Atoguard

Uses

Aspirin is used for its antiplatelet activity in the initial treatment of cardiovascular disorders such as angina pectoris and myocardial infarction and for the prevention of cardiovascular events in a variety of conditions or procedures for patients at risk.

• Aspirin is used as part of the initial treatment of unstable angina.
• It is given in the early treatment of myocardial infarction.
• It may also be of some benefit in the initial treatment of acute ischaemic stroke.
• It is of value for the secondary prevention of cardiovascular events in patients with stable or unstable angina or those with acute or prior myocardial infarction.
• Aspirin reduces the risk of future serious vascular events, including stroke, in patients who have already suffered an ischaemic stroke or transient ischaemic attack.
• It is of use in the long-term management of atrial fibrillation, for the prevention of stroke in patients with contraindications to warfarin or if there are no other risk factors for stroke.
• It is recommended for use in preventing thrombotic complications associated with procedures such as angioplasty and coronary bypass grafting.

Patients with mild to moderate hypertension (alone or in combination with other antihypertensives).

The treatment of chronic stable and vasospastic angina.

Raynaud\'s disease.

Atenolol is used for: Hypertension, Angina pectoris, Cardiac arrhythmia, Myocardial infarction

Atoguard is also used to associated treatment for these conditions: Acute Coronary Syndrome (ACS), Anxiety, Arthritis, Atherothrombotic cerebral infarction, Cardiovascular Disease (CVD), Cardiovascular Events, Cardiovascular Mortality, Colorectal Adenomas, Colorectal Cancers, Common Cold, Coronary artery reocclusion, Death, Dyspeptic signs and symptoms, Fever, Flu Like Symptom, Flu caused by Influenza, Headache, Heterozygous Familial Hypercholesterolemia, Inflammation, Juvenile Idiopathic Arthritis (JIA), Kawasaki Syndrome, Major Adverse Cardiovascular and Cerebrovascular Events (MACCE), Migraine, Morbidity, Mucocutaneous Lymph Node Syndrome, Muscle Contraction, Myocardial Infarction, Myocardial Infarction (MI), first occurrence, Neuralgia, Pain, Pain caused by Common Cold, Pain, Menstrual, Pericarditis, Polycythemia Vera (PV), Preeclampsia, Rheumatic Pain, Rheumatism, Rheumatoid Arthritis, Rhinosinusitis, Severe Pain, Soreness, Muscle, Spondyloarthropathies, Stroke, Systemic Lupus Erythematosus (SLE), Tension Headache, Thromboembolism, Toothache, Transient Ischemic Attack, Venous Thromboembolism, Acute Inflammation, Atherothrombotic events, Death by myocardial infarction, Moderate Pain, Thrombotic events, Antiplatelet Therapy, Hemodialysis Treatment, Secondary PreventionAnginal Pain, Cardiovascular Events, Chronic Stable Angina Pectoris, Coronary Artery Disease (CAD), High Blood Pressure (Hypertension), Homozygous Familial Hypercholesterolemia, Hypertension,Essential, Mixed Dyslipidemias, Primary Hypercholesterolemia, Vasospastic AnginaAlcohol Withdrawal Syndrome, Angina Pectoris, Atrial Fibrillation, Heart Failure, High Blood Pressure (Hypertension), Migraine, Myocardial Infarction, Refractory Hypertension, Secondary prevention Myocardial infarction, Supra-ventricular Tachyarrhythmias, Thyrotoxicosis, Ventricular Tachyarrhythmias

How Atoguard works

Acetylsalicylic acid (ASA) blocks prostaglandin synthesis. It is non-selective for COX-1 and COX-2 enzymes . Inhibition of COX-1 results in the inhibition of platelet aggregation for about 7-10 days (average platelet lifespan). The acetyl group of acetylsalicylic acid binds with a serine residue of the cyclooxygenase-1 (COX-1) enzyme, leading to irreversible inhibition. This prevents the production of pain-causing prostaglandins. This process also stops the conversion of arachidonic acid to thromboxane A2 (TXA2), which is a potent inducer of platelet aggregation . Platelet aggregation can result in clots and harmful venous and arterial thromboembolism, leading to conditions such as pulmonary embolism and stroke.

