Amlodipine Besylate Tablets

Clinical pharmacology Mechanism of action: 1. Amlodipine is a dihydropyridine calcium antagonist (also known as calcium ion antagonist or slow channel blocker), which can inhibit calcium ions from entering vascular smooth muscle and myocardium across the membrane. Experimental data show that amlodipine can bind to both dihydropyridine and non-dihydropyridine binding sites. 2. The contraction process of myocardial and vascular smooth muscle depends on the entry of extracellular calcium ions into the cell through ion channels. Amlodipine can selectively inhibit calcium ion transmembrane transport, and its effect on vascular smooth muscle cells is stronger than that on myocardial cells. In vitro experiments have shown that the drug has a negative inotropic effect, but this effect has not been observed in live animal experiments at clinical therapeutic doses. Amlodipine does not affect serum calcium concentration. Within the physiological pH range, amlodipine is an ionized complex (pKa=8.6) that achieves its gradual onset of action by slowly binding/decomposing with calcium channel receptors at the binding site. 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 can relieve angina pectoris has not been fully determined, but it is considered to be related to the following factors: 5. Exertional angina pectoris: Norvasc reduces the heart rate-systolic blood pressure product by reducing peripheral vascular resistance (cardiac afterload), thereby reducing myocardial oxygen demand at different levels of exercise. 6. Vasospastic angina pectoris: Norvasc has been proven in animal experiments and in vitro human coronary vascular experiments to inhibit vasospasm, restore blood perfusion in coronary arteries and arterioles, and thus adapt to changes in calcium, adrenaline potassium, serotonin and thromboxane A2 isomers. In vasospastic (Prinzmetal's or variant) angina pectoris, the effect of Norvasc mainly comes from its inhibition of coronary artery spasm. Pharmacodynamic hemodynamics: 1. After taking a therapeutic dose of Norvasc in hypertensive patients, vasodilation can be caused, resulting in a decrease in supine and standing blood pressure. 2. With long-term administration, the reduction in blood pressure is not accompanied by significant changes in heart rate or plasma catecholamine concentrations. In a hemodynamic study of patients with chronic stable angina, it was found that rapid intravenous administration of Norvasc can reduce arterial blood pressure and increase heart rate, but in a clinical study of patients with angina pectoris with normal blood pressure, long-term oral administration of amlodipine had no significant effect on heart rate or blood pressure. 3. Long-term oral administration of Norvasc once a day can maintain the blood pressure control effect for at least 24 hours. The antihypertensive effect of young and elderly patients is related to plasma concentration. The degree of blood pressure reduction with amlodipine is also related to the degree of blood pressure increase before treatment. 4. Therefore, the antihypertensive effect in patients with moderate hypertension (diastolic blood pressure 105-114 mmHg) is 50% stronger than that in patients with mild hypertension (diastolic blood pressure 90-104 mmHg). There was no clinically significant change in blood pressure in normotensive subjects (1/-2 mmHg). 5. In hypertensive patients with normal renal function, the therapeutic dose of Norvasc can lead to a decrease in renal vascular resistance, an increase in glomerular filtration rate, and an increase in effective renal blood flow, without affecting the filtration fraction and proteinuria. 6. As with other calcium channel antagonists, hemodynamic testing of cardiac function in patients with normal cardiac function after treatment with Norvasc showed 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 within the therapeutic dose range in animals or humans, even in combination with beta-blockers in humans, did not show negative inotropic effects. Similar findings were found in normal healthy people and patients with well-compensated heart failure using other drugs with significant negative inotropic effects. Electrophysiological effects: 7. In vivo animal experiments and clinical trials, Norvasc did not affect the sinus node or atrioventricular conduction function. In patients with chronic stable angina pectoris, intravenous administration of 10 mg did not significantly change A-H, H-V conduction and sinus node recovery time after pacing. 8. Similar results were observed in patients taking beta-blockers in combination with Norvasc. In clinical studies of the combined use of amlodipine and beta-blockers in patients with hypertension or angina pectoris, no adverse effects on ECG parameters were observed. In patients with angina pectoris only, the use of amlodipine did not change the conduction interval of the ECG, nor did it increase AV conduction block. Carcinogenicity, teratogenicity, reproductive toxicity: 9. Rats and mice were given amlodipine 0.5, 1.25 and 2.5 mg/kg/day by food for 2 years, and no carcinogenic effects were observed. The maximum dose used in mice is equivalent to the maximum recommended human dose of 310 mg converted to mg/m2. 10. The maximum dose used in rats is twice the maximum recommended human dose of 310 mg converted to mg/m2. 11. Teratogenicity studies of amlodipine showed no drug-related teratogenic effects at either the genetic or chromosomal level. 12. Rats (64 days before mating for male rats and 14 days before mating for female rats) were given amlodipine at a dose of 10 mg/kg/day (8 times the maximum recommended human dose3 in mg/m2) with no effect on fertility. 13. Calculated based on a patient weight of 50 kg.

