DAWNRAYS ANNEIZHEN Amlodipine Besylate Tablets For Hypertension 10mg*7

[Drug Name]
Generic Name: Amlodipine Besylate Tablets
Trade Name: An Nei Zhen Amlodipine Besylate Tablets 10mg*7 Tablets
Pinyin Code: AnNeiZhen BenHuangSuanAnLvDiPingPian 10mg*7 Tablets

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

[Properties]
This product is white or off-white tablets.

[Indications/Main Functions]
1. Treatment of hypertension. Can be used alone or in combination with other antihypertensive drugs. 2. Chronic stable angina and variant angina. Can be used alone or in combination with other antianginal drugs.

[Precautions]
1. Angina pectoris and/or myocardial infarction. Rare. Patients with severe obstructive coronary artery disease may experience an increase in the frequency, duration, and/or severity of angina attacks, or the development of acute myocardial infarction, when starting or increasing the dose of calcium channel antagonists. The mechanism is unknown. 2. Hypotension. Because this drug gradually develops 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 valve 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 initial dose can remain unchanged in patients with renal failure. 6. Discontinuation of beta-blockers. This drug does not protect against rebound symptoms associated with abrupt discontinuation of beta-blockers. Therefore, a gradual reduction in the beta-blocker dose is necessary. 7. This drug is safe for use in patients with obstructive pulmonary disease, well-compensated heart failure, peripheral vascular disease, diabetes mellitus, and lipid disorders.

[Drug Interactions]
This drug is contraindicated in patients with hypersensitivity to dihydropyridines or any of the ingredients in this drug.

[Pediatric Use]
Safety and efficacy in children have not been established.

[Use in Elderly Patients]
Clinical studies have not confirmed 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 experience decreased clearance of this drug, with the area under the curve (AUC) increasing by approximately 40% to 60%, necessitating a lower initial dose.

[Use in Pregnant and Lactating Women]
There is a lack of research data on its use in pregnant women. However, based on animal studies, this drug should only be used in pregnant women when absolutely necessary. It is unknown whether this drug is excreted in breast milk; lactating women taking this drug should discontinue breastfeeding.

[Specifications]
10mg*7 tablets

[Dosage and Administration]
1. For the treatment of hypertension: Initial dose is 5 mg once daily, maximum dose is 10 mg once daily. The initial dose for frail or elderly patients, or those with hepatic impairment, is 2.5 mg (amlodipine besylate tablets: half a tablet) once daily. This dose may also be the dose used in conjunction with other antihypertensive medications. The dose should be adjusted based on individual patient response, and dose adjustments should generally begin after 7-14 days. If clinically necessary, dose adjustments may be initiated sooner under close patient monitoring. 2. Treatment of angina pectoris: The initial dose is 5 mg-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]
1. This product is well tolerated within the dose range of 10 mg/day, and most adverse reactions are mild to moderate. The discontinuation rate of this product due to adverse reactions is only 1.5%, which is not significantly different from placebo (about 1%). The most common adverse reactions are headache and edema. 2. The dose-related adverse reactions with an incidence rate of >1% are as follows: edema, dizziness, flushing, and palpitations. The dose-related adverse reactions with an incidence rate of more than 1.0% are as follows: headache, fatigue, nausea, abdominal pain, and drowsiness. Among the above adverse reactions, edema, flushing, palpitations, and drowsiness are more common in women than in men. 3. The incidence of the following adverse events is ≤1% but >0.1%, and the causal relationship with the drug is unclear. (1) General: allergic reaction, weakness, back pain, hot flashes, discomfort, pain, stiffness, weight gain. (2) Cardiovascular: arrhythmias (including tachycardia, bradycardia, or atrial fibrillation), chest pain, hypotension, peripheral ischemia, syncope, postural dizziness, postural hypotension, and vasculitis. (3) Central and peripheral nervous systems: hypoesthesia, peripheral neuropathy, paresthesia, tremor, and vertigo. (4) Gastrointestinal: anorexia, constipation, dyspepsia, dysphagia, diarrhea, flatulence, pancreatitis, vomiting, and gingival hyperplasia. (5) Musculoskeletal system: arthralgia, arthritis, muscle cramps, and myalgia. (6) Psychiatric: sexual dysfunction, insomnia, tension, depression, nightmares, anxiety, and depersonalization. (7) Skin and appendages: angioedema, erythema, pruritus, rash, and maculopapular rash. (8) Special senses: visual disturbances, conjunctivitis, diplopia, eye pain, and tinnitus. (9) Urinary system: frequent urination, dysuria, and nocturia. (10) Autonomic nervous system: dry mouth, night sweats. (11) Metabolism and nutrition: hyperglycemia, thirst. (12) Hematopoietic system: leukopenia, purpura, thrombocytopenia. 4. The incidence of the following adverse events is ≤ 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 perversion, visual accommodation disorder, dry eye syndrome. 5. Other occasional reactions such as myocardial infarction and angina pectoris cannot be distinguished as drug effects or disease states. 6. Routine laboratory test items showed no significant changes, and no significant changes were found in serum potassium, blood glucose, triglycerides, total cholesterol, high-density lipoprotein (HDL), uric acid, blood urea nitrogen, or creatinine. Post-marketing, there have been occasional reports of gynecomastia in patients receiving this drug, but a causal relationship to 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 components.

