PFIZER NORVASC Amlodipine Besylate Tablets For Hypertension 10mg*10

[Drug Name]
Generic Name: Amlodipine Besylate Tablets
Trade Name: Norvasc
English Name: Amlodipine Besylate Tablets
Chinese Pinyin: BENHUANGSUAN ANLUDIPING

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

[Appearance]
This product is a white tablet.

[Indications]
This product is indicated for the treatment of hypertension; symptomatic treatment of chronic stable angina pectoris; and treatment of confirmed or suspected vasospastic angina pectoris. It can be used alone or in combination with other antihypertensive or antianginal drugs.

[Dosage and Administration]
Adults
1. The usual starting dose for the treatment of hypertension is 5 mg once daily, with a maximum dose of 10 mg once daily.
2. For patients of small stature, frailty, the elderly, or those with hepatic insufficiency, the starting dose is 2.5 mg once daily.
3. This dose may also be used in combination with other antihypertensive drugs.
4. Dose adjustments should be made based on individual patient response. Generally, dose adjustments should be initiated after 7-14 days. If clinically necessary, dose adjustments can be made more quickly under close patient monitoring.
5. 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 (see [Adverse Reactions]).
6. The recommended dose for the treatment of coronary artery disease is 5-10 mg once daily. In clinical studies, most patients required a dose of 10 mg/day.

[Adverse Reactions]
The most common adverse events in clinical trials were headache and edema. In controlled clinical studies, open-label studies, or post-marketing use, the following events occurred in 1% but not 0.1% of patients. Their relevance is uncertain and is listed here to alert physicians: 1. Cardiovascular: arrhythmias (including ventricular tachycardia and atrial fibrillation), bradycardia, chest pain, hypotension, peripheral ischemia, syncope, tachycardia, postural dizziness, postural hypotension, vasculitis. 2. Central and Peripheral Nervous System: hypoesthesia, peripheral neuropathy, paresthesia, tremor, vertigo. 3. Gastrointestinal: decreased appetite, constipation, dyspepsia, dysphagia, diarrhea, flatulence, pancreatitis, vomiting, gingival hyperplasia. 4. Systemic: allergic reaction, fatigue, back pain, hot flashes, malaise, pain, stiffness, weight gain, weight loss. 5. Musculoskeletal: arthralgia, arthritis, muscle cramps, myalgia. 6. Psychiatric: Sexual dysfunction (males and females), insomnia, nervousness, depression, abnormal dreams, anxiety, personality disorders. 7. Respiratory: Dyspnea, epistaxis. 8. Skin and Appendages: Angioedema, erythema multiforme, pruritus, rash, erythematous rash, maculopapular rash. 9. Special Senses: Visual disturbances, conjunctivitis, diplopia, eye pain, tinnitus. 10. Urinary: Frequent urination, abnormal urination, nocturia. 11. Autonomic Nervous System: Dry mouth, hyperhidrosis. 12. Nutritional Metabolism: Hyperglycemia, thirst. 13. Hematopoietic System: Leukopenia, purpura, thrombocytopenia. In placebo-controlled studies, the incidence of these events was less than 1%, but in all multiple-dose studies, the incidence of these side effects was between 1% and 2%. 1. The following events occurred in 0.1% of patients: heart failure, arrhythmia, premature beats, skin discoloration, urticaria, dry skin, alopecia, dermatitis, muscle weakness, muscle contractions, ataxia, increased muscle tone, migraine, clammy skin, apathy, agitation, amnesia, gastritis, increased appetite, loose stools, cough, rhinitis, dysuria, polyuria, olfactory disturbances, dysgeusia, visual accommodation disturbances, and dry eyes. 2. Other occasional adverse reactions were difficult to distinguish from the effects of concomitant medications or concomitant conditions, such as myocardial infarction or angina. 3. No clinically significant changes were observed in routine laboratory test results during amlodipine treatment. There were no clinically relevant changes in serum potassium, blood glucose, triglycerides, total cholesterol, high-density lipoprotein cholesterol, uric acid, urea nitrogen, or creatinine. 4. Adverse reactions in the CAMELOT and PREVENT studies were similar to those reported previously (see above). 5. Peripheral edema was the most common adverse event. Postmarketing Reports 1. Because these reactions were reported voluntarily from a population of unknown sample size, it is not possible to reliably assess their frequency or establish a causal relationship to drug exposure. 2. The following events have been reported rarely in postmarketing use, and their relationship to the drug has not been established: male breast enlargement. In postmarketing use, there have been reports of jaundice and marked elevations in transaminases (often consistent with biliary obstruction or hepatitis) requiring hospitalization in patients receiving amlodipine. 3. Norvasc is safe for use in the following patients: chronic obstructive pulmonary disease, well-compensated congestive heart failure, coronary artery disease, peripheral vascular disease, diabetes mellitus, and dyslipidemia.

[Contraindications]
This product should not be used in patients with hypersensitivity to any of the ingredients in this product.

