Kanarb pills 120mg, 30pcs

Composition

>of 1 tab. contains: Active ingredients: fimasartan potassium trihydrate – 132.02 mg, which corresponds to the content of fimasartan potassium 120 mg

Auxiliary substances:  

– Lactose monohydrate-87.98 mg;

– Microcrystalline cellulose-23.5 mg;

– Croscarmellose sodium-45 mg;

– Hydroxypropylcellulose-7 mg;

– Magnesium stearate-4.5 mg.

Shell composition:  

– Opadry 03B63253 orange – 7.5 mg (hypromellose (E464) 62.5%, titanium dioxide (E 171) 25.23%, macrogol (E1521) 6.25%,

dye sunset yellow (E110) 6%, dye iron oxide black (E 172) 0.01%, dye iron oxide yellow (E 172) 0.01%);

– Carnauba wax (E 903) – 0.5 mg.

Pharmacological action of

Pemasaran is a non-peptide antagonist of angiotensin II receptor (type at 1) for oral use. Angiotensin II is a key effector compound of the RAAS, which plays an important role in the regulation of blood pressure and the pathogenesis of arterial hypertension. Angiotensin II increases blood pressure due to a pronounced vasoconstrictor effect and an increase in PPS, activation of epinephrine production, release of aldosterone, an effect on sodium reabsorption in the distal renal tubules, and an increase in BCC. Its action is carried out through specific angiotensin receptors, while the main physiological effects, including adverse ones, are mediated by AT1 receptors. The effect of fimasartan is due to selective binding to angiotensin II AT1 receptors: fimasartan does not have a partial agonistic effect on angiotensin II receptors, which is typical for peptide blockers of angiotensin II receptors (for example, saralazine). When studying various animal models, fimasartan after a single or repeated oral and intravenous use effectively and dose-dependently reduced blood pressure. In humans, fimasartan increased plasma renin activity in combination with an increase in the concentration of angiotensin I and II, which confirms the specific blockade of angiotensin II receptors. Thus, after a single oral use of fimasartan at a dose of 20 to 480 mg, it caused an increase in the activity of plasma renin, angiotensin I and angiotensin II with a maximum increase, usually between 6 and 8 hours after the dose, which persisted for a long time (up to 48 hours after use). At the same time, drug-related changes in the activity of ACE and aldosterone were not observed. Fimasartan increased plasma renin activity and angiotensin II concentrations after repeated use of 120 and 360 mg per day for 7 days. The maximum increase in these parameters was noted, as a rule, in 6-8 hours after application, and remained for a long time (up to 24 hours after use). A decrease in plasma aldosterone levels was observed with longer use of fimasartan (for 28 days). The efficacy of fimasartan at therapeutic doses of 60 and 120 mg in reducing blood pressure has been proven in comparative randomized clinical trials. At the same time, it was found that blood pressure when taking the drug decreases within 2 weeks from the start of treatment, the maximum effect is observed after approximately 8-12 weeks. Fimasartan acts on blood pressure for 24 hours, providing a stable and smooth blood pressure profile, which is also achieved by taking fimasartan at the same time of day (to minimize pressure fluctuations). When fimasartan was prescribed for a long period (24 weeks), tolerance to it did not develop. Pharmacokineticsabsorption Simasartan is rapidly absorbed after oral use: Tmax in blood plasma after use in healthy individuals and patients with arterial hypertension was 0.5-3 hours and 0.5-1.3 hours, respectively. When studying the pharmacokinetic characteristics of the drug directly in the population of Russian patients with arterial hypertension, Tmax was also determined in the range from 0.5 to 4 hours (with a single dose of 60 mg). After reaching Cmax, a two-phase decrease in fimasartan plasma concentration was observed, with the beginning of the elimination phase observed 2.5-8 hours after taking the drug in all patients. Quantifiable plasma concentrations of fimasartan were observed up to the last time point of sample collection 24 hours after use of the drug in the range from 1.33 to 11.2 ng / ml. The variability of parameters between patients (geometric mean CV%) was high, while the values for AUC0-1last, AUC0-∞ and Cmax were 50.1%,53.9% and 86.8%, respectively. In the Russian study No. SS 09042014, pharmacokinetic parameters were obtained in female patients. Comparison of the data with a population of healthy male volunteers showed that after a single oral dose of fimasartan 60 mg, healthy volunteers had 2 hours more Tmax compared to patients with arterial hypertension. Peak systemic