Product Overview
[Drug name]
Generic name: Amlodipine besylate tablets
Trade name: YaNiAn Amlodipine besylate tablets 5mg*7 tablets*4 boards
Pinyin full code: YaNiAn BenHuangSuanAnLvDiPingPian 5mg*7Pian*4Ban
[Main ingredients]
Amlodipine besylate.
[Properties]
This product is white or off-white tablets.
[Indications/main functions]
Hypertension This product is suitable for the treatment of hypertension. This product can be used alone or in combination with other antihypertensive drugs. The control of hypertension is part of the comprehensive management of cardiovascular risk. Comprehensive management measures may include: blood lipid control, diabetes management, antithrombotic treatment, smoking cessation, physical exercise and sodium salt intake restriction. Increases in systolic or diastolic blood pressure increase cardiovascular risk. At higher baseline blood pressure levels, the absolute risk increase brought about by an increase in blood pressure per millimeter of recording column will be higher. The relative degree of risk reduction achieved by lowering blood pressure is similar in people with different absolute cardiovascular risks. For patients with severe hypertension, a slight reduction in blood pressure can bring greater clinical benefits. For adult patients with hypertension, generally speaking, lowering blood pressure can reduce the risk of cardiovascular events, mainly stroke and myocardial infarction. 2. Chronic stable angina pectoris in coronary heart disease This product is suitable for the symptomatic treatment of chronic stable angina pectoris. It can be used alone or in combination with other anti-anginal drugs. Vasospastic angina pectoris (Prinzmetals or variant angina pectoris) This product is suitable for the treatment of confirmed or suspected vasospastic angina pectoris. It can be used alone or in combination with other anti-anginal drugs. For patients with coronary heart disease confirmed by angiography, but with an ejection fraction ≥ 40% and no heart failure, this product can reduce the risk of hospitalization due to angina pectoris and reduce the risk of coronary artery reconstruction.
[Specification model]
5mg*7 tablets*4 plates
[Usage and dosage]
1. The initial dose for the treatment of hypertension is 5mg, once a day, and the maximum dose is 10mg, once a day. The initial dose for weak or elderly patients and patients with liver dysfunction is 2.5 mg once a day; this dose can also be the dose for the original treatment with other antihypertensive drugs that require the addition of amlodipine besylate tablets. Dose adjustment should be based on the individual response of the patient. General dose adjustment should be started after 7 to 14 days. If clinically necessary, dose adjustment can be started faster after close observation of the patient. 2. The initial dose for the treatment of angina pectoris is 5 to 10 mg once a day. A lower dose is recommended for elderly patients and patients with liver dysfunction. The effective dose for most people is 10 mg/day.
[Adverse Reactions]
Amlodipine has good tolerance. In placebo-controlled clinical trials for the treatment of hypertension or angina pectoris, the most common side effects are: autonomic nervous system: flushing; whole body: fatigue; cardiovascular, general: edema; central and peripheral nervous system: dizziness, headache; gastrointestinal: abdominal pain, nausea; heart rate/heart rhythm: palpitations; psychological: drowsiness. No significant clinical laboratory abnormalities related to this product were found in these clinical trials. Less common side effects observed after marketing are: Autonomic nervous system: dry mouth, increased sweating; Systemic: weakness, back pain, malaise, pain, weight gain/loss; Cardiovascular, general: hypotension, syncope; Central and peripheral nervous system: high muscle tone, hypoesthesia/paresthesia, peripheral neuropathy, tremor; Endocrine: breast hyperplasia; Gastrointestinal: changes in bowel habits, dyspepsia (including gastritis), gingival hyperplasia, pancreatitis, vomiting; Metabolic/nutritional: hyperglycemia; Musculoskeletal: joint pain, muscle Spasmodic pain, myalgia; Platelet/bleeding/coagulation: purpura, thrombocytopenic purpura; Psychological: impotence, insomnia, attitude change; Respiratory: cough, dyspnea, rhinitis; Skin/appendages: alopecia, skin discoloration, urticaria; Special senses: taste disturbances, tinnitus; Urinary: urinary frequency, dysuria, enuresis; Vascular (extracardiac): vasculitis; Visual: visual disturbances Leukocyte/reticuloendothelial system: leukopenia; Allergic reactions are rare and include pruritus, rash, angioedema, and erythema multiforme. Very rare cases of hepatitis, jaundice, and elevated aminotransferases (usually associated with cholestasis) have been reported. Some serious cases requiring hospitalization have been reported in association with the use of amlodipine. However, in most cases, a causal relationship has not been established. Similar to other calcium channel blockers, the following adverse events have also been reported in rare cases, but the events are difficult to distinguish from the natural course of the underlying disease, such as myocardial infarction, arrhythmias (including bradycardia, ventricular tachycardia and atrial fibrillation) and chest pain.
