Instructions for Kasark tablets 32 mg No. 30
Composition
active ingredient: candesartan cilexetil;
1 tablet contains candesartan cilexetil, calculated as 100% substance, 8 mg or 16 mg, or 32 mg;
Excipients: carmellose calcium; corn starch; hydroxypropylcellulose; lactose monohydrate; magnesium stearate; polyethylene glycol (PEG 8000).
Dosage form
Pills.
Main physicochemical properties:
Kasark®, tablets of 8 mg or 16 mg: tablets of white or almost white color, round shape, with a biconvex surface. Marbling is allowed on the surface of the tablet.
Kasark®, 32 mg tablets: white or almost white, round tablets with a biconvex surface, with a score on one side of the tablet. Marbling on the surface of the tablet is allowed.
Pharmacotherapeutic group
Angiotensin II receptor antagonists.
ATX code C09C A06.
Pharmacological properties
Pharmacodynamics
Angiotensin II is the main vasoactive hormone of the renin-angiotensin-aldosterone system, which plays a role in the pathophysiological mechanism of hypertension, heart failure, and other cardiovascular diseases. It also plays a role in the pathogenesis of end-stage hypertrophy and target organ damage. The main physiological effects of angiotensin II, such as vasoconstriction, stimulation of aldosterone secretion, regulation of salt and water homeostasis, and stimulation of cell growth, occur with the participation of type 1 (AT1) receptors.
Pharmacodynamic effects.
Candesartan cilexetil is an orally administered prodrug. It is rapidly converted to the active substance, candesartan, by ester hydrolysis during absorption from the gastrointestinal tract. Candesartan is an angiotensin II receptor antagonist (ARBI), selective for the ATI receptor, with tight binding and slow dissociation from the receptor. It has no agonist activity.
Candesartan does not inhibit angiotensin-converting enzyme (ACE), which converts angiotensin I to angiotensin II and destroys bradykinin. No effect on ACE and no potentiation of bradykinin or substance P was observed. In controlled clinical trials comparing candesartan with ACE inhibitors, the incidence of cough was lower in patients receiving candesartan cilexetil. Candesartan does not bind to or block receptors for other hormones or ion channels known to be important in cardiovascular regulation. Antagonism of angiotensin II (AT1) receptors results in dose-dependent increases in plasma renin, angiotensin I and angiotensin II levels and in a decrease in plasma aldosterone concentrations.
Clinical efficacy and safety.
Arterial hypertension
In hypertension, candesartan produces a dose-dependent, long-lasting reduction in blood pressure (BP). The antihypertensive effect is due to a decrease in systemic peripheral resistance without a reflex increase in heart rate. There is no evidence of serious or excessive hypotension after the first dose or of a withdrawal syndrome after discontinuation of treatment.
After a single dose of candesartan cilexetil, the onset of the antihypertensive effect usually occurs within 2 hours. With long-term treatment, the greatest reduction in blood pressure with any dose is usually achieved within 4 weeks and is maintained during long-term treatment. According to the meta-analysis, the average additional effect when increasing the dose from 16 mg to 32 mg 1 time per day was insignificant. Taking into account interindividual variability, a more pronounced than average effect can be expected in some patients. Candesartan cilexetil, when taken once a day, provides an effective and smooth reduction in blood pressure over 24 hours with a small difference between the maximum and minimum effects during the dosing interval.
When candesartan cilexetil is used together with hydrochlorothiazide, an additional reduction in AT is observed. An enhanced antihypertensive effect is also noted if candesartan cilexetil is combined with amlodipine or felodipine.
Drugs that block the renin-angiotensin-aldosterone system have a less pronounced antihypertensive effect in black patients (usually a low-renin population) than in patients of other races. This is also characteristic of candesartan.
Candesartan increases renal blood flow and either has no effect on glomerular filtration rate or increases it, while renal vascular resistance and filtration fraction are reduced. In a 3-month clinical study in patients with hypertension, type 2 diabetes mellitus, and microalbuminuria, antihypertensive treatment with candesartan cilexetil reduced urinary albumin excretion. There are currently no data on the effect of candesartan on the progression of diabetic nephropathy.
There was no statistically significant difference in the primary endpoint, the number of major cardiovascular events (cardiovascular mortality, non-fatal stroke, and non-fatal myocardial infarction) between the candesartan treatment group and the control group.
