Wednesday, March 22, 2017


For The Medical Profession Only
Regcor@ Tablets
Each tablet contains:
Amlodipine (as besylate) 5 or 10 mg
Inactive ingredients: microcrystalline cellulose,
anhydrous, sodium starch glycolate, colloidal
Clinical Pharmacology:
phosphate dibasic
oxide, magnesjurn
Mechanism of Action: Regcor is a dihydropyridine calcium antagonist (calcium
ion antagonist or slow-channel blocker) that inhibits the trarismembrane influx of
calcium ion into vascular smooth muscle and cardiac musqe. Experimental data
suggest that amlodipine binds to both dihydropyridine and nondihydropyridine
binding The contractile processes of cardiac muscle and vascular smooth
muscle are dependent upon the movement of extracellular calcium ions into
these cells through specific ion channels. Regcor inhibits calcium ion influx
across cell membranes selectively, with a greater effect on vascular smooth
muscle cells than on cardiac muscle cells. Negative inogropjc effects can be
detected in vitro but such effects have not been seen tin intact animals at
therapeutic doses. Serum calcium concentration is not affected by Regcor Within
the physiologic pH range, Regcor is an ionized compound (pKa:8.6), and its
kinetic interaction with the calcium channel receptor i$ characterized by a
gradual rate of association and dissociation with the receptor binding Site,
resulting in a gradual onset of effect.
Regcor is a peripheral. arterial vasodilator that acts directly on vascular smooth
muscle to cause a reduction in peripheral vascular resistance and reduction in
blood pressure.
The precise mechanisms by which Regcor relieves angi have not been fully
delineated, but are thought to include the following:
Exertional Angina: In patients With exertional angina, Regcor reduces the total
peripheral resistance (afterload) against which the heart works and reduces the
rate pressure product, and thus myocardial oxygen deman at any given level of
Vasospastic Angina: Regcor has been demonstrated to block constriction and
restore blood flow in coronary arteries and arterioles in response to calcium,
potassium, epinephrine, serotonin, and thromboxane A2 analog in expertrnental
animal models and in human coronary vessels in Vitro. This inhibition of
coronary spasm is responsible for the effectiveness of Regcor in vasospastic
(Prinzmetal's or variant) angina.
Pharmacokinetics and Metabolism: After oral administration of therapeutic-
doses of Regcor, absorption produces peak plasma concentrations between 6
and 12 hours. Absolute bioavailability has been estimated to be between 64 and
90%. The bioavailability of Regcor is not altered by the presence of food.
Regcor is extensively (about 90%) converted to inactive metabolites via hepatic
metabolism with 10% of the parent compound and 60% metabolites excreted in
the urine. Ex vivo studies have shown that approximately 93% of the circulating
drug is bound to plasma proteins in hypertensive patients. Elimination from the
plasma is biphasic with a terminal elimination half-life of about 30 — 50 hours,
Steady-state plasma levels of Regcor are reached after 7 to 8 days of consecutive
daily dosing. The pharmacokinetics of Regcor are not significantly influenced by
renal impairment. Patients with renal failure may therefore receive the usual
initial dose. Elderly patients and patients with hepatic insufficiency have
decreased clearance of amlodipine with a resulting increase in AUC of
approximately 40-60%, and a lower initial dose may be required. A similar
increase in AUC was observed in patients With moderate to severe heart failure.
Pharmacodynamics: Hemodynamics following administration of therapeutic
doses to patients with hypertension, Regcor produces vascxlilation resulting in a
reduction of supine and standing blood pressures.
These decreases in blood pressure are not accompanied b a significant change
in heart rate or plasma catecholamine levels with chronicdosing. Although the
acute intravenous administration of amlodipjne decreases arterial blood pressure
and increases heart rate in hemodynamic studies of patients with chronic stable
angina, chronic administration of oral amlodipine in clinical trials did not lead to
clinically. significant changes in heart rate or blood pressUres in normotensive
patients with angina.