[Precautions]
1. Hypotension: Symptomatic hypotension may occur, particularly in patients with severe aortic stenosis. Because the vasodilatory effect of this product is gradual, acute hypotension has rarely been reported following administration. 2. Worsening of angina or myocardial infarction: A very small number of patients, especially those with severe coronary artery disease, may experience worsening of angina or acute myocardial infarction when starting treatment with Norvasc or increasing the dose. 3. Discontinuation of beta-blockers: Abrupt discontinuation of beta-blockers can be dangerous. Since amlodipine is not a beta-blocker, it does not provide effective protection against the risks associated with beta-blocker discontinuation. All beta-blockers should be discontinued gradually. 4. Use in Patients with Impaired Hepatic Function: Because Norvasc is extensively metabolized by the liver and has a plasma elimination half-life (t½) of 56 hours in patients with hepatic impairment, Norvasc should be titrated slowly in patients with severe hepatic impairment.

[Use in Special Populations]
Precautions for Children:
1. The recommended dose of Norvasc for hypertensive children aged 6 to 17 years is 2.5 mg to 5 mg once daily. No studies have been conducted in pediatric patients using doses exceeding 5 mg daily. 2. There are no data on the effects of this product on blood pressure in children under 6 years of age.
Pregnancy and Lactation Precautions:
Pregnancy Category C 1. Adequate and well-controlled studies have not been conducted in pregnant women. Amlodipine should be used during pregnancy only if the potential benefit outweighs the potential risk to the fetus. 2. No teratogenicity or other embryo/fetal toxicity was observed in pregnant rats and rabbits when they were orally administered amlodipine maleate at doses up to 10 mg amlodipine/kg/day (8 times and 23 times the maximum recommended human dose of 10 mg, calculated on a mg/m² basis, based on a 50 kg patient weight, respectively) during the period of major organogenesis. However, a significant decrease in litter size (approximately 50%) and a significant increase in intrauterine mortality (approximately 5-fold) were observed in rats treated with amlodipine maleate (equivalent to 10 mg amlodipine/kg/day) for 14 days prior to mating, throughout mating, and during pregnancy. Studies have demonstrated that amlodipine maleate at this dose can prolong gestation and parturition in rats. 3. It is unknown whether this drug is excreted in breast milk. Breastfeeding women taking this drug should discontinue breastfeeding.
Precautions for Elderly Patients:
1. Currently, there are no adequate clinical studies to determine whether elderly patients (over 65 years of age) respond differently to this drug than younger patients. Other clinical studies have not found differences in responses between elderly and younger patients. 2. Generally, given that elderly patients often have decreased liver, kidney, or heart function, and are more likely to have concurrent diseases or take other medications, dose selection for elderly patients should be cautious, and a lower dose within the recommended starting dose range is generally recommended. Elderly patients have decreased clearance of this drug, resulting in an approximately 40-60% increase in the area under the curve (AUC). Therefore, a lower starting dose is recommended (see [Dosage and Administration]).

[Drug Interactions]
1. In vitro data: In vitro data indicate that Norvasc does not affect the plasma protein binding of digoxin, phenytoin, warfarin, or indomethacin. 2. Coadministration of cimetidine with cimetidine does not alter the pharmacokinetics of amlodipine. 3. Grapefruit juice: Coadministration of Norvasc with grapefruit or grapefruit juice is not recommended because it may increase bioavailability and enhance the antihypertensive effect in certain patients. 4. Magnesium-aluminum hydroxide antacids: Concomitant administration of magnesium-aluminum hydroxide antacids and a single dose of Norvasc has not been shown to significantly affect the pharmacokinetics of amlodipine. 5. A single 100mg dose of sildenafil did not affect the pharmacokinetics of amlodipine in patients with essential hypertension. Each drug exerts its own antihypertensive effect when used together. 6. Multiple doses of atorvastatin 10mg: Coadministration of atorvastatin 80mg did not significantly alter the steady-state pharmacokinetic parameters of atorvastatin. 7. Concomitant administration of Norvasc and digoxin did not alter plasma digoxin levels or renal clearance in normal volunteers. 8. Single or multiple doses of 10 mg of ethanol (alcohol) had no significant effect on the pharmacokinetics of ethanol. 9. Concomitant administration of 10 mg ... Caution should be exercised when coadministering amlodipine with CYP3A4 inducers. 12. Interactions with other drugs and laboratory tests are unknown.

