Candecor

Candecor is a member of a group of drugs that affect the activity of the RA system. It is an angiotensin 2 antagonist.

Indications Candecora

It is used to eliminate the following disorders:

• elevated blood pressure;
• CHF and left ventricular systolic dysfunction (left ventricular ejection fraction ≤40%) – in combination with ACE inhibitors or instead of them in case of increased patient sensitivity to them.

Release form

The drug is released in tablets, 14 pieces inside a blister plate. The box contains 2, 4 or 7 such blisters.

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Pharmacodynamics

Angiotensin 2 is the main hormone of the RAAS complex, which has a vasoactive effect. It is an important participant in the pathogenesis of increased blood pressure and other pathologies affecting the function of the cardiovascular system. In addition, it is important in the pathogenesis of damage to various limbs and hypertrophy. Among its main physiological properties are: vasoconstrictor effect, stimulation of aldosterone, stabilization of water-salt homeostasis, and stimulation of cell growth activity (cells, the transmission of which occurs through the ending of type 1 AT1).

Candecor is a prodrug that after absorption from the gastrointestinal tract is quickly converted into the active element candesartan (in the process of ester hydrolysis). The drug is a selective antagonist of the angiotensin 2 and AT1 terminal, has a strong synthesis and slow dissociation from the terminal. It has no affinity for the terminal. The drug does not slow down the activity of ACE, which converts angiotensin 1 to angiotensin 2, and also destroys the integrity of bradykinin.

The drug is not synthesized and does not block other hormonal endings or ion channels that are important participants in the stabilization of the cardiovascular system. Due to antagonism of the angiotensin 2 (AT1) endings, a portion-size-dependent increase in plasma renin values and angiotensin 1 and 2 indicators, as well as a decrease in the plasma aldosterone level, develops.

When reducing elevated blood pressure values, the drug (taking into account the dose size) has a long-term antihypertensive effect. The antihypertensive properties of the drug depend on the total peripheral resistance, but not on the reflex increase in heart rate. There were no symptoms of a significant decrease in blood pressure when administering the initial dose or the development of a reverse effect after the end of therapy.

After taking a single dose of the drug, the hypotensive effect develops over 120 minutes. With permanent therapy, a decrease in blood pressure occurs mainly with any dosage; this effect is often achieved over 4 weeks, persisting during long-term treatment. The average additive effect associated with increasing the dose from 16 to 32 mg taken once a day is insignificant. Given individual variability, some patients may experience more than the average effect.

A single daily use of Candecor results in a smooth and effective reduction in blood pressure over 24 hours. At the same time, only an insignificant difference is observed between the peak and residual effects of the drug during the dosing interval.

Cilexetil candesartan increases blood circulation inside the kidneys without affecting them, or increases the glomerular filtration rate during a decrease in the filtration fraction, as well as the resistance of blood vessels inside the kidneys.

In people with elevated blood pressure values in combination with type 2 diabetes mellitus, as well as with microalbuminuria, antihypertensive treatment using the drug reduces the excretion of albumin with urine. At the moment, there is no information on the effect of the drug on the progression of diabetic nephropathy. In people with the above-mentioned disorders, no complications (negative effects on the lipid profile and blood sugar levels) were observed after 12 weeks of therapy using doses of 8-16 mg.

Heart failure.

In people with CHF and weakened systolic activity of the left ventricle (left ventricular ejection fraction is ≤40%), the drug reduces the total vascular resistance and the wedge pressure inside the capillaries of the pulmonary arteries. In addition, Candecor increases the functional activity of renin in the blood plasma and angiotensin 2 levels, and at the same time reduces aldosterone values.

Pharmacokinetics

After oral administration, the active ingredient is converted into the candesartan component. Its absolute bioavailability after oral administration is 14%. At the same time, the drug reaches average peak values in the serum after 3-4 hours. The level of candesartan in the blood serum increases linearly - along with an increase in the portion in the therapeutic dosage range. The AUC values of the substance in the blood serum do not change under the influence of food.

Candesartan has a high plasma protein binding rate (greater than 99%), with an apparent distribution volume of 0.1 l/kg.

Excretion of unchanged substance is mainly via urine and bile. Only a very small part of the drug is excreted via metabolism in the liver (CYP2C9). The half-life of the drug is approximately 9 hours. No accumulation of the drug in the body is observed.

The total clearance of the drug in the blood is approximately 0.37 ml/minute/kg, and the clearance in the kidneys is approximately 0.19 ml/minute/kg. The drug is excreted through the kidneys, by glomerular filtration and active tubular secretion.

The unchanged part of the drug and inactive products of drug metabolism are excreted in the urine (26% and 7%, respectively), as well as in the feces (56% and 10% of the substance, respectively).

In elderly people (65 years and older), peak values and AUC levels increase by approximately 50% and 80%, respectively, compared to younger patients. However, blood pressure values and the incidence of adverse events after drug use remain the same in both groups of patients.

In subjects with mild to moderate renal impairment, peak plasma levels and AUC after repeated administration are increased by approximately 50% and 70%, respectively, although half-life remains unchanged.

In people with the above pathology in a severe stage, these indicators changed by approximately 50% and 110%. The terminal half-life of the drug in such patients doubles.

Pharmacokinetic properties in subjects undergoing hemodialysis are consistent with those observed in patients with severe renal impairment. In subjects with mild to moderate renal impairment, the mean AUC of the substance increases by approximately 23%.

Dosing and administration

Candecor is taken once a day, without tying the use of the drug to food intake.

Reduction of elevated blood pressure values.

