infrequently - cough;
- from the side of metabolism: infrequently - hyperkalemia;
- from the digestive system: infrequently - nausea, diarrhea; unspecified frequency - liver dysfunction;
- from the musculoskeletal system: rarely - rhabdomyolysis; unspecified frequency - myalgia;
- from the nervous system: often - dizziness (including postural); infrequently - headache, fainting;
- on the part of hematopoietic organs: unspecified frequency - thrombocytopenia;
- on the part of the skin: unspecified frequency - itching, skin rash;
- from the senses: infrequently - vertigo;
- others: infrequently - asthenia, increased fatigue.
Overdose
Taking an excessive dose of Valsartan Zentiva leads to a significant decrease in blood pressure, which is fraught with loss of consciousness, the development of collapse and / or shock.
As a first aid measure, gastric lavage and the intake of activated charcoal are indicated. Further treatment is symptomatic. A 0.9% sodium chloride solution is injected intravenously. Dialysis is ineffective.
special instructions
With a pronounced sodium deficiency and / or a reduced volume of circulating blood (for example, due to taking diuretics), arterial hypotension may develop at the beginning of taking Valsartan Zentiva. In this regard, before therapy, it is recommended to correct these conditions, for example, by reducing the dose of a diuretic.
In studies of valsartan, conducted in 12 patients with renovascular hypertension, secondary to unilateral renal artery stenosis, no significant changes in renal hemodynamics, urea nitrogen and serum creatinine concentrations were detected. However, there are cases of increased serum urea and creatinine levels in patients with bilateral or unilateral renal artery stenosis who received other drugs that affect the RAAS. In this regard, during the period of therapy, it is recommended to monitor these indicators.
In patients with CHF or after a myocardial infarction at the beginning of treatment, blood pressure often decreases slightly, so it should be carefully monitored at the initial stage of therapy. Patients who strictly follow the dosage recommendations, as a rule, do not have to discontinue the course due to the development of arterial hypotension.
In sensitive patients, renal function may change due to inhibition of the RAAS. In severe CHF, ACE inhibitors and angiotensin receptor antagonists can cause oliguria and / or an increase in azotemia, in some cases - acute renal failure and death. For this reason, before the appointment of Valsartan Zentiva, patients who have had an acute myocardial infarction and patients with heart failure must necessarily assess the state of renal function.
For the treatment of arterial hypertension, Valsartan Zentiva can be used as a monopreparation or in combination with diuretics.
In CHF, Valsartan Zentiva can be used as a monopreparation or in combination with other drugs, such as cardiac glycosides, diuretics, ACE inhibitors or beta-blockers. Particular care is required with the simultaneous administration of a beta-blocker or an ACE inhibitor.
Perhaps the appointment of Valsartan Zentiva in conjunction with other drugs used after myocardial infarction, such as acetylsalicylic acid as an antiplatelet agent, thrombolytics, beta-blockers, inhibitors of HMG-CoA reductase (statins).
Influence on the ability to drive vehicles and complex mechanisms
Given the likelihood of dizziness and even fainting during the use of Valsartan Zentiva, special care is recommended when driving a car and other activities that require quick psychophysical reactions and concentration.
Application during pregnancy and lactation
According to retrospective data, the use of ACE inhibitors in the first trimester of pregnancy is accompanied by an increased risk of having children with birth defects. In the II and III trimesters of pregnancy, ACE inhibitors, due to the effect on the RAAS, can lead to damage and death of the fetus. There are known cases of spontaneous abortions, oligohydramnios and functional renal disorders in newborns whose mothers unintentionally took valsartan during pregnancy. In this regard, pregnant women are contraindicated to take Valsartan Zentiva. In case of pregnancy during the period of taking the drug, treatment should be stopped as soon as possible.
There is no data on the release of valsartan with mother's milk, therefore, the use of the drug during lactation is not recommended.
Pediatric use
Valsartan Zentiva is not used in children and adolescents (under 18 years of age).
With impaired renal function
If CC> 10 ml / min, there is no need to adjust the dose in patients with impaired renal function.
With CC <10 ml / min, including during hemodialysis and after kidney transplantation, Valsartan Zentiva should be used with caution. Careful monitoring of renal function and plasma potassium levels is required.
For violations of liver function
The appointment of Valsartan Zentiva is contraindicated in patients with severe functional disorders of the liver, biliary cirrhosis and cholestasis.
In case of mild and moderate liver dysfunctions without the development of cholestasis, a daily dose of 80 mg should not be exceeded.
Use in the elderly
Elderly patients are prescribed Valsartan Zentiva in standard doses.
Drug interactions
Other antihypertensive drugs and diuretics enhance the hypotensive effect of Valsartan Zentiva.
There were no clinically significant interactions in patients with arterial hypertension while using other drugs with valsartan, for example, hydrochlorothiazide, cimetidine, furosemide, amlodipine, atenolol, digoxin, warfarin, indomethacin, glibenclamide.
Non-steroidal anti-inflammatory drugs, including selective inhibitors of cyclooxygenase (COX) -2, can weaken the antihypertensive effect of Valsartan Zentiva.
The risk of developing hyperkalemia increases with the simultaneous use of potassium preparations, potassium-sparing diuretics, potassium-containing salts, as well as drugs that increase the level of potassium in the blood plasma (such as heparin). If it is necessary to prescribe any of these agents, the plasma potassium concentration should be carefully monitored.
It was reported about a reversible increase in the level of lithium in plasma and the development of toxic effects while using valsartan with lithium preparations. There is no clinical experience of their combined use, so the appointment of such a combination is not recommended. If the need for joint use of drugs is clinically justified, you should regularly check the plasma concentration of lithium.
Analogs
Analogues of Valsartan Zentiva are Angiakand, Aprovel, Artinova, Atakand, Bloktran, Valaar, Vazotenz, Valsartan, Valz, Valsakor, Diovan, Giposart, Ibertan, Canarb, Kozaar, Lozap, Losartan, Mikardis, Nortivan, Ordiss, Prezkardkard Tanidol, Telmisartan, Edarbi and many others.
Terms and conditions of storage
Store at a temperature not exceeding 30 ° C, out of the reach of children.
Shelf life is 2 years.
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews about Valsartan Zentiva
Reviews of Valsartan Zentiva are few, but mostly positive: the drug effectively reduces high blood pressure, is suitable for long-term use, is well tolerated, does not cause a dry hacking cough.
The price of Valsartan Zentiva in pharmacies
Approximate prices for Valsartan Zentiva, film-coated tablets:
- dosage 80 mg: a pack of 28 tablets - 202-236 rubles, a pack of 84 tablets - 497-563 rubles;
- dosage 160 mg: pack of 28 tablets - 320-339 rubles, pack of 84 tablets - 786-792 rubles.
Anna Kozlova Medical journalist About the author
Education: Rostov State Medical University, specialty "General Medicine".
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!