It is important to note that there is 60% homology between the protein structures of COX-1 and COX-2. ASA binds to serine 516 residue on the active site of COX-2 in the same fashion as its binding to the serine 530 residue located on the active site of COX-1. The active site of COX-2 is, however, slightly larger than the active site of COX-1, so that arachidonic acid (which later becomes prostaglandins) manages to bypass the aspirin molecule inactivating COX-2 . ASA, therefore, exerts more action on the COX-1 receptor rather than on the COX-2 receptor . A higher dose of acetylsalicylic acid is required for COX-2 inhibition .

Mechanism of action on blood pressure

Amlodipine is considered a peripheral arterial vasodilator that exerts its action directly on vascular smooth muscle to lead to a reduction in peripheral vascular resistance, causing a decrease in blood pressure. Amlodipine is a dihydropyridine calcium antagonist (calcium ion antagonist or slow-channel blocker) that inhibits the influx of calcium ions into both vascular smooth muscle and cardiac muscle. Experimental studies imply that amlodipine binds to both dihydropyridine and nondihydropyridine binding sites, located on cell membranes. The contraction of cardiac muscle and vascular smooth muscle are dependent on the movement of extracellular calcium ions into these cells by specific ion channels. Amlodipine blocks calcium ion influx across cell membranes with selectivity. A stronger effect of amlodipine is exerted on vascular smooth muscle cells than on cardiac muscle cells . Direct actions of amlodipine on vascular smooth muscle result in reduced blood pressure .

Mechanism of action in angina

The exact mechanism by which amlodipine relieves the symptoms of angina have not been fully elucidated to this date, however, the mechanism of action is likely twofold:

Amlodipine has a dilating effect on peripheral arterioles, reducing the total peripheral resistance (afterload) against which the cardiac muscle functions. Since the heart rate remains stable during amlodipine administration, the reduced work of the heart reduces both myocardial energy use and oxygen requirements .

Dilatation of the main coronary arteries and coronary arterioles, both in healthy and ischemic areas, is another possible mechanism of amlodipine reduction of blood pressure. The dilatation causes an increase in myocardial oxygen delivery in patients experiencing coronary artery spasm (Prinzmetal's or variant angina) and reduces coronary vasoconstriction caused by smoking .

Atenolol is a cardioselective beta-blocker, called such because it selectively binds to the β1-adrenergic receptor as an antagonist up to a reported 26 fold more than β2 receptors. Selective activity at the β1 receptor produces cardioselectivity due to the higher population of this receptor in cardiac tissue. Some binding to β2 and possibly β3 receptors can still occur at therapeutic dosages but the effects mediated by antagonizing these are significantly reduced from those of non-selective agents. β1 and β2 receptors are G_s coupled therefore antagonism of their activation reduces activity of adenylyl cyclase and its downstream signalling via cyclic adenosime monophosphate and protein kinase A (PKA).

In cardiomyocytes PKA is thought to mediate activation of L-type calcium channels and ryanodine receptors through their phosphorylation. L-type calcium channels can then provide an initial rise in intracellular calcium and trigger the ryanodine receptors to release calcium stored in the sarcoplasmic reticulum (SR) and increased contractility. PKA also plays a role in the cessation of contraction by phosphorylating phospholamban which in turn increases the affinity of SR Ca²⁺

Similar inihibitory events occur in the bronchial smooth muscle to mediate relaxation including phosphorylation of myosin light-chain kinase, reducing its affinity for calcium. PKA also inhibits the excitatory G_q coupled pathway by phosphorylating the inositol trisphosphate receptor and phospholipase C resulting in inhibition of intracellular calcium release. Antagonism of this activity by beta-blocker agents like atenolol can thus cause increased bronchoconstriction.

Dosage

Atoguard dosage

Pain, Inflammatory diseases and as Antipyretic: Aspirin 300 mg 1-3 tablets 6 hourly with a maximum daily dose of 4 g.

Thrombotic cerebrovascular or Cardiovascular disease: Aspirin 300 mg 1 tablet or Aspirin 75 mg 4 tablets daily.

After Myocardial infarction: Aspirin 75 mg 2 tablets daily for 1 month.

Following By-pass surgery: Aspirin 75 mg 1 tablet daily.

For treatment of both hypertension and angina pectoris, the usual initial dose is 5 mg once daily. If the desired therapeutic effect cannot be achieved within 2-4 weeks, the dose may be increased to a maximum dose of 10 mg once daily. Amlodipine 10 mg once daily provides symptomatic improvement in patients with Raynaud's disease.

Use in children: Use of Amlodipine in children (under 12 years of age) is not recommended.

