Exforge pills 5 mg + 80 mg 28 pcs
Condition: New product
1000 Items
Rating:
Be the first to write a review!
More info
Active ingredients
Amlodipine + Valsartan
Release form
Pills
Composition
amlodipine besylate 6.94 mg, which corresponds to the content of amlodipine 5 mgvalsartan 80 mg Auxiliary substances: microcrystalline cellulose - 54.06 mg, crospovidone - 20 mg, magnesium stearate - 4.5 mg, colloidal silicon dioxide - 1.5 mg. The composition of the film shell: premix white (hypromellasis, titanium dihydrogen , polyethylene glycol 4000, talc) - 4.4 mg, premix yellow (hypromellose, iron yellow oxide, polyethylene glycol 4000, talc) - 3.6 mg, purified water - qs
Pharmacological effect
Combined antihypertensive drug containing active substances with the BP control mechanism that complements each other. Amlodipine, a derivative of dihydropyridine, belongs to the class of slow calcium channel blockers (BCCA), valsartan - to the class of angiotensin II receptor antagonists. The combination of these components has a mutually complementary antihypertensive effect, which leads to a more pronounced decrease in blood pressure compared to that on the background of monotherapy with each drug. AmlodipineAmlodipine, which is part of Exforge, inhibits transmembrane entry of calcium ions into cardiomyocytes and vascular smooth muscle cells. The mechanism of antihypertensive action of amlodipine is associated with a direct relaxing effect on vascular smooth muscle, causing a decrease in OPSS and a decrease in blood pressure. After taking therapeutic doses in patients with arterial hypertension, amlodipine causes vasodilation, leading to a decrease in blood pressure (in the position of the patient lying down and standing). Reduction in blood pressure is not accompanied by a significant change in heart rate and catecholamine level with prolonged use. The plasma concentration of the drug correlates with the clinical effect in both young and elderly patients. In arterial hypertension in therapeutic doses, amlodipine reduces the resistance renal vessels, increasing the glomerular filtration rate and effective renal blood flow of the plasma without changing the filtration fraction and the level of proteinuria. As well as the use of other BMCC, taking amlodipine in patients with normal left ventricular function caused a change in the hemodynamic parameters of heart function at rest and during exercise: there was a slight increase in cardiac index without a significant effect on the maximum pressure buildup rate in the left ventricle, end-diastolic pressure and volume of the left ventricle.Hemodynamic studies in intact animals and humans have shown that a decrease in blood pressure under the influence of amlodipine in the range of therapeutic doses is not accompanied by a negative inotropic effect even with simultaneous use with beta-blockers. Amlodipine does not change the sinoatrial node function or AV conductivity in intact animals and in humans. When using amlodipine in combination with beta-adrenergic blockers in patients with arterial hypertension or with angina pectoris, a decrease in blood pressure is not accompanied by undesirable changes in ECG parameters. Clinical efficacy of amlodipine in patients with chronic stable angina, vasospastic stenocardia and angiogram-confirmed coronary arteries, is unacceptable for the use of iHeart cases. specific angiotensin II receptor antagonist for oral administration. It acts selectively on the AT1 receptor subtype, which is responsible for the known effects of angiotensin II. An increase in plasma concentration of free angiotensin II due to blockade of AT1 receptors under the influence of valsartan can stimulate unblocked AT2 receptors, which counteract the effects of stimulation of AT1 receptors. Valsartan does not have any pronounced agonistic activity against AT1 receptors. The affinity of valsartan for the AT1 receptor subtype is about 20,000 times higher than that for the AT2 receptor subtype. Valsartan does not inhibit ACE, also known as kininase II, which converts angiotensin I to angiotensin II and causes the destruction of bradykinin. when using angiotensin II antagonists, ACE inhibition and accumulation of bradykinin or substance P do