The recommended initial and standard maintenance dose is 8 mg taken once a day. The dose can be doubled to 16 mg/day. If there is no result after 1 month of therapy with 16 mg/day, the dose can be increased to the maximum permissible 32 mg/day. If the desired effect cannot be achieved even after using this dose, it is recommended to consider alternative treatments.

The treatment regimen is selected taking into account the patient's reaction - changes in blood pressure. Often, the hypotensive effect develops within 1 month from the start of therapy.

If there is no result after treatment (blood pressure indicators do not decrease to the optimal level), it is necessary to change the treatment regimen – try a combination system (candesartan with hydrochlorothiazide).

Older adults do not need to change portion sizes of medications.

For individuals with depleted intravascular volume values, an initial dose of 4 mg should be prescribed.

People with kidney problems (including patients undergoing hemodialysis) should use an initial dose of 4 mg. The dose should be adjusted based on the patient's response. The drug was almost never used in people with extremely severe or terminal renal failure (creatinine clearance <15 ml/minute).

People with mild or moderate liver failure should take the drug at an initial dosage of 2 mg (single dose per day). The dosage is selected based on the patient's response. There is no data on the use of Candecor in people with severe liver failure.

Treatment regimen for CHF.

The standard recommended starting dose is 4 mg taken once a day. Increasing the dose to the planned daily dose of 32 mg or to the maximum dose by doubling it is allowed at intervals of at least 2 weeks.

The use of the drug is permitted in the combined treatment of heart failure (together with diuretics, ACE inhibitors, β-blockers and digitalis drugs) or with the use of a complex of these drugs.

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Use Candecora during pregnancy

It is prohibited to prescribe Candecor to pregnant women.

Contraindications

Main contraindications:

• the presence of hypersensitivity to the active ingredient and auxiliary elements of the drug;
• breastfeeding women;
• cholestasis or severe liver failure.

Side effects Candecora

The use of drugs to reduce high blood pressure often causes the following side effects:

• infection in the respiratory tract;
• vertigo or headaches;
• an increase in C-ALT (C-GPT), urea, creatinine or potassium levels, as well as a decrease in sodium values;
• When combined with other agents that inhibit the activity of the RAAS, a slight decrease in hemoglobin levels was observed.

During the treatment of heart failure, the following disorders often developed:

• an increase in urea or creatinine levels, as well as the development of hyperkalemia;
• a strong decrease in blood pressure values;
• kidney failure.

At the stage of post-marketing studies, the following were noted in isolated cases:

• neutro- or leukopenia, as well as agranulocytosis;
• hyponatremia or hyperkalemia;
• headaches with dizziness, as well as nausea;
• increased activity of liver enzymes and liver dysfunction or hepatitis;
• rashes, angioedema, itching and urticaria;
• arthralgia, back pain and myalgia;
• renal failure (this also includes functional renal disorders in individuals predisposed to them).

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Overdose

Signs of poisoning: dizziness and a marked decrease in blood pressure.

To eliminate the disorder, symptomatic measures should be taken, as well as the functioning of vital organs should be monitored. It is necessary to lay the victim on his back and raise his legs. If this action is insufficient, it is necessary to increase the plasma volume by introducing a special infusion system (such as isotonic salt solution). If there is no result after using the above procedures, sympathomimetics should be used. The drug is not excreted by hemodialysis.

Interactions with other drugs

No significant drug interactions have been noted with warfarin, hydrochlorothiazide and digoxin, as well as nifedipine, glibenclamide, enalapril and oral contraception (for example, ethinyl estradiol and levonorgestrel).

Candesartan is excreted only to a small extent via intrahepatic metabolism (CYP2C9). The hypotensive effect of the drug may be increased by other drugs that lower blood pressure, regardless of the prescription of antihypertensive drugs or other indications for use.

Experience with the use of other drugs that affect RAAS activity in combination with potassium-containing salt substitutes, potassium-sparing diuretics, potassium supplements, and other drugs that can increase potassium levels (such as heparin) suggests that serum potassium levels may increase with this combination.

Combining lithium with ACE inhibitors results in a treatable increase in serum lithium levels and an increase in its toxic effects. This effect may be seen with angiotensin 2 inhibitors, so serum lithium levels should be closely monitored when used in combination.

The combination of angiotensin II endpoint antagonists with NSAIDs (e.g., selective agents that inhibit COX-2 activity), aspirin (use >3 g/day), and also with non-selective NSAIDs, may provoke a decrease in the hypotensive properties of the drug. When combining angiotensin II endpoints with NSAIDs, the likelihood of weakening of renal function (e.g., suspected acute renal failure) may increase, as well as an increase in serum potassium levels (especially in individuals with chronic renal failure). Therefore, these drugs should be combined with caution, especially in elderly patients. Patients should drink a sufficient volume of fluid and monitor renal function after the start of complementary treatment, and periodically thereafter.

Storage conditions

Candecor should be kept in a place closed to small children. The temperature level should not exceed 30ºС.

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Shelf life

Candecor can be used for 2 years from the date of release of the drug.

Application for children

Since there is no information regarding the safety and effectiveness of the drug in individuals under 18 years of age, it is prohibited to prescribe it to this group.

Analogues

Analogues of the drug are Angiacard, Angiakan, Ordiss, Atacand, as well as Hyposart with Candesartan, Candesartan-SZ, Xarten and Candesartan cilexetil.

Reviews

Candecor usually receives positive feedback from patients who have used this product. People note that the drug helps to normalize blood pressure values, reducing them to an optimal level.

However, there are also individual reviews that indicate the presence of certain side effects, such as heaviness and severe pain in the chest area.