Hypertension: 50 mg once daily, the daily dose can be raised to 100 to 200 mg.

Angina pectoris: 50 to 100 mg daily.

Cardiac arrhythmia: Atenolol in low dose, 25-50 mg once daily, can be used in combination with digoxin to control the ventricular rate in atrial fibration or atrial flutter which is refractory to digoxin alone.

Side Effects

Side effects for usual dosage of Aspirin are mild including nausea, dyspepsia, gastrointestinal ulceration and bronchospasm etc.

Amlodipine is generally well tolerated. The most commonly observed side effects are headache, peripheral oedema, palpitations, flushing, dizziness, nausea, abdominal pain.

In general, atenolol is well tolerated although in a small number of patients (approximately 2-3%) therapy must be withdrawn because of troublesome symptomatic adverse effects. The commonest of these are cold extrimities, fatigue, vivid dreams, insomnia, diarrhoea, constipation, impotence and paraesthesia. Bronchospasm has been occurred with atenolol although this is very much less common than with the non-selective β-blockers.

Toxicity

Lethal doses

Acute oral LD50 values have been reported as over 1.0 g/kg in humans, cats, and dogs, 0.92 g/kg - 1.48 g/kg in albino rats, 1.19 g/kg in guinea pigs, 1.1 g/kg in mice, and 1.8 g/kg in rabbit models .

Acute toxicity

Salicylate toxicity is a problem that may develop with both acute and chronic salicylate exposure . Multiple organ systems may be affected by salicylate toxicity, including the central nervous system, the pulmonary system, and the gastrointestinal system. Severe bleeding may occur. In the majority of cases, patients suffering from salicylate toxicity are volume-depleted at the time of presentation for medical attention. Fluid resuscitation should occur immediately and volume status should be monitored closely. Disruptions in acid-base balance are frequent in ASA toxicity .

The acute toxicity of acetylsalicylic in animals has been widely studied. The signs of poisoning in rats from lethal doses are mild to severe gastroenteritis, hepatitis, nephritis, pulmonary edema, encephalopathy, shock and some toxic effects on other organs and tissues. Mortality has been observed following convulsions or cardiovascular shock. An important differentiating property between various animal species is the ability to vomit toxic doses. Humans, cats and dogs have this ability, but rodents or rabbits do not .

Chronic toxicity and carcinogenesis

Chronic ASA toxicity is frequently accompanied by atypical clinical presentations that may be similar to diabetic ketoacidosis, delirium, cerebrovascular accident (CVA), myocardial infarction (MI) or cardiac failure. Plasma salicylate concentrations should be measured if salicylate intoxication is suspected, even if there no documentation available to suggest ASA was ingested. In older age, nephrotoxicity from salicylates increases, and the risk of upper gastrointestinal hemorrhage is increased, with higher rates of mortality . It is also important to note that ASA toxicity may occur even with close to normal serum concentrations. Prevention of chronic ASA includes the administration of smallest possible doses, avoidance of concurrent use of salicylate drugs, and therapeutic drug monitoring. Renal function should be regularly monitored and screening for gastrointestinal bleeding should be done at regular intervals .

Chronic toxicity studies were performed in rodents. ASA was administered at doses measured to be 2 to 20 times the maximum tolerated clinical dose to mice for up to one year. Negative dose-related effects were seen. These include decreased mean survival time, decreased number of births and progeny reaching an appropriate age for weaning. No evidence of carcinogenesis was found in 1-year studies . At daily doses of 0.24 g/kg/day given for 100 days to albino rats, ASA led to signs to excessive thirst, aciduria, diuresis, drowsiness, hyperreflexia, piloerection, changes in respiration, tachycardia, followed by soft stools, epistaxis, sialorrhea, dacryorrhea and mortality during hypothermic coma in the second study month .

Use in pregnancy and lactation

While teratogenic effects were observed in animals nearly lethal doses, no evidence suggests that this drug is teratogenic in humans . It is advisable, however, to avoid ASA use the first and second trimester of pregnancy, unless it is clearly required. If acetylsalicylic acid containing drugs are ingested by a patient attempting to conceive, or during the first and second trimester of pregnancy, the lowest possible dose at the shortest possible duration should be taken . This drug is contraindicated in the 3rd trimester of pregnancy .

Acute oral toxicity (LD50): 37 mg/kg (mouse) .

