Coaprovel pill 12.5 mg + 150 mg 28 pcs
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Active ingredients
Hydrochlorothiazide + Irbesartan
Release form
Pills
Composition
Active ingredient: Irbesartan (Irbesartan), Hydrochlorothiazide (Hydrochlorothiazide) Active ingredient concentration (mg): 162.5
Pharmacological effect
Combined antihypertensive drug containing angiotensin II receptor antagonist irbesartan and thiazide diuretic hydrochlorothiazide. The combination of ingredients has an additive antihypertensive effect, reducing blood pressure to a higher degree than each of the individual components. Irbesartan Irbesartan is a selective antagonist of angiotensin II receptors (type AT1) that does not require metabolic activation to acquire pharmacological activity. Angiotensin II is an important component of the RAAS and is involved in the pathogenesis of arterial hypertension, as well as sodium homeostasis. Irbesartan blocks all physiologically significant effects of angiotensin II, regardless of the source or route of its synthesis, including pronounced vasoconstrictor effect and increased secretion of aldosterone, realized through AT1 receptors, located on the surface of vascular smooth muscle cells and in the adrenal cortex. Does not possess agonistic activity with respect to AT1 receptors and has a much greater (more than 8500 times) affinity for AT1 receptors than to AT2 receptors (receptors that are not associated with the regulation of the cardiovascular system). Irbesartan does not inhibit RAAS enzymes (such as renin, ACE) and does not affect the receptors of other hormones or ion channels involved in the regulation of blood pressure and sodium homeostasis. The blocking of AT1 receptors by irbesartan interrupts the feedback circuit in the renin-angiotensin system, which leads to an increase in plasma renin and angiotensin II concentrations. After taking irbesartan at recommended doses, the plasma concentration of aldosterone decreases, without significantly affecting the serum potassium content (the average value of its increase is <0.1 mEq / l). Irbesartan does not significantly affect the serum concentrations of triglycerides, cholesterol and glucose. Irbesartan does not affect the concentration of uric acid in the blood serum or the rate of excretion of uric acid by the kidneys. Hydrochlorothiazide Hydrochlorothiazide is a thiazide diuretic with diuretic, natriuretic and antihypertensive effects. The mechanism of the antihypertensive action of thiazide diuretics, for example, hydrochlorothiazide, is not fully known.Thiazide diuretics affect the tubular mechanisms of electrolyte reabsorption in the kidneys, increasing the excretion of sodium and chlorides in approximately equal amounts. Natriuresis leads to the secondary loss of potassium and bicarbonate. Hydrochlorothiazide increases plasma renin activity and aldosterone secretion, and also reduces the content of potassium in blood serum. The simultaneous use of an angiotensin II receptor antagonist helps to reduce potassium losses associated with the action of thiazide diuretics. -8 week treatment. In long-term clinical studies, the antihypertensive effect of the combination of irbesartan / hydrochlorothiazide was observed for more than one year. The combination of irbesartan / hydrochlorothiazide, when used in a therapeutic dose range, has a dose-dependent and additive antihypertensive effect. In patients who, on the background of monotherapy with irbesartan at a dose of 300 mg, a sufficient reduction in blood pressure was not observed, adding 300 mg of irbesartan at a dose of 300 mg 1 time / day of hydrochlorothiazide at a dose of 12.5 mg 1 time / day resulted in an additional decrease in diastolic blood pressure by the end of the interval (ie, 24 hours after taking the drugs) at 6.1 mm Hg. st. (compared with the addition of placebo). There was a general decrease in systolic blood pressure (MAP) / diastolic blood pressure (DBP) with a combination of irbesartan at a dose of 300 mg and hydrochlorothiazide at a dose of 12.5 mg (compared with placebo) to -13.6 / -11.5 mm Hg. st. A single dose of irbesartan at a dose of 150 mg and hydrochlorothiazide at a dose of 12.5 mg per day showed (compared with placebo) an average decrease in GARDEN / DBP at the end of the interdose interval of 12.9 / 6.9 mm Hg. Art., respectively. The maximum antihypertensive effect developed after 3-6 hours. With daily monitoring of blood pressure, taking