not occur, dry cough development is unlikely. In comparative clinical studies of valsartan with an ACE inhibitor, the incidence of dry cough was significantly lower (less than 0.05) in patients who received valsartan (2.6%) patients treated with valsartan, and in 7.9% who received an ACE inhibitor). In a clinical study that included patients who had previously developed a dry cough when treated with an ACE inhibitor, this complication was observed in 19.5% of cases in treatment with valsartan, and in 19% of cases in treatment with thiazide diuretic. At the same time, in the group of patients treated with an ACE inhibitor, cough was observed in 68.5% of cases (less than 0.05).Valsartan does not interact and does not block receptors of other hormones or ion channels that are important for regulating the functions of the cardiovascular system. When treating patients with arterial hypertension with valsartan, a decrease in blood pressure is observed, which is not accompanied by a change in heart rate. The antihypertensive effect is manifested within 2 hours. most patients after a single dose. The maximum decrease in blood pressure develops after 4-6 hours. After taking the drug, the duration of the hypotensive effect lasts for more than 24 hours. With repeated use, the maximum decrease in blood pressure, regardless of the dose taken, is usually reached within 2-4 weeks. and maintained at the achieved level during long-term therapy. Abrupt cessation of valsartan is not accompanied by a sharp increase in blood pressure or other undesirable clinical consequences. The use of valsartan in patients with chronic heart failure (functional class II-IV according to the NYHA classification) leads to a significant decrease in the number of hospitalizations. This effect is most pronounced in patients not receiving ACE inhibitors or beta-blockers. When taking valsartan in patients with left ventricular failure (stable clinical course) or with impaired left ventricular function after myocardial infarction, a decrease in cardiovascular mortality is observed. Amlodipine / valsartan in patients with arterial hypertension who received Exforge 1 time / day antihypertensive effect. h. Exforge in doses of 5/80 mg and 5/160 mg in patients with baseline systolic blood pressure of 153-157 mm Hg. st. and diastolic blood pressure ≥95 mm Hg. and less than 110 mm Hg lowers blood pressure by 20-28 / 14-19 mmHg (compared with 7-13 / 7-9 mmHg when taking a placebo). Exforge at a dose of 10/160 mg and 5/160 mg normalizes blood pressure (decrease in diastolic blood pressure in a sitting position less than 90 mmHg in at the end of the study) in 75% and in 62% of patients with inadequate control of blood pressure against monotherapy with valsartan at a dose of 160 mg / day. Exforge at a dose of 10/160 mg normalizes blood pressure in 78% of patients with inadequate control of blood pressure at the background of amlodipine monotherapy at a dose of 10 mg. In patients with arterial hypertension with a combination of valsartan at a dose of 160 mg with amlodipine at doses of 10 mg and 5 mg, an additional decrease in systolic and diastolic blood pressure is reached at 6.0 / 4.8 mm Hg. and 3.9 / 2.9 mmHg.accordingly, compared with patients who continued to receive only valsartan at a dose of 160 mg or only amlodipine at a dose of 5 and 10 mg. When titrating the dose of Exforge from 5/160 mg to 10/160 mg in patients with arterial hypertension with diastolic blood pressure ≥110 mmHg. and less than 120 mm Hg. there is a decrease in blood pressure in the sitting position at 36/29 mm Hg, comparable to a decrease in blood pressure during the titration of the dose of the combination of an ACE inhibitor and a thiazide diuretic. In two long-term studies with a long observation period, the effect of Exforge remained for 1 year. Sudden cessation of Exforge is not accompanied by a sharp increase in blood pressure in patients, with adequate control of blood pressure achieved, but developed severe edema against amlodipine monotherapy, while using combination therapy, comparable blood pressure control was achieved with less likelihood of edema. Therapeutic efficacy of Exforge does not depend on age, gender and race of the patient.