Overdose

An overdose of amlodipine could result in a high degree of peripheral vasodilatation with a possibility of reflex tachycardia. Significant and prolonged hypotension leading to shock and fatal outcomes have been reported .

Carcinogenesis, mutagenesis, impairment of fertility

Rats and mice treated with amlodipine maleate in the diet on a long-term basis for up to 2 years demonstrated no evidence of a carcinogenic effect of the drug. For the mouse, the highest dose was comparable to the maximum recommended human dose of 10 mg amlodipine per day. For the rat, the highest dose was measured to be about twice the maximum recommended human dose .

Mutagenicity studies using amlodipine maleate showed no drug-related gene or chromosomal effects .

There was no impact on the fertility of rats given oral amlodipine maleate (males for 64 days and females for 14 days before mating) at doses up to 10 mg amlodipine/kg/day (8 times the maximum recommended human dose) .

Use in pregnancy

The safety of amlodipine in human pregnancy or lactation has not been proven. Amlodipine is therefore considered a pregnancy category C drug . Use amlodipine only if the potential benefit justifies the potential risk .

Use in nursing

Discontinue when administering amlodipine .

LD₅₀ Values

Mouse: 2 g/kg (Oral), 57 mg/kg (IV), 134 mg/kg (IP), 400 mg/kg (SC)

Rat: 2 g/kg (Oral), 77 mg/kg (IV), 600 mg/kg (SC)

Rabbit: 50 mg/kg (IV)

Carcinogenicity & Mutagenicity

Studies in rats and mice at doses of 300 mg/kg/day, equivalent to 150 times maximum recommended human dose, for durations of 18 and 24 months showed no carcinogenicity. One study in rats at doses of 500-1500 mg/kg/day, 250-750 times maximum human dose, resulted in increases benign adrenal medullary tumors in both sexes and increase mammary fibroadenomas in females.

Atenolol showed no mutagenicity in the Ames test using S. typhinarium, dominant lethal test in mice, or in vivo cytogenetics test in chinese hamster ovary cells.

Reproductive Toxicity

No adverse effects on fertility were observed in either male or female mice after receiving doses of 200 mg/kg/day, equivalent to 200 times the maximum human dose. In humans, atenolol is known to cross the placenta and fetuses exposed to the drug have been reported to be smaller than expected considering gestational age. Embryo-fetal resorption has been observed in rats at doses of 50mg/kg/day, 50 times the max human dose, but not in rabbits at doses of 25mg/kg/day.

Lactation

Atenolol appears in breast milk at a ratio of 1.5-6.8 to plasma concentrations. It has been estimated that infant exposure occurs at 5.7-19.2% maternal weight-adjusted dosage. Effects in infants include bradycardia, hypothermia, and lethargy.

Precaution

It should be administered cautiously in asthma, uncontrolled blood pressure and pregnant women.It is specially important not to use aspirin during the last 3 months of pregnancy unless specifically directed to do so by a doctor because it may cause problems in unborn child or complication during delivery. It should be administered with caution to patients in nasal polyp and nasal allergy. Aspirin penetrates into breast milk. So, it should be administered with caution to lactating mothers.

Hypotension: Since the vasodilUse in renal failure

Although Amlodipine is excreted primarily via kidney, mild renal impairment does not appear to have an effect on the plasma concentrations. Severe renal impairment may however require a dosage reduction. Amlodipine is not dialyzable.

Use in patients with impaired hepatic function

Amlodipine half-life is prolonged in patient with impaired hepatic function. Amlodipine should therefore be administered at lower (5mg) initial dose in these patients.

Use in heart failure

An increased number of pulmonary oedema has been reported.atation induced by Amlodipine is gradual in onset, acute hypotension has rarely been reported after oral administration of Amlodipine. Nonetheless, caution should be exercised when administering the drug with any other peripheral vasodilator particularly in patients with severe aortic stenosis.

Cardiac failure: Patients with heart failure should be treated with caution. Calcium channel blockers, including Amlodipine, should be usedwith caution in patients with congestive heart failure, as they may increase the risk of future cardiovascular events and mortality.

Beta blocker withdrawal: Amlodipine gives no protection against the danger of abrupt beta blocker withdrawal; any such withdrawal should be gradualreduction of the dose of beta blocker.

Hepatic failure: The half-life of amlodipine is prolonged and AUC values are higher in patients with impaired liver function. Amlodipine should therefore be initiated at the lower end of the dosing range and caution should be used, both on initial treatment and when increasing the dose. Slow dose titration and careful monitoring may be required in patients with severe hepatic impairment.