the drug Coaprovel at a dose of 12.5 / 150 mg 1 time / day caused a steady decrease in blood pressure during the day (the average decrease in GARDEN / DAP was respectively -15.8 / -10 mm Hg. v. versus placebo).The percentages of TUR (percentage of blood pressure measured at the end of the inter-dose interval [residual effect] to blood pressure during the maximum effect of the combination of irbesartan / hydrochlorothiazide) were at least 68%. In a clinical study in patients with insufficient blood pressure reduction with hydrotherapy at a dose of 25 mg, the addition of irbesartan to hydrochlorothiazide caused an additional average decrease in SBP / DBP by 11.1 / 7.2 mm Hg. st. accordingly, compared with hydrochlorothiazide monotherapy. Blood pressure decreased to the same degree in standing and lying. Orthostatic effects were rarely observed, however, their occurrence is possible in patients with hyponatremia and / or hypovolemia. The effectiveness of irbesartan / hydrochlorothiazide does not depend on age, race, or gender. The overall antihypertensive reaction to the combination in patients of the Negroid race and patients of other races was similar. After the withdrawal of irbesartan, the BP gradually returned to baseline values. Withdrawal from irbesartan and hydrochlorothiazide was not observed. When taking hydrochlorothiazide orally, the diuretic effect occurred during the first 2 hours, diuresis reached a maximum after about 4 hours and remained around 6-12 hours. patients with moderately severe (baseline mean blood pressure 162/98 mmHg) and severe (baseline mean blood pressure 172/113 mmHg) arterial hypertension. In both studies, a significant advantage was shown of the antihypertensive effect of the drug Coaprovel (at doses of 12.5 / 150 mg to 25/300 mg) as the initial therapy, compared with the use of irbesartan monotherapy (at doses of 150 mg to 300 mg) as initial therapy and hydrochlorothiazide (in doses from 12.5 mg to 25 mg).
Pharmacokinetics
Neither irbesartan nor hydrochlorothiazide does not alter the pharmacokinetics of each other. Absorption After ingestion of the drug Coaprovel, the absolute bioavailability of irbesartan is 60-80%, and hydrochlorothiazide is 50-80%. Eating does not affect the bioavailability of the active substances of the drug. After oral administration, Cmax of irbesartan in the blood plasma is reached in 1.5-2 hours, hydrochlorothiazide in 1-2.5 hours. Distribution: The binding of irbesartan to plasma proteins is approximately 96%, binding to cellular components is insignificant. Vd of irbesartan is 53-93 l (0.72-1.24 l / kg).With daily once daily administration of irbesartan, Css is achieved after 3 days, while there is a limited accumulation of irbesartan in the blood plasma (less than 20%). Binding to plasma proteins of hydrochlorothiazide is 68%, Vd - 3.6-7.8 l / kg. Hydrochlorothiazide penetrates the placental barrier and is excreted in breast milk. Metabolism After ingestion or in / into the administration of 14C-irbesartan, 80-85% of the radioactivity circulating in the blood plasma falls on unchanged irbesartan. Irbesartan is metabolized in the liver by oxidation and conjugation with glucuronic acid. The main metabolite in the systemic circulation is irbesartan glucuronide (approximately 6%). Irbesartan is oxidized mainly by the CYP2C9 isoenzyme, CYP3A4 isoenzyme participation in the metabolism of irbesartan is insignificant. Irbesartan is not metabolized by most isoenzymes, which are usually involved in the metabolism of drugs (CYP1A1, CYP1A2, CYP2A6, CYP2B6 CYP2D6 or CYP2E1), and does not cause their inhibition or induction. Irbesartan does not induce and does not inhibit the CYP3A4 isoenzyme. Hydrochlorothiazide is not metabolized. Excretion of Irbesartan and its metabolites are eliminated from the body both through the intestine (with bile) and the kidneys. After ingestion or intravenous administration of 14C-irbesartan, 20% of the radioactivity is found in the urine, and the rest is in the feces. Less than 2% of the administered dose is excreted by the kidneys as unchanged irbesartan. The final T1 / 2 of irbesartan is 11–15 hours. The total clearance of intravenously administered irbesartan is 157–176 ml / min, and its renal clearance is 3–3.5 ml / min. Hydrochlorothiazide is eliminated by the kidneys. The mean values of plasma T1 / 2 hydrochlorothiazide are 5–15 hours. The pharmacokinetics in special groups of patients (compared with men) women