The ONTARGET and VA NEPHRON-D randomized controlled clinical trials examined the benefits of combining an ACE inhibitor with an angiotensin II receptor blocker. ONTARGET was conducted in patients with a history of cardiovascular or cerebrovascular disease or type 2 diabetes mellitus with evidence of target organ damage. VA NEPHRON-D was conducted in patients with type 2 diabetes mellitus and diabetic nephropathy.
These studies did not show a significant beneficial effect on renal and/or cardiovascular parameters and mortality, while there was an increased risk of hyperkalemia, acute kidney injury and/or arterial hypotension compared with monotherapy. Due to the similar pharmacodynamic properties of the above drugs, the results obtained are relevant for other ACE inhibitors and angiotensin II receptor antagonists.
Therefore, ACE inhibitors and angiotensin II receptor antagonists should not be used concomitantly in patients with diabetic nephropathy.
The ALTITUDE study was conducted in patients with type 2 diabetes and chronic kidney disease and/or cardiovascular disease to test the benefits of adding aliskiren to standard therapy with an ACE inhibitor or an angiotensin II receptor blocker.
This study was terminated early due to an increased risk of adverse reactions. Cardiovascular death and stroke occurred more frequently in the aliskiren group than in the placebo group. The incidence of adverse reactions, including serious adverse reactions (hyperkalemia, hypotension, and renal failure), was higher in the aliskiren group than in the placebo group.
Heart failure.
Treatment with candesartan cilexetil reduces mortality, reduces hospitalizations for heart failure, and improves symptoms in patients with left ventricular systolic dysfunction, as demonstrated in the Candesartan in Heart Failure - Evaluation of Mortality and Morbidity Reduction (CHARM) trial.
The beneficial effect of candesartan on reducing cardiovascular mortality or the incidence of first hospitalization for chronic heart failure (CHF) was consistent regardless of age, gender, and concomitant medication. Candesartan was also effective in patients receiving both beta-blockers and ACE inhibitors, and the beneficial effect was obtained regardless of whether the patient was taking ACE inhibitors at the target dose recommended by treatment guidelines.
In patients with CHF and reduced left ventricular systolic function (left ventricular ejection fraction ≤40%), candesartan reduces systemic vascular resistance and pulmonary capillary wedge pressure, increases plasma renin activity and angiotensin II concentrations, and reduces aldosterone levels.
Pharmacokinetics
Absorption and distribution.
After oral administration of candesartan cilexetil, it is converted to the active substance candesartan. The absolute bioavailability of candesartan is approximately 40% after oral administration of candesartan cilexetil solution. The relative bioavailability of the tablet formulation compared to the same oral solution is approximately 34% with very little variability. The calculated absolute bioavailability of the tablet is therefore 14%. The mean peak serum concentration (Cmax) is reached 3-4 hours after tablet administration. The serum concentration of candesartan increases linearly with increasing doses within the therapeutic dose range. No gender differences in the pharmacokinetics of candesartan have been identified. The area under the serum concentration versus time curve (AUC) of candesartan is not significantly affected by food.
Candesartan is highly bound to plasma proteins (>99%). The apparent volume of distribution of candesartan is 0.1 l/kg.
The bioavailability of candesartan is not affected by food.
Metabolism and excretion.
Candesartan is excreted mainly unchanged in the urine and bile, and only to a minor extent by hepatic metabolism (CYP2C9). Available interaction studies indicate no effect on CYP2C9 and CYP3A4.
Based on in vitro data, no in vivo interactions are expected with drugs metabolized by cytochrome P450 isoenzymes CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1 or CYP3A4. The terminal elimination half-life of candesartan is approximately 9 hours. There is no accumulation of the drug after multiple administration.
Pharmacokinetics in special categories of patients.
In elderly subjects (65 years and older), Cmax and AUC of candesartan were increased by approximately 50% and 80%, respectively, compared with young subjects. However, the BP response and the incidence of adverse events were similar after dosing with Kasark® in young and elderly subjects.
In patients with mild and moderate renal impairment, Cmax and AUC of candesartan increased with repeated dosing by approximately 50% and 70%, respectively, but t½ remained unchanged compared to patients with normal renal function. The corresponding changes in patients with severe renal impairment were approximately 50% and 110%, respectively.
