KANGBOSHI Amlodipine Besylate Tablets For Hypertension 5mg*42

[Drug Name]
Generic Name: Amlodipine Besylate Tablets
Trade Name: KangBoShi Amlodipine Besylate Tablets 5mg*42 Tablets
Pinyin Full Code: KangBoShi BenHuangSuanAnLvDiPingPian 5mg*42 Tablets

[Main Ingredient]
The main ingredient of this product is amlodipine besylate.

[Properties]
This product is a white tablet.

[Indications/Main Functions]
1. Hypertension: This product is indicated for the treatment of hypertension. It can be used alone or in combination with other antihypertensive drugs. Hypertension control is part of a comprehensive cardiovascular risk management approach that may include lipid control, diabetes management, antithrombotic therapy, smoking cessation, physical exercise, and sodium restriction. Increases in systolic or diastolic blood pressure increase cardiovascular risk. At higher baseline blood pressure levels, the absolute risk increase per mmHg increase is greater. The relative magnitude of risk reduction achieved by lowering blood pressure is similar among individuals with varying absolute cardiovascular risk. For patients with severe hypertension, even a small reduction in blood pressure can provide significant clinical benefit. For adults with hypertension, lowering blood pressure generally reduces the risk of cardiovascular events, primarily stroke and myocardial infarction. 2. Coronary Artery Disease (CAD) - Chronic Stable Angina: This product is indicated for the symptomatic treatment of chronic stable angina. It can be used alone or in combination with other anti-anginal medications. Vasospastic Angina (Prinzmetal's or variant angina): This product is indicated for the treatment of confirmed or suspected vasospastic angina. It can be used alone or in combination with other anti-anginal medications. For patients with angiographically confirmed CAD, an ejection fraction >40%, and no heart failure, this product can reduce the risk of hospitalization for angina and the need for coronary revascularization.

[Specifications]
5mg*42 tablets

[Dosage and Administration]
1. The initial dose for the treatment of hypertension is 5mg once daily, with a maximum dose of 10mg once daily. The initial dose for frail or elderly patients, or those with hepatic impairment, is 2.5 mg once daily. This dose may also be the dose used in addition to other antihypertensive medications. Dose adjustments should be made based on individual patient response. Generally, dose adjustments should be initiated after 7 to 14 days. If clinically necessary, dose adjustments may be initiated sooner, with close observation of the patient. 2. The initial dose for the treatment of angina pectoris is 5 to 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/day.

Adverse Reactions:
This drug is well tolerated within the 10 mg/day dose range, with most adverse reactions being mild to moderate. Discontinuation of this drug due to adverse reactions was only 1.5%, not significantly different from placebo (approximately 1%). The most common adverse reactions were headache and edema. Dose-related adverse reactions occurring in 1% of patients were as follows: edema, dizziness, flushing, and palpitations. The dose relationship is unclear, but the incidence rate exceeds 1.0% of adverse reactions are as follows: headache, fatigue, nausea, abdominal pain and drowsiness. Among the above adverse reactions, edema, flushing, palpitations and drowsiness occur more frequently in women than in men. The incidence rate of the following adverse events is less than 1% but 0.1%, and the causal relationship with the drug is unclear: General: allergic reaction, weakness, back pain, hot flashes, discomfort, pain, stiffness, weight gain; Cardiovascular: arrhythmia (including tachycardia, bradycardia or atrial fibrillation, chest pain, hypotension, peripheral ischemia, syncope, postural dizziness, postural hypotension and vasculitis; Central and peripheral nervous system: decreased sensation, peripheral neuropathy, paresthesia, tremor, dizziness; Gastrointestinal: anorexia, constipation, dyspepsia, Dysphagia, diarrhea, flatulence, pancreatitis, vomiting, gingival hyperplasia; Musculoskeletal System: Arthralgia, arthritis, muscle cramps, myalgia; Psychiatric System: Sexual dysfunction, insomnia, tension, depression, nightmares, anxiety, depersonalization; Skin and Appendages: Angioedema, erythema, pruritus, rash, maculopapular rash; Special Senses: Visual disturbances, conjunctivitis, diplopia, eye pain, tinnitus; Urinary System: Frequent urination, dysuria, nocturia; Autonomic Nervous System: Dry mouth, night sweats; Metabolism and Nutrition: Hyperglycemia , thirst; Hematopoietic system: leukopenia, purpura, thrombocytopenia. The incidence of the following adverse events is less than 0.1%: heart failure, irregular pulse, extrasystoles, skin discoloration, urticaria, dry skin, dermatitis, alopecia, muscle weakness, twitching, ataxia, hypertonia, migraine, cold and clammy skin, apathy, agitation, amnesia, gastritis, increased appetite, loose stools, cough, rhinitis, dysuria, polyuria, parosmia, taste disturbance, visual accommodation disorder, dry eye syndrome. Other occasional reactions For example, in cases of myocardial infarction and angina pectoris, it is difficult to distinguish between drug effects and disease states. Routine laboratory tests showed no significant changes in serum potassium, blood glucose, triglycerides, total cholesterol, high-density lipoprotein (HDL), uric acid, blood urea nitrogen, or creatinine. Since the drug's launch, there have been occasional reports of gynecomastia in patients taking it, but the causal relationship with the drug is unclear. In some cases, jaundice and elevated liver enzymes (often accompanied by cholestasis and hepatitis) have been severe, requiring hospitalization.