have slightly higher plasma concentrations of irbesartan. However, gender-related differences in T1 / 2 and accumulation of irbesartan are not detected. Dose adjustment of irbesartan in women is not required. Gender-related differences in the effects of irbesartan were not observed. The AUC and Сmax values of irbesartan in elderly patients (65-80 years) with normal kidney and liver function were approximately 20-50% higher than in younger patients (18- 40 years). Their final T1 / 2 were comparable.No age-related differences in the effects of irbesartan were observed. In patients with liver failure (due to cirrhosis), mild (functional class A or 5-6 points on the Child-Pugh scale) and moderate (functional class B or 7-9 points on the scale Child-Pugh) pharmacokinetic parameters of irbesartan do not change significantly. Patients with impaired renal function or patients undergoing hemodialysis do not significantly change the pharmacokinetics of irbesartan. Irbesartan is not excreted through hemodialysis. In volunteers without arterial hypertension, AUC and T1 / 2 irbesartan were approximately 20-25% higher in people of the Negroid race than in people of the European race; Their irbesartan was almost the same.
Indications
Arterial hypertension.
Contraindications
- II and III trimesters of pregnancy; - hypersensitivity to the components of Coaprovel; - hypersensitivity to other drugs derived sulfonamida. For the use of hydrochlorothiazide: - severe renal failure (CC <30 ml / min); - refractory hypokalemia, hypercalcemia; - severe form of liver failure; - biliary cirrhosis; - cholestasis.
Precautionary measures
Do not exceed recommended doses.
Use during pregnancy and lactation
Experience in the use of the drug Coaprovel during pregnancy is missing. Taking into account the fact that during the use of ACE inhibitors by pregnant women in the second and third trimesters of pregnancy damage and death of the developing fetus was observed, Coaprovel, like any other drug that directly affects the RAAS, cannot be used during pregnancy. and are detected in cord blood. The use of diuretics in pregnant women is not recommended, because fetal or neonatal jaundice, thrombocytopenia, and possibly other undesirable reactions that occur in adults may develop. Hydrochlorothiazide is excreted in breast milk.Thiazide diuretics when used in high doses, causing intense diuresis, can suppress lactation. The drug Coaprotell is contraindicated for use during the entire period of breastfeeding because of the potential risk to the infant. Therefore, after assessing the ratio of the perceived benefits of taking the drug for the mother and the potential risk to the child, either breastfeeding or taking the drug Coaprovel should be stopped.
Dosage and administration
Co-cap can be applied 1 time / day. before or during meals in patients whose blood pressure is not sufficiently controlled by irbesartan or hydrochlorothiazide separately. Coaprovel150 / 12. 5 mg is prescribed to patients whose blood pressure is insufficiently controlled by hydrochlorothiazide or irbesartan (150 mg / day) with monotherapy. Use of the drug in doses of more than 300 mg of irbesartan / 25 mg of hydrochlorothiazide 1 time / day. not recommended.
Side effects
From the hemopoietic system: aplastic anemia, bone marrow depression, hemolytic anemia, leukopenia, neutropenia / agranulocytosis, thrombocytopenia. On the part of the central nervous system and peripheral nervous system: depression, sleep disorders, dizziness, paresthesias, anxiety. On the part of the organ of vision: transient blurred vision, xantopsia. Since the cardiovascular system: arrhythmias, postural hypotension. On the part of the respiratory system: respiratory distress syndrome (including pneumonitis and pulmonary edema). On the part of the digestive system: jaundice (intrahepatic cholestatic jaundice). Allergic reactions: anaphylactic reactions, toxic necrosis of the epidermis, skin reactions such as lupus erythematosus, necrotized angiitis (vasculitis, skin vasculitis), photosensitivity reactions, rash, exacerbation of skin manifestations of lupus erythematosus, urticaria. From the musculoskeletal system: muscle spasms, weakness. On the part of the urinary system: interstitial nephritis, renal dysfunction. Other: fever. From the laboratory indicators: electrolyte imbalance (including hypokalemia and hyponatremia), glucosuria, hyperglycemia, hyperuricemia, increased cholesterol and TG.
