Fredun Amlodipine Besylate Tablets

Amlodipine Besylate Tablets USP 10 mg

For the use only of a Registered Medical Practitioner or a hospital ma Laboratory



Each uncoated tablet contains:

Amlodipine Besylate USP

Equivalent to Amlodipine 10mg

Excipients: q.s.


Pharmacological action

i) Amlodipine is a calcium ion influx inhibitor of the dihydropyridine group (slow channel blocker or calcium ion antagonist) and inhibits the transmembrane influx of calcium ions into cardiac and vascular smooth muscle.

ii) The mechanism of the entihypertensive action of Amlodipine is due to a direct relaxant effect on vascular smooth muscle.

iii) The precise mechanism by which Amlodipine relieves and reduces total ischaemic burden by the following two actions:

1. It dilates peripheral arterioles and thus, reduces the total peripheral resistance (after load) against which the heart works. Since the heart rate remains stable, this unloading of the heart reduces myocardial energy consumption and oxygen requirements.

2. The mechanism of action of Amlodipine also probably involves dilatation of the main coronary arteries and coronary arterioles, both in normal and ischaemic regions. This dilatation increases myocardial oxygen delivery in patients with coronary artery spasm.


Pharmacokinetic Data

Absorption, distribution, plasma protein binding

After oral administration of therapeutic doses, Amlodipine is well absorbed with peak blood levels between 6-12 hours post dose. Absolute bioavailability has been estimated to be between 64 and 80%. The volume of distribution is approximately 21 l/kg. In vitro studies have shown that approximately 97.5% of circulating Amlodipine is bound to plasma proteins. The bioavailability of Amlodipine is not affected by food intake.



The terminal plasma elimination half life is about 35-50 hours and is consistent with once daily dosing. Amlodipine is extensively metabolized by the liver to inactive metabolites With 10% of the parent compound and 60% of metabolites excreted in the urine.


Use in children

A population PK study has been conducted in 74 hypertensive children aged from 12 months to 17 years (with 34 patients aged 6 to 12 years and 28 patients aged 13 to 17 years) receiving Amlodipine between 1.25 and 20 mg given either once or twice daily.

In children 6 to 12 years and in adolescents 13-17 years of age the typical oral clearance (CL/F) was 22.5 and 27.4 L/hr respectively in males and 16.4 and 21.3 L/hr respectively in females. Large variability in exposure between individuals was observed. Data reported in children below 6 years is limited.


Use in Elderly

The time to reach peak plasma concentrations of Amlodipine is similar in elderly and younger subjects. Amlodipine clearance tends to be decreased with resulting increases in AUC and elimination half-life in elderly patients. Increases in AUC and elimination half-life in patients with congestive heart failure were as expected for the patient age group studied.


Patients with impaired hepatic function

Very limited clinical data are available regarding Amlodipine administration in patients with hepatic impairment. Patients with hepatic insufficiency have decreased clearance of Amlodipine resulting in a longer half-life and an increase in AUC of approximately 40-60%.


Therapeutic category

Calcium channel blocker.


Therapeutic Indications

For the relief and treatment of pain and inflammation in:

1. Hypertension

2. Chronic stable angina pectoris

3. Vasospaatic (Prinzmetal’s) angina


Posology and Method of Administration

Route of Administration




i) The usual initial dose is 5mg Amlodipine once daily which may be increased to a maximum dose of 10 mg depending on the individual patient’s response.

ii) In hypertensive patients, it has been used in combination with a thiazide diuretic, alpha blocker, beta blocker, or an angiotensin converting enzyme inhibitor. For angina, Amlodipine may be used as monotherapy or in combination with other anti-anginal medicinal products in patients with angina that is refractory to nitrates and/or to adequate doses of beta blockers.

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


Paediatric population (Children and adolescents with hypertension from 6-17 years age)

The recommended dose is 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 paediatric patients.


Children under 6 years old

No data are available.


Elderly patients

Normal dosage regimens are recommended in the elderly, but increase of the dosage should take place with care.


Patients with renal impairment

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


Patients with hepatic impairment

Dosage recommendations have not been established in patients with mild to moderate hepatic impairment; therefore dose selection should be cautious and should start at the lower end of the dosing range.



i) Hypersensitivity to dihydropyridine derivatives, Amlodipine or any of the excipients.

ii) Severe hypotension.

iii) Shock (including cardiogenic shock).

iv) Obstruction of the outflow tract of the left ventricle (e.g. high grade sonic stenosis).

v) Haemodynamically unstable heart failure after acute myocardial infarction.


