A specific selective AT receptor antagonist1 angiotensin II. By blocking the AT1 receptor, it increases the plasma levels of angiotensin II, which can stimulate the AT2 receptor. It does not inhibit the angiotensin-converting enzyme (kininase II), also responsible for the breakdown of bradykinin. In patients with hypertension, it causes a reduction in blood pressure without affecting the heart rate. Abrupt discontinuation of the drug does not cause a sudden increase in blood pressure. In people with hypertension and type 2 diabetes with microalbuminuria, valsartan has been shown to reduce urinary albumin excretion. After administrationafter. absorbs quickly; the percentage of the drug that is absorbed varies greatly among individuals; the food decreases the AUC of the drug, but it does not significantly affect clinical efficacy. Biological availability is on average 23%. The maximum plasma concentration of the drug reaches 2-4 h after administration. Valsartan in 94-97% binds to plasma proteins, mainly to albumin, so the use of dialysis to remove it is not very effective. The onset of hypotensive effect occurs within 2 h and maximal effect within 4-6 h. During long-term use, the hypotensive effect persists for 24 hours. The drug demonstrates multi-exponential elimination kinetics: t1/2α is <1 h, t1/2β - about 9 h. Excreted mainly in unchanged form in approx. 83% with faeces and in approx. 13% with urine.
Treatment of essential hypertension in adults, adolescents and children from the age of 6. Treatment of symptomatic heart failure if an ACE inhibitor can not be used, or in combination with an ACE inhibitor, if β-blockers can not be used. Treatment of patients in a clinically stable condition with symptomatic heart failure or asymptomatic left ventricular systolic failure after a recent (12 h-10 days) myocardial infarction. Also used in diabetic nephropathy (indication not registered in Poland).
Hypersensitivity to any component of the preparation, 2nd and 3rd trimester of pregnancy, severe liver dysfunction, biliary cirrhosis, cholestasis, parallel use with aliskiren in patients with diabetes mellitus or renal dysfunction (GFR <60 ml / min / 1.73 m2). No dosage adjustment is necessary for adult patients with impaired renal function and creatinine clearance> 10 ml / min. Caution is advised in adult patients with creatinine clearance <10 ml / min and in patients undergoing dialysis (no data on safety concerns). Use with caution in people with mild and moderate hepatic impairment. In patients with a decreased intravascular volume and / or a significant sodium deficiency caused by, for example, intensive dehydration therapy, reduced salt supply in the diet, diarrhea or vomiting, symptomatic hypotension may occur, especially at the beginning of treatment. In such patients, such conditions should be evened out before starting treatment. Use with caution at the beginning of treatment of people after a recent myocardial infarction and in people with heart failure. The assessment of the condition of a patient with heart failure or after having a heart attack should always include assessment of renal function. In patients treated with drugs that affect the RAA system, there is an increased risk of severe hypotension and renal failure in patients with bilateral renal artery stenosis or stenosis of the artery to the sole active kidney; The safety of valsartan in these patients has not been established. In patients with impaired renal function, renal function should be checked periodically before and during treatment. Caution should be exercised in patients with aortic valve stenosis or mitral valve or hypertrophic cardiomyopathy with narrowing of the outflow pathway. In patients with essential hypertension in the course of primary hyperaldosteronism, the response to antihypertensive drugs acting through RAA inhibition is usually less pronounced; valsartan should not be used in this group of patients.In patients with arterial tension and renal function depending on RAA activity (eg patients with severe congestive heart failure or with kidney disease, including renal artery stenosis), treatment with angiotensin II receptor antagonists may lead to a sharp fall in blood pressure, azotemii, oligurii and rare acute renal failure. Cases of angioneurotic edema have been reported during treatment with valsartan; in some of these patients, angioneurotic edema has occurred in the past after the use of other drugs, including ACE inhibitors. If angioedema occurs, the drug should be discontinued and should not be administered again. No dose adjustment is required in children and adolescents with a creatinine clearance> 30 ml / min; this medicine is not recommended for people of this age with a creatinine clearance <30 ml / min and those undergoing dialysis. During treatment of children and adolescents, renal function and serum potassium should be closely monitored, especially in the presence of other disorders (fever, dehydration) that may affect renal function.
