Amdocal Final PDF

®
Amlodipine
5 mg and 10 mg Tablet
Description
®
Amdocal is a preparation of Amlodipine. Amlodipine is a dihydropyridine calcium antagonist, with a long duration of action,
used for the treatment of hypertension and angina pectoris.
Mode of Action
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.
The mechanism of the antihypertensive action is due to a direct relaxant effect on vascular smooth muscle. The precise
mechanism by which amlodipine relieves angina has not been fully determined but Amlodipine reduces total ischemic burden
by the following two actions:
1. Amlodipine dilates peripheral arterioles and thus, reduces the total peripheral resistance (afterload) 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 ischemic regions. This dilation increases myocardial oxygen delivery in patients with coronary
artery spasm (prinzmetals or variant angina).
Indications
Hypertension
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Amdocal is indicated for the treatment of hypertension. It may be used alone or in combination with other antihypertensive
agents.
Stable angina
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Amdocal is indicated for the treatment of chronic stable angina. It may be used alone or in combination with other
antianginal agents.
Vasospastic angina
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Amdocal is indicated for the treatment of confirmed or suspected vasospastic angina. The drug may be used as single
therapy or in combination with other antianginal drugs.
Dosage and Administration

The dose should be individualized according to the goal of therapy and patient response.
Usual Adult Dose
The usual initial oral dose for stable or vasospastic angina and hypertension is 5 mg once daily with a maximum dose of 10
mg once daily.
Pediatric use
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.
Contraindications
®
Amdocal 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
Special Warnings and Precautions

Hypotension
Since the vasodilatation 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 used
with 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 gradual
reduction 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.
Drug Interactions
Effects of other medicinal products on amlodipine
CYP3A4 inhibitors
Concomitant use of Amlodipine with strong or moderate CYP3A4 inhibitors (protease inhibitors, azole antifungals,
macrolides like erythromycin or clarithromycin, verapamil or diltiazem) may give rise to significant increase in amlodipine
exposure. The clinical translation of these PK variations may be more pronounced in the elderly. Clinical monitoring and dose
adjustment may thus be required.
CYP3A4 inducers
There is no data available regarding the effect of CYP3A4 inducers on amlodipine. The concomitant use of CYP3A4 inducers
(e.g., rifampicin, hypericum perforatum) may give a lower plasma concentration of amlodipine. Amlodipine should be used
with caution together with CYP3A4 inducers.
Grapefruit or grapefruit juice
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 intravenous dantrolene. Due to risk of hyperkalemia, it is recommended that the
coadministration 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
Other antihypertensive agents.
The blood pressure lowering effects of amlodipine adds to the blood pressure-lowering effects of other antihypertensive
agents.
Atorvastatin, digoxin, warfarin or ciclosporin
In clinical interaction studies, amlodipine did not affect the pharmacokinetics of atorvastatin, digoxin, warfarin or ciclosporin.
Simvastatin
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.
Fertility, Pregnancy and Lactation

Pregnancy
Pregnancy Category C
The safety of amlodipine in human pregnancy has not been established. In animal studies, reproductive toxicity was
observed at high doses. Use in pregnancy is only recommended when there is no safer alternative and when the disease
itself carries greater risk for the mother and fetus.
Lactation
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.
Side Effects
Peripheral edema may occasionally be severe but is fully reversible. As with other calcium antagonist drugs, peripheral
edema and skin erythema occur in a proportion of patients (5-10%) and facial flushing in 2-5% of patients. Complaint of
fatigue was also reported more frequently than in placebo-treated patients. There is evidence that these effects are more
common in patients treated with doses greater than 10 mg daily.
Common or very common
Abdominal pain, dizziness, fatigue, flushing, headache, nausea, edema, palpitation, sleep disturbances.
Uncommon
Alopecia, arthralgia, asthenia, back pain, chest pain, dry mouth, dyspnoea, gastro-intestinal disturbances, gynaecomastia,
hypotension, impotence, mood changes, muscle cramps, myalgia, paresthesia, pruritus, purpura, rashes, rhinitis, skin
discolouration, sweating, syncope, taste disturbances, tinnitus, tremor, urinary disturbances, visual disturbances, weight
changes.
Very rare
Angioedema, arrhythmias, cholestasis, coughing, gastritis, gingival hyperplasia, hepatitis, hyperglycaemia, jaundice,
myocardial infarction, pancreatitis, peripheral neuropathy, tachycardia, thrombocytopenia, urticaria, vasculitis.
Frequency not known
Erythema multiforme.
Overdose
In humans, experience with intentional overdose is limited.
Symptoms
Available data suggest that large overdosage 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.
Management
Clinically significant hypotension due to amlodipine overdosage 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.
A vasoconstrictor may be helpful in restoring vascular tone and blood pressure, provided that there is no contraindication to
its use. Intravenous calcium gluconate may be beneficial in reversing the effects of calcium channel blockade. Gastric lavage
may be worthwhile in some cases. In healthy volunteers the use of charcoal up to 2 hours after administration of amlodipine
10mg has been shown to reduce the absorption rate of amlodipine. Since amlodipine is highly protein-bound, dialysis is not
likely to be of benefit.
Pharmaceutical Precautions
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.
Commercial Pack
®
Amdocal 5 Tablet: Box containing 100 tablets in 10 x 10’s blister strips. Each tablet contains Amlodipine Besylate BP
equivalent to Amlodipine 5 mg.
®
Amdocal 10 Tablet: Box containing 60 tablets in 6 x 10’s blister strips. Each tablet contains Amlodipine Besylate BP
equivalent to Amlodipine 10 mg.
Manufactured by
BEXIMCO PHARMACEUTICALS LTD.
TONGI, BANGLADESH
® Amdocal is a registered trademark of Beximco Pharmaceuticals Ltd.

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Dosage and Administration

Special Warnings and Precautions

Fertility, Pregnancy and Lactation

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