exposure (Cmax) was 1.4 times higher in hypertensive patients. Overall systemic exposure (AUC0-∞ and AUC0-tlast) was comparable in both populations. Comparison of the data with the Korean population of patients with arterial hypertension showed that after a single oral use of fimasartan at a dose of 60 mg, the median Tmax in the populations of Russian and Korean patients was approximately 1 hour with an individual range of values from 0.5 to 4.0 hours and from 0.5 to 6.0 hours after taking the drug, respectively. Peak systemic exposure (Cmax) and total systemic exposure (AUC0 – ∞ and AUC0-tlast) of fimasartan were comparable in the populations of Russian and Korean patients. The absolute bioavailability of fimasartan in healthy subjects with oral use of 60 mg is about 19%. Distribution In preclinical studies, limited distribution of the drug after oral use has been shown. When the concentration of fimasartan is from 0.01 to 100 mcg / ml in vitro, the protein binding in human blood plasma is from 95.6 to 97.2% and does not depend on the dose. Metabolism CYP3A4 was the main enzyme that metabolizes fimasartan. However, the role of metabolism in the elimination of fimasartan is insignificant, since the initial drug is ≥85% of the forms of fimasartan found in human blood plasma, in addition, the level of systemic exposure to fimasartan is slightly increased by specific CYP3A4 inhibitors. Desulfo-fimasartan and fimasartan-S-oxide were identified as the most common circulating plasma metabolites of fimasartan in healthy men. Fimasartan is not an inducer or inhibitor of other cytochrome P450 enzymes. Elimination After a single dose of fimasartan in a dose of 20 to 480 mg in healthy subjects, T1 / 2 is from 5 to 16 hours, in the Korean population of patients with essential hypertension when administered in doses of 20 to 180 mg, T1 / 2 was in the range of 7 to 10 hours, in the population of Russian patients with hypertension-from 4.4 to 7.9 hours with a single dose of the drug in a dose of 60 mg. Systemic exposure is estimated to be linear over a wide dose range. The accumulation index ranged from 1.20 to 1.26 in healthy individuals and from 1.02 to 1.08 in those with arterial hypertension. When evaluated in healthy men and in patients with arterial hypertension, approximately 3-5% of the administered dose of fimasartan was detected in the urine within 24 or 144 hours after oral use. Thus, the involvement of the kidneys in the elimination of fimasartan is insignificant. The main route of elimination is with feces. Thus, after oral use of a single dose of 120 mg of 14C-labeled fimasartan in a group of 6 healthy men, the average total excretion of the radioactive drug in feces and urine was about 86% of the prescribed dose, while urinary excretion was about 4.6%. Pharmacokinetics in special clinical cases in elderly patients. In elderly patients (over 65 years of age) the systemic effect of the drug is 1.69 times more pronounced than in young people. However, an increase in systemic exposure in elderly patients does not seem to lead to a more significant decrease in blood pressure, since RAAS activity in this population group is usually lower than in young people. Patients with renal insufficiency. The pharmacokinetic parameters of fimasartan were studied in patients with renal insufficiency; patients on hemodialysis were excluded from the study. When taking the drug at a dose of 120 mg in patients with severe renal impairment (estimated GFR less than 30 ml / min/1.73 m2 of body surface area), Cmax and AUC were compared with those in healthy volunteers: Cmax and AUC in patients with renal insufficiency increased 1.87 and 1.73 times, respectively. When evaluating the safety profile in the two groups, no differences were found. For patients with severe renal insufficiency (CCPatients with hepatic insufficiency. Fimasartan 120 mg was administered to patients with hepatic insufficiency (Child-Pugh class A and B). Cmax and AUC were compared with the same values in healthy volunteers. Geometric mean coefficients of the Cmax and AUC ratios were 0.77 and 1.10, respectively, when calculating indicators for patients with Class A hepatic insufficiency and healthy volunteers. When calculating indicators in groups of patients with class B hepatic insufficiency and healthy volunteers – 6.55 for Cmax and 5.2 for AUC. There were no significant differences in blood pressure and safety profile between the three groups. For patients with mild hepatic insufficiency, no initial dose adjustment is required. In patients with moderate to severe hepatic insufficiency, the drug is not recommended.

Indications

Arterial hypertension of 1 and 2 degrees.

