equipoise results is a potent, active when taken orally selective angiotensin II receptor antagonists (ATI type). It blocks all the physiologically relevant effects of angiotensin II of, realized through the ATI type receptors, regardless of the source or route of synthesis of angiotensin II. Specific antagonizing angiotensin receptor II (ATI) results in increased plasma concentrations of renin and angiotensin II and aldosterone plasma concentrations decrease. When using the recommended doses of the drug serum concentration of potassium ions does not change significantly. equipoise results does not inhibit kininase-II (angiotensin converting enzyme), by which the formation of angiotensin II and destruction of bradykinin to inactive metabolites. To detect the action of equipoise results is not required of its metabolic activation.
equipoise results lowers blood pressure (BP) with minimal change in heart rate. When taken at doses up to 300 mg once per day reduction in blood pressure is dose-dependent, however with higher doses of hypotensive effect equipoise results increase is insignificant.
The maximum reduction in blood pressure is achieved within 3-6 hours after ingestion of the drug and the antihypertensive effect persists for at least for 24 hours. At 24 hours after administration of the recommended doses of equipoise results blood pressure reduction is 60-70% compared to the maximum hypotensive response to the drug by the diastolic and systolic blood pressure. When taken once daily at a dose of 150-300 mg of lowering blood pressure value by the end of dosing interval (i.e., 24 hours after drug administration) in the position of a patient lying or sitting on average 8-13 / 5-8 mmHg .st. (Systolic / diastolic blood pressure) compared to that of placebo.
The drug at a dose of 150 mg once a day is the same hypotensive response (decrease in blood pressure before taking the next dose and mean blood pressure reduction over 24 hours) as the same dose divided into two stages.
The antihypertensive effect of Aprovel drug develops within 1-2 weeks, and the maximum therapeutic effect is achieved 4-6 weeks after the start of treatment. The antihypertensive effect on the background of long-term care is maintained. After cessation of treatment blood pressure gradually returns to the initial value. When you remove the drug withdrawal syndrome absent.
The effectiveness of the drug Aprovel does not depend on age and sex. Patients blacks less responsive to mototerapiyu Aprovelem (as well as all other drugs that affect the renin-angiotensin-aldosterone system).
equipoise results has no effect on uric acid in the serum or on the excretion of uric acid in urine.
Pharmacokinetics
After oral administration, equipoise results is well absorbed, its absolute bioavailability is approximately 60-80%. Simultaneous food intake does not significantly influence the bioavailability of equipoise results.
Communication to plasma proteins is approximately 96%. Binding to cellular components of blood is insignificant. The volume of distribution is 53-93 liters.
After oral or intravenous administration of 14 C-equipoise results 80-85% of circulating plasma radioactivity accounted for unmodified equipoise results. equipoise results is metabolized by the liver by oxidation and conjugation with glucuronic acid. Oxidation of equipoise results is carried out mainly through the cytochrome P450 CYP2C9, CYP3A4 isoenzyme participate in the metabolism of equipoise results is negligible. The major metabolite being in the systemic circulation is equipoise results glucuronide (approximately 6%).
equipoise results has linear pharmacokinetics and dose proportional in the dose range from 10 to 600 mg; at doses greater than 600 mg (dose, twice exceeding the maximum recommended dose) becomes nonlinear kinetics of equipoise results (decrease absorption). After oral administration the maximum plasma concentration achieved after 1.5-2 hours. Total clearance and renal clearance and 157-176 comprise 3-3.5 ml / min., Respectively. The final half-life of equipoise results is 11-15 hours. With daily single dose of the drug equilibrium plasma concentration (Css) is reached after 3 days. With a daily intake of equipoise results 1 time per day marked accumulation of its limited plasma (less than 20%). In women (compared to men) occur somewhat higher plasma concentrations of equipoise results. However, gender-related differences in half-life and accumulation of equipoise results is not detected. Correction doses of equipoise results in women is required. The values of AUC (area under the concentration-time concentration curve) and C max (maximum plasma concentration) of equipoise results in elderly patients (> 65 years) is slightly higher than that of younger patients, but the end half-lives they do not differ significantly. No dose adjustment in elderly patients is not required.
equipoise results and its metabolites are excreted as the bile and urine. After oral or intravenous administration of 14 C-20% equipoise results radioactivity detected in urine, and the rest – in the feces. Less than 2% of the administered dose is excreted in the urine as unchanged equipoise results.
Renal impairment: In patients with impaired renal function or patients kotorm hemodialysis, pharmacokinetics of equipoise results are not significantly altered. equipoise results is not removed from the body during hemodialysis.