Overdose
Irbesartan is used in doses up to 900 mg / day for 8 weeks without developing toxic effects. Symptoms: The most common symptoms observed in adults with hydrochlorothiazide overdose were symptoms caused by electrolyte disturbances in the blood (hypokalemia, hypochloraemia, hyponatremia) and dehydrate resulting from excessive diuretic effect. In the case of simultaneous use of cardiac glycosides (eg, digoxin) or antiarrhythmic drugs (eg, sotalol), hypokalemia may contribute to the development of rhythm disturbances. With an overdose of the drug, an excessive decrease in blood pressure, the development of bradycardia and tachycardia is possible. Treatment: there is no specific information regarding the treatment of an overdose of the drug Coaprovel. Constant monitoring of the patient’s condition should be established and, if necessary, symptomatic and supportive therapy, including restoration of fluid and electrolyte loss, should be carried out. In case of overdose, it is recommended to induce vomiting and / or gastric lavage. Irbesartan is not excreted through hemodialysis. The degree of elimination of hydrochlorothiazide using hemodialysis has not been established.
Interaction with other drugs
Based on in vitro research, it is not expected that Irbesartan will interact with drugs metabolized by isoenzymes CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2E1 or CYP3A4. Irbesartan is mainly metabolized by the CYP2C9 isoenzyme and, to a lesser extent, is glucuronidated. No significant pharmacokinetic and pharmacodynamic interactions were observed with the combined use of irbesartan with warfarin, a drug metabolized by the isoenzyme CYP2C9. Irbesartan does not change the pharmacokinetics of digoxin and simvastatin. The combined use of irbesartan with hydrochlorothiazide or nifedipine does not change the pharmacokinetics of irbesartan. The combination of Coaprovel with drugs containing aliskiren is contraindicated in patients with diabetes mellitus or renal insufficiency of moderate and severe (GFR <60 ml / min / 1.73 m2) and It is recommended in other patients. The use of Coaprovel in combination with ACE inhibitors is contraindicated in patients with diabetic nephropathy and is not recommended in other patients. Experience obtained when using other drugs that affect the RAASwith the simultaneous use of potassium preparations, salt substitutes containing potassium, potassium-saving diuretics or other drugs that can increase the potassium content of blood (heparin), it is possible to increase the content of potassium in the blood serum. Hydrochlorothiazide concurrently with irbesartan can reduce the incidence of this effect. In elderly patients, patients with hypovolemia, or patients with impaired renal function, the use of NSAIDs, including COX-2 inhibitors, simultaneously with antagonists of angiotensin II receptors, including irbesartan, can lead to a deterioration in function of angiotensin II receptor antagonists, including irbesartan kidney, including the possible development of acute renal failure. These effects are usually reversible. Renal function should be monitored periodically in patients simultaneously taking irbesartan and NSAIDs. With the simultaneous use of angiotensin II receptor antagonists, including irbesartan, and NSAIDs, including selective COX-2 inhibitors, a decrease in the antihypertensive effect of angiotensin II receptor inhibitors is possible. Simultaneous use with ethanol, barbiturates or narcotic drugs can result in an increase in orthostatic hypotension caused by thiazide-adrenal pulmonary anesthesia, which is thiazide-induced, and can be caused by thiazide. When combined with oral hypoglycemic agents and insulin, it may be necessary to increase the dose of hypoglycemic of funds, since hydrochlorothiazide may increase the concentration of glucose in the blood. With simultaneous use of the drug Coaprovel and anti-arthritic drugs, it may be necessary to adjust the doses of the latter due to the possibility of increasing serum uric acid concentrations when using hydrochlorothiazide. When used in conjunction with cardiac glycosides, antiarrhythmic agents in the event of hypokalemia and hypomagnemia, caused by the thiazide diuretic which is part of the drug Coaprovel, the risk of arrhythmias increases y.Tiazidnye diuretics may increase serum calcium levels. If the patient requires the use of calcium preparations or calcium-preserving drugs (for example, vitamin D), it is necessary to control the calcium content in blood serum and carry out a corresponding correction of the dosage regimen of calcium preparations. The absorption of