Pharmacological properties Diovan 160 mg:
Diovan 160 mg Valsartan a specific antagonist of angiotensin II. Acts selectively on the receptor subtype AT1, which is responsible for the known effects of angiotensin II. Elevated levels of angiotensin II in blood plasma after the blockade of AT1-receptor Valsartan can stimulate non blocking AT2 receptor, which balances the effect of AT1-receptor. Pronounced agonistic activity with respect to receptor subtype AT1 Valsartan does not show. Affinity receptor subtype Valsartan AT1 approximately 20 000 times higher than the receptor subtype AT2.
Valsartan does not inhibit ACE, also known as kininazy II, which converts angiotensin I to angiotensin II, destroying bradykinin. As a result of the drug in patients with hypertension reduced blood pressure without affecting heart rate.
Top of the hypotensive action observed within 2 hours, maximum – 4-6 hours after ingestion. After taking the drug antihypertensive effect persists over 24 h. The maximum therapeutic effect develops after 2-4 weeks of treatment and maintained during prolonged therapy. In the case of a combination product with hydrochlorothiazide achieved significant additional blood pressure reduction.
Sudden discontinuation of the drug is not accompanied by the development of withdrawal syndrome. During the course using the drug in patients with hypertension found that the drug had no significant effect on total cholesterol, uric acid, as well as the study on an empty stomach – the concentration of triglycerides and glucose in the blood serum.
Use of the drug causes a decrease in the incidence of hospitalization for heart failure, slowing the progression of heart failure, improve functional class classification of NYHA (New York Heart Association), an increase in ejection fraction, as well as reducing the signs and symptoms of heart failure and improved quality of life compared with placebo.
Results of the study demonstrated the effectiveness of VALIANT Valsartan as captopril in reducing all-cause mortality after myocardial infarction. Valsartan was also effective in reducing mortality due to cardiovascular disease, reduced the number of hospitalizations due to heart failure and recurrent cases of myocardial infarction.
Combination with captopril Valsartan less efficient than using one of captopril. There were no differences in overall mortality by age, sex, race, baseline treatment or underlying disease.
Valsartan as captopril reduce mortality due to any reason after myocardial infarction. These cases were similar in the groups valzartana (19.9%), captopril (19.5%) and group Valsartan + captopril (19.3%). Valsartan was also effective in reducing deaths due to cardiovascular disease, hospitalization due to heart failure, recurrent myocardial infarction, cardiac arrest revived, non-lethal attack (secondary composite end point).
In addition, the benefits of treatment with a combination Valsartan + captopril monotherapy with captopril monotherapy Valsartan and was confirmed in patients taking blockers-blockers.
After oral ingestion valzartan absorbed quickly, but the extent of absorption varies considerably. The average value of the absolute bioavailability is 23%. Pharmacokinetic curve is downward Valsartan multieksponentsialny character (t1/2b
In the range of doses studied kinetics Valsartan is linear. Repeated use of the drug changes the kinetic parameters were observed. While taking the drug once a day a slight accumulation. Drug concentration in blood plasma of women and men were equal.
Valsartan largely (at 94-97%) is bound to serum proteins, primarily albumin. Volume of distribution at steady state is low (about 17 liters). Compared with hepatic blood flow (30 l / h), plasma clearance is relatively slow Valsartan (about 2 l / h). Number Valsartan, excreted in feces, 70% (the value of an oral dose). Since urine output of about 30%, mainly in unchanged form.
In appointing the food Valsartan AUC decreased by 48%, although from about 8 hours after taking the drug concentration in blood plasma Valsartan as in the case of receiving it on an empty stomach and in the case of reception with food, are the same. Decrease AUC nevertheless not accompanied by clinically significant reduction in therapeutic effect, and the drug can be taken on an empty stomach, and during the meal.
The average time to reach the highest concentration and elimination half-life Valsartan patients with heart failure and healthy volunteers are identical. The AUC and maximum concentration increased linearly and Valsartan almost proportional increase doses above the clinical range (40-160 mg 2 times a day). Cumulation coefficient is an average of 1.7. Valsartan clearance after oral administration is approximately 4.5 l / h. Age does not affect the clearance of the drug in patients with heart failure.
Elderly patients. Some elderly patients had systemic exposure Valsartan more pronounced than in young patients, but did not show any clinical significance of this.
Patients with impaired renal function. There was no correlation between renal function and systemic exposure Valsartan. Therefore, in patients with impaired renal function, dosage adjustment is required. So far, no trials of the drug pharmacokinetics in patients on hemodialysis. However Valsartan has a high degree of binding to plasma proteins, so its removal by hemodialysis is unlikely.
