Angiacand pills 16mg, 28pcs

Composition

1 tablet contains:  

Active ingredient:

candesartan cilexetil 16 mg;

excipients:  

pregelatinized corn starch-23.8 mg,

croscarmellose sodium (primellose) – 5 mg,

lactose monohydrate (milk sugar) – 90 mg,

magnesium stearate-1 mg,

povidone-K 30-4.2 mg

Pharmacological action

Candesartan is a selective antagonist of type 1 angiotensin II receptors (AT1 receptors) and forms a strong bond with them with subsequent slow dissociation. It has vasodilating, hypotensive and diuretic effects. It does not exhibit agonist properties (it does not inhibit angiotensin-converting enzyme (ACE) and does not lead to the accumulation of bradykinin or substance P, does not bind to other hormone receptors, and does not block ion channels involved in the regulation of cardiovascular functions).

As a result of blocking the AT1 receptors of angiotensin II, there is a compensatory dose-dependent increase in the activity of renin, the concentration of angiotensin I, angiotensin II, and a decrease in the concentration of aldosterone in blood plasma.

Arterial hypertension

The antihypertensive effect is due to a decrease in total peripheral vascular resistance (OPSS), while there is no effect on the heart rate (HR). There were no cases of severe hypotension after taking the first dose of the drug, as well as “withdrawal” syndrome after discontinuation of therapy. The onset of antihypertensive effects after the first dose usually develops within 2 hours. While continuing therapy with the drug in a fixed dose, the maximum reduction in blood pressure (BP) is usually achieved within 4 weeks and persists throughout treatment.

Candesartan increases renal blood flow and does not alter or increase glomerular filtration rate, while renal vascular resistance and filtration fraction are reduced.

It does not affect glucose concentration and lipid profile in patients with arterial hypertension and type 2 diabetes mellitus. Provides a dose-dependent smooth reduction of blood pressure. Age and gender do not affect the effectiveness of the drug.

Chronic heart failure

In patients with chronic heart failure and a decrease in the left ventricular ejection fraction of less than 40%, candesartan use contributed to a decrease in OPSS and capillary pressure in the lungs, an increase in renin activity and angiotensin II concentration in blood plasma, as well as a decrease in aldosterone concentration.

Pharmacokinetics

Candesartan is an oral prodrug. It is rapidly converted (via ether hydrolysis) to pharmacologically active candesartan. The absolute bioavailability of candesartan after oral use of candesartan cilexetil solution is about 40%.

The relative bioavailability of the tablet preparation compared to the oral solution is approximately 34%. Thus, the estimated absolute bioavailability of the tablet form is about 14% and does not depend on the time of food intake. The maximum concentration (Cmax) in the blood serum is reached after 3-4 hours. The concentration in the blood plasma increases linearly with increasing dose in the therapeutic interval (up to 32 mg). The volume of distribution is 0.13 l / kg. Binding to plasma proteins is 99.8%.

It is slightly metabolized in the liver (20-30%) with the participation of the cytochrome P450 isoenzyme CYP2C9 with the formation of an inactive derivative. The final half-life (T1 / 2) is 9 h. It does not accumulate. Total clearance is 0.37 ml / min / kg, while renal clearance is about 0.19 ml / min/kg. It is excreted by the kidneys and bile mainly in unchanged form, to a small extent-in the form of a metabolite: by the kidneys (by glomerular filtration and active tubular secretion) – 26% in the form of candesartan and 7% in the form of an inactive metabolite, with bile – 56% and 10%, respectively. After a single oral dose, more than 90% of the dose is eliminated within 72 hours.

In elderly patients (over 65 years of age) Cmax and area under the concentration-time curve (AUC) increased by 50% and 80%, respectively, compared with younger patients. However, the antihypertensive effect and the frequency of side effects when using the drug do not depend on the age of patients.

In patients with mild and moderate renal impairment, Cmax and AUC increase by 50% and 70%, respectively, while T1 / 2 of the drug does not change compared to patients with normal renal function.

In patients with severe renal impairment, Cmax and AUC increase by 50% and 110%, respectively, and T1 / 2 of the drug increases 2-fold.

In patients with mild to moderate hepatic impairment, AUC increased by 23%.

Indications

• arterial hypertension;
• chronic heart failure and impaired left ventricular systolic function (reduced left ventricular ejection fraction less than 40%) as adjunctive therapy to angiotensin-converting enzyme (ACE) inhibitors or in case of intolerance to ACE inhibitors.

Use during pregnancy and lactation

In animal studies, kidney damage in the embryonic and neonatal periods was detected with the use of candesartan. It is assumed that the mechanism of damage is due to the pharmacological effect of the drug on the renin-angiotensin-aldosterone system (RAAS).

