1. NAME OF MEDICINAL PRODUCT
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Active Ingredient: amlodipine
The tablets contain amlodipine besylate equivalent to 5 and 10mg amlodipine.
3. PHARMACEUTICAL FORM
4. CLINICAL PARTICULARS
4.1 Therapeutic Indications
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
4.2 Posology and Method of 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, beta-blockers, 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 section 4.4 Special Warnings and Special Precautions for Use.
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.
4.4 Special Warnings and Special Precautions for Use
Use in Patients with Heart
In a long-term, placebo controlled study (PRAISE-2) of amlodipine in
patients with NYHA III and IV heart failure of nonischemic etiology,
amlodipine was associated with increased reports of pulmonary edema despite
no significant difference in the incidence of worsening heart failure as
compared to placebo (see section 5.1 Pharmacodynamic Properties).
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
4.5 Interaction with Other Medicaments and Other Forms of Interaction
Amlodipine has been safely administered with thiazide diuretics, alpha
blockers, beta blockers, angiotensinconverting enzyme inhibitors,
long-acting nitrates, sublingual nitroglycerine, anti-inflammatory drugs,
antibiotics, and oral hypoglycemic drugs.
In vitro data from studies with human plasma indicate that amlodipine
has no effect on protein binding of the drugs tested (digoxin, phenytoin,
warfarin, or indomethacin).
In the following studies listed below, there were no significant changes in
the pharmacokinetics of either amlodipine or another drug within the study.
Special Studies: Effect of other agents on amlodipine.
CIMETIDINE: Co-administration of amlodipine with cimetidine did not alter
the pharmacokinetics of amlodipine.
GRAPEFRUIT JUICE: Co-administration of 240 mL of grapefruit juice with a
single oral dose of amlodipine 10 mg in 20 healthy volunteers had no
significant effect on the pharmacokinetics of amlodipine.
ALUMINUM/MAGNESIUM (antacid): Co-administration of an aluminum/magnesium
antacid with a single dose of amlodipine had no significant effect on the
pharmacokinetics of amlodipine.
SILDENAFIL: A single 100 mg dose of sildenafil in subjects with essential
hypertension had no effect on the pharmacokinetic parameters of amlodipine.
When amlodipine and sildenafil were used in combination, each agent
independently exerted its own blood pressure lowering effect.
Special Studies: Effect of amlodipine on other agents.
ATORVASTATIN: Co-administration of multiple 10 mg doses of amlodipine with
80 mg of atorvastatin resulted in no significant change in the steady state
pharmacokinetic parameters of atorvastatin.
DIGOXIN: Co-administration of amlodipine with digoxin did not change serum
digoxin levels or digoxin renal clearance in normal volunteers.
ETHANOL (alcohol): Single and multiple 10 mg doses of amlodipine had no
significant effect on the pharmacokinetics of ethanol.
WARFARIN: Co-administration of amlodipine with warfarin did not change the
warfarin prothrombin response time.
CYCLOSPORIN: Pharmacokinetic studies with cyclosporin have demonstrated that
amlodipine does not significantly after the pharmacokinetics of cyclosporin.
Drug/Laboratory Test Interactions: None known.
4.6 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.
4.7 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.