Impaired Hepatic Function: In patients with cirrhosis of mild or medium severe course of the pharmacokinetic parameters of equipoise results are not significantly altered. Pharmacokinetic studies in patients with severe hepatic impairment have not been conducted.
Indications
– Essential hypertension
– Nephropathy with hypertension and type 2 diabetes (as part
of combination antihypertensive therapy).
Contraindications
– Hypersensitivity to any component of the drug.
– Pregnancy.
– Lactation.
– Age 18 years (effectiveness and safety have been established).
– Hereditary galactose intolerance, lactase deficiency or
malabsorption of glucose and galactose.
Use with caution in: stenosis of the aortic or mitral valve, hypertrophic obstructive cardiomyopathy (GOKMP), dehydration, hyponatremia, diarrhea, vomiting, a diet with restriction of salt intake, diuretics, bilateral renal artery stenosis, unilateral stenosis of the artery only functioning kidney, chronic heart failure stage III-IV (classification NYHA), ischemic heart disease and / or atherosclerotic lesions of the brain vessels, hyperkalemia, renal failure, hemodialysis, a recent kidney transplantation (no clinical experience), severe hepatic insufficiency (lack of clinical experience) .
Pregnancy and lactation Pregnancy
Like any other drug that acts directly on the renin-angiotensin-aldosterone system, equipoise results can not be used during pregnancy (I, II, III trimesters).
Switching to the appropriate alternative therapy should be made before the start of pregnancy planning.
If pregnancy occurs during treatment with equipoise results, it should be abolished as soon as possible.
lactation
During lactation receiving equipoise results is contraindicated. It is not known whether equipoise results is excreted in breast milk.
Dosing and Administration
Inside, the tablet is swallowed whole with water.
Usually takes the original and maintenance dose is 150 mg 1 time per day regardless of the meal. Aprovel at a dose of 150 mg 1 once daily generally provides a better 24 hour blood pressure control than 75 mg. However, in some patients, especially in patients who are on hemodialysis or in patients over 75 years of age, shall receive an initial dose should be 75 mg (Aprovel is possible to use the drug in tablets of 75 mg).
Patients who have a therapeutic effect when receiving Aprovelya 150 mg 1 time per day is insufficient, Aprovelya dose may be increased to 300 mg, or can assign another antihypertensive agent. In particular it has been shown that administration of a diuretic such as hydrochlorothiazide, increases the effects of Aprovelya (see. “Interaction with other medicinal products”).
In patients with hypertension and type 2 diabetes, treatment should start with a dose of 150 mg! once a day, which should be gradually increased up to 300 mg – doses being preferred maintenance dose for the treatment of nephropathy.
Evidence of the beneficial effects of Aprovelya the kidneys in patients with hypertension and type 2 diabetes comes from studies in which it was used in combination with other antihypertensive drugs necessary to achieve target blood pressure levels.
Impaired renal function. In patients with impaired renal function correct dosing regimen is required. For patients on hemodialysis, initially accepted the dose should be 75 mg (Aprovel is possible to use the drug in tablets of 75 mg).
Violation of water and electrolyte balance. Before you start taking Aprovelya to restore blood volume and / or eliminate hyponatremia.
Abnormal liver function. Not required Aprovelya correction dosing regimen in patients with impaired hepatic function or mild to moderate severity. There is no clinical experience with the drug in patients with severe hepatic impairment.
Elderly patients. Although the recommended treatment for patients over the age of 75 years, starting with a dose of 75 mg (possible use of the drug Aprovel tablets of 75 mg), usually elderly patients correct dosing regimen is required.
Use in pediatric patients. Safety and efficacy of Aprovel in patients with the drug for children and youth has not been established.
Side effect
The following side effects are given in the following forward bringing gradations frequency ihvozniknoveniya :: very common (> 1/10), common (> 1/100, <1/10); sometimes (> 1/1000, <1/100); rare (> 1/10000, <1/1000); very rare (<1/10000), (including isolated reports).
Arterial hypertension
In placebo-controlled studies, the incidence of side effects while taking equipoise results was the same as in the placebo and not dependent on the dose (in the recommended dose range), gender, age, race, or duration of therapy.
In the placebo-controlled trials in patients with arterial gapertenziey where 1965 patients received equipoise results were observed following side reactions.
On the part of the central nervous system
Common: dizziness.
Cardio-vascular system
Sometimes: tachycardia.
Vascular disorders
Sometimes: flushing of the skin.