In a human embryo, the kidney’s blood supply system, which depends on the development of RAAS, begins to form in the second trimester of pregnancy. Thus, the risk to the fetus increases with the use of candesartan in the second and third trimesters of pregnancy. Drugs that have a direct effect on the RAAS can cause fetal developmental disorders or have a negative effect on the newborn, up to a fatal outcome, when the drug is used in the second and third trimesters of pregnancy.

Angiacand should not be used during pregnancy. If pregnancy is detected during treatment with the drug, therapy should be discontinued as soon as possible.

It is not known whether candesartan is excreted in breast milk. Due to possible adverse effects on infants, Angiacand should not be used during breast-feeding.

Contraindications

• hypersensitivity to candesartan or other components of the drug;
• lactase deficiency, lactose intolerance, glucose-galactose malabsorption;
• pregnancy;
• lactation period;
• primary hyperaldosteronism (resistance to therapy);
• severe liver function disorders and / or cholestasis;
• age up to 18 years.

  With caution Severe renal insufficiency (creatinine clearance less than 30 ml / min), bilateral renal artery stenosis, stenosis of the renal artery of a single kidney, after a kidney transplant in the anamnesis, hemodynamically significant aortic and mitral valve stenosis, cerebrovascular diseases, coronary heart disease, hypertrophic obstructive cardiomyopathy, decreased circulating blood volume (BCC), hyperkalemia.

Side effects

Arterial hypertension, the most common side effects (≥1/100,

From the central nervous system:  dizziness, weakness, headache.

Musculoskeletal and connective tissue disorders:  back pain.

Other services:  respiratory infections.

Laboratory parameters:  decreased hemoglobin, hypercreatininemia, increased blood urea concentration, hyperkalemia, hyponatremia, increased ALT activity.

Chronic heart failure, most common side effects (≥1/100,

From the CCC side:  marked decrease in blood pressure.

From the urinary system:  impaired renal function.

Laboratory changes:  hypercreatininemia, increased urea concentration in the blood, hyperkalemia.

The following side effects (frequency less than 1/10000)have been reported during post — marketing use of candesartan:

From the side of hematopoietic organs:  leukopenia, neutropenia, and agranulocytosis.

Laboratory parameters:  hyperkalemia, hyponatremia.

From the central nervous system:  dizziness, weakness, headache.

From the digestive system:  nausea.

Liver and biliary tract disorders:  increased activity of hepatic transaminases, impaired liver function, or hepatitis.

Allergic reactions:  angioedema, skin rash, pruritus, urticaria.

Musculoskeletal and connective tissue disorders:  back pain, arthralgia, myalgia.

From the urinary system:  impaired renal function, including acute renal failure in predisposed patients.

Respiratory system disorders:  cough.

Interaction

No clinically significant interactions were observed when candesartan was co-administered with hydrochlorothiazide, warfarin, digoxin, oral contraceptives (ethinyl estradiol/levonorgestrel), glibenclamide, nifedipine, and enalapril.

A reversible increase in serum lithium concentrations and the development of toxic reactions have been reported when lithium preparations are co-administered with ACE inhibitors. Adverse reactions may also occur with the use of angiotensin II receptor antagonists, and therefore it is recommended to monitor the level of lithium in the blood serum with the combined use of these drugs.

Concomitant use of angiotensin II receptor antagonists and NSAIDs, including selective COX-2 inhibitors and non-selective NSAIDs (for example, acetylsalicylic acid at a dose of more than 3 g/day), may reduce the hypotensive effect of candesartan. As with ACE inhibitors, concomitant use of angiotensin II receptor antagonists and NSAIDs increases the risk of decreased renal function up to the development of renal failure, which leads to hyperkalemia in patients with impaired renal function. This combination should be used with caution, especially in elderly patients. All patients should receive sufficient fluids. It is necessary to monitor renal function at the beginning of therapy and in the future.

Medications that affect RAAS may increase blood urea and creatinine concentrations in patients with bilateral renal artery stenosis or single-kidney artery stenosis.

Diuretics and other antihypertensive agents increase the risk of hypotension Potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium, and other drugs that may increase serum potassium (such as heparin) increase the risk of hyperkalemia.

Candesartan is only slightly metabolized in the liver (CYP2C9 isoenzyme). Interaction studies have not revealed the effect of candesartan on the isoenzymes CYP2C9 and CYP3A4. The effect on other cytochrome P 450 isoenzymes has not been studied.

How to take, course of use and dosage

Inside, regardless of food intake,1 time a day.

Arterial hypertension. The recommended starting and maintenance dose is 8 mg once daily.

Patients who need a further reduction in blood pressure, it is recommended to increase the dose to 16 mg once a day. The maximum daily dose of the drug is 32 mg once a day.

The maximum antihypertensive effect occurs 4 weeks after the start of treatment.

If Angiacand therapy does not reduce blood pressure to the optimal target level, it is recommended to add a thiazide diuretic to therapy.