[Contraindications] Amlodipine besylate tablets are contraindicated for patients who are allergic to dihydropyridine calcium antagonists.
[Drug Interactions] This product is safe to be used in combination with the following drugs: thiazide diuretics, α~ adrenergic receptor blockers, adrenergic receptor blockers, angiotensin-converting enzyme inhibitors, long-acting nitrates, sublingual nitroglycerin, nonsteroidal anti-inflammatory drugs, antibiotics and oral hypoglycemic drugs. In vitro study data using human plasma showed that this product did not affect the plasma protein binding rate of digoxin, phenytoin sodium, warfarin or indomethacin. Effects of other drugs on amlodipine: Cimetidine: Combination with cimetidine does not change the pharmacokinetics of amlodipine. Grapefruit juice: 20 healthy volunteers took 240 mg grapefruit juice and 10 mg amlodipine at the same time, and no significant effect on the pharmacokinetics of amlodipine was observed. Aluminum/magnesium (antacids): The simultaneous administration of aluminum/magnesium antacids and a single dose of amlodipine did not significantly affect the pharmacokinetics of amlodipine. Sildenafil (Viagra): A single dose of 100 mg of sildenafil did not affect the pharmacokinetics of amlodipine in patients with essential hypertension. When the two drugs are used together, each drug exerts its antihypertensive effect independently. Effects of amlodipine on other drugs: Atorvastatin: Multiple doses of 10 mg of amlodipine combined with 80 mg of atorvastatin did not significantly change the steady-state pharmacokinetic parameters of atorvastatin. Digoxin: The combination of amlodipine and digoxin did not change the plasma digoxin concentration or renal clearance of normal volunteers. Ethanol (alcohol): Single or multiple doses of 10 mg of amlodipine had no effect on the pharmacokinetics of ethanol. Warfarin: The combination of amlodipine and warfarin did not change the prothrombin reaction time of warfarin. Cyclosporine: Pharmacokinetic studies have shown that amlodipine does not significantly change the pharmacokinetics of cyclosporine. Drug/laboratory test interactions: Unknown.
[Precautions]
1. Warning: A very small number of patients, especially those with severe coronary artery obstructive disease, experience increased frequency, prolonged duration and/or aggravated severity of angina pectoris, or acute myocardial infarction when starting calcium antagonist treatment or increasing the dose. The mechanism of action is currently unclear. 2. Because the vasodilator effect of this product is gradually produced, there are rare reports of acute hypotension after taking this product. However, in patients with severe aortic stenosis, attention should be paid when it is used in combination with other peripheral vasodilators. 3. Use in patients with heart failure: Calcium antagonists should be used with caution in patients with congestive heart failure. In a long-term, placebo-controlled study (PRAISE-2) of patients with non-ischemic heart failure (NYHA II-IV), although the incidence of worsening heart failure was not significantly different from placebo, there was an increase in reports of pulmonary edema associated with amlodipine. 4. Use in patients with impaired liver function: Like all other calcium antagonists, the half-life of amlodipine besylate tablets is prolonged when liver function is impaired, but the corresponding recommended dose has not yet been determined. Therefore, this product should be used with caution. 5. Use in patients with renal failure: The change in blood concentration of amlodipine is not correlated with the degree of renal impairment, so a normal dose can be used. This product cannot be dialyzed.
[Medication for elderly patients]
Clinical studies have not confirmed that the elderly react differently to this drug than young people, but considering that the elderly often have decreased liver, kidney and heart function, and are accompanied by other diseases and corresponding drug treatments, the lower limit of the dose range is generally used for initial medication. The clearance rate of this product is reduced in the elderly, and the drug-time curve (AUC) increases by about 40%-60%, so a lower initial dose is also required.
