Product Overview
[Drug Name]
Generic Name: Amlodipine Besylate Tablets
Trade Name: Norvasc Amlodipine Besylate Tablets 5mg*7 Tablets
Pinyin Full Code: LuoHuoXi BenHuangSuanAnLvDiPingPian 5mg*7 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. 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 antianginal drugs.
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 antianginal drugs. In patients with angiographically confirmed coronary artery disease (CAD), an ejection fraction ≥40%, and no heart failure, this medication can reduce the risk of hospitalization for angina and the need for coronary revascularization.
[Precautions]
1. Hypotension: Symptomatic hypotension may occur, particularly in patients with severe aortic stenosis. Because the vasodilatory effect of this medication is gradual, rare cases of acute hypotension have been reported after taking this medication. 2. Worsening of angina or myocardial infarction: In rare cases, especially those with severe obstructive coronary artery disease, amlodipine besylate may worsen angina or cause acute myocardial infarction when initiating or increasing the dose of amlodipine besylate. 3. Beta-blocker discontinuation: 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 this drug is extensively metabolized by the liver and has a plasma elimination half-life (t½) of 56 hours in patients with hepatic impairment, this drug should be administered slowly in increasing doses in patients with severe hepatic impairment. (See package insert for details.) Please read the package insert carefully and use as directed by your doctor.
[Drug Interactions]
This drug is contraindicated in patients with a hypersensitivity to amlodipine.
[Pediatric Use]
The recommended dose of this drug for hypertensive children aged 6 to 17 years is 2.5 mg to 5 mg once daily. There are no studies on daily doses of this drug exceeding 5 mg in pediatric patients. There are no data on the effects of this drug on blood pressure in children under 6 years of age.
[Elderly Use]
There are currently 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 demonstrated differences in responses between elderly and younger patients. In general, given that elderly patients are often more likely to have impaired liver, kidney, or heart function, as well as concurrent medical conditions or concomitant medications, dose selection for elderly patients requires caution, and it is generally advisable to start with a lower dose within the dosage range. Elderly patients have decreased clearance of this drug, resulting in an approximately 40-60% increase in the area under the curve (AUC), so a lower starting dose is recommended.
[Use During Pregnancy and Lactation]
Pregnancy Category C (FDA classification): 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. No teratogenicity or other embryo/fetal toxicity was observed in pregnant rats and rabbits receiving oral doses of amlodipine maleate up to 10 mg/kg/day (8 times and 23 times the maximum recommended human dose of 10 mg, respectively, based on a mg/m² conversion [based on a patient weight of 50 kg]) during their respective periods of major organogenesis. However, in rats treated with amlodipine maleate (equivalent to 10 mg amlodipine/kg/day) for 14 days prior to mating, throughout mating, and during conception, a significant decrease in litter size (approximately 50%) and a significant increase in intrauterine mortality (approximately 5-fold) were observed. Studies have shown that amlodipine maleate at this dose can prolong gestation and parturition in rats. It is unknown whether this drug is excreted in breast milk; lactating women taking this drug should discontinue breastfeeding.
[Specifications]
5mg x 7 tablets (Norvasc)
[Dosage and Administration]
Adults: The typical starting dose for hypertension is 5 mg once daily, with a maximum dose of 10 mg once daily. For small, frail, elderly patients, or those with hepatic impairment, the starting dose is 2.5 mg once daily; this dose can also be used in combination with other antihypertensive medications. Dose adjustments should be made based on individual patient response. Dosage adjustments should generally be initiated after 7-14 days. If clinically necessary, dose adjustments can 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, with 10 mg once daily being the effective dose for most patients. 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]
Adverse Events in Clinical Trials
Due to the wide variability in clinical trial conditions, adverse reaction rates observed in clinical trials of one drug cannot be directly compared with those of another drug and may not reflect the rates observed in clinical practice.
The safety of this drug has been demonstrated in clinical studies in the United States and other countries, involving over 11,000 patients. Overall, this drug was well tolerated by patients at doses up to 10 mg daily. Adverse reactions reported during treatment with this drug were mostly mild or moderate. In clinical studies of 10 mg of amlodipine (N=1730) directly compared with placebo (N=1250), only 1.5% of patients in the amlodipine group discontinued due to adverse reactions, which was not significantly different from the placebo group (approximately 1%).
[Contraindications]
This product is contraindicated in patients with a hypersensitivity to amlodipine.
[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 been fatal in mice and rats. In dogs, 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) caused marked peripheral vasodilation and hypotension. If excessive doses are taken, active cardiopulmonary monitoring should be performed. 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. Due to its high plasma protein binding, dialysis is not beneficial.
[Pharmacology and Toxicology]
1. Pharmacological Action: Amlodipine besylate is a dihydropyridine calcium antagonist (calcium ion antagonist or slow-channel blocker). Myocardial and smooth muscle contraction depends on the entry of extracellular calcium ions into cells through specific ion channels. Amlodipine selectively inhibits the transmembrane entry of calcium ions into smooth muscle cells and myocardial cells, with a greater effect on smooth muscle than on myocardial cells. 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. 2. Toxicological Effects: Carcinogenicity, Mutagenesis, and Teratogenesis: Amlodipine was administered to rats and mice at daily doses of 0.5, 1.25, and 2.5 mg/kg for two years without confirmed carcinogenicity. This highest dose reached the maximum tolerated dose in mice, but not in rats (calculated based on the maximum recommended clinical dose of 10 mg/m²). No drug-related mutagenicity was observed at either the genomic or chromosomal levels. Amlodipine administered at a daily dose of 10 mg/kg (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 administered at a dose of 10 mg/kg (8 and 23 times the maximum recommended human dose) to pregnant rats and rabbits during the period of major organogenesis did not cause 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. 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.
[Pharmacokinetics]
After oral administration of therapeutic doses of Norvasc, peak plasma concentrations are reached 6-12 hours later, with an absolute bioavailability of approximately 64-90%. Norvasc's bioavailability is unaffected by food intake. Amlodipine is extensively metabolized (approximately 90%) in the liver to inactive metabolites, with the remaining 10% excreted as unchanged drug and 60% of metabolites excreted in the urine. In vitro studies have shown that plasma protein binding is approximately 93% in hypertensive patients. Its plasma clearance rate is biphasic, with a terminal elimination half-life of approximately 35 to 50 hours. After 7 to 8 days of continuous daily administration, the plasma concentration of amlodipine reaches a steady state.