In elderly patients, no adjustment of the initial dose is required.

In patients with mild or moderate renal impairment (creatinine clearance >30 ml / min), no change in the initial dose of the drug is required.

Patients with severe renal impairment (creatinine clearance, chronic heart failure. The recommended starting dose is 4 mg once a day (it is possible to use candesartan in another Form of production).

Increasing the dose to 32 mg once a day or to the maximum tolerated dose is carried out by doubling it at intervals of at least 2 weeks.

Elderly patients and patients with impaired renal and/or hepatic function do not need to change the initial dose of the drug.

Overdose

Symptoms: marked decrease in blood pressure, dizziness, tachycardia.

Treatment: symptomatic, lay the patient on his back, raise the lower limbs above the level of the head, if necessary-increase the volume of circulating blood (BCC) by infusion of 0.9% sodium chloride solution, use sympathomimetics. Hemodialysis is ineffective.

Special instructions

Before and during treatment, it is necessary to monitor blood pressure, kidney function (creatinine in blood plasma), potassium and lithium content in blood serum (with combined use of drugs). Arterial hypotension Patients with chronic heart failure may develop arterial hypotension during Angiacand therapy. As with other drugs that affect the RAAS, the cause of hypotension in patients with hypertension may be a decrease in BCC, as is observed in patients receiving high doses of diuretics. Therefore, at the beginning of therapy, care should be taken and, if necessary, correction of hypovolemia should be carried out.

Renal artery stenosis In patients with bilateral renal artery stenosis or stenosis of the artery to a single kidney, drugs that affect the RAAS, in particular ACE inhibitors, can cause an increase in serum urea and creatinine concentrations. Similar effects can be expected with angiotensin II receptor antagonists.

There are no data on the use of candesartan in patients who have recently undergone a kidney transplant.

Impaired renal function During Angiacand therapy, as with other agents that inhibit RAAS, some patients may experience impaired renal function. When using Angiacand in patients with arterial hypertension and severe renal insufficiency, it is recommended to periodically monitor the content of potassium and creatinine in the blood serum. Clinical experience with candesartan in patients with severe renal impairment or end-stage renal failure (creatinine clearance less than 15 ml / min) is limited. In patients with chronic heart failure, renal function should be monitored periodically, especially in patients aged 75 years and older, as well as in patients with impaired renal function. When increasing the dose of Angiacand, it is also recommended to monitor the content of potassium and creatinine in blood plasma.

Concomitant use with ACE inhibitors in chronic heart failureWhen Angiacand is used in combination with ACE inhibitors, the risk of side effects may increase, especially impaired renal function and hyperkalemia. In these cases, careful monitoring and monitoring of laboratory parameters is necessary.

General anesthesia and surgery Patients receiving angiotensin II receptor antagonists may develop hypotension during general anesthesia and surgery as a result of RAAS blockade. Very rarely, there may be cases of severe hypotension requiring intravenous fluid and/or vasopressors.

Aortic and mitral valve stenosis (hypertrophic obstructive cardiomyopathy) Caution should be exercised when using Angiacand, as with other vasodilators, in patients with hypertrophic obstructive cardiomyopathy or hemodynamically significant aortic and/or mitral valve stenosis.

Primary hyperaldosteronism Patients with primary hyperaldosteronism are usually resistant to therapy with antihypertensive drugs that affect the activity of RAAS. In this regard, the drug Angiacand is not recommended for use in such patients.

Hyperkalaemia Clinical experience with other drugs that affect the RAAS suggests that concomitant use of candesartan with potassium-sparing diuretics, potassium preparations or salt substitutes containing potassium, or other drugs that may increase the potassium content in the blood (for example, heparin) may lead to the development of hyperkalaemia in patients with hypertension.

General information Patients whose vascular tone and renal function are predominantly affected by RAAS activity (for example, patients with severe chronic heart failure or kidney disease, including renal artery stenosis) are particularly sensitive to drugs acting on RAAS. The use of such drugs is accompanied in these patients by severe hypotension, azotemia, oliguria and, less often, acute renal failure. The possibility of developing these effects cannot be excluded even with the use of angiotensin II receptor antagonists. A sharp decrease in blood pressure in patients with ischemic heart disease or cerebrovascular diseases of ischemic origin, with the use of any antihypertensive agents, can lead to the development of myocardial infarction or stroke.

Influence on the ability to drive vehicles and mechanisms During the treatment period, dizziness and weakness may occur, so caution should be exercised when driving vehicles and engaging in other potentially dangerous activities that require increased concentration of attention and speed of psychomotor reactions.

Form of production

Tablets are white or almost white in color, round, biconvex.

Storage conditions

Store in a dry place, protected from light, at a temperature not exceeding 25 °C

Shelf life

2 years

Active ingredient

Candesartan

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as directed by your doctor

Indications

Heart Failure, Hypertension