Caution should be exercised in the parallel use of angiotensin receptor antagonists (including valsartan) with other RAA blocking agents, such as ACE inhibitors or aliskiren; there may be an increased risk of hypotension, syncope, stroke, hyperkalemia and renal dysfunction. Parallel use of angiotensin receptor antagonists (including valsartan) or ACE inhibitors with aliskiren is contraindicated in patients with diabetes mellitus or renal dysfunction (GFR <60 ml / min / 1.73 m2). Parallel use of potassium-sparing diuretics, potassium supplements, potassium-containing potassium substitutes, ACE inhibitors or other drugs that may increase serum potassium (eg heparin) may result in increased serum potassium. In the case of parallel use with lithium salts, there is a possibility of a reversible increase in plasma lithium concentration; if this combination is necessary, monitoring of serum lithium levels is recommended. In the parallel use of angiotensin II antagonists with NSAIDs, the hypotensive effect may be reduced, and the risk of worsening of renal function, including acute renal failure, may also increase. it may also lead to an increase in serum potassium, especially in patients with impaired renal function. In the case of this combination of drugs, extreme caution should be exercised, especially in the elderly, care for adequate hydration of the patients and consideration of monitoring of renal function during treatment. There were no clinically relevant interactions with cimetidine, digoxin, atenolol, indomethacin, hydrochlorothiazide, amlodipine, glibenclamide, furosemide, warfarin. researchin vitro indicate that valsartan is a substrate of the hepatic uptake carrier OATP1B1 / OATP1B3 and hepatic burst transporter MRP2; the clinical significance of these data is unknown. The concomitant use of inhibitors of the uptake transporter (e.g., rifampicin, cyclosporine) or inhibitors of the episodic transporter (e.g., ritonavir) may increase exposure to valsartan; caution should be exercised when initiating or ending the combination therapy with these medicines.
The drug is usually well tolerated, the frequency of side effects after using angiotensin II receptor antagonists is determined to be comparable to that of placebo. In adults, the treatment of hypertension was uncommon: dizziness, cough, abdominal pain, fatigue and an unknown frequency: hematocrit reduction, hemoglobin, neutropenia, thrombocytopenia, hypersensitivity, including serum sickness, angioneurotic edema, rash pruritus , increase in serum potassium, hyponatraemia, vasculitis, increased liver enzymes and serum bilirubin. In adults with heart failure and / or in the state after myocardial infarction, there have often been: dizziness (also related to the position of the body), hypotension and orthostatic, renal dysfunction; uncommon: hyperkalemia, headache, fainting, dizziness, heart failure, cough, nausea, diarrhea, angioneurotic edema, acute renal failure, increased serum creatinine, asthenia, fatigue; unknown frequency of occurrence: thrombocytopenia, hypersensitivity, including serum sickness, rash, pruritus, increase in serum potassium, blood urea nitrogen and liver enzymes, hyponatremia, vasculitis, muscle pain. In adolescents and children after 6 years.patients treated for hypertension, there were no significant differences in the type, frequency and severity of adverse reactions compared to adults (no significant differences in safety profiles). The only exceptions were isolated gastrointestinal disorders such as abdominal pain, nausea and vomiting and dizziness. In adolescents and children after six years of age, hyperkalaemia was more commonly observed with coexisting kidney disease. In the event of overdose, significant hypotension should be expected. Symptomatic treatment. Valsartan can not be removed from the body by hemodialysis.
Category C (I trimester) and D (II and III trimester). In pregnant women, valsartan should be replaced with a medicine from another group. For women planning pregnancy, the treatment method should be changed. Do not use during breast-feeding.
Hypertension. Adults. 80 mg 1 × / d, if necessary, increase the dose or use in combination with a diuretic; dose max 320 mg / d. Children 6-18. At first, children <35 kg 40 mg 1 × / d,> 35 kg body weight 80 mg 1 × / d, then the dose should be adjusted. The dose of max. 18-35 kg body weight - 80 mg / d, 35-80 kg - 160 mg / d, 80-160 kg - 320 mg / d. Condition after a recent heart attack. In adults in a stable clinical condition, treatment can be started 12 hours after the diagnosis of a recent myocardial infarction. Initially 20 mg 2 × / d, then increased gradually over several weeks to 40 mg, 80 mg and 160 mg administered 2 × / d; dose max. 160 mg 2 × / d; it is usually recommended that patients should receive a dose of 80 mg 2 × / d after the start of treatment for 2 weeks, and a maximum target dose of 160 mg 2 × / d should be achieved within 3 months of starting treatment, depending on the tolerability of the drug ; in this indication, it is not recommended to be used in combination with an ACE inhibitor. Heart failure. Adults. Initially 40 mg 2 × / d, then increase the dose at intervals of at least 2 weeks to 80 mg and 160 mg administered 2 × / d to obtain the maximum dose tolerated by the patient; the maximum dose in clinical trials was 320 mg / d; in this indication, concomitant use with an ACE inhibitor and a β-blocker is not recommended. There is no need to change the dosage in adult patients with creatinine clearance> 10 ml / min, and in children and adolescents> 30 ml / min. In people with mild or moderate hepatic impairment, the maximum dose is 80 mg / d.
There is no evidence of impairment of physical and mental fitness by valsartan, however, due to the possibility of dizziness or fatigue in the course of antihypertensive therapy, caution should be exercised when driving vehicles and operating mechanical devices in motion.