The terminal t½ of candesartan was approximately doubled in patients with severe renal impairment. The AUC of candesartan in patients on haemodialysis was close to that in patients with severe renal impairment.
In two studies involving patients with mild to moderate hepatic impairment, an increase in the mean AUC of candesartan was observed by approximately 20% in one study and 80% in the other study. There is no experience in patients with severe hepatic impairment.
Indication
Treatment of essential hypertension in adults.
Treatment of adult patients with heart failure and impaired left ventricular systolic function (left ventricular ejection fraction ≤40%) in patients who are intolerant to angiotensin-converting enzyme (ACE) inhibitors or as add-on therapy to ACE inhibitor therapy in patients with symptoms of heart failure despite optimal therapy and intolerant to mineralocorticoid receptor antagonists (see sections 5.1, 5.2, 5.3 and 5.4).
Contraindication
Hypersensitivity to candesartan cilexetil or to any of the excipients.
Severe hepatic impairment and/or cholestasis.
In patients with diabetes mellitus or renal impairment (GFR <60 mL/min/1.73 m2), the concomitant use of candesartan cilexetil and aliskiren-containing products is contraindicated.
Pregnant women or women planning to become pregnant (see section “Use during pregnancy or breastfeeding”).
Interaction with other medicinal products and other types of interactions
Drugs studied in clinical pharmacokinetic studies include hydrochlorothiazide, warfarin, digoxin, oral contraceptives (i.e. ethinyl estradiol/levonorgestrel), glibenclamide, nifedipine and enalapril. No clinically significant pharmacokinetic interactions were observed with these drugs.
Concomitant use of potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium, or other medicinal products (e.g. heparin) may increase potassium levels. Potassium levels should be monitored appropriately (see section 4.4).
Reversible increases in serum lithium concentrations and toxicity have been reported during concomitant administration of lithium and ACE inhibitors.
A similar effect may be observed with ARBs. The use of candesartan with lithium is not recommended. If the need for the combination is confirmed, careful monitoring of serum lithium levels is recommended.
When ARA II is administered simultaneously with non-steroidal anti-inflammatory drugs (NSAIDs) (e.g. selective COX-2 inhibitors, acetylsalicylic acid (> 3 g/day) and non-selective NSAIDs), a weakening of the antihypertensive effect may be observed.
As with ACE inhibitors, concomitant use of ARA II and NSAIDs may lead to an increased risk of worsening of renal function, including possible acute renal failure and an increase in serum potassium, particularly in patients with compromised renal function at the start of treatment. The combination should be used with caution, especially in elderly patients. The patient should be adequately hydrated and attention should be paid to monitoring renal function after initiation of concomitant therapy and periodically thereafter.
Clinical trial data suggest that dual blockade of the renin-aldosterone-angiotensin system (RAAS) through the combined use of ACE inhibitors and angiotensin II blockers or aliskiren is associated with a higher incidence of adverse events, such as hypotension, hyperkalemia, and worsening renal function (including acute renal failure), compared with the use of a drug that affects the RAAS as monotherapy.
Application features
Dual blockade of the renin-angiotensin-aldosterone system (RAAS).
ACE inhibitors and angiotensin II receptor blockers should not be used concomitantly in patients with diabetic nephropathy.
Kidney dysfunction.
As with other agents that inhibit the renin-angiotensin-aldosterone system, changes in renal function may be expected in susceptible patients taking candesartan cilexetil.
When using candesartan cilexetil in patients with arterial hypertension and impaired renal function, periodic monitoring of serum potassium and creatinine levels is recommended.
Experience in patients with very severe or end-stage renal failure (creatinine clearance < 15 ml/min) is limited. In such patients, the dose of Kasark® should be selected with caution, with careful monitoring of blood pressure (BP). Monitoring of patients with heart failure should include periodic assessment of renal function, especially in elderly patients (75 years of age and older) and in patients with impaired renal function. Monitoring of serum creatinine and potassium levels is recommended when selecting the dose of candesartan cilexetil. Clinical studies in heart failure did not include patients with serum creatinine levels > 265 μmol/l (> 3 mg/dl).
Concomitant therapy with ACE inhibitors in heart failure.
The risk of adverse reactions, especially hypotension, hyperkalemia and worsening of renal function (including acute renal failure), may be increased when candesartan cilexetil is used in combination with ACE inhibitors. The triple combination of an ACE inhibitor, a mineralocorticoid receptor antagonist and candesartan cilexetil is also not recommended. The use of these combinations should only be carried out under specialist supervision and with frequent and careful monitoring of renal function, electrolytes and blood pressure.
