Amlodipine Sandoz, tablets 10 mg 30 pcs

Pharmgroup:

Slow calcium channel blocker.

Pharm Action:

Amlodipine Sandoz is a slow calcium channel blocker, a dihydropyridine derivative. It has antihypertensive and antianginal action. By binding to dihydropyridine receptors, it blocks calcium channels, reduces transmembrane transfer of calcium ions into the cell (more in vascular smooth muscle cells than in cardiomyocytes).

It has a long-term dose-dependent hypotensive effect. The hypotensive effect is due to the direct vasodilating effect on the vascular smooth muscles. In arterial hypertension a single dose provides clinically significant BP reduction for 24 hours (in a patient lying and standing position). It does not cause a sharp decrease in BP, decreases exercise tolerance and left ventricular ejection fraction. It reduces the degree of myocardial hypertrophy of the left ventricle, has anti-atherosclerotic and cardioprotective effect in CHD. It does not affect myocardial contractility and conduction, does not cause reflex increase in heart rate, inhibits platelet aggregation, increases glomerular filtration rate, has a weak natriuretic effect.

The antianginal action is caused by the dilation of coronary and peripheral arteries and arterioles: in angina pectoris it reduces myocardial ischemia; by dilation of peripheral arterioles it reduces myocardial hypertension, decreases myocardial oxygen demand. By dilating the main coronary arteries and arterioles in the unchanged and ischemic areas of the myocardium, increases the flow of oxygen to the myocardium (especially in vasospastic angina); prevents the development of coronary artery constriction (including that caused by smoking). In patients with angina a single daily dose increases time of physical activity, slows down the development of angina and ischemic ST-segment depression, reduces the frequency of angina attacks and nitroglycerin consumption.

In diabetic nephropathy, it does not increase the severity of microalbuminuria. It has no adverse effect on metabolism and blood plasma lipids.

The time of onset of effect is 2-4 hours, the duration of effect is 24 hours.

Pharmacokinetics:

Intake
After oral administration amlodipine is slowly absorbed from the gastrointestinal tract. Mean absolute bioavailability is 64%, Cmax in plasma is observed after 6-9 h. Css is reached after 7 days of therapy. Food intake does not affect absorption of amlodipine.

Distribution
Average Vd is 21 l/kg body weight, indicating that most of the drug is in the tissues and relatively less in the blood. Most of the drug that is in the blood (95%) is bound to plasma proteins.
Passes through the BBB.

Metabolism
Amlodipine undergoes slow but extensive metabolism (90%) in liver with formation of inactive metabolites. It has a “first pass” effect through the liver. Metabolites have no significant pharmacological activity.

Elimation
After a single oral administration, the T1/2 ranges from 31 to 48 hours, with repeated administration the T1/2 is approximately 45 hours. About 60% of the oral dose is excreted with the urine, mainly as metabolites, 10% – unchanged, and 20-25% – in the feces, as well as with the breast milk. Total clearance of amlodipine is 0.116 ml/s/kg (7 ml/min/kg, 0.42 l/h/kg).

Pharmacokinetics in special clinical cases

The excretion of amlodipine is slower (T1/2 – 65 h) in elderly patients (over 65 years) compared to younger patients, but this difference has no clinical significance.

In patients with hepatic impairment, a prolonged T1/2 is expected, and the cumulation of the drug in the body will be higher with long-term administration (T1/2 increases to 60 h).

Renal insufficiency has no significant effect on the kinetics of amlodipine.

It is not eliminated by hemodialysis.

Indications

Arterial hypertension (including in combination therapy), stable angina, unstable angina (including Prinzmetal angina).

Active ingredient

Composition

1 tablet contains amlodipine (in the form of besylate) 10 mg.

Auxiliary substances:

microcrystalline cellulose – 142.73 mg,

calcium hydrophosphate dihydrate – 75 mg,

sodium carboxymethyl starch (type A) – 4.8 mg,

magnesium stearate – 3.6 mg.

How to take, the dosage

In adults, when taken orally, the initial dose is 5 mg once daily.

The dose can be increased if necessary.

The maximum dose is 10 mg/day if taken orally.

Interaction

When concomitant use of Amlodipine with other antihypertensive drugs may increase the hypotensive effect; with agents for inhalation anesthesia – possible increase in hypotensive effect;

with lithium preparations – possible manifestations of neurotoxicity, including nausea, vomiting, diarrhea, ataxia and/or tinnitus.nausea, vomiting, diarrhea, ataxia, tremor and/or tinnitus; with sympathomimetics – possible decrease of hypotensive effect.

Indomethacin and other NSAIDs may decrease the hypotensive effect of amlodipine by inhibiting the synthesis of prostaglandins in the kidneys and/or causing fluid retention.

Special Instructions

Amlodipine with caution is used in patients with hepatic impairment, aortic stenosis, chronic heart failure.

Patients with impaired renal function and elderly patients do not require dose reduction.

Amlodipine may be used to treat patients with dilated (non-ischemic) cardiomyopathy accompanied by severe chronic heart failure.

There are no clinical data on the use of amlodipine in children.

Contraindications

Severe arterial hypotension.

Hypersensitivity to dihydropyridine derivatives.

Side effects

Cardiovascular system: peripheral edema, palpitation, skin hyperemia are possible; when used in high doses – arterial hypotension, arrhythmias, shortness of breath.

The digestive system: nausea, abdominal pain; rarely – gum hyperplasia.

CNS disorders: headache, fatigue, drowsiness, dizziness are possible.

Allergic reactions: skin rash, itching.

Overdose

Symptoms: excessive peripheral vasodilation with pronounced and possibly prolonged BP decrease, collapse, shock.

Treatment: gastric lavage, administration of activated charcoal, maintenance of cardiovascular function, control of cardiac and pulmonary function parameters, elevated, above head level, position of lower extremities, control of CPR and diuresis.

In order to restore vascular tone – administration of vasoconstrictors (if there are no contraindications for their use); in order to eliminate the effects of calcium channel blockade – intravenous injection of calcium gluconate. Hemodialysis is ineffective.

Pregnancy use

The safety of Amlodipine administration during pregnancy and lactation has not been established.

The use is possible only in cases when the estimated benefit to the mother exceeds the potential risk to the fetus or child.

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