Product Overview
[Drug Name]
Generic Name: Amlodipine Besylate Tablets
Trade Name: Yashida
English Name: Amlodipine Besylate Tablets
Chinese Pinyin: Benhuangsuan Anlvdiping Pian
[Ingredients]
The main ingredient of this product is amlodipine besylate, whose chemical name is: 3-ethyl-5-methyl-2-(2-aminoethoxymethyl)-4-(2-chlorophenyl)-1,4-dihydro-6-methyl-3,5-pyridinedicarboxylate benzenesulfonate. [Molecular Formula] C20H25N2O5Cl·C6H6O3S [Molecular Weight] 567.1
[Properties]
This product is a white tablet.
[Indications]
1. High direct pressure. This product is indicated for the treatment of hypertension. It can be used alone or in combination with other antihypertensive drugs. 2. Coronary artery disease (CAD) and chronic stable angina. This drug is indicated for the symptomatic treatment of chronic stable angina pectoris, either alone or in combination with other antianginal drugs. It is also indicated for the treatment of confirmed or suspected vasospastic angina pectoris, either alone or in combination with other antianginal drugs. In patients with angiographically confirmed coronary artery disease (CAD) but an ejection fraction of 40% and no heart failure, this drug can reduce the risk of hospitalization for angina pectoris and the need for coronary revascularization.
[Dosage and Administration]
Adults: The usual starting dose for hypertension is 5 mg once daily, with a maximum dose of 10 mg once daily. For patients who are small, frail, elderly, or have hepatic insufficiency, the starting dose is 2.5 mg once daily, which can also be used in combination with other antihypertensive drugs. Dose adjustments should be made based on individual patient response. Generally, dose adjustments should be initiated after 7-14 days. If clinically indicated, dose adjustments may be made more quickly under close patient monitoring. The recommended dose for the treatment of chronic stable or vasospastic angina is 5-10 mg once daily. Lower doses are recommended for elderly patients and those with hepatic impairment. The effective dose for most patients is 10 mg once daily.
[Adverse Reactions]
This product is well tolerated within the 10 mg/day dose range, with most adverse reactions being mild to moderate. Discontinuation due to adverse reactions was only 1.5%, which was not significantly different from placebo (approximately 1%). The most common adverse reactions were headache and edema. Dose-related adverse reactions with an incidence of 1% were edema, dizziness, hot flashes, and palpitations. Adverse reactions with unclear dose relationships but an incidence exceeding 1.0% were headache, fatigue, nausea, abdominal pain, and somnolence. Among these adverse reactions, edema, hot flashes, palpitations, and somnolence were more common in women than in men. The following adverse events have an incidence of <1% but not >0.1%, and a causal relationship to the drug is unclear: General: allergic reaction, asthenia, back pain, hot flashes, malaise, pain, stiffness, and weight gain.
[Contraindications]
Allergy to dihydropyridine calcium channel blockers.
[Precautions]
1. Angina and/or Myocardial Infarction: Rare. In patients with severe obstructive coronary artery disease, the frequency, duration, and/or severity of angina attacks, or the development of acute myocardial infarction, may increase when initiating or increasing the dose of calcium channel blockers. The mechanism is unknown. 2. Hypotension: Due to the gradual onset of vasodilation, acute hypotension is rarely seen with oral administration. However, caution is advised when using this drug in combination with other peripheral vasodilators, especially in patients with severe aortic stenosis. 3. Patients with Heart Failure: Calcium channel blockers should be used with caution in patients with heart failure. 4. Patients with Hepatic Impairment: This drug should be used with caution in patients with severe hepatic impairment. 5. Patients with Renal Failure: The starting dose for patients with renal failure can remain unchanged. 6. Discontinuation of Beta-Blockers: This drug does not protect against rebound symptoms caused by abrupt discontinuation of beta-blockers. Therefore, a gradual dose reduction is still required when discontinuing beta-blockers. 7. This drug can be used safely in patients with obstructive pulmonary disease, well-compensated heart failure, peripheral vascular disease, diabetes, and lipid disorders.
[Use in Special Populations]
Precautions for Children:
Safety and efficacy in children have not been established.
Precautions for Pregnancy and Lactation:
There is a lack of research data on the use of this drug in pregnant women. However, based on animal studies, this drug should only be used in pregnant women when absolutely necessary. It is not known whether this drug is excreted in breast milk; lactating women taking this drug should discontinue breastfeeding.
Precautions for the Elderly:
Clinical studies have not demonstrated that elderly individuals respond differently to this drug than younger individuals. However, given that elderly individuals often have impaired liver, kidney, and heart function, as well as other medical conditions and medications, the lower end of the starting dose range is generally used. Elderly individuals have decreased clearance of this drug, with an approximately 40%-60% increase in the area under the curve (AUC), necessitating a lower initial dose.
[Drug Interactions]
1. Cimetidine, grapefruit juice, and acidogens: Coadministration does not alter the pharmacokinetics of this drug. 2. Atorvastatin, digoxin, and ethanol: This drug does not affect their pharmacokinetics. 3. Sildenafil: A single dose of sildenafil (Viagra) has no effect on the pharmacokinetics of this drug in patients with essential hypertension. The two drugs produce an independent antihypertensive effect when taken together. 4. Warfarin: This drug does not alter the prothrombin action time of warfarin. 5. Digoxin, phenytoin, and warfarin: Coadministration with this drug has no effect on plasma protein binding. 6. Anesthetics: Coadministration of inhaled hydrocarbons with this drug may cause hypotension. 7. Nonsteroidal anti-inflammatory drugs: Indomethacin, in particular, may attenuate the antihypertensive effect of this drug. 8. Beta-blockers: Coadministration with this drug is well tolerated, but may cause excessive hypotension and rarely worsen heart failure.