Warning and Precautions

Use in patients with Heart Failure

Amlodipine was associated with increased reports of pulmonary oedema despite no significant difference in the incidence of worsening heart failure as compared to placebo.


Use in patients with impaired hepatic function

As with all calcium antagonists, amlodipine’s half-life is prolonged in patients with impaired liver function and dosage recommendations have not been established. The drug should therefore be administered with caution in these patients.


Pregnancy and Lactation

Although some dihydropyridine compounds have been found to be teratogenic in animals, data in the rat and rabbit for Amlodipine provide no evidence for a teratogenic effect. There is, however, no clinical experience with the preparation in pregnancy or lactation. Accordingly, it should not be administered during pregnancy, or lactation, or to women of childbearing potential unless effective contraception is used.


Adverse effects

i) The following events occurred in <0.1% of patients: cardiac failure, pulse irregularity, extrasystoles, skin discoloration, urticaria, skin dryness, alopecia, dermatitis, muscle weakness, twitching, ataxia, hypertonia, migraine, cold and clammy skin, apathy, agitation, amnesia, gastritis, increased appetite, loose stools, coughing, rhinitis, dysuria, polyuria, parosmia, taste perversion, abnormal visual accommodation, and xerophthalmia.

ii) Other reactions occurred sporadically and cannot be distinguished from medications or concurrent disease states such as myocardial infarction and angina.

iii) It has not been associated with clinically significant changes in routine laboratory tests like serum potassium, serum glucose, total triglycerides, total cholesterol, HDL cholesterol, uric acid, blood urea nitrogen, or creatinine.


Drug interactions

Effects of other medicinal products on Amlodipine


CYP3A4 inhibitors

Concomitant use of Amlodipine with strong or moderate CYP3A4 inhibitors (protease inhibitors, azole antifungal, and macrolides like erythromycin or Clarithromycin, verapamil or diltiazem) may give rise to significant increase in Amlodipine exposure. Clinical monitoring and dose adjustment may thus be required.


CYP3A4 Inducers

The concomitant use of CYP3A4 inducers (e.g., rifampicin, hypericum perforatun,) may give a lower plasma concentration of Amlodipine. It should be used with caution together.

Administration of Amlodipine with grapefruit or grapefruit juice is not recommended as bioavailability may be increased in some patients resulting in increased blood pressure lowering effects.


Dantrolene (infusion)

In animals, lethal ventricular fibrillation and cardiovascular collapse are observed in association with hyperkalemia after administration of verapamil and dantrolene I.V. Due to risk of hyperkalemia, it is recommended that the co administration of calcium channel blockers such as Amlodipine be avoided in patients susceptible to malignant hyperthermia and in the management of malignant hyperthermia.


Effects of Amlodipine on other medicinal products

The blood pressure lowering effects of Amlodipine adds to the blood pressure-lowering effects of other medicinal products with antihypertensive properties. In clinical interaction studies, Amlodipine did not affect the pharmacokinetics of atorvastatin, digoxin, Warfarin or cyclosporine.



Co-administration of multiple doses of 10 mg of Amlodipine with 80 mg Simvastatin resulted in a 77% increase in exposure to Simvastatin compared to Simvastatin alone. Limit the dose of Simvastatin in patients on Amlodipine to 20 mg daily.




Available data suggest that gross over dosage could result in excessive peripheral vasodilatation and possibly reflex tachycardia. Marked and probably prolonged systemic hypotension up to and including shock with fatal outcome have been reported.



i) Clinically significant hypotension due to Amlodipine over dosage calls for active cardiovascular support including frequent monitoring of cardiac and respiratory function, elevation of extremities and attention to circulating fluid volume and urine output.

ii) A vasoconstriotor may be helpful in restoring vascular tone and blood pressure, provided that there is no contraindication to its use. lntravenous calcium gluconate may be beneficial in reversing the effects of calcium channel blockade.

iii)Gastric lavage may be worthwhile in some cases. In healthy volunteers the use of charcoal up to 2 hours after administration of Amlodipine 10 mg has been shown to reduce the absorption rate of Amlodipine.

iv) Since Amlodipine is highly protein-bound, dialysis is not likely to be of benefit.


Pharmaceutical information

Storage conditions

Store below 30o Protect from direct sunlight, heat and moisture.

Keep all medicines out of reach of children.


Shelf Life

36 months.


Pack size

Blister pack of 10 tablets


Description of the product

White coloured, circular, flat, beveled, uncoated tablet with break line on one side and other side plain.


Manufactured by

Fredun Pharmaceuticals Ltd.

