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| Cardiovascular and Cerebrovascular |
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| Ningliping |
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| Brand Name: Ningliping |
| Generic Name: Amlodipine Maleate Tablet |
| Indication: |
1. Hypertension: This product is indicated for the treatment of hypertension. It may be used alone or in combination with other antihypertensive agents.
2. Chronic stable angina pectoris and prinzmetal's or variant angina: This product may be used as monotherapy or in combination with other antianginal drugs.
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| Detailed introduction: |
Amlodipine is a dihydropyridine calcium antagonist (calcium ion antagonist or
slow-channel blocker) that inhibits the transmembrane influx of calcium ions into vascular smooth muscle and cardiac muscle. Experimental data suggest that amlodipine binds to both dihydropyridine and nondihydropyridine binding sites. The contractile processes of cardiac muscle and vascular smooth muscle are dependent upon the movement of extracellular calcium ions into these cells through specific ion channels. Amlodipine inhibits calcium ion influx across cell membranes selectively, with a greater effect on vascular smooth muscle cells than on cardiac muscle cells. Negative inotropic effects can be detected in vitro.
But such effects have not been seen in intact animals at therapeutic doses. Serum calcium concentration is not affected by amlodipine. Within the physiologic pH range, amlodipine is an ionized compound (pKa=8.6), and its kinetic interaction with the calcium channel receptor is characterized by a gradual rate of association and dissociation with the receptor binding site, resulting in a gradual onset of effect.
Amlodipine is a peripheral arterial vasodilator that acts directly on vascular smooth muscle to cause a reduction in peripheral vascular resistance and reduction in blood pressure.
We are uncertain about the antianginal mechanism of this product. However, this product can help relieve angina pectoris by dilating peripheral small artery and coronary artery, reducing total peripheral vascular resistance, eliminating coronary artery spasm, lowering cardiac afterload and reducing cardiac energy consumption and myocardial oxygen demand.
Pharmacokinetics
According to clinical studies, plasma drug concentration reached Cmax 7.6 hours after healthy volunteers were orally administered with 5 mg amlodipine maleate tablets, with peak molecular weight of 3.05 ug/ml and elimination half life of 48.6 hours. This product is extensively converted into inactive metabolites via hepatic metabolism. Metabolites will be excreted in the urine.
Indications
1. Hypertension: This product is indicated for the treatment of hypertension. It may be used alone or in combination with other antihypertensive agents.
2. Chronic stable angina pectoris and prinzmetal's or variant angina: This product may be used as monotherapy or in combination with other antianginal drugs.
Adverse Reactions
Patients have good tolerance with this product given at a dose of 10 mg daily. In experiment on clinical treatment of hypertension or angina pectoris in placebo-controlled trials, the most familiar adverse reactions include headache, edema, fatigue, hypersomnolence, nausea, bellyache, flush, heart throb and vertigo. In these clinical experiments, we have not found that clinical examination indicators related to this product are abnormal.
Scarcely occurred adverse reactions after the product comes into the market include alopecia, change in bowel habit, arthralgia, weakness, backache, dyspepsia, dyspnea, gingival hyperplasia, gynecomastism, hyperglycemia, sexual impotence, urinal frequency, leucopenia, feeling uncomfortable, emotional change, dry mouth, myalgia, peripheral neuropathy, pancreatitis, desudation, swoon, thrombopenia, vasculitis and visual impairment. In many cases, casual relationship between the abovementioned change and this product is still unknown.
Allergic reaction is rare, including pruritus, tetter, vasogenic brain edema and erythema multiforme.
There is scarce report on hepatitis, icterohepatitis and elevated liver enzyme (usually identical with Intrahepatic cholestasis). According to reports, some cases of hospitalization are related to amlodipine. In many cases, casual relationship is still unknown.
Like other calcium antagonists, there are reports on the following events caused by this product: myocardial infarction, arrhythmia (including ventricular tachycardia and atrial fibrillation) and chest pain, but it is difficult to differentiate these events from natural history of these basic diseases.
Contraindication
Ningliping is contraindicated in patients with known sensitivity to dihydropyridines or the excipients.
Warning
Increased Angina and/or Myocardial Infarction: Rarely, patients, particularly those with severe obstructive coronary artery disease, have developed documented increased frequency, duration and/or severity of angina or acute myocardial infarction on starting calcium channel blocker therapy or at the time of dosage increase. The mechanism of this effect has not been elucidated.
Precaution
1. General
Since the vasodilation induced by NORVASC is gradual in onset, acute hypotension has rarely been reported after oral administration. Nonetheless, caution, as with any other peripheral vasodilator, should be exercised when administering NORVASC, particularly in patients with severe aortic stenosis.
2. Use in patients with congestive heart failure
In general, calcium channel blockers should be used with caution in patients with heart failure. In placebo-controlled PRAISE (Prospective Randomized Amlodipine Survival Evaluation) study, this product was given to patients with cardiac dysfunction (NYHAIII¡ªIV grade) in combination with digoxin, diuretics and ACEI
(Angiotensin-Converting Enzyme Inhibitor). During 14-moth follow-up visit, we didn't detect negative impact of this product on survival rate or incidence of fatal arrhythmia, acute myocardial infarction or hospitalization caused by exacerbation of heart failure. In
8-week to 12-week clinical study of 679 patients with cardiac dysfunction in placebo control group, indicators including exercise tolerance, left ventricular ejection fraction and clinical symptoms indicates that this product won¡¯t aggravate heart failure.
3. Patients with hepatic impairment
Like other calcium antagonists, half life of this product would prolong in the event of hepatic impairment. Recommended dose for patients with hepatic dysfunction is still unknown. Therefore, caution should be exercised when administering Ningliping to patients with severe hepatic impairment.