Patients with impaired liver function. About 70% of the dose excreted grown deep in the bile, mainly in unchanged form. Valsartan not carry any significant biotransformation and, as might be expected, systemic exposure Valsartan not correlate with the degree of liver dysfunction. Therefore, in patients with liver failure nebiliarnogo origin and without cholestasis does not require dose adjustment Valsartan. It has been shown that patients with biliary cirrhosis or biliary obstruction increases the AUC Valsartan approximately two-fold.
Indications Diovan 160 mg:Hypertension.
Heart failure. Therapy of heart failure (II-IV class classification NYHA) in patients receiving conventional therapy with diuretics, digitalis preparations, as well as other ACE inhibitors or blockers of-adrenoceptor, the application of all these drugs is not required.
Postinfarction state. Diovan is indicated for improvement after myocardial infarction in clinically stable patients with signs, symptoms and radiological data of left ventricular failure and / or left ventricular systolic dysfunction.
USE Diovan 160 mg:AG.
The recommended dose of Diovan is 80 mg or 160 mg 1 time per day, regardless of race, age and sex of the patient. The antihypertensive effect is achieved in the first 2 weeks of treatment, the maximum effect observed after 4 weeks. Patients who fail to achieve adequate blood pressure reduction, the daily dose can be increased by Diovan 320 mg or extra nominated diuretics. Diovan may be administered also in conjunction with other antihypertensive drugs.
Heart failure. Recommended initial dose of Diovan is 40 mg 2 times a day every day. Diovan dose should be increased by the “titration” to 80 or 160 mg 2 times a day, that is, to the maximum well tolerated dose. The maximum daily dose of Diovan in clinical trials, adopted in stages, was 320 mg. Evaluation of patients with heart failure should always include assessment of renal function.
Postinfarction state. Treatment can be started within 12 hours after myocardial infarction. After the initial dose of 20 mg 2 times a day dose Valsartan must be increased to 40, 80 and 160 mg 2 times a day for the next few weeks. To receive an initial dose of 40 mg tablet split in half.
The planned maximum dose – 160 mg twice a day. Recommended dose to achieve 80 mg 2 times a day for up to 2 weeks after starting treatment and the planned maximum dose for 3 months, based on patient tolerability Valsartan during dose titration. If there is symptomatic hypotension or renal dysfunction should consider lowering the dose.
Perhaps the use of Valsartan patients treated with other drugs used after myocardial infarction, such as thrombolytics, aspirin, angiotensin-receptor and a statin. Assessing the condition of patients after myocardial infarction should always evaluate kidney function.
Note for all indications: patients with renal impairment or hepatic insufficiency nezhelchnogo origin and without cholestasis dose adjustment is required.
Safety and efficacy of Diovan in children and adolescents (under 18) are not installed.
CONTRAINDICATIONS Diovan 160 mg:
Hypersensitivity to any component of Diovan. During pregnancy.
SIDE EFFECTS Diovan 160 mg:
AG. In a placebo-controlled trials the overall incidence of adverse events demonstrated to study drug was comparable to that of placebo.
The results of the extended six-month open study with the participation of patients with hypertension, Valsartan applying a dose of 320 mg showed that the total number of cases of side effects comparable to those observed in placebo-controlled studies. Also included are adverse drug reactions in patients with hypertension from postmarketing reports. The frequency of adverse events is estimated as follows: “very often» – ≥ 1 / 10, “frequently” – of ≥ 1 / 100,20%), respectively. For comparison – in patients treated with placebo, reduced as the hematocrit and hemoglobin was noted in 0.1% of cases.
Neutropenia was found in 1.9% of patients receiving Valsartan, and 1.6% – an ACE inhibitor.
In controlled clinical trials in patients with hypertension there was a significant increase in serum creatinine, potassium, and total serum bilirubin, respectively, in 0.8, 4.4 and 6% of patients treated with Diovan and at 1.6, 6.4 and 12, 9% of patients treated with an ACE inhibitor. There are reports of increased liver function tests in patients treated with Valsartan.
In heart failure the creatinine level increases by more than 50% was noted in 3.9% of patients taking Diovan, compared with 0.9% in the placebo group. At the same time increase the level of potassium in the blood serum of more than 20% was noted in 10.0% of patients taking Diovan, and 5.1% – placebo. In the postinfarction period marked increase in serum creatinine of 2 times in 4.2% of patients on therapy Valsartan, 4.8% – a combination of captopril and Valsartan and 3.4% – captopril.