[Contraindications]
This product is contraindicated in patients with hypersensitivity to dihydropyridines or any of its ingredients.

[Drug Interactions]
This product is safe for co-administration with the following medications: 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 agents. In vitro data using human plasma indicate that this product does not affect the plasma protein binding of digoxin, phenytoin, warfarin, or indomethacin. Effects of Other Drugs on Amlodipine: Cimetidine: Co-administration with cimetidine did not alter the pharmacokinetics of amlodipine. Grapefruit Juice: Concomitant administration of 240 ml of grapefruit juice and 10 mg of amlodipine to 20 healthy volunteers did not significantly affect the pharmacokinetics of amlodipine. Aluminum/Magnesium (Antacids): Concomitant administration of aluminum/magnesium antacids with a single dose of amlodipine did not significantly affect the pharmacokinetics of amlodipine. Sildenafil (Viagra): A single 100 mg dose of sildenafil did not affect the pharmacokinetics of amlodipine in patients with essential hypertension. When used together, each drug exerts its antihypertensive effect independently. Effects of Amlodipine on Other Drugs: Atorvastatin: Multiple doses of 10 mg amlodipine combined with 80 mg atorvastatin did not significantly alter the steady-state pharmacokinetic parameters of atorvastatin. Digoxin: Coadministration of amlodipine and digoxin did not alter plasma digoxin concentrations or renal clearance in normal volunteers. Ethanol: Single or multiple doses of 10 mg amlodipine had no effect on the pharmacokinetics of ethanol. Warfarin: Coadministration of amlodipine with warfarin did not alter the prothrombin reaction time of warfarin. Cyclosporin: Pharmacokinetic studies have shown that amlodipine does not significantly alter the pharmacokinetics of cyclosporin. Drug/Laboratory Test Interactions: Unknown.

[Precautions]
1. Warning: A very small number of patients, particularly those with severe coronary artery obstructive disease, may experience increased frequency, prolonged duration, and/or worsening of angina pectoris, or acute myocardial infarction, when initiating calcium channel blocker therapy or increasing the dose. The mechanism of action is currently unknown. 2. Because the vasodilatory effect of this drug is gradual, rare cases of acute hypotension have been reported following administration of this drug. However, caution should be exercised when using this drug in combination with other peripheral vasodilators in patients with severe aortic stenosis. 3. Use in Patients with Heart Failure: Calcium channel blockers should be used with caution in patients with congestive heart failure. In a long-term, placebo-controlled study (PRAISE-2) in patients with non-ischemic heart failure (NYHA class I-IV), although the incidence of heart failure exacerbations was not significantly different from placebo, there was an increase in reports of pulmonary edema associated with amlodipine. 4. Use in Patients with Impaired Hepatic Function: As with all other calcium channel blockers, the half-life of this drug is prolonged in patients with impaired hepatic function, but a recommended dose has not yet been established. Therefore, caution should be exercised in this setting. 5. Use in Patients with Renal Failure: Changes in amlodipine plasma concentrations are not correlated with the degree of renal impairment; therefore, a normal dose can be used. This drug cannot be dialyzed.

[Pediatric Use]
This study has not been conducted and no reliable references are available.