[Pharmacology]
Clinical Pharmacology: Mechanism of Action: 1. Amlodipine is a dihydropyridine calcium antagonist (also known as a calcium ion antagonist or slow-channel blocker) that inhibits the transmembrane entry of calcium ions into vascular smooth muscle and myocardium. Experimental data indicate that amlodipine binds to both dihydropyridine and non-dihydropyridine binding sites. 2. The contraction of myocardial and vascular smooth muscle depends on the entry of extracellular calcium ions into the cell through ion channels. Amlodipine selectively inhibits transmembrane calcium transport, with a stronger effect on vascular smooth muscle cells than on myocardial cells. Negative inotropic effects have been observed in vitro, but these effects have not been observed in live animals at therapeutic doses. Amlodipine does not affect serum calcium concentrations. Within the physiological pH range, amlodipine is an ionized complex (pKa = 8.6) that achieves its gradual onset of action by slowly binding and dissociating from the binding site of calcium channel receptors. 3. Amlodipine is a peripheral arterial vasodilator that acts directly on vascular smooth muscle, thereby reducing peripheral vascular resistance and blood pressure. 4. The specific mechanism by which amlodipine relieves angina pectoris has not been fully determined, but is believed to be related to the following factors: 5. Exertional angina: Norvasc reduces peripheral vascular resistance (cardiac afterload), thereby lowering the heart rate-systolic blood pressure product and reducing myocardial oxygen demand at different levels of exercise. 6. Vasospastic angina: Norvasc has been demonstrated in animal studies and in vitro human coronary studies to inhibit vasospasm and restore blood flow in the coronary arteries and arterioles, thereby adapting to changes in calcium, epinephrine potassium, serotonin, and thromboxane A2 isomers. In vasospastic (Prinzmetal's or variant) angina, the effect of Norvasc is primarily due to its inhibition of coronary artery spasm. Pharmacodynamics Hemodynamics: 1. In hypertensive patients, Norvasc at therapeutic doses causes vasodilation, resulting in a decrease in supine and standing blood pressure. 2. With chronic administration, the decrease in blood pressure is not accompanied by a significant change in heart rate or plasma catecholamine concentrations. In hemodynamic studies of patients with chronic stable angina, rapid intravenous administration of Norvasc lowered arterial blood pressure and increased heart rate, but in clinical studies of normotensive patients with angina, long-term oral administration of amlodipine had no significant effect on heart rate or blood pressure. 3. Long-term oral administration of Norvasc once daily maintains blood pressure control for at least 24 hours. The antihypertensive effect in both young and elderly patients is related to plasma concentrations. The degree of blood pressure reduction with amlodipine is also related to the degree of blood pressure elevation before treatment. 4. Thus, the blood pressure-lowering effect is 50% greater in patients with moderate hypertension (diastolic blood pressure 105-114 mmHg) than in patients with mild hypertension (diastolic blood pressure 90-104 mmHg). Normotensive subjects experience no clinically significant changes in blood pressure (+1/-2 mmHg). 5. In hypertensive patients with normal renal function, therapeutic doses of Norvasc result in decreased renal vascular resistance, increased glomerular filtration rate, and increased effective renal blood flow, without affecting filtration fraction or proteinuria. 6. As with other calcium channel blockers, in patients with normal cardiac function, hemodynamic assessments of cardiac function after treatment with Norvasc show a small increase in cardiac index at rest and during exercise (or stepping), without changes in dP/dt or left ventricular end-diastolic pressure or volume. In hemodynamic studies, Norvasc has not demonstrated negative inotropic effects in animals or humans at therapeutic doses, even when used in combination with beta-blockers. Similar findings have been observed in healthy individuals and patients with well-compensated heart failure using other drugs with significant negative inotropic effects. Electrophysiological Effects: 7. In vivo animal studies and clinical trials, Norvasc did not affect sinus node or atrioventricular (AV) conduction function. In patients with chronic stable angina, intravenous administration of 10 mg did not significantly alter A-H and H-V conduction, nor did it significantly alter sinus node recovery time after pacing. 8. Similar results were observed in patients receiving beta-blockers in combination with Norvasc. In clinical studies of patients with hypertension or angina pectoris receiving amlodipine and beta-blockers, no adverse effects on electrocardiographic (ECG) parameters were observed. In patients with angina pectoris alone, amlodipine did not alter ECG conduction intervals or increase AV block. Carcinogenicity, Teratogenesis, and Reproductive Toxicity: 9. Amlodipine was administered to rats and mice at doses of 0.5, 1.25, and 2.5 mg/kg/day in the diet for 2 years without observed carcinogenic effects. The maximum dose used in mice is equivalent to the maximum recommended human dose of 310 mg (mg/m²). 10. The maximum dose used in rats is twice the maximum recommended human dose of 310 mg (mg/m²). 11. Teratogenicity studies with amlodipine revealed no drug-related teratogenic effects at either the genetic or chromosomal levels. 12. Amlodipine administered to rats (male rats starting 64 days before mating and female rats starting 14 days before mating) at doses up to 10 mg/kg/day (8 times the maximum recommended human dose3 (mg/m²)) did not affect fertility. 13. Calculations are based on a patient weight of 50 kg.

[Storage]
Store in a dark, airtight container.

[Strength]
10 mg

[Packaging]
10 mg x 10 tablets

[Expiry Date]
24 months.

[Approval Number]
National Medicine Standard H20093660

[Manufacturer]
Company Name: Huizhi Pharmaceutical (Dalian) Co., Ltd.