Patients already on a β-blocker must be evaluated carefully before Atenolol is administered. Atenolol may aggravate peripheral arterial circulatory disorders. Impaired Renal Function: Caution should be excised.

Interaction

Salicylates may enhance the effect of anticoagulants, oral hypoglycaemic agents, phenytoin and sodium valporate. They inhibit the uricosuric effect of probenecid and may increase the toxicity of sulphonamides. They may also precipitate bronchospasm or induce attacks of asthma in susceptible subjects.

Use of Amlodipine together with thiazide diuretics or angiotensin-converting-enzyme inhibitors in the treatment of hypertension is additive. There are no hazardous interaction of Amlodipine with Digoxin, Cimetidine, Warfarin and food.

Catecholamine-depleting drugs (e.g., Reserpine) and Calcium channel blockers may have an additive effect when given with Atenolol. Clonidine and aspirin may have some drug reactions.

Volume of Distribution

This drug is distributed to body tissues shortly after administration. It is known to cross the placenta. The plasma contains high levels of salicylate, as well as tissues such as spinal, peritoneal and synovial fluids, saliva and milk. The kidney, liver, heart, and lungs are also found to be rich in salicylate concentration after dosing. Low concentrations of salicylate are usually low, and minimal concentrations are found in feces, bile, and sweat .

21 L/kg , .

Total Vd of 63.8-112.5 L. Atenolol distributes into a central volume of 12.8-17.5 L along with two peripheral compartments with a combined volume of 51-95 L. Distribution takes about 3 hrs for the central compartment, 4 hrs for the shallower peripheral compartment, and 5-6 hrs for the deeper peripheral compartment.

Elimination Route

Absorption is generally rapid and complete following oral administration but absorption may be variable depending on the route, dosage form, and other factors including but not limited to the rate of tablet dissolution, gastric contents, gastric emptying time, and gastric pH .

Detailed absorption information

When ingested orally, acetylsalicylic acid is rapidly absorbed in both the stomach and proximal small intestine. The non-ionized acetylsalicylic acid passes through the stomach lining by passive diffusion. Ideal absorption of salicylate in the stomach occurs in the pH range of 2.15 - 4.10. Intestinal absorption of acetylsalicylic acid occurs at a much faster rate. At least half of the ingested dose is hydrolyzed to salicylic acid in the first-hour post-ingestion by esterases found in the gastrointestinal tract. Peak plasma salicylate concentrations occur between 1-2 hours post-administration .

Amlodipine absorbed slowly and almost completely from the gastrointestinal tract. Peak plasma concentrations are achieved 6-12 hours after oral administration. The estimated bioavailability of amlodipine is 64-90%. Steady-state plasma amlodipine levels are achieved after 7-8 days of consecutive daily dosing. Absorption is not affected by food .

Approximately 50% of an oral dose is absorbed from the gastrointestinal tract, with the remainder being excreted unchanged in the feces. Administering atenolol with food can decrease the AUC by about 20%. While atenolol can cross the blood-brain barrier, it does so slowly and to a small extent.

Half Life

The half-life of ASA in the circulation ranges from 13 - 19 minutes. Blood concentrations drop rapidly after complete absorption. The half-life of the salicylate ranges between 3.5 and 4.5 hours .

The terminal elimination half-life of about 30–50 hours .

Plasma elimination half-life is 56 hours in patients with impaired hepatic function, titrate slowly when administering this drug to patients with severe hepatic impairment .

6-7 hrs.

Clearance

The clearance rate of acetylsalicylic acid is extremely variable, depending on several factors . Dosage adjustments may be required in patients with renal impairment . The extended-release tablet should not be administered to patients with eGFR of less than 10 mL/min .

Total body clearance (CL) has been calculated as 7 ± 1.3 ml/min/kg (0.42 ± 0.078 L/ h/kg) in healthy volunteers , .

Elderly patients show a reduced clearance of amlodipine with an AUC (area under the curve) increase of about 40–60%, and a lower initial dose may be required .

Total clearance is estimated at 97.3-176.3 mL/min with a renal clearance of 95-168 mL/min.

Elimination Route

Excretion of salicylates occurs mainly through the kidney, by the processes of glomerular filtration and tubular excretion, in the form of free salicylic acid, salicyluric acid, and, additionally, phenolic and acyl glucuronides .