[Elderly Use]
Clinical studies have not demonstrated that elderly patients respond differently to this drug than younger patients. However, given that elderly patients often have impaired liver, kidney, and heart function, as well as concurrent medical conditions and medications, the lower end of the initial dose range is generally used. Elderly patients have decreased clearance of this drug, with the average active over (AUO) curve (AUO) increasing by approximately 40%-60%, necessitating a lower initial dose.

[Overdose]
Drug overdose can cause excessive peripheral vasodilation, leading to hypotension and possibly reflex tachycardia. Blood pressure monitoring, along with cardiac and respiratory monitoring, is essential after an overdose. If hypotension develops, supportive care should be implemented, including limb elevation and volume expansion as needed. If these measures are ineffective, pressors (such as phenylephrine) may be considered, provided circulating blood volume and urine output permit. Intravenous calcium gluconate may help reverse the calcium antagonist effect. Because this drug is highly bound to plasma proteins, dialysis is ineffective.

[Pharmacology and Toxicology]
Pharmacological Action: 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 product is a peripheral arterial dilator that acts directly on vascular smooth muscle, reducing peripheral vascular resistance and thereby lowering blood pressure. At therapeutic doses, negative inotropic effects were observed in vitro but not in whole-animal studies. This product does not affect plasma calcium concentrations. Its antihypertensive effects have been confirmed in 15 randomized, double-blind, placebo-controlled clinical trials. Once daily, it can lower supine and standing blood pressure in patients with mild to moderate hypertension 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-related, and the magnitude of the reduction is related to pretreatment blood pressure. The efficacy is greater in patients with moderate hypertension (diastolic blood pressure 105-114 mmHg) than in those with mild hypertension (diastolic blood pressure 90-104 mmHg). No significant effect is observed in normotensive subjects. This product's diastolic blood pressure-lowering effect is similar in older and younger patients, while the systolic blood pressure-lowering effect is greater in older patients. The precise mechanism by which this drug relieves angina is unclear, but it may treat exertional angina by reducing peripheral resistance (afterload) during exercise, reducing cardiac work and the heart rate-blood pressure product, thereby decreasing myocardial oxygen demand. It also treats spontaneous angina by inhibiting calcium, epinephrine, 5-hydroxytryptamine, 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 this drug prolonged the time to a 1mm ST-segment depression and reduced the frequency of angina attacks. This effect is sustained and does 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). Resting and exercise hemodynamics in patients with normal cardiac function were assessed after taking this drug, which showed an increase in ejection fraction but no significant effect on dP/dt or left ventricular end-diastolic pressure/volume. At therapeutic doses, amlodipine does not cause negative inotropic effects when used alone or in combination with beta-blockers. In a placebo-controlled study, 697 patients with class I/I (INYHA) heart failure showed no worsening of heart failure after 8-12 weeks of treatment, including exercise tolerance testing, NYHA class, symptoms, and left ventricular ejection fraction. (In another placebo-controlled, long-term survival trial, 1,153 patients with class I/V heart failure were randomized to receive amlodipine or placebo in addition to standard care. The results showed that all-cause mortality and cardiac morbidity were 39% in the amlodipine group and 42% in the placebo group.) Amlodipine does not affect sinus node function or atrioventricular conduction. No electrocardiographic abnormalities were observed when amlodipine was used in combination with beta-blockers in patients with hypertension or angina. Amlodipine does not alter the electrocardiogram in patients with angina and does not worsen atrioventricular block. In hypertensive patients with normal renal function, amlodipine administration reduced renal vascular resistance, increased glomerular filtration rate (GFR) and renal blood flow, but did not affect filtration fraction or urinary protein. Toxicological effects: Carcinogenicity, mutagenicity, and teratogenicity: Amlodipine was administered to rats and mice daily at doses of 0.5, 1.25, and 2.5 mg/kg for two years without confirmed carcinogenicity. 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 gene or chromosomal level. 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 starting 14 days before mating did not affect reproductive capacity. Amlodipine administration of 10 mg/kg daily (8 and 23 times the maximum recommended human dose) to pregnant rats and rabbits during the period of major organogenesis did not reveal teratogenicity or other embryotoxic effects. However, administration of 10 mg/g amlodipine to rats, starting 14 days before mating and continuing throughout the mating and gestation period, 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 amlodipine up to 40 mg/kg and 100 mg/kg, respectively, can cause lethality in mice and rats. Single doses of 4 mg/kg or higher in dogs cause significant peripheral vasodilation and hypotension.