ACE inhibitors should not be used concomitantly with angiotensin II receptor blockers in patients with diabetic nephropathy.
Hemodialysis.
During dialysis, blood pressure may be particularly sensitive to AT1 receptor blockade due to decreased plasma volume and activation of the renin-angiotensin-aldosterone system. Therefore, in patients undergoing hemodialysis, the dose of candesartan cilexetil should be titrated with caution, with blood pressure monitored.
Renal artery stenosis.
Medicinal products that affect the renin-angiotensin-aldosterone system, including angiotensin II receptor antagonists (ARBs), may increase blood urea and serum creatinine in patients with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney.
Kidney transplantation.
Experience with the use of Kasark® in patients with a recent kidney transplant is limited.
Arterial hypotension.
Hypotension may occur in patients with heart failure during treatment with Kasark®. It may also develop in patients with arterial hypertension and intravascular dehydration due to high doses of diuretics. Therapy should be initiated with caution and measures should be taken to correct hypovolemia.
Anesthesia and surgical interventions.
In patients receiving angiotensin II antagonists, hypotension may occur during anesthesia and surgery as a result of blockade of the renin-angiotensin system. Very rarely, hypotension may be severe and require intravenous fluids and/or the use of vasoconstrictors.
Aortic and mitral valve stenosis (obstructive hypertrophic cardiomyopathy).
As with other vasodilators, special caution is indicated in patients with hemodynamically significant aortic or mitral valve stenosis or obstructive hypertrophic cardiomyopathy.
Primary hyperaldosteronism.
Patients with primary hyperaldosteronism will in most cases not respond to antihypertensive medicinal products that act through inhibition of the renin-angiotensin-aldosterone system. Therefore, the use of candesartan cilexetil in this population is not recommended.
Hyperkalemia.
Concomitant use of Kasark® with potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium, or other medicinal products that may increase potassium levels (e.g. heparin) may lead to increases in serum potassium levels in patients with arterial hypertension. Potassium levels should be monitored appropriately.
Hyperkalemia may occur in patients with heart failure taking Kasark®. Periodic monitoring of serum potassium is recommended. The triple combination of ACE inhibitors, potassium-sparing diuretics (e.g. spironolactone) and candesartan cilexetil is not recommended and should be used only after careful consideration of the potential benefits and risks.
In patients whose vascular tone and renal function depend predominantly on the activity of the renin-angiotensin-aldosterone system (e.g. patients with severe congestive heart failure or underlying renal disease, including renal artery stenosis), treatment with other medicinal products that affect this system has been associated with acute hypotension, azotemia, oliguria or, rarely, acute renal failure. The possibility of similar effects cannot be excluded with ARA II. As with any antihypertensive agent, excessive reduction of blood pressure in patients with ischaemic cardiopathy or ischaemic cerebrovascular disease could result in myocardial infarction or stroke.
The antihypertensive effect of candesartan may be enhanced by other medicinal products with blood pressure-lowering properties, whether prescribed as antihypertensives or used for other indications.
Kasark® contains lactose. Patients with rare hereditary forms of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Pregnancy.
AIIRAs should not be initiated during pregnancy. Unless continued AIIRA therapy is considered essential, patients planning pregnancy should be changed to alternative antihypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, AIIRA treatment should be stopped immediately, and, if appropriate, alternative therapy should be started.
In postmenarcheal patients, the possibility of becoming pregnant is assessed on a general basis. Appropriate information should be provided and/or measures should be taken to prevent the risk of exposure to the drug during pregnancy (see sections “Contraindications”, “Use during pregnancy or lactation”).
Use during pregnancy or breastfeeding
The use of candesartan cilexetil is contraindicated during pregnancy. Candesartan cilexetil is not recommended for use during breastfeeding.
Pregnancy.
Epidemiological evidence regarding the risk of teratogenicity following exposure to ACE inhibitors during the first trimester of pregnancy is inconclusive, but a small increased risk cannot be excluded. In the absence of controlled epidemiological data on the risk with ARBs, similar risks may exist for this class of drugs. Unless continued ARB therapy is considered essential, patients planning pregnancy should be changed to alternative antihypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, ARB treatment should be stopped immediately, and, if appropriate, alternative therapy should be started.