The respiratory system
sometimes coughing.
On the part of the gastrointestinal tract
Common: nausea / rvota.Inogda: diarrhea, indigestion / heartburn.
Reproductive system
Sometimes: sexual dysfunction.
General
Common: fatigue.
Sometimes:. Chest pain From the laboratory parameters
Often (1.7%): a significant increase in plasma creatine phosphokinase in patients receiving equipoise results; None of these increases are not accompanied by clinical manifestations on the part of the musculoskeletal system.
Hypertension and type 2 diabetes with renal disease
In addition to adverse reactions identified in patients with hypertension in patients with hypertension, type 2 diabetes with microalbuminuria without renal dysfunction while taking equipoise results orthostatic dizziness and orthostatic hypotension were observed in 0.5% of patients (compared to the frequency of occurrence of these adverse reactions placebo).
In patients with hypertension, type 2 diabetes with severe proteinuria and renal impairment following adverse reactions were observed at> 2% of patients (compared to the frequency of their occurrence in patients receiving placebo).
From the nervous system
Common: orthostatic dizziness.
Vascular disorders
Common: orthostatic hypotension.
On the part of the musculoskeletal system
often: pain in the muscles and bones.
From the laboratory parameters
Hyperkalemia when taking equipoise results patients with diabetes are more common than with placebo. Diabetic patients with high blood pressure and microalbuminuria with normal renal function, hyperkalemia (> 5.5% mmol / l) when taking 300 mg of equipoise results was observed in 29.4% of patients (often) in the placebo group – 22% of patients . Diabetic patients with high blood pressure, chronic renal failure and severe proteinuria, hyperkalemia (> 5.5% mmol / l) while taking equipoise results met in 46.3% of patients (often) in the placebo group – 26.3 % of patients. In patients with high blood pressure and diabetic nephropathy treated with equipoise results, from 1.7% of patients experienced a clinically insignificant decrease in hemoglobin concentration (often).
Furthermore, with the appearance on the market of equipoise results, the following adverse reactions were also identified:
On the part of the immune system
Rare: as with all receptor antagonists angiotensin II, marked
rare cases of allergic reactions such as rash, urticaria, angioedema.
On the part of metabolism and nutrition Very rare: hyperkalemia.
From the nervous system
Very rare: headache.
On the part of the organ of hearing and vestibular
Very rare: tinnitus.
From the gastrointestinal tract
Very rare: dysgeusia (taste perversion).
From the hepato-biliary system
Very rare: abnormal liver function, hepatitis.
On the part of the musculoskeletal system
Very rare: myalgia, arthralgia (sometimes in combination with an increase in creatine kinase levels), seizures.
On the part of the kidney and urinary system
Very rare: impaired renal function including isolated cases of renal failure in patients at risk (see section “Special instructions”).
Overdose
Experience with the drug in adult humans at doses up to 900 mg / day for 8 weeks did not reveal any toxicity. The most likely manifestations of overdose are pronounced reduction in blood pressure and tachycardia; manifestation of overdose may be bradycardia. No further specific information regarding the treatment of an overdose of the drug Aprovel. It is necessary to establish a permanent monitoring of the patient and symptomatic and supportive therapy if required. In case of overdose it is recommended to induce vomiting, and / or to gastric lavage. may be useful for reducing the activated carbon overdose. Hemodialysis is ineffective.
Interaction with other drugs
Diuretics and other antihypertensives. When equipoise results combination with other antihypertensive agents may increase the hypotensive action; equipoise results without any problem were used in combination with other antihypertensive drugs, such as beta-blockers, blockers “slow” long-acting calcium channel blockers and thiazide diuretics.
Antihypertensive effects of equipoise results and thiazide diuretics are additive in nature. Patients whose blood pressure can not be controlled with monotherapy equipoise results, hydrochlorothiazide purpose small doses (12.5 mg) leads to a further reduction (compared to placebo) in blood pressure 7-10 / 3-6 mm Hg. Art. (Systolic / diastolic blood pressure at the end mezhdozovogo period). When receiving equipoise results with small doses of hydrochlorothiazide (12.5 mg per day), the hypotensive effect of this combination in patients blacks closer to that of the patients of the European races. Previous treatment with diuretics in high doses can lead to dehydration and increase the risk of hypotension at the beginning of treatment with Aprovel.
Potassium supplements and potassium-sparing diuretics, heparin. On the basis of experience gained in the use of other drugs that affect the renin-angiotensin-aldosterone system, while the use of potassium preparations containing potassium electrolyte solutions, potassium-sparing diuretics or other can raise blood potassium levels preparations (heparin), may increase the level of potassium in serum.