14,15,16, Zorabian Industrial Complex,

Veoor, Palghar (E) -401 404. INDIA


Manufactured for


20 Erhuvwa Club Street,

Asaba Delta State, Nigeria


Preferred Groups LLC, Maryland U.S.A.

Eden Atenolol Tablets

Eden Atenolol 50 mg
(Atenolol Tablets BP 50mg)

For the use of a Registered Medical Practitioner or Hospital or a Laboratory only



Each uncoated tablet contains

Atenolol BP 50mg



Pharmacological Action

Beta- adrenoceptor antagonists complete with beta-adrenergic agonists for available beta-receptor sites. Unselective beta-blockers inhibit the beta1 receptors (located chiefly in cardiac muscle) and beta2 receptors (located chiefly in the bronchial and vascular musculature) inhibiting the chronotropic, inotroptic and vasodilator responses to beta-adrenergic stimulation. Atenolol is cardioselective and preferentially inhibits beta1 adrenoceptors. Beta1 selectively has been confirmed by the inability of atenolol to reverse the beta2 mediated vasodilating effects of adrenaline or isoprenaline. This contrasts with the effect of nonselective beta-blockers which completely reverse the vasodilating effects of adrenaline. Atenolol does not have membrane stabilizing effects, little direct myocardial depressant activity and little or no intrinsic sympathomimetic activity.

Clinical response to beta-blockage includes slowing of the sinus heart rate, depressed AV conduction, decreased cardiac output at rest and on exercise, reduction of systolic blood pressure on exercise, reduction of both supine and standing blood pressure, inhibition of isoprenaline-induced tachycardia amid reduction of reflex orthostatic tachycardia.



Absorption: Atenolol is consistently absorbed when administered orally; with approximately 50-60% of the dose administered being absorbed. After an oral dose of 100 mg a mean peak serum level of 880ng/ml was reached in approximately 3 hours, declining to approximately 63 ng/ml in 24 hours.

Distribution: Atenolol is widely distributed throughout the body, but only a small amount of the drug reaches the brain. Atenolol is not significantly bound to serum proteins. In pregnancy atenolol readily crosses the placenta, the umbilical and maternal serum being approximately equal at birth.

Metabolism: Metabolism of atenolol in man is minimal. In animal studies, hydroxilated compound, with minor beta-blocking activity, has been identified as a minor metabolite of atenolol, but atenolol does not appear to be metabolised to any significant extent in man.

Excretion: Atenolol is excreted unchanged, mainly through the kidneys. About 40-50% of a single oral dose is excreted in the urine of healthy subjects. The elimination half life of atenolol is approximately 6-7 hours.

In renal dysfunction, the elimination of atenolol is closely related to the glomerular-filtration rate, although important accumulation probably only occurs if the glomerular filtration is less than 30 ml/min.



• In the management of hypertension

• In the management of angina pectoris

• In the management of cardiac dysrhythmias

• In the management of myocardial infarction: early intervention in the acute phase and long term prophylaxis after recovery from myocardia infarction.



As with other beta-adrenoceptor blocking drugs, atenolol should not be used in the following circumstances

• Patients with second degree or third degree hearth block.

• Patients with severe bradycardia.

• Uncontrolled or digitalis/diuretic-refractory heart failure.

• Patients with cardiogenic shock.

• Patients with sick sinus syndrome.

• Patients with untreated phaeochromocytoma.

• Patients with hypersensitivity to Atenolol or to any other ingredients of the preparation.

• Patients with severe peripheral circulatory disturbances.

• Patients with metabolic acidiosis.

• Patients with hypotension.



• The beta-blocker should only he used with great caution in patients who are receiving concomitant myocardial depressants such as chloroform, lignocaine, procainamide, beta-adrenoceptor stimulants such as isoprenaline, or verapamil or alpha-adrenoceptor stimulants such as noradrenaline, adrenaline (which reverse the hypotensive effects and increase the vasoconstrictor activities).

• Neurotic blocking agents such as guanethidine, reserpine, diuretics and other antihypertensive agents, including the vasodilator group, will have an additive effect on the hypotensive action of the drug.

• The beta-blocker may mask the symptoms of thyrotoxicosis.

• Caution should be exercised when transferring patients from clonidine to beta-adrenoceptor blocking drugs. If the beta-blocker and clonidine are given concurrently, the clonidine should not be discontinued until several days after withdrawal of the beta-blocker.

