Pharmacodynamics and pharmacokinetics
The drug prevents the entry of calcium ions through the membranes into vascular and myocardial cells. Blood pressure decreases as a result of vasodilatation. The antianginal effect is provided by amlodipine , which dilates peripheral arterioles and helps reduce peripheral vascular resistance without causing reflex tachycardia . Due to this, the myocardium's need for oxygen is reduced, and the heart muscle consumes less energy. Amlodipine helps increase oxygen delivery to all areas of the myocardium when spasms of the coronary arteries occur.
After administration, it is well absorbed from the gastrointestinal tract (the rate of absorption is not affected by food intake). After 6-12 hours it reaches its maximum concentration in the blood. Bioavailability – 65-80%. It is transformed in the liver, forming inactive metabolites . Excreted through the kidneys (about 60%) and intestines (25%).
pharmachologic effect
Pharmacological action - antianginal, antihypertensive.
Blocks the flow of calcium ions through membranes into the smooth muscle cells of the myocardium and blood vessels (calcium channels). Vasodilation leads to a decrease in blood pressure. The antianginal effect is due to both a decrease in oxygen consumption, due to the dilation of arterioles and a decrease in peripheral vascular resistance (afterload), and an increase in oxygen delivery due to dilatation of the main coronary arteries and arterioles in ischemic and unchanged areas of the myocardium.
Indications for use of Vero-Amlodipine
The drug is prescribed for the following diseases:
- arterial hypertension (monotherapy or together with other drugs);
- vasoconstriction or vasospasm ;
- stable angina ;
- dilated (non-ischemic) cardiomyopathy with stage III-IV chronic heart failure;
- vasospastic angina.
This drug should also be prescribed as monotherapy or together with antianginal drugs to those patients who are refractory to therapy with beta-blockers or nitrates .
Side effects
While taking this medicine you may experience:
- tachycardia , arrhythmia , hyperemia , palpitations, peripheral edema, shortness of breath , arterial hypotension ;
- gum hyperplasia , severe abdominal pain, nausea;
- paresthesia , drowsiness , fatigue, dizziness, headache;
- itching, rash.
With a long duration of the course, pain in the limbs may occur.
Instructions for use of Vero-Amlodipine (Method and dosage)
Take the medicine orally.
For patients with arterial hypertension or angina pectoris , the minimum daily dose is 5 mg. Later, if necessary, you can increase it to 10 mg.
For dilated cardiomyopathy, treatment should begin with a dose of 2.5 mg, which can be increased to 10 mg if the drug is well tolerated.
According to the instructions, it is not recommended to exceed the dosage up to 10 mg per day, since it is the maximum.
Concomitant use of amlodipine with beta-blockers , thiazide diuretics or ACE inhibitors does not require dose adjustment.
Vero-Amlodipine
Amlodipine can be safely used for the treatment of arterial hypertension together with thiazide diuretics, alpha-blockers, beta-blockers or ACE inhibitors. In patients with stable angina, amlodipine can be combined with other antianginal agents, for example, long-acting and short-acting nitrates, beta-blockers.
Unlike other BMCCs, no clinically significant interaction of amlodipine (III generation BMCCs) was found when used together with non-steroidal anti-inflammatory drugs (NSAIDs), including indomethacin.
It is possible to enhance the antianginal and hypotensive effect of BMCC when used together with thiazide and loop diuretics, ACE inhibitors, beta-blockers and nitrates, as well as enhance their hypotensive effect when used together with alpha1-blockers, antipsychotics.
Although negative inotropic effects have generally not been observed in amlodipine studies, some CBMCs may enhance the negative inotropic effects of antiarrhythmic drugs that cause QT prolongation (eg, amiodarone and quinidine).
Amlodipine can also be safely used concomitantly with antibiotics and oral hypoglycemic agents.
A single dose of 100 mg of sildenafil in patients with essential hypertension does not affect the pharmacokinetic parameters of amlodipine.
Repeated use of amlodipine at a dose of 10 mg and atorvastatin at a dose of 80 mg is not accompanied by a significant change in the pharmacokinetics of atorvastatin.
Simvastatin: simultaneous repeated use of amlodipine at a dose of 10 mg and simvastatin at a dose of 80 mg leads to an increase in simvastatin exposure by 77%. In such cases, the dose of simvastatin should be limited to 20 mg.
Ethanol (drinks containing alcohol): amlodipine with single and repeated use in a dose of 10 mg does not affect the pharmacokinetics of ethanol.
Antiviral agents (ritonavir): increases plasma concentrations of BMCC, including amlodipine.
Neuroleptics and isoflurane: enhancing the hypotensive effect of dihydropyridine derivatives.
Calcium supplements can reduce the effect of BMCC.
When BMCC is used together with lithium preparations (no data are available for amlodipine), their neurotoxicity (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus) may increase.
Studies of the simultaneous use of amlodipine and cyclosporine in healthy volunteers and all groups of patients, with the exception of patients after kidney transplantation, have not been conducted. Various studies of the interaction of amlodipine with cyclosporine in patients after kidney transplantation show that the use of this combination may not lead to any effect, or increase the minimum concentration of cyclosporine to varying degrees, up to 40%. These data should be taken into account and cyclosporine concentrations should be monitored in this group of patients when cyclosporine and amlodipine are co-administered.