In studies of heart failure, increased urea nitrogen was observed in 16.6% of patients treated with Valsartan, and 6.3% – in the placebo group.
Precautions: Patients with a deficit in body sodium and / or BCC. In patients with severe deficiency in the body of sodium and / or BCC, for example, receiving high-dose diuretic, in rare cases, early treatment can occur Diovan symptomatic hypotension. Before treatment Diovan should be corrected concentrations for sodium and / or BCC, for example, by reducing the dose of diuretic.
In the case of hypotension the patient should be laid and, if necessary, to I / O infusion of isotonic Valium sodium chloride. Once blood pressure stabilized, treatment may continue Diovan.
Renal artery stenosis. The use of Diovan short course in 12 patients with renovascular hypertension, which developed secondary to unilateral renal artery stenosis, has not led to significant changes in renal hemodynamics, serum creatinine or blood urea nitrogen. However, given that other drugs affecting the renin-angiotensin-aldosterone system, can cause increased levels of urea and creatinine in the blood serum of patients with unilateral or bilateral renal artery stenosis, as a precautionary measure recommended that systematic monitoring of these indicators.
Impaired renal function. Patients with impaired renal function does not require correction dose. However, when expressed disorders (creatinine clearance
Abnormal liver function. In patients with hepatic insufficiency does not require correction dose. Valsartan appears mostly unchanged in the bile, and it was shown that patients with biliary tract obstruction clearance valzartana reduced. In appointing Valsartan patients with biliary tract obstruction should be very careful.
Congestive heart failure / post-infarction state. In patients with heart failure or postinfarction state taking Diovan to conventional doses, there is a slight decrease in blood pressure, but cessation of therapy because of long-term symptomatic treatment is usually not necessary if you follow the instructions regarding the dosage of the drug. Starting therapy, caution should be exercised in patients with heart failure or postinfarction state.
As a consequence of inhibiting the renin-angiotensin-aldosterone system in patients sensitive to changes in renal function. In patients with severe heart failure whose renal function depends on the activity of the renin-angiotensin-aldosterone system, treatment with ACE inhibitors and angiotensin receptor antagonists may be associated with oliguria and / or growth of azotemia and rarely – acute renal failure and / or fatal. Evaluation of patients with heart failure or postinfaktnym state should always include assessment of renal function.
Caution should be exercised in patients with heart failure in the application of a triple combination of ACE inhibitors, blockers and-blockers Valsartan.
Pregnancy and breast-feeding. Given the mechanism of action of antagonists of angiotensin II, we can not exclude the risk to the fetus. The action of ACE inhibitors on the uterus, in the event of their assignment during pregnancy in the II and III trimester, causes damage and death in the developing fetus. There are reports of cases of spontaneous abortion, low water and renal function in newborns, when pregnant women accidentally took Valsartan. Diovan, like any other drug that has a direct effect on the renin-angiotensin-aldosterone system should not be used during pregnancy. If pregnancy is detected during treatment Diovan, the drug should be discontinued as soon as possible.
Is not known whether Valsartan in breast milk in humans. It is therefore not recommended for use Diovan in lactation.
Effects on ability to drive and use machines. Precaution.
INTERACTION Diovan 160 mg:
clinically significant interactions with other drugs has not yet been observed. In clinical trials, were examined following drugs: cimetidine, warfarin, furosemide, digoxin, atenolol, indomethacin, hydrochlorothiazide, amlodipine, and glyburide.
As Diovan not be substantially metabolized, it is unlikely for clinically significant interactions with other drugs at the level of metabolism that result from induction or inhibition of cytochrome P450. Although Valsartan largely bound to plasma proteins, in vitro studies have not been identified any interaction at this level with a number of molecules that have the same high binding to plasma proteins, such as diclofenac, furosemide, and warfarin.
Concomitant use of potassium-sparing diuretics (eg spironolactone, triamterene, amiloride), potassium preparations or salts containing potassium may cause the increase in the concentration of potassium in the blood serum. If such a combination treatment deemed necessary, caution should be exercised.
Overdose Diovan 160 mg:
Symptoms: severe hypotension, which may cause the depression of consciousness, collapse and / or shock.
Treatment: If the drug has been approved recently – to induce vomiting. If hypotension – in / introduction of isotonic Valium sodium chloride. It is unlikely that dialysis would be effective.
