MIOSIL-10 Tablet

For the first-line treatment of hypertension and of angina pectoris.

For hypertension treatment, in the majority of patients it can be used as the sole agent to control blood pressure. However, if necessary Amlodipine can also be given in combination with a thiazide diuretic, -adrenoceptor- blocking agent or an angiotensin-converting enzyme inhibitor.

Amlodipine is indicated for the first-line treatment of angina pectoris, whether due to fixed obstruction (stable angina) and/or vasospasm/vasoconstriction of coronary vasculature (Prinzmetal’s to variant angina). Amlodipine may be used where the clinical presentation suggests a possible vasospastic/vasoconstrictive component but where vasospasm/vasoconstrication has not been confirmed.

Amlodipine may be used alone, as monotherapy, or in combination with other antianginal drugs in patients with angina that is refractory to nitrated and/or adequate dose of - blockers.

Amlodipine is also indicated for the treatment of patients with severe (NYHA Class Ⅲ-Ⅳ)chronic heart failure Without clinical signs or symptoms suggestive of underlying ischemic disease.

Dosage

The usual initial dose is 5mg once daily, both for hypertension and angina.

This may be increased to a maximum dose of 10mg once daily, depending on the individual patient’s response. For patients with severe (NYHA ClassⅢ-Ⅳ) chronic heart failure without symptoms of underlying ischemic disease, the usual dose is 10mg once daily. However, also in these patients treatment should be initiated with 5mg once daily and increased to 10mg once daily if tolerated.

No dose adjustment of Amlodipine is required upon concomitant administration of thiazide diuretics. Beta-blockers and angiotensin converting enzyme inhibitors.

In individuals who have shown hypersensitivity to its components or other dihydropyridines.

In clinical trials most commonly observed side effects were vasodilatory effects such as oedema, headaches, flushing and dizziness. However oedema is usually mild to moderate in severity and rarely requires treatment withdrawal. Other side effects reported clinical studies were important abnormalities in laboratory test have not been observed. In marketing experience rarely pruritus, rash, dyspnoea, asthenia, muscle cramps, dyspepsia, gingival hyperplasia and erythema multiforme have been reported. As with other calcium channel blockers the following adverse events have been reported rarely and may also be related to the natural history of the underlying disease: myocardial infarction, arrhythmia (including ventricular tachycardia and atrial fibrillation) and chest pain.

Amlodipine has been administered with thiazide diuretics, -blockers, ACE inhibitors, nitrates (long acting and sublingual), NSAIDs, antibiotics and oral hypoglycaemic agents without untoward interactive effects. Studies have indicated that Amlodipine does not affect digoxin or cyclosporin pharmacokinetics in healthy volunteers, nor does co-administration of cimetidine alter the pharmacokinetic profile of amlodipine.

In vitro studies using human plasma have indicated that Amlodipine does not affect the protein biding of digoxin, phenytoin, warfarin, or indomethacin. In healthy male volunteers, the co-administration of Amlodipine does not significantly alter the effect of warfarin on prothrombin response time.

(See the package insert about the details below.)

Use in pregnancy is only recommended when there is no safer alternative and when the disease itself carries greater risk for the mother and foetus.

Amlodipine should be administered with caution in patients with impaired hepatic functions, as the half-life is prolonged in these patients. Dosage adjustment has not been established. Amlodipine may be prescribed at the usual dosage in patients with renal failure. It is extensively metabolized to inactive metabolites with only 10% excreted as unchanged drug in the urine. Changes in Amlodipine plasma concentrations have not been found to be correlated with the degree of renal impairment. Although the Amlodipine clearance tends to be somewhat lower in elderly patients. Amlodipine has been found to be equally well tolerated in elderly and younger patients. Thus, amlodipine can be used by elderly patients without a need for dose adjustment. There is no experience available for use of the drug in children.

Amlodipine　Belongs to the dihydropyridine class of calcium channel blockers and inhibits calcium influx into cardiac and vascular smooth muscle via L-type calcium channels. Its main site of action is the peripheral vasculature, although it also produces vasodilation in coronary vascular beds.

The antihypertensive action is directly related to the relaxant effect on vascular smooth muscle, leading to dilation of both arteries and arterioles. The anti-angina mode of action has not been fully elucidated but is thought to depend on two actions:

1) The dilation of the peripheral arterioles and thereby reduction of the total peripheral resistance against which the heart works.

2) The dilation of the coronary arteries and arterioles, which increases myocardial oxygen delivery. Amlodipine has a sustained and gradual onset of the antihypertensive effect.

Once-daily dosing provides blood pressure control over the 24-hour interval, without interfering with the normal circadian changes in blood pressure. Due to the gradual onset of action, acute hypotension and reflux tachycardia are generally not observed. In patients with angina, Amlodipine improves both subjective (anginal attack frequency and nitroglycerin use) and objective (exercise duration, time to angina onset, and ST-segment deviation) symptoms of ischemia. Amlodipine has not been associated with any adverse metabolic effects or changes in plasma lipids and it is suitable for use in patients with asthma, diabetes and gout. In patients with chronic heart failure Amlodipine did not lead to clinical deterioration or an increased risk of mortality or morbidity. In fact, in patients with chronic heart failure without underlying ischemic disease, Amlodipine treatment resulted in a statistically significant reduction in mortality and morbidity.