hydrochlorothiazide in the presence of anion-exchange resins (colestiramine, colestipol) is reduced.It should be divided in time for taking the drug Coaprovel and these drugs for at least 4 hours. Diuretics reduce the renal clearance of lithium, in turn, irbesartan increases serum concentrations of lithium, which increases the risk of developing the toxic effects of lithium. Caution should be exercised while using the drug Coapprovel with lithium salts; It is recommended to control the serum lithium content. In some patients, inhibitors of endogenous prostaglandin synthesis (eg, NSAIDs) may reduce the effects of thiazide diuretics. Hydrochlorothiazide may interact with diazoxide; when combined, blood glucose concentration, serum uric acid concentration and blood pressure should be controlled. correction of their dosing regimen will be required. When combined with the use of hydrochlorothiazide funds for local anesthesia, funds for general anesthesia and means for sedation before general anesthesia should be used in reduced doses. If possible, hydrochlorothiazide should be discontinued 1 week before surgery. Simultaneous use of carbamazepine and hydrochlorothiazide may be associated with the risk of developing hyponatremia with clinical manifestations. The content of electrolytes in the blood should be monitored during co-administration of these drugs. If necessary, the use of carbamazepine, if possible, it is recommended to use diuretics with a different mechanism of action. When used simultaneously with GCS, ACTH increases the risk of developing hypokalemia. , biperidenom) increases the bioavailability of thiazide diuretics by slowing gastrointestinal motility. Thiazide diuretics can reduce kidney excretion and cytotoxic drugs (cyclophosphamide, methotrexate) and enhance their myelosuppressive effects.
special instructions
The use of the drug Coaprovel has so far rarely been accompanied by an excessive decrease in blood pressure in patients with arterial hypertension without other risk factors for the development of excessive arterial hypotension. An excessive decrease in blood pressure, accompanied by clinical symptoms, may develop in patients with hyponatremia / hypovolemia. Hypovolemia and / or hyponartemia should be corrected before starting the use of the drug Coaprovel. Thiazide diuretics may potentiate the action of other antihypertensive drugs. The drug Coaprovel is not recommended for patients with severe renal insufficiency (CC ≤30 ml / min). In patients with impaired renal function, an increase in azotemia may be associated with the content of hydrochlorothiazide in the formulation. There are no clinical data on the use of the drug in patients who have recently undergone a kidney transplant. When Coaprovel is used in patients with impaired renal function, periodic monitoring of potassium, serum creatinine and uric acid concentrations is recommended. Co-Copel should be used with caution in patients with impaired liver function or progressive liver disease, since even small changes in water electrolyte balance may provoke the development of hepatic coma. Thiazides, including hydrochlorothiazide, can cause an imbalance of water and electrolyte balance (g ipocalmia, hyponatremia and hypochloremic alkalosis). Although the use of thiazide diuretics in monotherapy, especially in high doses, may develop hypokalemia, the simultaneous use of irbesartan may reduce the hypokalemia caused by hydrochlorothiazide. On the contrary, due to the presence of irbesartan in the composition of the drug Coaprovel, hyperkalemia can occur, especially in patients with renal insufficiency, heart failure, and diabetes mellitus. Regular monitoring of serum potassium in patients at risk is recommended. Potassium-sparing diuretics, potassium supplements or potassium-containing salt substitutes should be used with caution with the drug Coaprovel. Chloride deficiency is usually insignificant and, as a rule, does not require treatment.Thiazides reduce the excretion of calcium through the kidneys and cause a non-constant and insignificant increase in the calcium content in the blood serum. The development of clinically significant hypercalcemia may indicate the possibility of hyperparathyroidism in the patient. Reception of thiazides should be stopped before the study of the function of the parathyroid glands. It has been demonstrated that thiazides increase the excretion of magnesium ions by the kidneys, which can lead to the development of hypomagnesemia. When treated with thiazide diuretics, hyperglycemia and exacerbation of gout can develop in some patients. In the treatment of thiazide