Pharmacokinetics
The pharmacokinetics of valsartan and amlodipine are characterized by linearity. Amlodipine Absorption After ingestion of amlodipine in therapeutic doses of Cmax of amlodipine in the blood plasma is achieved in 6-12 hours. The absolute bioavailability averages 64-80%. Food intake does not affect the bioavailability of amlodipine. The distribution of Vd is approximately 21 l / kg. In vitro studies of amlodipine have shown that in patients with arterial hypertension, approximately 97.5% of the circulating drug binds to plasma proteins. Metabolism Amlodipine is extensively (approximately 90%) metabolized in the liver to form active metabolites. Excretion of amlodipine from plasma is biphasic with T1 / 2 approximately 30 to 50 hours. Css in the blood plasma is achieved after prolonged use for 7-8 days. 10% unchanged amlodipine and 60% amlodipine in the form of metabolites are excreted by the kidneys. Valsartan Absorption After plasma ingestion of valsartan Cmax is reached in 2-3 hours. The average absolute bioavailability is 23%. The pharmacokinetic curve of valsartan has a descending multiexponential pattern (T1 / 2α is less than 1 h and T1 / 2β is about 9 h). When taking valsartan with food, there is a decrease in bioavailability (by AUC value) by 40% and Cmax in blood plasma by almost 50%, although approximately 8 hours after taking the drug, the concentration of valsartan in blood plasma in the group of patients who took it with food and fasting group are aligned.The decrease in AUC, however, is not accompanied by a clinically significant decrease in the therapeutic effect, therefore, valsartan can be prescribed regardless of the time of eating. Valsartan is largely associated with serum proteins (94-97%), mainly with albumin. Metabolism Valsartan is not subject to pronounced metabolism (about 20% of the dose taken is determined as metabolites). The hydroxyl metabolite is detected in plasma in low concentrations (less than 10% of the AUC of valsartan). This metabolite is pharmacologically inactive. ExcretionValsartan is excreted mainly unchanged through the intestine (about 83% of the dose) and the kidneys (about 13% of the dose). After the on / in the introduction, plasma clearance of valsartan is about 2 l / h and its renal clearance is 0.62 l / h (about 30% of the total clearance). T1 / 2 of valsartan is 6 hours. Amlodipine / valsartan After ingestion of Exforge Cmax, valsartan and amlodipine are reached after 3 hours and 6-8 hours, respectively. The speed and extent of absorption of Exforge are equivalent to the bioavailability of valsartan and amlodipine when they are taken in separate pills. In elderly patients, the clearance of amlodipine is slightly reduced, which leads to an increase in AUC and T1 / 2. In elderly patients, the systemic effect of valsartan was slightly more pronounced than in younger patients, but this was not clinically significant. Since the tolerance of the components of the drug in the elderly and younger patients is equally good, it is recommended to use the usual dosing regimens. In patients with impaired renal function, the pharmacokinetic parameters of amlodipine do not significantly change. No correlation was found between kidney function (CC) and systemic exposure to valsartan (AUC) in patients with varying degrees of renal dysfunction. There is no need to change the initial dose in patients with initial and moderate renal dysfunction (CC 30-50 ml / min). Patients with liver failure have reduced clearance of amlodipine, which leads to an increase in AUC of approximately 40-60%.On average, in patients with chronic liver diseases of weak and moderate degrees, the bioavailability (AUC) of valsartan doubles compared with healthy volunteers (of appropriate age, sex, and body weight).
Indications
- arterial hypertension (for patients for whom combination therapy is indicated).
Contraindications
- pregnancy; - hypersensitivity to the components of the drug. The safety of using Exforge in patients with unilateral or bilateral stenosis of the renal arteries or stenosis of the artery of a single kidney, in patients after recently transferred kidney transplantation, as well as children and adolescents under 18 years of age has not been established. drug for: violations of the liver (especially in obstructive diseases of the biliary tract); severe renal dysfunction (KK less than 10 ml / min); patients with mitral or aortic stenosis, hypertrophic obstructive cardiomyopathy; with hyperkalemia, deficiency of sodium in the body and / or a decrease in bcc.