• Combined use of beta-adrenoceptor blocking drugs and calcium channel blockers with negative inotropic effects e.g. verapamil, dilitiazem, can lead to an exaggeration of these effects, particularly in patients with impaired ventricular function and /or sino-atrial or antrio-ventricular conduction abnormalities. This may result in severe hypotension, bradycardia and cardiac failure. Neither the beta-adrenoceptor blocking drug nor the calcium channel blocker should be administered intravenously within 48 hours of discontinuing the other.

• Digitalis glycosides, in association with beta-adrenoceptor-blocking drugs, may increase atrio-ventricular conduction time.

• Caution must be exercised when prescribing a beta-adrenoceptor blocking drug with Class1 antiarrythmic agents such as disopyramide.

• Beta-blockers may have hypoglyaemic or hyperglycaemic actions and may decrease or increase the patient’s requirements for insulin or oral antidiabetic agents. Beta-blockers may mask some of the symptoms of hypoglycaemia.

• Plasma concentrations of beta-adrenoceptor blocking drugs may be increased by cimetidine, which is believed to impair beta-blocker metabolism.

• Reduction in first-pass metabolism of oral beta-adrenoceptor blocking drugs may occur in patients also receiving hydralazine.

• Plasma clearance of beta-adrenoceptor blocking drugs can be affected by alcohol intake.

• Concomitant use of prostaglandin synthetase inhibiting drug e.g. ibuprofen or indomethacin may decrease the hypotensive effects of beta-adrenoceptor blocking drugs.

• Plasma concentrations of some beta-adrenoceptor blocking drugs may be reduced by barbiturates.

• Concomitant use of phenothiazines and beta-adrenoceptor blocking drugs may cause increased plasma concentrations and bioavailability and reduced



• Sudden withdrawal of beta-adrenoceptor blocking agents in patients with ischaemic heart disease may result in the appearance of anginal attacks of increased frequency or severity or deterioration in cardiac state. Discontinuation of therapy should be gradual.

• In Anaesthesia: Care should be taken when using anaesthetic agents with atenolol. The anaesthetist should be informed to enable the necessary precautions to be taken.

• If a beta-blocker is withdrawn prior to surgery it should be discontinued for at least 24 hours.

• Atenolol should only be used with caution in patients with controlled congestive cardiac failure. Evidence of development of this condition should be regarded as a signal to discontinue therapy.

• Beta-blockers, even those with apparent cardioselectivity, should not be used in patients with asthma or a history of obstructive airways disease, unless no alternative treatment is available. In such cases the risk of inducing bronchospasm should be appreciated and appropriate precautions taken.

• The initial treatment of severe malignant hypertension should be designed as to avoid sudden reduction in diastolic blood pressure with impairment of autoregulatory mechanisms.

• Patients with psoriasis should take beta-blockers only after careful consideration.

• Beta-blockers may increase both the sensitivity towards allergens and the seriousness of anaphylactic reactions.

• Atenolol may increase the number and duration of angina attacks in patients with Prinzmetal’s angina due to unopposed alpha-receptor mediated coronary artery vasoconstriction. Atenolol is a beta1 selective beta adrenoceptor-blocking drug; consequently, its use maybe considered although utmost caution must be exercised.

• Although contraindicated in severe peripheral arterial circulatory disturbance, atenolol may also aggravate less severe peripheral arterial circulatory disturbances.

• Due to atenolol’s negative effect on conduction time, caution must be exercised if it is given to patients with first-degree heart block.



The safety of amlodipine in human pregnancy has not been established. In animal studies, re-productive toxicity was observed at high doses. Use in pregnancy is only recomnmended when there is no safer alternative and when the disease itself carries greater risk for the mother and foetus.

Breast-Feeding: It is not known whether amlodipine is excreted in breast milk. A decision on whether to continue/discontinue breast-feeding or to continue/discontinue therapy with amlodipine should be made taking into account the benefit of breast-feeding to the child and the benefit of amlodipine therapy to the mother.

Fertility: Reversible biochemical changes in the head of spermatozoa have been reported in some patients treated by calcium channel blockers. Clinical data are insufficient regarding the potential effect of amlodipine on fertility. In one rat study, adverse effects were found on male fertility.



Atenolol is generally well-tolerated and side effects associated with it are infrequent and generally mild. These can include: coldness of the extremities and muscular fatigue may occur and, in isolated cases, bradycardia. Sleep disturbances which are associated with some other beta-blocking preparations are rare.

There have been reports of skin rashes and/or dry eyes associated with the use of beta-adrenergic blocking drugs. The reported incidence is small and in most cases the symptoms have cleared when treatment is withdrawn. Discontinuance of the drug should be considered if any such reaction is not otherwise explicable. Cessation of therapy with a beta- blocker should be gradual.