[Pharmacology and toxicology]
Pharmacological actionAmlodipine besylate is a dihydropyridine calcium antagonist (calcium ion antagonist or slow channel blocker). The contraction of myocardial and smooth muscle depends on the entry of extracellular calcium ions into cells through specific ion channels. This product selectively inhibits the transmembrane entry of calcium ions into smooth muscle cells and cardiomyocytes, and has a greater effect on smooth muscle than on myocardium. Its interaction with calcium channels is determined by the progressive rate of its binding and dissociation with receptor sites, so the pharmacological effect is gradually produced. This product is a peripheral artery dilator that acts directly on vascular smooth muscle, reduces peripheral vascular resistance, and thus lowers blood pressure. At therapeutic doses, negative inotropic effects can be observed in in vitro experiments, but not in whole animal experiments. This product does not affect plasma calcium concentration. 15 randomized double-blind, placebo-controlled clinical trials have confirmed the antihypertensive effect of this product. Patients with mild to moderate hypertension take the drug once a day, which can reduce supine and standing blood pressure for 24 hours. Long-term use does not cause significant changes in heart rate or plasma catecholamines. The antihypertensive effect is stable. The antihypertensive effect is related to the dose, and the blood pressure reduction amplitude is related to the blood pressure before treatment. The efficacy of moderate hypertension patients (diastolic blood pressure 105-114mmHg) is higher than that of mild hypertension patients (diastolic blood pressure 90-104mmHg), and there is no obvious effect after taking the drug in patients with normal blood pressure. The effect of this product in reducing diastolic blood pressure is similar in the elderly and young people, and the effect of reducing systolic blood pressure is stronger in the elderly. The exact mechanism of this product in relieving angina pectoris is not clear, but it may be that during exercise, this product reduces the work of the heart and the heart rate-blood pressure product by reducing peripheral resistance (afterload), reducing myocardial oxygen demand, and treating exertional angina pectoris; it restores blood supply to the ischemic area by inhibiting the contraction of coronary arteries and arterioles caused by calcium ions, adrenaline, 5-hydroxytryptamine and thromboxane A2. Treat spontaneous angina pectoris. Five of the eight clinical trials showed that this product significantly prolonged the time of exercise-induced exertional angina pectoris; some studies showed that this product prolonged the time of ST segment depression by 1mm and reduced the frequency of angina pectoris. This effect is persistent and does not significantly affect blood pressure and heart rate. In a clinical trial of 50 patients with spontaneous angina pectoris, this product can reduce 4 angina attacks per week (placebo reduces 1 per week). After taking this product, patients with normal heart function measured hemodynamics at rest and under exercise, and the cardiac ejection fraction increased, but there was no significant effect on dP/dt or left ventricular end-diastolic pressure/volume. At therapeutic doses, this product alone or in combination with β-blockers does not cause negative inotropic effects. In a placebo-controlled study, 697 patients with heart failure of heart function/grade I (NYHA) did not show signs of worsening heart failure in exercise tolerance tests, NYHA classification, symptoms and left ventricular ejection fraction after taking the drug for 8-12 weeks. (Another placebo-controlled long-term survival trial, 1153 patients with heart failure of grade III/V heart function were randomly given this product or placebo on the basis of conventional treatment. The results showed that the mortality rate and cardiac morbidity from various causes were 39% in the amlodipine group and 42% in the placebo group.) This product does not affect sinus node function and atrioventricular conduction. No abnormal electrocardiogram was found in patients with hypertension or angina pectoris who used this product and β-blockers in combination. Amlodipine besylate tablets do not change the electrocardiogram of patients with angina pectoris, nor do they aggravate atrioventricular block. After taking the drug, hypertensive patients with normal renal function have reduced renal vascular resistance, increased glomerular filtration rate and renal blood flow, but the filtration fraction or urine protein remains unchanged. Toxicological effects Carcinogenicity, mutagenicity and teratogenicity Rats and mice were fed amlodipine for two years at doses of 0.5, 1.25 and 2.5 mg/kg per day, and no carcinogenicity was confirmed. The highest dose has reached the maximum tolerance of mice, but not rats (calculated based on the clinical maximum recommended dose of 10 mg mg/m2). No drug-related mutagenicity was revealed at the gene and chromosome levels. Male rats were given amlodipine 64 days before mating and female rats were given amlodipine 14 days before mating, 10 mg/kg per day (8 times the maximum recommended human dose), without affecting reproductive capacity. Pregnant rats and rabbits were given amlodipine at 10 mg/kg (8 times and 23 times the maximum recommended dose for humans) during the period of major organ formation, and no teratogenicity or other embryotoxicity was found. However, rats were given amlodipine at 10 mg/kg starting 14 days before mating and throughout the mating and gestational periods, which resulted in a significant reduction in the size of the pups (about 50%), a significant increase in the number of intrauterine deaths (about 5 times), and a prolonged gestational time and delivery time. Toxicity mice and rats were given amlodipine at a single dose of up to 40 mg/kg and 100 mg/kg, respectively, which can cause death. A single dose of 4 mg/kg or higher in dogs will cause significant peripheral vasodilation and hypotension.