Does not affect the serum concentration of digoxin and its renal clearance.
Does not significantly affect the effect of warfarin (prothrombin time). Cimetidine does not affect the pharmacokinetics of amlodipine.
In in
vitro
, amlodipine does not affect the plasma protein binding of digoxin, phenytoin, warfarin and indomethacin.
Grapefruit juice: simultaneous administration of 240 ml of grapefruit juice and 10 mg of amlodipine orally is not accompanied by a significant change in the pharmacokinetics of amlodipine. However, it is not recommended to use grapefruit juice and amlodipine at the same time, since genetic polymorphism of the CYP3A4 isoenzyme may increase the bioavailability of amlodipine and, as a result, enhance the hypotensive effect.
Aluminum- or magnesium-containing antacids: their single dose does not have a significant effect on the pharmacokinetics of amlodipine.
Inhibitors of the CYP3A4 isoenzyme: with simultaneous use of diltiazem at a dose of 180 mg and amlodipine at a dose of 5 mg in patients from 69 to 87 years of age with arterial hypertension, there is an increase in systemic exposure of amlodipine by 57%. Concomitant use of amlodipine and erythromycin in healthy volunteers (18 to 43 years of age) does not lead to significant changes in amlodipine exposure (increase in area under the concentration-time curve (AUC) by 22%). Although the clinical significance of these effects is unclear, they may be more pronounced in older patients.
Potent inhibitors of the CYP3A4 isoenzyme (for example, ketoconazole, itraconazole) may increase the plasma concentration of amlodipine to a greater extent than diltiazem. Amlodipine and inhibitors of the CYP3A4 isoenzyme should be used with caution.
Clarithromycin: CYP3A4 inhibitor. Patients taking clarithromycin and amlodipine at the same time have an increased risk of low blood pressure. Patients taking this combination are advised to be under close medical supervision.
Inducers of the CYP3A4 isoenzyme: there is no data on the effect of inducers of the CYP3A4 isoenzyme on the pharmacokinetics of amlodipine. Blood pressure should be carefully monitored during concomitant use of amlodipine and inducers of the CYP3A4 isoenzyme.
Tacrolimus: When used concomitantly with amlodipine, there is a risk of increasing the concentration of tacrolimus in the blood plasma. To avoid toxicity of tacrolimus when used concomitantly with amlodipine, the concentration of tacrolimus in the blood plasma of patients should be monitored and the dose of tacrolimus should be adjusted if necessary.
mTOR inhibitors (mammalian Target of Rapamycin - mechanistic target of rapamycin in mammalian cells): mTOR inhibitors (for example, temsirolimus, sirolimus, everolimus) are substrates of the CYP3A4 isoenzyme. Since amlodipine is a weak inhibitor of the CYP3A4 isoenzyme, co-administration of amlodipine with mTOR inhibitors may increase their exposure.
Interaction
The hypotensive effect may be enhanced when taken concomitantly with calcium channel blockers . This result can also be observed when using inhalation anesthesia or orlistat , which can lead to a sharp increase in pressure, a hypertensive crisis.
A delay in sodium in the body and, as a result, a decrease in the antihypertensive effect is possible when taking estrogens and sympathomimetics . The antihypertensive effect can also be enhanced with amiodarone or quinidine .
The occurrence of symptoms of neurotoxicity, such as tinnitus, nausea, ataxia, diarrhea, vomiting, can be caused by taking lithium carbonate simultaneously with Vero-Amlodipine.
Concomitant use of amlodipine with indomethacin or other NSAIDs leads to a decrease in the antihypertensive effect.
Amlodipine-Vero tablets 10 mg No. 30
A country
Russia
The country of production may vary depending on the batch of goods. Please check with the operator for detailed information when confirming your order.
Active substance
Amlodipine
pharmachologic effect
Selective class II calcium channel blocker. The antihypertensive effect is due to a direct relaxing effect on vascular smooth muscle. It is assumed that the antianginal effect of amlodipine is associated with its ability to dilate peripheral arterioles; this leads to a decrease in peripheral vascular resistance, and reflex tachycardia does not occur. As a result, there is a decrease in myocardial oxygen demand and energy consumption by the heart muscle. On the other hand, amlodipine appears to cause dilation of large-caliber coronary arteries and coronary arterioles in both intact and ischemic areas of the myocardium. This ensures the supply of oxygen to the myocardium during spasms of the coronary arteries.
Indications for use
Arterial hypertension (as monotherapy or as part of combination therapy). Stable angina, unstable angina, Prinzmetal's angina (as monotherapy or as part of combination therapy).