Li. Reversible increasing concentrations of lithium in blood serum and its toxicity was observed while using lithium angiotensin-converting enzyme. To date, while taking equipoise results similar effects have been observed very rarely. If there is a need to use this combination, during the treatment should be carefully monitored the concentration of lithium in blood serum.
Nonsteroidal anti-inflammatory drugs (NSAIDs). With the simultaneous use of angiotensin II antagonists and NSAIDs (ie selective COX-2 inhibitors, acetylsalicylic acid (more than 3 g / day) and non-selective NSAIDs) may weaken the antihypertensive effect. As with the joint application of angiotensin-converting enzyme inhibitors and NSAIDs, when used together angiotensin II antagonists and NSAIDs may increase the risk of renal impairment, including the possibility of acute renal failure, and an increase in serum potassium, especially in patients with already impaired renal function . It should be used with caution in this combination, especially in elderly patients. Patients need to restore blood volume and throughout the combination therapy and periodically after the end monitor renal function.
Additional information on equipoise results interactions. When combined with equipoise results hydrochlorothiazide pharmacokinetics of equipoise results is not affected. equipoise results is mainly metabolised by CYP2C9 and to a lesser extent undergoes glucuronidation. There were no significant pharmacokinetic or pharmacodynamic interactions with the combination of equipoise results and warfarin, drugs metabolized via CYP2C9. Studies of the effect of inducers of CYP2C9 activity, such as rifampicin, the pharmacokinetics of equipoise results are not carried out, equipoise results does not change farmakrokinetiku digoxin.
special instructions
Violation of water and electrolyte balance. In patients with dehydration and / or hyponatremia (as a result of intensive diuretic therapy, diarrhea or vomiting, dieting limited reception salt, diuretics), as well as in patients on hemodialysis can develop clinically significant hypotension, especially after the receiving the first dose. Necessary to correct all violations of water-electrolyte balance before the beginning of application of the drug Aprovel.
Renovascular hypertension. Patients with bilateral renal artery stenosis or stenosis of the artery only functioning kidney, while taking drugs that affect the renin-angiotensin-aldosterone system are at high risk with regard to the development of severe arterial hypotension or renal failure. Although the documentary evidence of such effects while taking Aprovel no drug should still take into account the possibility of their occurrence using angiotensin II receptor blockers (ATI type) in these patients.
Renal impairment and kidney transplantation. In applying Aprovelya in patients with renal impairment is recommended periodic monitoring of potassium and creatinine serum. No clinical data on the use of Aprovelya in patients with recent kidney transplantation.
Patients with hypertension and type 2 diabetes with damage . Kidney marked in Aprovelya beneficial effect against progression of renal and cardiovascular lesions had varying degrees of severity in different groups of patients: less pronounced, it was women and persons not belonging to the European race.
Hyperkalemia. As with other agents that affect the renin-angiotensin-aldosterone system, treatment with Aprovelem may develop hyperkalemia, especially in the presence of renal insufficiency and / or heart disease. In these patients, it is recommended to monitor the level of potassium in the blood serum.
Stenosis of the aortic or mitral valve, hypertrophic obstructive cardiomyopathy. As with other vasodilators, when appointing Aprovelya patients with aortic or mitral stenosis, or hypertrophic obstructive cardiomyopathy must be careful.
Primary aldosteronizm. Patients with primary aldosteronism normally do not respond to anti-hypertensive drugs acting through inhibition of the renin-angiotensin system. Therefore Aprovelya use in such cases not feasible.
Other. In the group of patients whose vascular tone and renal function in predominantly depend on the activity of the renin-angiotensin-aldosterone system (patients with chronic heart failure III and stage IV [on classification NYHA] or with underlying renal disease, including renal artery stenosis ), treatment with angiotensin-converting enzyme inhibitors was associated with hypotension, azotemia, oliguria and, in rare cases with acute renal failure. As with other antihypertensive drugs, a significant reduction in blood pressure in patients with ischemic heart disease and / or atherosclerosis of cerebral vessels can lead to myocardial infarction or stroke. Treatment of such patients should be under the strict control of blood pressure.
Effects on ability to drive vehicles
Aprovelya Effect on ability to drive and perform work requiring increased attention, have not been studied, but based on its pharmacodynamic properties, Aprovel should not affect this ability. In road management, please note that during the treatment of dizziness and increased fatigue.
steroiden kaufen