Beta-adrenergic blocking drugs can cause dry mouth and gastrointestinal disturbances including nausea and vomiting, diarrhea, constipation and abdominal cramping. The signs of thyrotoxicosis maybe masked by atenolol treatment.

Bronchospasm may occur in patients with bronchial asthma or history of asthmatic complaints.

An increase in ANA(antinuclear antibodies) has been observed, however, the clinical relevance of this is not clear.






Symptoms: Signs of overdosage are bradycardia, severe hypotension, bronchospasm, hypoglycaemia, acute cardiac insufficiency and heart failure.

Treatment: General treatment should include: close supervision: treatment in an intensive care ward, if ingestion is recent, the stomach should be emptied by aspiration and lavage; activated charcoal and a laxative to prevent absorption of any drug still present in the gastrointestinal tract; the use of plasma or plasma substitutes to treat hypotension and shock. The possible uses of haemodialysis or haemoperfusion may be considered.

From first principles, excessive bradycardia may be countered by atropine 1-2mg intravenously and/or a cardiac pacemaker, followed, if necessary, by a bolus dose of glucagon 10 mg intravenously. If required, this may be repeated or followed by an intravenous infusion of glucagon 1-10 mg/hour depending on response. If no response to glucagon occurs or if glucagon is unavailable, a beta-adrenoceptor stimulant such as prenalterol 5 mg intravenously, followed if necessary by an intravenous infusion of 5 mg/hour or dobutamine 2.5 to 10 microgram/kg/minute by intravenous infusion may be given. Dobutamine, because of its positive inotropic effect could also be used to treat hypotension and acute cardiac insufficiency. It is likely that these doses would be inadequate to reverse the cardiac effects of beta-blocker blockade if a large overdose has been taken. The dose of dobutamine should therefore be increased if necessary to achieve the required response according to the clinical condition of the patient.
Any risk of hypotension occurring following the use of beta-adrenoceptor agonists will be reduced by the use of the more selective agents. e.g. prenalterol and dobutamine. Bronchospasm can usually be reversed by bronchodilators.





Hypertension: One tablet daily. Most patients respond to 100 mg daily given as a single dose. Some patients, however, will respond to 50 mg given as a single daily dose. The effect will be fully established after one to two weeks. A further reduction in blood pressure may be achieved by combining atenolol with other antihypertensive agents. For example, co-administration of atenolol with a diuretic provides a highly effective and convenient antihypertensive therapy.

Angina: Most patients with angina pectoris will respond to 100mg given orally once daily or 50mg given twice daily: It is unlikely that additional benefit will be gained by increasing the dose.

Dysrhythmias: Having controlled the dysrhythmias with intravenous atenlol a suitable maintenance dosage is 50mg – 100mg daily, given as a single dose.

Myocardial Infarction: 15 minutes after the administration of the intravenous dose an oral dose of 50mg may be given provided that no untoward effects occur from the intravenous dose.

This should be followed by a further 50mg orally 12 hours after the intravenous dose and then 12 hours later by 100mg orally to be given once daily for up to ten days. If bradycardia and/or hypotension require treatment, or may other untoward effects occur, atenolol should be discontinued.


Special Populations

Renal Failure: Atenolol is excreted via the kidneys, dosage adjustment should therefore be considered in patients with severe impairment of renal function. As a guide, for patients with a serum creatinine of 300- 600 µmol/L, the atenolol oral dose should be 50mg daily or 100mg once every two days, for patients with a serum creatinine of >600 µmol/L, the oral dose of atenolol should be 50mg on alternate days or 100mg once every four days.

Patients on haemodialysis should be given 50mg atenolol orally following each dialysis. Because of the possibility of marked falls in blood pressure: this should be carried out under hospital supervision.

Elderly: Dosage requirements may be reduced, especially in patients with impaired renal function.

Children: There is no paediatric experience with atenolol and for this reason it is not recommended for use in children.


Method of Administration

For oral administration.



Take the whole Tablet with a glass of water.


PRESENTATION: 2 x 14 Tablets packed in Alu-PVC Blister Pack.


STORAGE CONDITION: Store at temperature not exceeding 30oC in a dry place. Protect from light.




SHELF LIFE: 36 Months


Manufactured by

Scott- Edil Pharmacia Ltd.

56,EPIPP, Phase1, Jharmajri 173205,

Distt. Solan (H.P.), India.


Imported and distributed by

Eden U.K Pharmaceutical Ltd

J116, Daminja Avenue, Housing Estate,

Fegge, Anambram State, Nigeria.