Precautionary measures
During treatment, psoriasis may worsen. During pheochromocytoma, propranolol can only be used after taking an alpha blocker. After a long course of treatment, propranolol should be discontinued gradually, under the supervision of a physician. during anesthesia, you must stop taking propranolol or find a remedy for anesthesia with minimal negative inotropic effects. The impact on the ability to drive vehicles and control mechanisms of patients whose activities require increased attention, the question of the use of propranolol on an outpatient basis should be addressed only after evaluating the individual response of the patient.
Use during pregnancy and lactation
Exforge, like any other drug that has a direct effect on the RAAS, should not be given during pregnancy or for women who want to become pregnant. If pregnancy is detected during Exforge treatment, the drug should be canceled as soon as possible. Patients of childbearing age should be informed about the possible risk to the fetus associated with the use of drugs that affect the RAAS. Considering the mechanism of action of angiotensin II receptor antagonists, the risk to the fetus cannot be excluded. It is known that the appointment of ACE inhibitors that affect the RAAS, pregnant in the II and III trimesters, leads to damage or death of the developing fetus.According to a retrospective analysis of the use of ACE inhibitors in the first trimester of pregnancy was accompanied by the development of pathology of the fetus and newborn. In case of unintentional intake of valsartan in pregnant women, cases of development of spontaneous abortions, oligohydramnios and renal dysfunction in newborns are described. It is not known whether valsartan and / or amlodipine are released from breast milk. Since experimental studies have noted the release of valsartan with breast milk, it is not recommended to use Exforge during lactation (breastfeeding).
Dosage and administration
The drug should be taken orally with a small amount of water, 1 time / day, regardless of the time of the meal. The recommended daily dose is 1 tab. at a dose of 5/80 mg or 5/160 mg or 10/160 mg. When prescribed to elderly patients, patients with initial or moderate renal impairment (CK more than 30 ml / min), with impaired liver function or with liver diseases, with cholestasis no change in dosage regimen is required.
Side effects
The safety of Exforge has been evaluated in more than 2,600 patients. Criteria for assessing the incidence of adverse reactions: very often, more than 10% of cases; often 1-10%; sometimes 0.1–1%; rarely, 0.001-0.1%; in some cases, less than 0.001%. Within each group identified by the frequency of occurrence, adverse reactions are distributed in order of decreasing their importance. From the side of the respiratory system: often - nasopharyngitis, flu; sometimes - cough, sore throat and larynx. For the sense organs: rarely - visual disturbances, tinnitus; sometimes - dizziness associated with dysfunction of the vestibular apparatus. On the side of the central nervous system and the peripheral nervous system: often - a headache; sometimes - dizziness, drowsiness, orthostatic dizziness, paresthesias; rarely - anxiety. From the cardiovascular system: sometimes - tachycardia, palpitations, orthostatic hypotension; rarely - syncope, pronounced decrease in blood pressure. From the digestive system: sometimes - diarrhea, nausea, abdominal pain, constipation, dry mouth. Dermatological reactions: sometimes - skin rash, erythema; rarely - hyperhidrosis, exanthema, pruritus. For the musculoskeletal system: sometimes - swelling of the joints, back pain, arthralgia; rarely muscle crampsa feeling of heaviness throughout the body. From the urinary system: rarely - pollakiuria, polyuria. From the reproductive system: rarely - erectile dysfunction. Others: often - pastoznost, swelling of the face, peripheral edema, increased fatigue, flushing, asthenia, feeling heat. In comparative and placebo-controlled clinical studies, the frequency of peripheral edema was significantly lower in patients receiving the combination of amlodipine and valsartan (5.8%) than in patients receiving amlodipine monotherapy (9%). indices: an increase in blood urea nitrogen (more than 3.1 mmol / l) was observed slightly more often