|
Zynor
Amlodipine
COMPOSITION
Zynor 5mg : Each tablet contains
Amlodipine Besylate equivalent to Amlodipine 5mg
Zynor 10mg : Each tablet contains
Amlodipine Besylate equivalent to Amlodipine 10mg
PHARMACODYNAMICS
Amlodipine is a calcium ion
influx inhibitor of the dihydrophyridine 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
anihypertensive action of amlodipine is due to a direct relaxant effect on
vascular smooth muscle. The precise mechanism by which amlodipine relieves
anglina has not been fully determined but amlodipine reduces total ischaemic
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
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 ( Prinzmetal's or variant angina ).
In patients with hypertension,
once daily dosing provides clinically significant reductions of blood
pressure in both the supine and standing positions throughout the 24 hour
interval. Due to he slow onset of action, acute hypotension is not a feature
of amlodipine administration.
In patients with angina, once
daily administration of amlodipine increases total exercise time, time to
angina onset, and time to 1mm ST segment depression, and decreases both
angina attack frequency and nitroglycerine tablet consumption.
Amlodipine has not been
associated with any adverse metabolic effects or changes in plasma lipids
and is suitable for use in patients with asthma, diabetes, and gout.
PHARMACOKINETICS
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. The absorption of amlodipine is unaffected by the concomitant intake
of food. 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 approxiately 97.5% of circulating amlodipine is bound to
plasma proteins.
Biotransformation/elimination
: The terminal plasma elimination half life is about 35-50 hours and is
consistent with once daily dosing. Steady state plasma levels are reached
after 7-8 days of consecutive dosing. Amlodipine is extensively metabolised
by the liver to inactive metabolites with 10% of the parent compound and 60%
of metabolites excreted in the urine.
Use in the 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 elerly patients.
Increases in AUC and elimination half-life in patients with congestive heart
failure were as expected for the patient age group studied.
INDICATIONS
Hypertension : Zynor is
indicated for the first line treatment of hypertension and can be used as
the sole agent to control blood pressure in the majority of patients.
Patients not adequately controlled on a single antihypertensive agent may
benefit from the addition of Zynor, which has been used in combination with
a thiazide diuretic, alpha blockers, beta adrenoceptor blocking agent, or an
angiotensin converting enzyme inhibitor.
Myocardial Ischemia :
Zynor is indicated for the first line treatment of myocardial ischemia,
whether due to fixed obstruction ( stable angina ) and/or
vasospasm/vasoconstriction ( Prinzmetal's or variant angina ) of coronary
vasculature. Zynor may be used where the clinical presentation suggests a
possible vasopastic/vasoconstrictive component but vasospastic/vasoconstrictive
has not been confirmed. Zynor may be used alone, as monotherapy, or in
combination with other antianginal drugs in patients with angina that is
refractory to nitrates and/or adequate doses of beta blockers.
DOSAGE AND ADMINISTRATION
Adults : For both
hypertension and angina the usual initial dose is 5mg Zynor once daily which
may be increased to a maximum dose of 10mg depending on the individual
patient's response.
No dose adjustment of Zynor is
required upon concomitant administration of thiazide diuretic, beta blockers
and angiotensin-converting enzyme inhibitors.
In children : Not
recommended
In the elderly : Normal
dosage regimens are recommended. Amlodipine, used at similar doses in
elderly or younger patients, is equally well tolerated.
Patients with hepatic
impairment : See section Precautions.
Patients with renal impairment
: Amlodipine may be used in such patients at normal doses. Changes in
amlodipine plasma concentrations are not correlated with degree of renal
impairment. Amlodipine is not dialyzable.
1
2
|