Mode of application
For adults, when taken orally, the initial dose is 5 mg 1 time / day. If necessary, the dose can be increased. Maximum dose: when taken orally - 10 mg/day. The safety of amlodipine during pregnancy has not been established, so use is only possible if the expected benefit to the mother outweighs the potential risk to the fetus. There are no data indicating the excretion of amlodipine in breast milk. However, other calcium channel blockers (dihydropyridine derivatives) are known to be excreted in breast milk. In this regard, if it is necessary to use amlodipine during lactation, the issue of stopping breastfeeding should be decided. There are no clinical data on the use of amlodipine in pediatrics.
Interaction
It is possible to enhance the antianginal and antihypertensive effect of slow calcium channel blockers when used together with thiazide and loop diuretics, ACE inhibitors, beta-blockers and nitrates, as well as enhance their antihypertensive effect when used together with alpha1-blockers, antipsychotics. Although negative inotropic effects have not generally been observed in amlodipine studies, some calcium channel blockers may enhance the negative inotropic effects of antiarrhythmic drugs that cause QT prolongation (eg, amiodarone and quinidine). Simultaneous repeated use of amlodipine at a dose of 10 mg and simvastatin at a dose of 80 mg leads to an increase in the bioavailability of simvastatin by 77%. In such cases, the dose of simvastatin should be limited to 20 mg. Antiviral drugs (for example, ritonavir) increase plasma concentrations of slow calcium channel blockers, incl. amlodipine. With the simultaneous use of sympathomimetics and estrogens, the antihypertensive effect may be reduced due to sodium retention in the body. Neuroleptics and isoflurane enhance the antihypertensive effect of dihydropyridine derivatives. With the simultaneous use of inhalation anesthesia, the hypotensive effect may be enhanced. With simultaneous use of amiodarone, the antihypertensive effect may be enhanced. With simultaneous use of lithium carbonate, manifestations of neurotoxicity (including nausea, vomiting, diarrhea, ataxia, tremors and/or tinnitus) are possible. With simultaneous use, orlistat reduces the antihypertensive effect of amlodipine, which can lead to a significant increase in blood pressure and the development of a hypertensive crisis. With the simultaneous use of indomethacin and other NSAIDs, the antihypertensive effect of amlodipine may be reduced due to inhibition of prostaglandin synthesis in the kidneys and fluid retention under the influence of NSAIDs. With simultaneous use of quinidine, the antihypertensive effect may be enhanced. Calcium supplements may reduce the effect of slow calcium channel blockers. With simultaneous use of diltiazem (CYP3A4 isoenzyme inhibitor) at a dose of 180 mg and amlodipine at a dose of 5 mg in elderly patients (69 to 87 years) with arterial hypertension, an increase in the bioavailability of amlodipine by 57% was observed. Concomitant use of amlodipine and erythromycin in healthy volunteers (18 to 43 years of age) does not lead to significant changes in amlodipine exposure (22% increase in AUC). Although the clinical significance of these effects is unclear, they may be more pronounced in older patients. Potent inhibitors of the CYP3A4 isoenzyme (for example, ketoconazole, itraconazole) may increase the plasma concentration of amlodipine to a greater extent than diltiazem. Amlodipine and inhibitors of the CYP3A4 isoenzyme should be used with caution. There are no data on the effect of inducers of the CYP3A4 isoenzyme on the pharmacokinetics of amlodipine. Blood pressure should be carefully monitored while using amlodipine and inducers of the CYP3A4 isoenzyme.
Side effect
From the cardiovascular system: peripheral edema, tachycardia, hyperemia of the skin; when used in high doses - arterial hypotension, arrhythmias, shortness of breath. From the digestive system: nausea, abdominal pain; rarely - gingival hyperplasia. From the central nervous system and peripheral nervous system: headache, fatigue, drowsiness, dizziness; with long-term use - paresthesia. Allergic reactions: skin rash, itching. Other: with long-term use - pain in the limbs.
Contraindications
Severe arterial hypotension (systolic blood pressure less than 90 mmHg); left ventricular outflow tract obstruction (including severe aortic stenosis); hemodynamically unstable heart failure after myocardial infarction; children and adolescents under 18 years of age (efficacy and safety have not been established); hypersensitivity to amlodipine and other dihydropyridine derivatives.
special instructions
Use with caution in patients with liver failure, chronic heart failure of non-ischemic etiology of functional class III-IV according to the NYHA classification, unstable angina, aortic stenosis, mitral stenosis, hypertrophic obstructive cardiomyopathy, acute myocardial infarction (and within 1 month after it), SSS (severe tachycardia, bradycardia), arterial hypotension, when used simultaneously with inhibitors or inducers of the CYP3A4 isoenzyme. During the use of amlodipine in patients with chronic heart failure (class III and IV according to the NYHA classification) of non-ischemic origin, an increase in the incidence of pulmonary edema was observed, despite the absence of signs of worsening heart failure. In elderly patients, T1/2 may increase and amlodipine clearance may decrease. No dose changes are required, but more careful monitoring of patients in this category is necessary. The effectiveness and safety of amlodipine in hypertensive crisis has not been established. Despite the absence of withdrawal syndrome with slow calcium channel blockers, it is advisable to discontinue treatment with amlodipine gradually. There are no clinical data on the use of amlodipine in pediatrics.
Dispensing conditions in pharmacies
On prescription