The main ingredient of this product is amlodipine besylate

This product is white tablets.

1. Hypertension This product is suitable for the treatment of hypertension. It can be used alone or in combination with other antihypertensive drugs. 2. Coronary artery disease (CAD) 2.1 Chronic stable angina 2.2 This product is suitable for the symptomatic treatment of chronic stable angina. It can be used alone or in combination with other anti-anginal drugs. 2.3 Vasospastic angina (Prinzmetal's or variant angina) 2.4 This product is suitable for the treatment of confirmed or suspected vasospastic angina. It can be used alone or in combination with other anti-anginal drugs. 2.5 Coronary heart disease confirmed by angiography 2.6 For patients with coronary heart disease confirmed by angiography but with an ejection fraction of 40% and no heart failure, this product can reduce the risk of hospitalization due to angina and reduce coronary artery recurrence.

Adults 1. Usually the starting dose of this product for the treatment of hypertension is 5 mg, once a day, and the maximum dose is 10 mg, once a day. 2. For patients with small stature, weakness, elderly, or liver dysfunction, the starting dose is 2.5 mg, once a day. 3. This dose can also be the dose of this product combined with other antihypertensive drugs. 4. Dose adjustment should be made according to the individual response of the patient. Generally, dose adjustment should be started after 7 to 14 days. If clinically necessary, the dose can also be adjusted quickly under close monitoring of the patient. 5. The recommended dose for the treatment of chronic stable or vasospastic angina is 5 to 10 mg, once a day. A lower dose is recommended for the elderly and patients with liver dysfunction. The effective dose for most patients is 10 mg, once a day (see [Adverse Reactions]). 6. The recommended dose for the treatment of coronary heart disease is 5 to 10 mg, once a day. In clinical studies, most patients require a dose of 10 mg/day.

The most common adverse events in clinical trials are headache and edema. In controlled clinical studies, open studies or post-marketing applications, the incidence of the following events in patients is 1% but 0.1%, and its relevance is uncertain. It is listed here to remind doctors to pay attention: 1. Cardiovascular system: arrhythmia (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, dizziness. 3. Gastrointestinal system: loss of appetite, constipation, dyspepsia1, dysphagia, diarrhea, flatulence, pancreatitis, vomiting, gingival hyperplasia. 4. Systemic: allergic reaction, fatigue1, back pain, hot flashes, general discomfort, pain, stiffness, weight gain, weight loss. 5. Musculoskeletal system: joint pain, arthritis, muscle cramps1, myalgia. 6. Psychiatric: sexual dysfunction (male1 and female), insomnia, nervousness, depression, abnormal dreams, anxiety, personality disorder. 7. Respiratory system: dyspnea1, epistaxis. 8. Skin and appendages: angioedema, erythema multiforme, pruritus1, rash1, erythematous rash, maculopapular rash. 9. Special senses: visual abnormalities, conjunctivitis, diplopia, eye pain, tinnitus. 10. Urinary system: frequent urination, abnormal urination, nocturia. 11. Autonomic nervous system: dry mouth, sweating. 12. Nutritional metabolism: hyperglycemia, thirst. 13. Hematopoietic system: leukopenia, purpura, thrombocytopenia. 1 In placebo-controlled studies, the incidence of these events was less than 1%, but in all multiple-dose studies, the incidence of these adverse reactions was between 1% and 2%. 1. The following events occurred at an incidence of 0.1%: heart failure, arrhythmia, premature beats, skin discoloration, urticaria, dry skin, alopecia, dermatitis, muscle weakness, muscle contraction, ataxia, increased muscle tension, migraine, cold and clammy skin, apathy, agitation, amnesia, gastritis, increased appetite, loose stools, cough, rhinitis, dysuria, polyuria, olfactory disturbances, taste disturbances, visual accommodation abnormalities, and dry eyes. 2. Other occasional adverse reactions are difficult to distinguish from the effects of concomitant medications or concomitant diseases, such as myocardial infarction or angina pectoris. 3. Routine laboratory test data did not change clinically significantly during amlodipine treatment. There were no clinically relevant changes in serum potassium, blood sugar, triglycerides, total cholesterol, high-density lipoprotein cholesterol, uric acid, urea nitrogen, or creatinine. 4. In the CAMELOT and PREVENT studies, the adverse reactions were similar to those reported previously (see above). 5. Peripheral edema was the most common adverse event. Post-Marketing Reports 1. Because these reactions are reported voluntarily from a population of unknown sample size, it is not possible to reliably assess the frequency of occurrence or determine a causal relationship to drug exposure. 2. The following events have been reported rarely in post-marketing applications, and their relevance to the drug has not been determined: male breast enlargement. In post-marketing applications, there have been reports of patients requiring hospitalization for jaundice and significantly elevated transaminases (mostly consistent with manifestations of biliary obstruction or hepatitis) due to the use of amlodipine. 3. Norvasc is safe to use in the following patients: chronic obstructive pulmonary disease, well-compensated congestive heart failure, coronary heart disease, peripheral vascular disease, diabetes, and dyslipidemia.