[Overdose]
Severe overdose may cause excessive peripheral vasodilation with marked hypotension and reflex tachycardia. Limited data are available on intentional overdose with this product in humans. Single oral doses of amlodipine maleate equivalent to 40 mg amlodipine/kg and 100 mg amlodipine/kg, respectively, have resulted in death in mice and rats. A single oral dose of amlodipine maleate equivalent to 4 mg/kg (at least 11 times the maximum recommended human dose based on mg/m²) in dogs caused marked peripheral vasodilation and hypotension. If excessive doses are taken, active cardiopulmonary monitoring is essential. Frequent blood pressure measurements are essential. If hypotension occurs, cardiovascular support should be provided, including limb elevation and adequate fluid replacement. If hypotension persists despite these conservative measures, vasoconstrictors (e.g., phenylephrine) may be considered, and attention should be paid to circulating fluid and urine output. Because this drug is highly protein-bound, dialysis is not beneficial.

[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 between receptor sites, resulting in a gradual onset of pharmacological action. This drug is a peripheral arterial dilator, acting directly on vascular smooth muscle to reduce peripheral vascular resistance and thereby lower blood pressure. At therapeutic doses, negative inotropic effects have been observed in vitro but not in whole animal studies. This drug does not affect plasma calcium concentrations. Fifteen randomized, double-blind, placebo-controlled clinical trials have confirmed its antihypertensive activity. 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 catecholamine levels. 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), while those with normal blood pressure 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 stronger in the elderly. The precise mechanism by which this drug relieves angina is unclear, but it may treat exertional angina by reducing peripheral resistance (afterload) during exercise, thereby reducing cardiac work and the heart rate-blood pressure product, and reducing myocardial oxygen demand. It also treats spontaneous angina by inhibiting calcium ion, 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 have also shown that this drug prolongs the time to a 1mm ST-segment depression and reduces the frequency of angina attacks. This effect is sustained and does not significantly affect blood pressure and heart rate. In a clinical trial of 50 patients with spontaneous angina, this product reduced angina attacks by 4 per week (placebo reduced it by 1 per week). Patients with normal cardiac function who took this product had hemodynamics measured at rest and during exercise, and their 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 did not cause negative inotropic effects when used alone or in combination with beta-blockers. In a placebo-controlled study, 697 patients with heart failure of NYHA class II/III (NYHA) after 8 to 12 weeks of medication showed no signs of worsening heart failure in exercise tolerance tests, NYHA classification, 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 amlodipine or placebo in addition to conventional treatment. The results showed that 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 observed when this drug was used in combination with beta-blockers in patients with hypertension or angina pectoris. This drug did not alter the electrocardiogram in patients with angina pectoris or worsen atrioventricular block. In hypertensive patients with normal renal function, this drug reduced renal vascular resistance and increased glomerular filtration rate and renal blood flow, but did not increase filtration fraction or proteinuria. Toxicological effects include carcinogenicity, mutagenicity, and teratogenicity. Amlodipine was not demonstrated to be carcinogenic in rats and mice when administered daily for two years at doses of 0.5, 1.25, and 2.5 mg/kg. 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 in mg/m²). No drug-related mutagenicity was revealed at either the genetic 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 the mating period and gestation, resulted in a significant reduction in pup size (approximately 50%), a significant increase in intrauterine mortality (approximately 5-fold), and prolonged gestation and delivery. Single doses of amlodipine up to 40 mg/kg and 100 mg/kg, respectively, have been fatal in mice and rats. Single doses of 4 mg/kg or higher in dogs have resulted in significant peripheral vasodilation and hypotension.

[Pharmacokinetics]
Amlodipine is a calcium channel blocker (also known as a slow-channel blocker or calcium antagonist) that blocks the entry of extracellular calcium ions into myocardial and smooth muscle cells via calcium channels in the cell membrane. Its antihypertensive mechanism is direct relaxation of vascular smooth muscle. While the exact mechanism of angina relief is not fully determined, it may relieve angina by dilating peripheral arterioles and coronary arteries, reducing total peripheral vascular resistance, relieving coronary artery spasm, lowering cardiac afterload, and reducing energy expenditure and oxygen demand. Two-year studies in rats and mice using amlodipine administered by diet at doses of 0.5 mg/kg/day, 1.25 mg/kg/day, and 2.5 mg/kg/day found no evidence of carcinogenicity. Induction studies revealed no drug-related effects at the genetic or chromosomal levels. Amlodipine at a dose of 10 mg/kg/day (8 times the maximum recommended human dose of 10 mg, calculated on a mg/m² basis) had no effect on reproductive capacity in rats.