Contraindications

• Hypersensitivity to any of the components of the drug;
• patients undergoing hemodialysis (there is no experience of using the drug in this patient population);
• moderate and severe violations of the liver (more than 7 points on a scale child-Pugh);
• patients with obstruction of the biliary tract;
• concurrent use with aliskiren and drugs containing aliskiren in patients with diabetes and/or moderate or severe renal impairment (GFR less than 60 ml/min/1.73 m 2);
• patients with diabetic nephropathy receiving ACE inhibitors;
• patients with genetic problems such as galactose intolerance, congenital lactase deficiency or malabsorption syndrome of glucose and galactose (product contains lactose);
• pregnancy;
• breastfeeding;
• women who are planning pregnancy;
• age up to 18 years.

With caution, special precautions should be taken when using fimasartan in patients with the following conditions/diseases. Reduced BCC or salt depletion: these patients (for example, patients receiving high-dose diuretics) with activated RAAS may experience symptomatic hypotension at the beginning of fimasartan therapy or with an increase in the dose of the drug. Such patients need to be closely monitored. Renal insufficiency: patients with hypersensitivity to RAAS inhibition may experience changes in renal function. The use of ACE inhibitors or angiotensin II receptor antagonists may be associated with the development of oliguria and progressive uremia and, in rare cases, acute renal failure or death in patients whose renal function depends on the activity of RAAS(for example, in patients with chronic heart failure, NYHA functional class IV). Renovascular hypertension: Patients with unilateral or bilateral renal artery stenosis have an increased risk of developing severe hypotension or renal failure when taking medications that affect the RAAS, such as fimasartan. As with other vasodilators, special care should be taken when treating patients with aortic or mitral valve stenosis, obstructive or hypertrophic cardiomyopathy. Primary hyperaldosteronism: the use of drugs that inhibit the renin-angiotensin system is usually ineffective. Therefore, it is not recommended to prescribe fimasratane to such patients. Hyperkalemia. Advanced age. Simultaneous use of lithium preparations. IHD. Cerebrovascular disease..

Side effects

The safety of fimasartan in the Korean population was studied in 406 patients out of 852 patients with essential hypertension who received fimasartan in doses from 60 to 120 mg for 4-12 weeks, and who were included in clinical studies and selected for safety analysis (i. e., information about which was compiled in a safety database).85 patients received fimasartan for 6 months or more. Most of the reported adverse events were mild or moderate in severity and transient in nature, the frequency of occurrence of events did not depend on the dose of the drug. The most common adverse events were headache and dizziness.

Table 1 lists adverse reactions (i. e., adverse events considered definitely related, probably related, or possibly related to the use of fimasartan) according to the WHO classification of adverse reactions by frequency of occurrence reported during clinical trials using fimasartan in Korea.

Table 1. Adverse reactions due to the use of fimasartan 1

1 Adverse events for which the relationship with the use of fimasartan was determined, probable, or possible.

2 Very common (≥1/10); common (≥1/100, <1/10); uncommon (≥1/1000, <1/100); rare (≥1/10 000, <1/1000); very rare (

In the Russian population, the safety of fimasartan was evaluated in 89 of 179 patients with grade I-II arterial hypertension who received fimasartan at a dose of 60 to 120 mg for 12 weeks in a study using losartan as a reference drug. In this study, the following adverse reactions were observed due to the use of fimasartan: nausea in 4 (4.5%) patients, increased ACT activity in 1 (1.1%) patient, increased ALT activity in 1 (1.1%) patient, dizziness in 1 (1.1%) patient, headache in 4 (4.5%) patients, pruritus in 1 (1.1%) patient. In the Russian patient population, adverse events were identified that were not associated with taking the drug (anemia, diarrhea, increased total cholesterol and LDL cholesterol in the blood, decreased creatinine clearance).