diuretics, the need for insulin in patients with diabetes mellitus may increase, as well as the manifestation of latent diabetes mellitus. Treatment with thiazide diuretics was associated with an increase in the concentration of cholesterol and triglycerides in the blood, however, the dose of 12.5 mg contained in the preparation Coaprovel had practically no effect on the concentration of cholesterol and triglycerides in the blood. With thiazide diuretic therapy, some patients may experience hyperuricemia or an exacerbation of the course of gout. Patients at risk of developing impaired water and electrolyte balance and metabolic disturbances may require monitoring of laboratory parameters. There were reports of worsening or worsening of the systemic lupus erythematosus when using thiazide diuretics. Sulfonamides or sulfonamide derivatives may cause idiosyncratic reactions leading to the development of transient myopia, and myopia will cause myopia, and myopia will cause myopia, and myopia will cause myopia, and myopia will cause myopia, and myopia will cause myopia and myopia, or sulfonamide derivatives. glaucoma. Despite the fact that hydrochlorothiazide is a derivative of sulfonamide, so far only individual cases of the development of acute angle-closure glaucoma have been reported without establishing a causal relationship with its use. Symptoms of acute angle-closure glaucoma are: acute decrease in visual acuity or eye pain, usually occurring from a few hours to several weeks after the start of the drug. Left untreated acute angle-closure glaucoma can lead to permanent loss of vision. If you experience these symptoms, you should stop taking the drug as soon as possible.If this fails to normalize intraocular pressure, urgent therapeutic or surgical treatment may be required. Risk factors for the development of acute angle-closure glaucoma are indications of a history of allergic reactions to sulfonamides and penicillins. The double blockade of RAAS when using a combination of the drug Coaprovel with ACE inhibitors or aliskiren is not recommended, because compared with monotherapy, there is an increased risk of a sharp decrease in blood pressure, the development of hyperkalemia and renal dysfunction. Use of the drug Coaprovel in combination with aliskiren is contraindicated in patients with diabetes mellitus or renal failure (GFR <60 ml / min / 1.73 m2) and is not recommended in other patients. The use of the drug Coaprovel in combination with ACE inhibitors is contraindicated in patients with diabetic nephropathy and is not recommended in other patients. As a result of inhibition of the RAAS, impaired renal function in susceptible patients can be expected. In patients with kidney function, depending on the activity of the RAAS (patients with arterial hypertension and renal artery stenosis of one or both kidneys, patients with chronic heart failure III and IV functional class [according to the NYHA classification]), treatment with drugs that affect the RAAS, associated with oliguria and / or progressive azotemia and, rarely, with acute renal failure and / or death. The possibility of a similar effect when using inhibitors of angiotensin II receptors, including Coaprovel, cannot be ruled out. Patients after sympathectomy may increase the antihypertensive effect of thiazide diuretics. Patients with stenosis of the aorta and mitral valve stenosis, hypertrophic obstructive cardiomyopathy need special caution when using the mitral valve, hypertrophic obstructive cardiomyopathy, special caution is necessary in patients with mitral valve stenosis and hypertrophic obstructive cardiomyopathy. drug Coaprovel. The use of the drug Coaprovel in primary hyperaldosteronism is not appropriate because Such patients usually do not respond to antihypertensive drugs that affect RAAS. Hydrochlorothiazide may give a positive result during doping control. The development of allergic reactions to hydrochlorothiazide is more likely in patients with severe allergies.anamnesis or patients with bronchial asthma. Effects on the ability to drive motor vehicles and control mechanisms The effect of Coaprovel on the ability to drive vehicles or engage in other potentially hazardous activities requiring increased attention and high speed psychomotor reactions has not been studied. On the basis of pharmacodynamic properties, Coaprovel should not affect the ability to drive vehicles and engage in other potentially hazardous activities (work at height, work of an air traffic controller, work with mechanisms, etc.). However, caution should be exercised when engaging in potentially hazardous activities.