[Pharmacological Actions]
Pharmacological Actions: Amlodipine besylate is a dihydropyridine calcium antagonist (calcium ion antagonist or slow-channel blocker). Cardiac and smooth muscle contraction depends on the entry of extracellular calcium ions into cells through specific ion channels. This drug selectively inhibits the transmembrane entry of calcium ions into smooth muscle cells and cardiomyocytes, with a greater effect on smooth muscle than on myocardium. Its interaction with calcium channels is determined by the progressive rate of binding and dissociation from receptor sites, resulting in a gradual onset of pharmacological action. This drug is a peripheral arterial dilator that acts directly on vascular smooth muscle, reducing peripheral vascular resistance and thereby lowering blood pressure. Negative inotropic effects have been observed in vitro at therapeutic doses, but not in whole animal studies. This drug does not affect plasma calcium concentrations. Its antihypertensive activity has been confirmed in 15 randomized, double-blind, placebo-controlled clinical trials. Patients with mild to moderate hypertension, taking the drug once daily, can lower 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 dose-dependent, and the magnitude of the reduction is related to pre-treatment blood pressure. Patients with moderate hypertension (diastolic blood pressure 105-114 mmHg) experience greater efficacy than those with mild hypertension (diastolic blood pressure 90-104 mmHg). Normotensive individuals experience no significant effect. The diastolic blood pressure-lowering effect of this drug is similar in older and younger adults, while the systolic blood pressure-lowering effect is greater in older adults. The precise mechanism by which this drug relieves angina pectoris is unclear, but it may treat exertional angina by reducing peripheral resistance (afterload), thereby reducing cardiac work and the heart rate-blood pressure product, and thus myocardial oxygen demand. It also treats spontaneous angina pectoris by inhibiting calcium, epinephrine, serotonin, and thromboxane A2-induced coronary artery and arteriolar constriction, thereby restoring blood supply to the ischemic area. Five of eight clinical trials showed that this drug significantly prolonged the duration of exercise-induced exertional angina; some studies also showed that it prolonged the time to a 1mm ST-segment depression and reduced the frequency of angina attacks. This effect was sustained and did not significantly affect blood pressure or heart rate. In a clinical trial of 50 patients with spontaneous angina, this drug reduced angina attacks by four per week (compared to one per week with placebo). In patients with normal cardiac function, resting and exercise hemodynamics were assessed with this drug, and cardiac ejection fraction increased, but there was no significant effect on dP/dt or left ventricular end-diastolic pressure/volume. At therapeutic doses, this drug did not cause negative inotropic effects when used alone or in combination with beta-blockers. In a placebo-controlled study of 697 patients with NYHA class II/III heart failure, treatment with this drug for 8-12 weeks showed no worsening of heart failure, as measured by exercise tolerance, NYHA class, symptoms, or left ventricular ejection fraction. (In another placebo-controlled long-term survival trial, 1,153 patients with class III/IV heart failure were randomized to receive this drug or placebo in addition to conventional treatment. The results showed that the rates of all-cause mortality and cardiac morbidity were 39% in the amlodipine group and 42% in the placebo group.) This drug does not affect sinus node function or atrioventricular conduction. No electrocardiographic abnormalities were found in patients with hypertension or angina pectoris when this drug was used in combination with beta-blockers. This drug did not change the electrocardiogram in patients with angina pectoris and did not aggravate atrioventricular block. In hypertensive patients with normal renal function, this drug reduced renal vascular resistance, increased glomerular filtration rate and renal blood flow, but did not change filtration fraction or urine protein. Toxic effects: Carcinogenicity, mutagenesis and teratogenicity: Amlodipine was fed to rats and mice continuously 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 reached the maximum tolerated dose in mice, but not in rats (calculated based on the maximum recommended clinical dose of 10 mg per square meter). No drug-related mutagenicity was observed at either the genomic or chromosomal levels. Amlodipine administration of 10 mg/kg daily (8 times the maximum recommended human dose) to male rats, starting 64 days before mating, and to female rats 14 days before mating, did not affect reproductive capacity. Administration of 10 mg/kg of amlodipine (8 and 23 times the maximum recommended human dose) to pregnant rats and rabbits during the period of major organogenesis did not result in teratogenicity or other embryotoxic effects. However, administration of 10 mg/kg of amlodipine to rats, starting 14 days before mating and continuing throughout mating and pregnancy, resulted in a significant reduction in pup size (approximately 50%), a significant increase in intrauterine mortality (approximately 5-fold), and prolonged gestation and delivery. Toxicity: Single doses of up to 40 mg/kg and 100 mg/kg of amlodipine, respectively, can cause death in mice and rats. A single dose of 4 mg/kg or higher in dogs will cause significant peripheral vasodilation and hypotension.
Storage: Store in a dark, sealed container.
Specifications: 5 mg x 14 tablets
Packaging: Box
Expiration Date: 36 months.
Approval Number: National Medicine Standard H20010700
Manufacturer: China Resources Secco Pharmaceutical Co., Ltd.