Interaction

Potassium-sparing diuretics and potassium-containing drugs. Concomitant use of fimasartan, as well as other medications that affect the RAAS, and potassium-sparing diuretics (for example, spironolactone), potassium supplements, salt substitutes containing potassium, and medications that may increase serum potassium levels (for example, heparin) may increase serum potassium levels. Fimasartan may increase blood pressure reduction when used concomitantly with other antihypertensive drugs, including diuretics. With previous use of high-dose diuretics, the initiation of fimasartan may be accompanied by an excessive decrease in blood pressure due to a decrease in intravascular BCC. Lithium preparations. Reversible increases in serum lithium concentrations and toxic effects were observed when lithium was administered with ACE inhibitors. In the case of combined use of lithium preparations with angiotensin II receptor antagonists, such reactions were observed very rarely. Although concomitant use of fimasartan with lithium preparations is generally not recommended, careful monitoring of blood lithium levels should be performed if such therapy is necessary. NSAIDs. Concomitant use of NSAIDs (for example, COX-2 inhibitors, acetylsalicylic acid at a dose of ≥3 g/day) with angiotensin II receptor antagonists may weaken the hypotensive effect. When angiotensin II receptor antagonists are used in combination with a COX inhibitor, some patients with renal insufficiency (for example, in patients with dehydration and in elderly patients with impaired renal function) have experienced an aggravation of the severity of excretory function disorders (including the development of acute renal failure, although reversible). Therefore, caution should be exercised when using fimasartan concomitantly with NSAIDs, especially in elderly patients. In these cases, adequate hydration and careful monitoring of renal function are necessary. Hydrochlorothiazide. No significant pharmacokinetic drug interaction was observed when fimasartan and hydrochlorothiazide were co-administered. Amlodipine. No significant pharmacokinetic drug interaction was observed when fimasartan and amlodipine were co-administered. Ketoconazole. The level of systemic exposure to fimasartan, determined by the AUC value, increased approximately 2-fold with concomitant use of ketoconazole. Caution should be exercised when using fimasartan and ketoconazole concomitantly. Rifampicin or other inhibitors of organic anion transfer proteins (OATP 1 In 1, OATP 1). Fimasartan is not a substrate for the ABC transfer system, but it is a substrate for OAT 1 and OART 1V1 transporters. When fimasartan was co-administered with rifampicin (a 1-in-1 OATP inhibitor), the AUC of fimasartan increased approximately 4.6 times. Therefore, concomitant use of fimasartan with rifampicin is not recommended.When combined with other 1-In-1 inhibitors of the OATRA transporter (for example, cyclosporine), an increase in systemic exposure to fimasartan may also occur, so such combinations should be prescribed with caution. Warfarin. Concomitant use of fimasartan did not significantly affect the pharmacokinetics and pharmacodynamics of warfarin. Atorvastatin. Concomitant use of fimasartan did not affect the AUC of atorvastatin and its active metabolites. Cmax of atorvastatin and its active metabolites in plasma increased by 1.9 and 2.5 times, respectively. There are no data on the clinical significance of this interaction. Digoxin. Concomitant use of fimasartan did not affect the pharmacokinetics and clearance of digoxin, with the exception of a 30% increase in digoxin Cmax. In combination therapy, careful monitoring of digoxin concentrations may be required. Other angiotensin receptor antagonists, ACE inhibitors, or aliskiren. Double blockade of the RAAS with angiotensin II receptor blockers and ACE inhibitors or aliskiren is associated with a higher risk of hypotension, syncope, hyperkalemia, and changes in renal function (including acute renal failure) than in the case of monotherapy. As a general rule, co-use of RAAS inhibitors should be avoided. Aliskiren and fimasartan should not be used concomitantly in patients with diabetes mellitus or impaired renal function (GFR). Concomitant use of ACE inhibitors and fimasartan is not recommended, and in patients with diabetic nephropathy, concomitant use of ACE inhibitors and fimasartan should be avoided. Other cases of drug interaction. Fimasartan does not inhibit or induce CYP450 isoenzymes.