Salicylate can be found in the urine soon after administration, however, the entire dose takes about 48 hours to be completely eliminated. The rate of salicylate is often variable, ranging from 10% to 85% in the urine, and heavily depends on urinary pH. Acidic urine generally aids in reabsorption of salicylate by the renal tubules, while alkaline urine increases excretion .

After the administration of a typical 325mg dose, the elimination of ASA is found to follow first order kinetics in a linear fashion. At high concentrations, the elimination half-life increases .

Elimination from the plasma occurs in a biphasic with a terminal elimination half-life of about 30–50 hours. Steady-state plasma levels of amlodipine are reached after 7-8 days of consecutive daily dosing . Amlodipine is 10% excreted as unchanged drug in the urine. Amlodipine can be initiated at normal doses in patients diagnosed with renal failure , .

85% is eliminated by the kidneys following IV administration with 10% appearing in the feces.

Pregnancy & Breastfeeding use

Aspirin should be avoided during the last 3 months of pregnancy. As aspirin is excreted in breast milk, aspirin should not be taken by patients who are breast-feeding.

Pregnancy: Safety in pregnancy has not been established.

Lactation: It is not known whether Amlodipine is excreted in breast milk. It is advised to stop breastfeeding during treatment with Amlodipine.

Pregnancy Category D. Caution should be exercised when Atenolol is administered to a nursing woman.

Contraindication

Aspirin is contraindicated to the children (Reye's syndrome) under 12 years, in breast-feeding and active peptic ulcer. It is also contraindicated in bleeding due to haemophilia and other ulceration. Hypersensitivity to aspirin, hypoprothrombinaemia is also contraindicated

Amlodipine is contraindicated in patients with-

• Hypersensitivity to amlodipine, dihydropyridine derivatives or any of the excipients
• Shock (including cardiogenic shock)
• Obstruction of the outflow-tract of the left ventricle (e.g. high grade aortic stenosis)
• Unstable angina
• Hemodynamically unstable heart failure after acute myocardial infarction (during the first 28 days)
• Severe hypotension

Atenolol is contraindicated for: Second and third degree heart block, Untreated heart failure, Overt cardiac failure, Cardiogenic shock.

Special Warning

Children with hypertension from 6 years to 17 years of age: 2.5 mg once daily as a starting dose, up-titrated to 5 mg once daily if blood pressure goal is not achieved after 4 weeks. Doses in excess of 5 mg daily have not been studied in pediatric patients.

Children under 6 years old: The effect of amlodipine on blood pressure in patients less than 6 years of age is not known.

Elderly: Amlodipine used at similar doses in elderly or younger patients is equally well tolerated. Normal dosage regimens are recommended in the elderly, but increase of the dosage should take place with care.

Renal impairment: Changes in amlodipine plasma concentrations are not correlated with degree of renal impairment, therefore the normal dosage is recommended. Amlodipine is not dialysable.

Hepatic impairment: Dosage recommendations have not been established in patients with mild to moderate hepatic impairment; therefore dose selection should be cautions and should start at the lower end of the dosing range. The pharmacokinetics of Amlodipine have not been studied in severe hepatic impairment. Amlodipine should be initiated at the lowest dose (2.5 mg once daily) and titrated slowly in patients with severe hepatic impairment.

Safety and effectiveness in pediatric patients have not been established.

Acute Overdose

Overdosage produces dizziness, tinnitus, sweating, nausea and vomiting, confusion and hyperventilation. Gross overdosage may lead to CNS depression with coma, cardiovascular collapse and respiratory depression. If overdosage is suspected, the patient should be kept under observation for at least 24 hours, as symptoms and salicylate blood levels may not become apparent for several hours. Treatment of overdosage consists of gastric lavage and forced alkaline diuresis. Haemodialysis may be necessary in severe cases.

There is no well documented experience with Amlodipine overdosage. In case of clinically significant hypotension due to Amlodipine over dosage, calls for active cardiovascular support including monitoring of cardiac and respiratory function, elevation of extremities and attention to circulating fluid volume and urine output. Since Amlodipine is highly protein-bound, dialysis is unlikely to be of benefit.

Overdosage with Atenolol has been reported with patients surviving acute doses as high as 5 gm. One death was reported in a man who may have taken as much as 10 gm acutely.

Storage Condition

Store in a cool and dry place, protected from light.

Keep out of the reach of children. Store below 30° C. Keep in the original package in a cool & dry place in order to protect from light and moisture.

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