DESCRIPTION & COMPOSITION
White to off white, shield shape tablet, with "CCM" on one side and scored
on the other side.
Each tablet contains amlodipine besylate equivalent to 5 mg amlodipine.
White to off white, shield shape tablet, with "CCM 10" on one side and
scored on the other side.
Each tablet contains amlodipine besylate equivalent to 10 mg amlodipine.
Amlodipine is a calcium ion influx inhibitor (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 of amlodipine 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.
• 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.
• 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 dilatation increases myocardial oxygen delivery in
patients with coronary artery spasm (Prinzmetal's or variant angina) and
blunts smoking induced coronary vasoconstriction.
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 the 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 1 mm ST segment
depression, and decreases both angina attack frequency and nitroglycerine
In vitro studies have shown that approximately 97.5% of circulating
amlodipine is bound to plasma proteins.
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.
Hemodynamic studies and exercise based controlled clinical trials in NYHA
Class II-IV heart failure patients have shown that amlodipine did not lead
to clinical deterioration as measured by exercise tolerance, left
ventricular ejection fraction and clinical symptomatology.
A placebo controlled study (PRAISE) designed to evaluate patients in NYHA
Class III-IV heart failure receiving digoxin, diuretics and ACE inhibitors
has shown that amlodipine did not lead to an increase in risk of mortality
or combined mortality and morbidity in patients with heart failure. In the
same study, in a group of patients without clinical signs or symptoms
suggestive of underlying ischemic disease, a clinically and statistically
significant reduction in mortality and combined mortality and morbidity was
observed with amlodipine.
After oral administration of therapeutic doses, amlodipine is well absorbed
with peak blood levels between 6-12 hours postdose. Absolute bioavailability
has been estimated to be between 64 and 80%. The volume of distribution is
approximately 21 l/kg. Absorption of amlodipine is unaffected by consumption
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 metabolized
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 elderly
patients. Increases in AUG and elimination half life in patients with
congestive heart failure were as expected for the patient age group studied.
Amlodipine 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 amlodipine, which has been used in
combination with a thiazide diuretic, alpha blockers, beta adrenoceptor
blocking agent, or an angiotensin-converting enzyme inhibitor.
Amlodipine 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. Amlodipine may be used where the clinical presentation suggests
a possible vasospastic/vasoconstrictive component but where
vasospasm/vasoconstriction has not been confirmed. Amlodipine 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
DOSAGE AND ADMINISTRATION
For both hypertension and angina the usual initial dose is 5mg amlodipine
once daily which may be increased to a maximum dose of 10mg depending on the
individual patient's response.
No dose adjustment of amlodipine is required upon concomitant administration
of thiazide diuretics, betablockers, and angiotensin-converting enzyme
Use in the Elderly
Normal dosage regimens are recommended. Amlodipine, used at similar doses in
elderly or younger patients, is equally well tolerated.
Use in Children
Safety and effectiveness of amlodipine in children have not been
Use in Patients with Impaired Hepatic Function
See Precautions / Warnings.
Use in Renal Failure
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.
Amlodipine is contraindicated in patients with a known sensitivity to
dihydropyridines, amlodipine, or any of the inert ingredients.
PRECAUTIONS / WARNINGS
Use In Patients with Impaired Hepatic Function
As with all calcium antagonists, amlodipine 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
Amlodipine has been safely administered with thiazide diuretics, alpha
blockers, beta blockers, angiotensin-converting enzyme inhibitors,
long-acting nitrates, sublingual nitroglycerine, non-steroidal
anti-inflammatory drugs, antibiotics, and oral hypoglycemic drugs.
Studies have indicated that the co-administration of amlodipine with digoxin
did not change serum digoxin levels or digoxin renal clearance in normal
volunteers, and that co-administration of cimetidine did not alter the
pharmacokinetics of amlodipine.
In vitro data from studies with human plasma indicate that amlodiplne has no
effect on protein binding of the drugs tested (digoxin, phenytoin, warfarin,
In healthy male volunteers, the co-administration of amlodipine does not
significantly alter the effect of warfarin on prothrombin response time.
Pharmacokinetic studies with cyclosporin have demonstrated that amlodipine
does not significantly alter the pharmacokinetics of cyclosporin.
Pregnancy And Lactation
Safety of amlodipine in human pregnancy or lactation has not been
established. Amlodipine does not demonstrate toxicity in animal reproductive
studies other than to delay parturition and prolong labor in rats at a dose
level fifty times the maximum recommended dose in
humans. Accordingly, 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.
Effects on Ability to Drive and Use Machines
Clinical experience with amlodipine indicates that it is unlikely to impair
a patient's ability to drive or use machinery.
Amlodipine is well tolerated, In placebo controlled clinical trials
involving patients with hypertension or angina, the most commonly observed
side effects were headache, edema, fatigue, somnolence, nausea, abdominal
pain, flushing, palpitations, and dizziness. In these clinical trials no
pattern of clinically significant laboratory test abnormalities related to
amlodipine has been observed.
Less commonly observed side effects in marketing experience include
alopecia, altered bowel habits, arthralgia, asthenia, back pain, dyspepsia,
dyspnea, gingival hyperplasia, gynecomastia, hyperglycemia, impotence,
increased urinary frequency, leucopenia, malaise, mood changes, dry mouth,
muscle cramps, myalgia, peripheral neuropathy, pancreatitis, increased
sweating, syncope, thrombocytopenia, vasculitis, and visual disturbances. In
many instances, causal association is uncertain.
Rarely, allergic reaction including pruritus, rash, angioedema, and erythema
Hepatitis, jaundice and hepatic enzyme elevations have also been reported
very infrequently (mostly consistent with cholestasis). Some cases severe
enough to require hospitalization have been reported in association with use
of amlodipine. In many instances, causal association is uncertain.
As with other calcium channel blockers the following adverse events have
been rarely reported and cannot be distinguished from the natural history of
the underlying disease: myocardial infarction, arrhythmia (including
ventricular tachycardia and atrial fibrillation) and chest pain.
In humans, experience with intentional overdose is limited. Gastric lavage
may be worthwhile in some cases. Available data suggest that gross
overdosage could result in excessive peripheral vasodilatation with
subsequent marked and probably prolonged systemic hypotension. 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. Since amlodipine is highly
protein-bound, dialysis is not likely to be of benefit.
FOR SPECIALIST'S USE ONLY.
PACKING / PACK SIZE
5mg: Blister packs of 3 x 10's and 10 x 10's.
10mg: Blister packs of 3 x 10's and 10 x 10's.
Keep container tightly closed.
Store in a dry place below 30°C.
Protect from light and moisture.