How to take, course of use and dosage

The recommended starting dose of fimasartan is 60 mg once a day, regardless of the time of meal. If blood pressure cannot be adequately controlled during the use of the drug at a dose of 60 mg, the dose of fimasartan can be increased to 120 mg 1 time / day. If possible, it is recommended to take fimasartan at the same time of day (for example, in the morning). The antihypertensive effect of fimasartan mainly develops within 2 weeks. Elderly patients. In a study comparing pharmacokinetics in elderly healthy volunteers aged 65 years or older and in young volunteers, the AUC of fimasartan in older patients increased by 69%. However, there were no differences in efficacy and safety between older and younger patients when comparing 21 elderly patients (>65 years,9.3%) out of 226 patients treated with fimasartan in phase III clinical trials. Therefore, dose adjustment in elderly patients (age >65 years) it is not required, although it is possible to exclude a slightly greater susceptibility in some elderly patients. Patients with renal insufficiency. For patients with mild to moderate renal insufficiency (creatinine clearance 30-80 ml/min), no initial dose adjustment is required. For patients with severe renal insufficiency (CC When prescribing fimasartan at a dose of 30 mg,1/2 part of the 60 mg tablet should be taken, divided along the fault line. Patients with renal insufficiency taking aliskiren, as well as patients undergoing hemodialysis, the drug is not indicated. Patients with hepatic insufficiency. For patients with mild hepatic insufficiency, no initial dose adjustment is required. The use of fimasartan is not recommended in patients with moderate or severe hepatic insufficiency. Children’s patients. The efficacy and safety of fimasartan in patients aged 18 years or less have not been established. Patients with reduced intravascular BCC (for example, patients receiving high-dose diuretics). For patients with an increased risk of arterial hypotension, for example, due to a decrease in intravascular BCC, the recommended initial dose of the drug is 30 mg 1 time/day.

Overdose

There are no data on overdose of fimasartan in humans. Symptoms:the most likely signs of overdose may be hypotension and tachycardia. Bradycardia can occur as a result of stimulation of the parasympathetic nervous system (vagus nerve). Treatment: in case of symptomatic hypotension, maintenance therapy is necessary. It is not known whether fimasartan is eliminated from plasma by hemodialysis.

Special instructions

Arterial hypotension and impaired water-electrolyte balance. Patients with reduced BCC or salt depletion (for example, patients receiving high-dose diuretics, following a diet with limited salt intake, patients with diarrhea or vomiting) may experience symptomatic hypotension, especially if fimasartan therapy is initiated or if the dose of the drug is increased. Reduction of intravascular BCC or salt depletion should be corrected before starting fimasartan therapy, or it is necessary to start therapy with a lower dose and then increase it. At the same time, careful monitoring of the patient’s condition is required. If symptomatic hypotension occurs, the patient should be placed in a horizontal position and, if necessary, start infusion therapy. Fimasartan may be resumed after blood pressure stabilizes. Hyperkalemia. Medications that have an effect on the RAAS may cause hyperkalemia in patients with chronic heart failure or renal failure. If fimasartan is used in these patients, regular monitoring of blood potassium levels is recommended. Renovascular hypertension. Elevated serum creatinine and urea nitrogen levels have been reported in patients with unilateral or bilateral renovascular hypertension when angiotensin II receptor antagonists, such as fimasartan, are used. Although fimasartan itself has not been used in patients with unilateral or bilateral renovascular hypertension, similar effects may occur in the case of such use. Double inhibition of RAAS. When taking medications that inhibit the RAAS system, especially if they are used simultaneously with drugs that can also affect the RAAS, renal function may change, including the development of acute renal failure in patients with hypersensitivity to these drugs. Therefore, dual inhibition of RAAS, i. e. the simultaneous use of an angiotensin II receptor antagonist and an ACE inhibitor, is usually not recommended. However, if necessary, such therapy can be performed in a number of patients after confirmation of its safety. During fimasartan therapy, transient symptomatic hypotension may occur (for example, shock, loss of consciousness, shortness of breath). If these symptoms occur, the drug should be discontinued and the necessary symptomatic therapy should be initiated. Hypotension may also develop in patients receiving an angiotensin II receptor antagonist during anesthesia (anesthesia) and surgery due to RAAS inhibition. In very rare cases, severe hypotension may develop, requiring infusion therapy and the use of vasopressors. As with other antihypertensive drugs, a marked decrease in blood pressure in patients with CHD or cerebral vascular ischemia can worsen the course of the underlying disease. Special care should be taken when treating this patient population. – There is no experience of using the drug Kanarb in patients after kidney transplantation; – In patients of the black race, there is a decrease in the antihypertensive effectiveness of angiotensin II receptor antagonists; – Effect on the ability to drive vehicles and mechanisms;- The effect of fimasartan on the ability to drive vehicles and mechanisms has not been studied. However, sometimes drowsiness and dizziness may occur during the use of antihypertensive drugs, so patients taking fimasartan should be warned about the existence of such a risk.

Storage conditions

The drug should be stored out of the reach of children, protected from light at a temperature not exceeding 25°C.

Shelf

life is 3 years.

Active ingredient

Fimasartan

Conditions of release from pharmacies

By prescription

Dosage form

Tablets