COMPOSITION
AmlocomTM : Each tablet contains Amlodipine Besilate BP equivalent to Amlodipine 5 mg and Atenolol BP 50 mg as a fixed dose combination.
PHARMACOLOGICAL INFORMATION
Pharmacological Action
Amlodipine is a calcium ion influx inhibitior(slow channel blocker or calcium ion antagonist) and inhibits the transmembrane influx of calcium ions into cardiac and smooth muscle without changing serum calcium concentrations. The mechanism of the antihypertensive action of amlodipine is due to a direct relaxant effect on vascular smooth muscle. Amlodipine dilates peripheral arterioles and thus reduces the total peripheral resistance against which the heart works.
Atenolol is a cardio-selective beta-blocker. Atenolol blocks the ß1-receptors in the heart. Thus it slows the heart rate which decrease cardiac output; decrease blood pressure.
Mechanism of Action
Amlocom is a fixed dose combination of amlodipine and atenolol. Amlodipine is a calcium antagonist that inhibits the transmembrane influx of calcium ions into vascular smooth muscle and cardiac muscle; it has a greater effect on vascular smooth muscle cells than on cardiac muscle cells. Amlodipine is a peripheral vasodilator that acts directly on vascular smooth muscle to cause a reduction in peripheral vascular resistance and reduction in blood pressure. Amlodipine reduces tone, decreases coronary vasoreactivity, and lowers cardiac demand by reducing afterload. Atenolol is a cardioselective beta-blocker. Atenolol causes a reduction in blood pressure by lowering cardiac output, decreasing the plasma renin activity and sympathetic outflow from CNS. It also causes a reduction in myocardial oxygen demand by virtue of its negative Inotropic and negative chronotropic effects.
PHARMACOKINETIC PROPERTIES
Absorption: Peak plasma concentrations of amlodipine reached 6-12 hours after administration of Amlocom; the extent of absorption is 64%-90%. Approximately 50% of an oral dose of atenolol is absorbed from the gastro-intestinal tract and the remainder being excreted unchanged in the feces. Peak plasma concentrations occur 2 to 4 hours after dosing and are subject to a 4-fold variability. Mean peak plasma concentrations of Atenolol approximately 300 ng/mL. The plasma half-life (t1/2) is 6-7 hours.
Distribution: The apparent volume of distribution of amlodipine and atenolol is about 21 L/kg and 0.7 L/kg respectively. Approximately 93% of circulating amlodipine is bound to plasma proteins. Atenolol is 6-16% plasma protein bound and is extensively distributed to extravascular tissues, but only a small amount is found in the CNS.
Metabolism: Amlodipine is extensively (about 90%) converted to inactive metabolites via hepatic metabolism with 10% of the parent compound and 60% of the metabolites excreted in the urine. Approximately 10% of atenolol is metabolised in man. About 3% of the material recovered in the urine is the hydroxylated metabolite which has been shown in animal studies to have 10% of the pharmacological activity of atenolol.
Elimination: Elimination of amlodipine from the plasma is biphasic with a terminal elimination half-life of about 30-50 hours. Elimination half life of atenolol approximately 6 to 7 hours. Approximately 47% and 53% of the oral dose is eliminated in the urine and feces, respectively. Recovery is complete after 72 hours.
CLINICAL INFORMATION
Therapeutic Indications
Amlocom is indicated for
Patients with essential hypertension
Patients with angina pectoris and hypertension as co-existing diseases
In post MI patients
In patients with refractory angina pectoris.
Dosage and Administration
The therapy is initiated with a single dose of Amlocom. Depending upon the therapeutic response, titration of the dosage is recommended. In elderly patients, it is advisable to initiate the therapy with ½ tablet of fixed dose combination of amlodipine & atenolol.
Use in patients with impaired renal function
The combination can be used in patient with renal impairment. However caution may be necessary if creatinine clearance is less than 30ml/min because of possible reduction in the excretion of unchanged urine.
Use in Pregnancy & Lactation
Pregnancy:
The combination should be used during pregnancy only if the expected benefit outweighs the potential fetal risk.
Lactation:
Nursing mothers should not use the combination. If its use is considered necessary, breast feeding should be stopped.
Side Effects
The combination of amlodipine and atenolol is well tolerated. Overall side effects include fatigue, headache, edema, nausea, drowsiness, anxiety and depression.
Contraindications
Hypersensitivity to either component.
In sinus bradycardia, second and higher degrees of heart block, cardiogenic shock, hypotension, congestive heart failure, poor left ventricular function.
Drug Interactions
Disopyramide: Atenolol reduces the clearance of disopyramide by 20%. Additive Inotropic effects on the heart may be produced. Ampicillin: Ampicillin at doses of 1g and above may reduce atenolol levels. Oral antidiabetic and Insulin: Atenolol may decrease tissue sensitivity to insulin and inhibit insulin secretion in response to oral antidiabetics.
Over dosage
There is no well documented experience with amlodipine overdosage. Gastric lavage may be worthwhile. Available data suggest that gross overdosage could result in excessive peripheral vasodilation with subsequent marked and probably prolonged systemic hypotension. Intravenous calcium gluconate may be beneficial in reversing the effects of calcium channel blockade. Since amlodipine is highly protein-bound, dialysis is not likely to be of benefit. In case of atenolol overdose, seek medical attention right away. Symptoms of overdose may include congestive heart failure, low blood pressure, low blood sugar, slow heartbeat, sluggishness, weakness and wheezing.
PHARMACEUTICAL INFORMATION
Storage Conditions
Store in a cool and dry place away from light. Keep out of reach of children.
Presentation & Packaging
AmlocomTM : Each commercial box contains 50 tablets in Alu-Alu blister-pack. |