Patients who are allergic to any ingredient in this product are contraindicated.

Precautions for children: 1. The recommended dose of this product for children aged 6 to 17 years with hypertension is 2.5 mg to 5 mg, once a day. There are no studies on the daily use of this product in children with a dose of more than 5 mg. 2. There is no data on the effect of this product on blood pressure in children under 6 years old. Precautions for pregnancy and lactation: Pregnancy category C1. No adequate and well-controlled studies have been conducted in pregnant women. Amlodipine can only be used during pregnancy when the potential benefits outweigh the potential risks to the fetus. 2. When pregnant rats and rabbits were orally administered amlodipine maleate up to 10 mg amlodipine/kg/day (based on mg/m2 conversion, 8 times and 23 times the maximum recommended human dose of 10 mg [calculated based on a patient's weight of 50 kg]) during the formation of their respective major organs, no teratogenicity or other embryo/fetal toxicity was found. However, in rats treated with amlodipine maleate (dose equivalent to 10 mg amlodipine/kg/day) for 14 days before mating, throughout mating and during pregnancy, a significant decrease in litter size (approximately 50%) and a significant increase in the number of intrauterine deaths (approximately 5 times) were observed. Studies have shown that amlodipine maleate can prolong the pregnancy and delivery period of rats at this dose. 3. It is not yet known whether this product can be secreted through breast milk. Lactating women taking the drug should stop breastfeeding. Precautions for the elderly: 1. There are currently no sufficient clinical studies to determine whether elderly patients (over 65 years old) and young patients respond differently to this product. No differences in responses between elderly and young patients have been found in other clinical applications. 2. In general, considering that in most cases the elderly have decreased liver, kidney or heart function and are more likely to have concurrent other diseases or take other drugs, the dose selection for elderly patients should be cautious, and it is usually appropriate to start with a low dose within the dose range. The clearance of this product is reduced in elderly patients, resulting in an increase in the area under the curve (AUC) by approximately 40% to 60%. Therefore, it is advisable to start with a small dose (see [Dosage and Administration]).

1. In vitro data In vitro research data show that: Norvasc does not affect the binding of digoxin, phenytoin, warfarin or indomethacin to plasma proteins. 2. The combination of cimetidine and cimetidine does not change the pharmacokinetics of amlodipine. 3. Grapefruit juice It is not recommended to take Norvasc with grapefruit or grapefruit juice because it may increase bioavailability in certain patients, thereby enhancing the antihypertensive effect. 4. Magnesium aluminum hydroxide antacids Taking magnesium aluminum hydroxide antacids and a single dose of Norvasc at the same time did not have a significant effect on the pharmacokinetics of amlodipine. 5. Sildenafil single dose 100mg Sildenafil does not affect the pharmacokinetics of amlodipine in patients with essential hypertension. When the two drugs are used together, each drug can independently exert its antihypertensive effect. 6. Atorvastatin 10mg Multiple doses of this product combined with 80mg atorvastatin did not significantly change the steady-state pharmacokinetic parameters of atorvastatin. 7. Digoxin Co-administration of Norvasc and digoxin does not change the plasma digoxin level or renal digoxin clearance rate of normal volunteers. 8. Ethanol (alcohol) Single or multiple administrations of 10 mg of this product have no significant effect on the pharmacokinetics of ethanol. 9. Warfarin Co-administration of this product with warfarin does not change the prothrombin reaction time of warfarin. 10. CYP3A4 inhibitors When this product is taken with erythromycin in young patients and with diltiazem in elderly patients, the plasma concentration of amlodipine increases by 22% and 50%, respectively. Strong CYP3A4 inhibitors (such as ketoconazole, itraconazole, ritonavir) may increase the plasma concentration of amlodipine more than diltiazem. Amlodipine should be taken with caution when CYP3A4 inhibitors are taken together, but no adverse events caused by this drug-related interaction have been reported. 11. CYP3A4 inducers There is currently no data on the effect of CYP3A4 inducers on amlodipine. Caution should be exercised when taking amlodipine with CYP3A4 inducers. 12. The interaction with drugs/laboratory tests is unclear.

Keep in a light-proof and airtight container.

5 mg

5 mg: 60 months; 10 mg: 24 months.

Viatris Pharmaceuticals (DALIAN) Co., Ltd.

• Founded in:

  1989-10-07

• Address:

  No. 22 Daqing Road, Dalian Economic and Technological Development Zone, Liaoning Province

• Tax NO.:

  912102006048147187

• Registered Funds:

  $80.4 million

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