It is known that human use of ARAII during the II and III trimesters of pregnancy can lead to fetotoxicity (decreased renal function, oligohydramnios, delayed ossification of the skull) and neonatal toxicity (renal failure, hypotension, hyperkalemia). If ARAII was used in the II trimester of pregnancy, it is recommended that pregnant women undergo an ultrasound examination to assess renal function and the condition of the skull in the fetus.
Newborns whose mothers have received ARBs require close observation for hypotension.
Breast-feeding.
As no information is available regarding the use of Kasark® during breastfeeding, the drug is not recommended. Alternative treatments with better established safety profiles during breastfeeding are preferable, especially while nursing a newborn or preterm infant.
Ability to influence reaction speed when driving vehicles or other mechanisms
No studies have been conducted on the effects of candesartan on the ability to drive and use machines. However, it should be taken into account that dizziness or fatigue may develop during treatment with Kasark®.
Method of administration and doses
Take internally.
Kasark® should be taken once a day, regardless of meals.
Food intake does not affect the bioavailability of candesartan.
Tablets of 8 mg, 16 mg and 32 mg cannot be divided into parts, therefore, if it is necessary to prescribe candesartan cilexetil at a dose of 4 mg, it is necessary to use a medicinal product that allows the possibility of dosing candesartan cilexetil 4 mg.
The recommended initial dose and usual maintenance dose of Kasark® is 8 mg once daily. The maximum antihypertensive effect is achieved within 4 weeks. In some patients whose blood pressure is not adequately controlled, the dose may be increased to 16 mg once daily and up to a maximum of 32 mg once daily. Therapy should be adjusted according to the blood pressure response to treatment. Kasark® can also be used together with other antihypertensive agents (see sections “Pharmacodynamics”, “Contraindications”, “Interaction with other medicinal products and other types of interactions” and “Special instructions for use”). The addition of hydrochlorothiazide has been shown to provide an additional antihypertensive effect with different doses of Kasark®.
Use in elderly patients
For elderly patients, no adjustment of the initial dose is required.
Use in patients with decreased intravascular volume of circulating fluid
A starting dose of 4 mg may be considered in patients at risk of hypotension, such as those with possible dehydration (see section 4.4).
Use in renal impairment
The starting dose for patients with renal impairment, including patients on haemodialysis, is 4 mg. The dose should be titrated according to the response to treatment. Experience in patients with very severe or end-stage renal failure (creatinine clearance < 15 ml/min) is limited (see section 4.4).
Use in liver dysfunction
In patients with mild to moderate hepatic impairment, a starting dose of 4 mg once daily is recommended. The dose may be adjusted according to response to treatment. Kasark® is contraindicated in patients with severe hepatic impairment and/or cholestasis (see sections “Pharmacokinetics” and “Contraindications”).
Use in patients of the Negroid race
The antihypertensive effect of candesartan is less pronounced in black patients than in non-black patients. Therefore, the need for an increase in the dose of Candesartan and concomitant therapy to control AT may occur more often in black patients than in non-black patients (see section "Pharmacodynamics").
Dosage for heart failure.
The usual recommended starting dose of candesartan cilexetil is 4 mg once daily. Titration to a target dose of 32 mg once daily (maximum dose) or the highest tolerated dose is by doubling the dose at intervals of at least 2 weeks (see section 4.4). Monitoring of patients with heart failure should always include assessment of renal function, including monitoring of serum creatinine and potassium.
Kasark® can be used with other heart failure treatments, including ACE inhibitors, beta-blockers, diuretics and digitalis, or a combination of these drugs.
Kasark® can be prescribed together with ACE inhibitors in patients with symptoms of heart failure despite optimal standard heart failure therapy, in case of intolerance to mineralocorticoid receptor antagonists.
The combination of ACE inhibitors, potassium-sparing diuretics (e.g. spironolactone) and Kasark® is not recommended and should only be used after careful assessment of the potential benefits and risks (see sections “Pharmacodynamics”, “Special warnings and precautions for use” and “Adverse reactions”).
Special categories of patients
There is no need to adjust the initial dose for elderly patients or for patients with reduced intravascular volume, impaired renal function, or mild to moderate hepatic impairment.
Children.