in the groups receiving amlodipine / valsartan (5.5%) and valsartan as monotherapy (5.5%), compared with the placebo group (4.5%). Allergic reactions: rarely - hypersensitivity to the components of the drug. The adverse events that were previously reported with each of the components may occur when using Exforge, even if they were not observed in clinical studies. Amlodipine In those clinical studies x, where amlodipine was used as monotherapy, other adverse events were also noted (regardless of their causal relationship with the studied drug): nausea is most often; less often - alopecia, changes in the frequency of bowel movements, dyspepsia, shortness of breath, rhinitis, gastritis, gum mucous membrane hyperplasia, gynecomastia, hyperglycemia, erectile dysfunction, increased urination, leukopenia, general malaise, mood lability, dry mouth, myalgia, mysticism, peripheral, uterine respiration. , increased sweating, thrombocytopenia, vasculitis, angioedema, erythema multiforme. In a long-term placebo-controlled study (PRAISE-2) in patients with heart failure III and IV functional class According to the NYHA classification of non-ischemic etiology, with the use of amlodipine, there was an increase in the incidence of pulmonary edema, in the absence of significant differences in the incidence of worsening heart failure compared with placebo. In rare cases, at the beginning of therapy with slow calcium channel blockers (BMCC) or with increasing doses BMCC, especially in patients with severe IHD, there was an increase in the frequency, duration and severity of angina or the development of acute myocardial infarction. Also during therapy with BMCC, there were cases of arrhythmia (including ventricular tachycardia and atrial fibrillation).It is not possible to distinguish the occurrence of these adverse events from the natural course of the underlying disease. Valsartan In clinical studies using valsartan as monotherapy, the following adverse events were noted (regardless of their causal relationship with the studied drug): viral infections, upper respiratory tract infections, sinusitis, rhinitis, neutropenia, insomnia. Neutropenia was detected in 1.9% of patients who received valsartan and in 1.6% of patients who received an ACE inhibitor. In controlled climates In 3.9% and 16.6% of patients with heart failure who received valsartan, an increase in creatinine and blood urea nitrogen was noted by more than 50%, respectively. For comparison, in patients receiving placebo, an increase in creatinine and urea nitrogen was observed in 0.9% and 6.3% of cases. A duplication of serum creatinine was detected in 4.2% of patients after myocardial infarction who received valsartan and in 3.4% of captopril. Studies in 10% of patients with heart failure showed an increase in serum potassium concentration by more than 20%. For comparison, in patients receiving placebo, an increase in potassium concentration was observed in 5.1% of cases.
Overdose
Overdose There are currently no cases of overdose for the drug. In case of valsartan overdose, a pronounced decrease in blood pressure and dizziness can be expected. An overdose of amlodipine can lead to excessive peripheral vasodilation and possible reflex tachycardia. It was also reported about the occurrence of severe and prolonged systemic arterial hypotension up to the development of a fatal shock. Treatment: in case of an accidental overdose, it is necessary to induce vomiting (if the drug was taken recently) or to carry out gastric lavage, appoint activated charcoal. The use of activated carbon in healthy volunteers immediately or 2 hours after taking amlodipine significantly reduced its absorption. In the case of clinically severe arterial hypotension, caused by Exforge, the patient should be placed with the legs elevated, active measures should be taken to support the cardiovascular system, including frequent monitoring of the function of the heart and respiratory system, the BCC and the amount of urine excreted. In the absence of contraindications to restore vascular tone and blood pressure, it is possible to use (with caution) a vasoconstrictor.In / in the introduction of calcium gluconate can be effective to eliminate blockade of calcium channels. Removal of valsartan and amlodipine during hemodialysis is unlikely.
