Included in the formulation
АТХ:C.09.C.A.06 Candesartan
Pharmacodynamics:Angiotensin II is the main hormone of the renin-angiotensin-aldosterone system, which plays an important role in the pathogenesis of arterial hypertension, heart failure and other cardiovascular diseases. The main effects of angiotensin are vasoconstriction, stimulation of aldosterone production, regulation of water-electrolyte equilibrium. Its action of angiotensin II realizes through the AT receptors1 (1 type). Candesartan competitively blocks receptors for angiotensin II type 1. The drug does not block ACE, which converts angiotensin I into angiotensin II.It does not block receptors to other hormones and ion channels involved in the regulation of cardiovascular homeostasis. As a result of the blockade of AT1 a dose-dependent increase in angiotensin I, angiotensin II in plasma and a decrease in aldosterone concentration. The antihypertensive effect is due to a decrease in total peripheral vascular resistance without affecting the heart rate. There was no syndrome of "bounce" with the cancellation of candesartan. The antihypertensive effect of candesartan occurs 2 hours after admission, it increases and becomes maximum by the 4th week of therapy. The vasodilating effect of candesartan appears 2 hours after ingestion, lasting up to 24 hours.
Pharmacokinetics:Candesartan cilexetil is a prodrug. It is converted into an active substance candesartan after absorption in the digestive tract. The bioavailability of candesartan in tableted form is 15%; the maximum concentration of the drug is observed 3-4 hours after taking the tablets. Eating does not affect bioavailability. The volume of distribution is 0.1 l / kg. Virtually completely binds to plasma proteins - by 99%.Plasma clearance 0.37, renal clearance - 0.19 ml / min / kg. Eliminated after ingestion by 33% kidneys, bile by 67%. At intravenous introduction on 59% it is deduced by kidneys, 36% with bile. Excreted unchanged. Half-life is about 9 hours. In patients with mild and moderate impairment of liver function, the AUC increased by 23%. In patients with severe renal dysfunction, Cmax and AUC of candesartan increase by 50% and 110%, respectively, the half-life increases by 2 times. In patients on hemodialysis, the pharmacokinetic parameters do not differ from those for severe renal dysfunction.
Indications:Arterial hypertension. Chronic heart failure with a lower left ventricular ejection fraction is less than 40%. Used as part of complex therapy together or instead of ACE inhibitors for their intolerance.
IX.I10-I15.I10 Essential [primary] hypertension
Contraindications:Hypersensitivity to the drug; pregnancy and the period of breastfeeding; primary hyperaldosteronism - therapy is meaningless, as resistance develops; children under 18 years of age(safety and efficacy not studied); severe violations of liver function and / or cholestasis; primary hyperaldosteronism (insufficient data on studies).
Carefully:Two-sided stenosis of the renal arteries or stenosis of the artery of a single kidney. Severe renal impairment with creatinine clearance less than 30 mL / min. Consider starting treatment with a daily dose of 4 mg.
Transplantation of the kidney in the anamnesis.
Hyperkalemia.
Severe aortic and / or mitral stenosis.
Severe liver dysfunction. Start treatment with 2 mg per day. The experience of using candesartan cilexetil in this group is limited.
Pregnancy and lactation:In the human embryo, the kidney blood supply system is formed in the second trimester of pregnancy. In this way, candesartan most dangerous for the fetus after the first trimester of pregnancy. Well-controlled studies in humans have not been conducted. In experiments on animals with the use of candesartan tsileksetil, kidney damage in the embryo has been revealed. Do not use during pregnancy! The action category for the fetus according to the FDA: in the I trimester C, in the II and III trimester - D. Lactation: Do not use the drug in lactation or stop breastfeeding for the period of treatment. There is no data on the penetration of the drug into breast milk.
Dosing and Administration:Tablets from 8 to 32 mg take inwards 1 per day. The maximum daily (and single) dose of 32 mg. The dose is increased by doubling it with an interval of at least 2 weeks. Application in elderly patients
In elderly people over the age of 65, Cmax and AUC increase by 50% and 80%, respectively. The hypotensive effect and frequency of side effects do not depend on the age of the patient. Reduces the risk of recurrent stroke in elderly people with hypertension of any origin. Reduces the functional class of chronic heart failure by NYHA.
Side effects:Vertigo 0.3%. Headache 0.6%.
Cough of 4.6%.
Arterial hypotension due to a decrease in the volume of circulating blood.
Infections of the upper respiratory tract - rhinitis, pharyngitis.
Hyperuricemia or gout, leukopenia, thrombocytopenia, back pain are extremely rare.
Overdose:There were no cases of overdose. Analysis of the pharmacological properties of the drug allows hypotension and dizziness as the main symptoms of a possible overdose. Therapy is symptomatic.Removing the drug from the body with hemodialysis is unlikely.
Interaction:When combined with diuretics (for example, hydrochlorothiazide) - increases the hypotensive effect. Admission with potassium-sparing diuretics can provoke hyperkalemia. ACE inhibitors - increases the risk of side effects in patients with initial hyperkalemia and impaired renal function.
Special instructions:The effectiveness of antihypertensive action is equal to enalapril, amlodipine, hydrochlorothiazide. Exceeds losartan. Slows the formation of neointima in the arteries, reducing the frequency of restenosis. Reduces the risk of recurrent stroke in elderly people with hypertension of any origin.
It reduces the risk of sudden death from the progression of the disease in patients with systolic dysfunction of the myocardium.
Reduces the functional class of the New York classification of chronic heart failure.
Patients with hypertension and severe renal insufficiency should periodically monitor the level of potassium and creatinine in the serum.
Patients with primary hyperaldosteronism are usually resistant to antihypertensive drugs that affect renin-angiotensin-aldosterone system.
Vascular tone and kidney function in patients with severe chronic heart failure and stenosis of the renal artery predominantly depend on the activity renin-angiotensin-aldosterone system. It is impossible to exclude a sharp arterial hypotension, azotemia, oliguria, acute renal failure in such patients with candesartan.