The safety and efficacy of Kasark® in children from birth to 18 years of age for the treatment of heart failure have not been established. Data are not available.
Children
The safety and effectiveness of Kasark® in children have not been established.
Overdose
Symptoms: Given the pharmacological properties of the drug, the main manifestations of overdose are likely to be symptomatic hypotension and dizziness. In isolated cases of overdose (up to 672 mg candesartan cilexetil) patients have been reported to recover without sequelae.
Treatment: If symptomatic hypotension develops, symptomatic treatment should be administered and vital signs monitored. The patient should be placed in the supine position with the legs elevated. If this is not sufficient, plasma volume should be increased by infusion, e.g., 0.9% sodium chloride solution. If the above measures are insufficient, sympathomimetic drugs may be used. Candesartan is not removed by hemodialysis.
Side effects
Treatment of arterial hypertension.
In a pooled analysis of clinical trials in patients with hypertension, adverse reactions to candesartan cilexetil were defined as adverse events occurring at a frequency of at least 1% greater than that observed with placebo. The most common adverse reactions were dizziness/vertigo, headache, and respiratory tract infection.
The following frequency definitions have been used: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000) and very rare (<1/10,000).
The following side effects are possible when using candesartan cilexetil:
Infections and infestations: common: respiratory tract infections.
From the blood and lymphatic system: very rarely - leukopenia, neutropenia, agranulocytosis.
Metabolism and nutrition disorders: very rarely - hyperkalemia, hyponatremia.
Nervous system disorders: often – dizziness/vertigo, headache.
Respiratory, thoracic and mediastinal disorders: very rare - cough.
On the part of the digestive system: very rarely - nausea, unknown - diarrhea.
On the part of the hepatobiliary system: very rarely - increased levels of liver enzymes, impaired liver function, hepatitis.
Skin and subcutaneous tissue disorders: very rarely - angioedema, rash, urticaria, itching.
Musculoskeletal system: very rarely - back pain, arthralgia, myalgia.
Renal and urinary disorders: very rarely - deterioration of renal function, including acute renal failure in susceptible patients.
Laboratory test results: In most cases, there was no clinically significant effect of Kasark® on routine laboratory parameters. As with other inhibitors of the renin-angiotensin-aldosterone system, a slight decrease in hemoglobin levels was noted. Usually, there is no need for continuous monitoring of laboratory parameters for patients taking Kasark®. However, periodic monitoring of serum potassium and creatinine levels is recommended in patients with impaired renal function.
Treatment of serial failure.
The adverse reaction profile of Kasark® in patients with heart failure was consistent with the pharmacological properties of the drug and the patient's health status. In the CHARM clinical program, comparing candesartan cilexetil at doses up to 32 mg (n=3803) with placebo (n=3796), 21.0% of the candesartan cilexetil group and 16.1% of the placebo group discontinued treatment due to adverse events. Adverse events, such as hyperkalemia, hypotension, and renal failure, were most frequently observed in patients aged 70 years or older, with diabetes mellitus, or in patients taking other drugs that affect the renin-angiotensin-aldosterone system, including ACE inhibitors and/or spironolactone.
The following side effects are possible when using candesartan cilexetil:
Blood and lymphatic system disorders: very rarely - leukopenia, neutropenia and agranulocytosis.
Metabolism and nutrition disorders: often - hyperkalemia, very rarely - hyponatremia.
From the nervous system: very rarely - dizziness, headache.
Vascular disorders: often - hypotension.
Respiratory, thoracic and mediastinal disorders: very rare - cough.
From the digestive tract: very rarely - nausea, unknown - diarrhea.
Hepatobiliary disorders: very rarely - increased liver enzymes, liver dysfunction, hepatitis.
Skin and subcutaneous tissue disorders: very rarely - angioedema, rash, urticaria, itching.
Musculoskeletal and connective tissue disorders: very rarely - back pain, arthralgia, myalgia.
Renal and urinary disorders: often - renal dysfunction, including renal failure in susceptible patients.
Laboratory Test Results: Hyperkalemia and renal dysfunction are common in patients receiving candesartan cilexetil for heart failure. Periodic monitoring of serum creatinine and potassium levels is recommended (see section 4.4).
Reporting of suspected adverse reactions
Reporting adverse reactions after the registration of a medicinal product is important. This allows monitoring of the benefit/risk ratio of the medicinal product. Medical and pharmaceutical workers