4. Patients with renal failure
10% of this product is excreted via urine. There is no correlation between change in plasma drug concentration and degree of renal dysfunction. Therefore, these patients can take this product at a usual dose. This product can not be used in dialysis.
5. Geriatric use
The peak time of plasma drug concentration is similar between elderly and young patients. Area under the curve of elderly patients increases, and prolonged elimination half life of this product leads to drop in rate of elimination. According to some report, when taking amlodipine maleate tablets at a similar dose, both senile and young patients have the same good tolerance. Therefore, senile patients can take this product at a usual dose. However, it is recommended that elderly patients should take this product at a dose lower than usual dose at the beginning and then gradually increase the dose. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Elderly patients have decreased clearance of amlodipine with a resulting
increase of AUC of approximately 40-60%, and a lower initial dose may be required.
6. Pregnancy category C and nursing mother
No evidence of teratogenicity or other embryo/fetal toxicity was found when pregnant rats and rabbits were treated orally with amlodipine maleate at doses up to 10 mg amlodipine/kg/day (respectively 8 times* and 23 times* the maximum recommended human dose of 10 mg on a mg/m2 basis) during their respective periods of major organogenesis. However, litter size was significantly decreased (by about 50%) and the number of intrauterine deaths was significantly increased (about 5-fold) in rats receiving amlodipine maleate at a dose equivalent to 10 mg amlodipine/kg/day for 14 days before mating and throughout mating and gestation. Amlodipine maleate has been shown to prolong both the gestation period and the duration of labor in rats at this dose. Animal experiments indicated that, when rats were administered with this product at a dose of 50 times higher than the recommended dose for human beings, there are no signs or symptoms of reproductive toxicity in addition to delayed delivery and prolonged labor. There are no adequate and well-controlled studies in pregnant women. Amlodipine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
It is not known whether amlodipine is excreted in human milk. In the absence of this information, it is recommended that nursing be discontinued while Ningliping is administered.
7. Pediatric use
The effect of Ningliping on blood pressure in patients less than 6 years of age is not known.
8. Overdosage
Overdosage might be expected to cause excessive peripheral vasodilation with marked hypotension and possibly a reflex tachycardia. In humans, experience with intentional overdosage of NORVASC is limited. Reports of intentional overdosage include a patient who ingested 250 mg and was asymptomatic and was not hospitalized; another (120 mg) was hospitalized, underwent gastric lavage and remained normotensive; the third (105 mg) was hospitalized and had hypotension (90/50 mmHg) which normalized following plasma expansion. A case of accidental drug overdose has been documented in a 19-month-old male who ingested 30 mg amlodipine (about 2 mg/kg). During the emergency room presentation, vital signs were stable with no evidence of hypotension, but a heart rate of
180 bpm. Ipecac was administered 3.5 hours after ingestion and on subsequent observation (overnight) no sequelae were noted.
If massive overdose should occur, active cardiac and respiratory monitoring should be instituted. Frequent blood pressure measurements are essential. Should hypotension occur, cardiovascular support including elevation of the extremities and the judicious administration of fluids should be initiated. If hypotension remains unresponsive to these conservative measures, administration of vasopressors (such as phenylephrine) should be considered with attention to circulating volume and urine output. Intravenous calcium
gluconate may help to reverse the effects of calcium entry blockade. As Ningiping is highly protein bound, hemodialysis is not likely to be of benefit.
Drug Interactions
Administration of this product in combination with the following drugs is safe: thiazide diuretics, ¦Â-adrenergic receptor blocker, Angiotensin-Converting Enzyme Inhibitor, nitrate esters, sublingual nitroglycerin, nonsteroidal anti-inflammatory drugs, antibiotics and oral hypoglycemic drugs.
Study of healthy volunteers indicates that combined administration of this product and digoxin does not change serum digoxin concentration and renal clearance of digoxin, and combined administration of this product and cimetidine does not change
pharmacokinetics of this product.
In vitro study of human plasma indicates that this product do not influence plasma protein binding rate of digoxin, phenytoin, warfarin or indomethacin.
Study of healthy male volunteers indicates that combined administration of this product and warfarin does not significantly change the influence of warfarin on prothrombin time. Study of pharmacokinetics indicates that this product does not significantly change pharmacokinetics of cyclosporine.
Administration and Dosage
1. Adults: The usual initial antihypertensive oral dose of Ningliping is 5 mg once daily with a maximum dose of 10 mg once daily. Small, fragile, or elderly individuals, or patients with hepatic insufficiency may be started on 2.5 mg once daily and this dose may be used when adding Ningliping to other antihypertensive therapy. Dosage should be adjusted according to each patient's need. In general, titration should proceed over 7 to 14 days so that the physician can fully assess the patient's response to each dose level. Titration may proceed more rapidly, however, if clinically warranted, provided the patient is assessed frequently.
2. The recommended dose for chronic stable or vasospastic angina is 5-10 mg, with the lower dose suggested in the elderly and in patients with hepatic insufficiency. Most patients will require 10 mg for adequate effect. See ADVERSE REACTIONS section for information related to dosage and side effects. The recommended dose range for patients with coronary artery disease is 5-10 mg once daily. In clinical studies the majority of patients required 10 mg.
Description
This product is a kind of white or white or off-white tablet.
How Supplied
Supplied as 5 mg tablets (C20H25ClN2O5•C4H4O4), box of 10
Package
Aluminum plastic package
Price
18 RMB/box
Storage
Amlodipine should be stored at room temperature in a tight, light resistant container. |
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