Interaction with other drugs
Amlodipine CYP3A4 isoenzyme inhibitors. With the use of amlodipine together with diltiazem, slower metabolism of amlodipine is observed in elderly patients, probably due to inhibition of the CYP3A4 isoenzyme, which leads to an increase in plasma concentration of amlodipine by approximately 50% and increased clinical effect. When using amlodipine together with potent inhibitors of CYP3A4 (for example, ketoconazole, itraconry and ritonavir), a marked increase in systemic exposure to amlodipine is possible. The inducers of the CYP3A4 isoenzyme. Since the use of amlodipine together with inducers of the CYP3A4 isoenzyme (for example, carbamazepine, phenobarbital, phenytoin, fosfenitoin, primidon, rifampicin, grapefruit juice, herbal preparations containing St. John's wort), can cause a marked decrease in its concentration in blood plasma; when assigning amlodipine with inductors CYP3A4, should control its clinical effekt.Pri amlodipine monotherapy not observed clinically significant interaction with thiazide diuretics, beta-blockers, ACE inhibitors, long-acting nitrates, nitroglycerin sublingual application, digoxin, warfarin, atorvastatin, sildenafil, Maalox (gel of aluminum hydroxide, magnesium hydroxide, simethicone), cimetidine, NSAIDs, antibiotics and oral hypoglycemic drugs. Val Artan It has been established that in monotherapy with valsartan, there is no clinically significant interaction with the following drugs: cimetidine, warfarin, furosemide, digoxin, atenolol, indomethacin, hydrochlorothiazide, amlodipine, glibenclamide. supplements containing potassium, potassium-sparing diuretics, potassium-containing salt substitutes, or with other drugs that may cause an increase in alia in the blood (for example, with heparin), care should be taken and frequent monitoring of potassium in the blood should be carried out. NPVS, including selective COX-2 inhibitors: the administration of angotensin II receptor antagonists simultaneously with NSAIDs can lead to a weakening of the hypotensive effect. In elderly patients, patients with BCC deficiency (includingreceiving diuretic therapy) or with impaired renal function, the simultaneous use of angiotensin II receptor antagonists and NSAIDs may lead to an increased risk of renal impairment. When an angiotensin II receptor antagonist is initiated or changed by patients with NSAIDs, regular monitoring of renal function is recommended.
special instructions
Caution should be exercised in the appointment of Exforge patients with liver disease (especially with obstructive diseases of the biliary tract). Valsartan is excreted mainly unchanged with bile, while amlodipine is extensively metabolized in the liver. Patients with initial and moderate renal impairment (CK 30–50 ml / min) do not require dose adjustment of Exforge. Care should be taken when prescribing the drug to patients with severely impaired renal function (less than 10 ml / min), because data on the safety of the drug in such cases are not obtained. Also, as with other vasodilators, special care should be taken when prescribing the drug to patients with mitral or aortic stenosis, hypertrophic obstructive cardiomyopathy. blockers should be reduced gradually. Since amlodipine is not a beta-blocker, the use of Exforge does not prevent the development of withdrawal syndrome that occurs when an abrupt cessation of treatment with beta-blockers occurs. Patients with activated RAAS (for example, with a deficit of BCC and / or sodium in patients receiving high doses of diuretics), while taking angiotensin receptor blockers, may develop symptomatic arterial hypotension. Before starting treatment with Exforge, the sodium content in the body and / or the BCC should be corrected or therapy should be started under close medical supervision. In the event of arterial hypotension, the patient should be placed with raised legs, if necessary, IV saline should be administered.After stabilization of blood pressure, treatment with Exforge can be continued. In case of simultaneous use of the drug with dietary supplements containing potassium, potassium-sparing diuretics, potassium-containing salt substitutes, or with other drugs that can cause an increase in the concentration of potassium in the blood (for example, with heparin), you should follow caution and conduct regular monitoring of the concentration of potassium in the blood. Effects on the ability to drive motor vehicles and control mechanisms and on the ability to drive vehicles and work with mechanisms. In connection with the possible occurrence of dizziness or increased fatigue, caution should be exercised when driving vehicles or working with mechanisms.