With chronic once daily oral administration, antihypertensive effectiveness is
maintained for at least 24 hours. Plasma concentrations correlate with effecf in
both young and elderly patients. The magnitude of reducüon in blood pressure
with Regcor is also correlated with the height of pretreatment elevation; thus,
individuals with moderate hypertension (diastolic pressure 105 - 114 mmHg) had
about a 50% greater response than patients with mild hypertension (diastolic
pressure 90 — 104 mmHg); Normotensive subjects experienced no clinically
Significant change in blood pressures (+1/-2 mmHg).
In hypertensive patients With normal renal function, therapeutic doses Of Regcor
resulted in a decrease in renal vascular resistance and an increase in glomerular
filtration rate and effective renal plasma flow Without change in filtration fraction
or proteinuria.
As with other calcium channel blockers, hemodynamic measurements of cardiac
function at rest and during exercise (or pacing) in patients with normal
ventricular function treated, with amlodipine have generally demonstrated a
small increase in cardiac index without significant influence on dp/dt or on left
ventricular end diastolic pressure or volume. In hemodynamic studies,
amlodipine has not been associated With a negative inotroptc effect when
administered in the therapeutic dose range to intact animals and man, even
when co-administered with beta-blockersto man. Similar findings, however, have
been observed in normals or well-compensated patients With heart failure with
agents possessing significant negative inotropic effects.
Indications And Usage:
- Hypertension:
Amlodipine besylate tablets are indicated for the treatment of hypertension. They
may be used alone or in combination With other antihypertensive agents.
- Coronary Artery Disease (CAD):
Chronic Stable Angina:
Regcor tablets are indicated for the symptomatic treatment of chronic stable
angina. Regcor tablets may be used alone or in combination with other
antianginal agents.
Vasospastic Angina (Prinzmetal's or Variant Angina):
Regcor tablets are indicated for the treatment of confirmed or suspected
vasospastic angina. Regcor tablets may be used as monotherapy or in
combination with other antianginal agents.
Angiographically Documented CAD:
In patients with recently documented COD by angiography and without heart
failure or an ejection fraction €40%, Regcor tablets are indicated to reduce the
risk of hospitalization due to angina fnd to reduce the risk of a coronary
revascularization procedure.
Regcor is contraindicated in patients wi known sensitivity to amlodipine.
Warnings and Precautions:
Symptomatic hypotension is possible, particularly in patients with severe aortic
stenosis. Because of the gradual onset of action, acute hypotension is unlikely.
Increased Angina or Myocardial Infarction:
Worsening angina and acute myocardial infarction can develop after starting or
increasing the dose of Regcor, particularly in patients with severe Obstructive
coronary artery disease.
Beta-Blocker Withdrawal:
Regcor is not a beta-blocker and therefore gives no protection against the
dangers of abrupt beta-blocker Withdrawal; any such withdrawal should be by
gradual reduction of the dose of beta-blocker.
Patients with Hepatic Failure:
Because Regcor is extensively metabolized by the liver and the plasma
elimination half-life (t1/2) is 56 hours in patients with impaired hepatic function,
titrate slowly when administering Regcor to patients with severe hepatic
Drug Interactions:
In Vitro data in human plasma indicate that amlodipine has no effect on the
protein binding of drugs tested (digoxin, phenytoin, warfarin, and indomethacin ).
- Co-administration of amlodipine With cirnetidine did not alter the pharmacokinet-
ics of amlodipine.
- Co-administration of the antacid with a single dose of amlodipine had no
significant effect on the pharmacokinetics of amlodipine.
- 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.
- 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.
- Co-administration of amlodipine with digoxin did not change serum digoxin
levels or digoxin renal clearance in norm$l volunteers.
- Single and multiple 10 mg doses of a
iPine had no significant effect on the
pharmacokinetics at ethanol.
- Co-administration of amlodipine with warfarin di not change the warfarin
prothrombin response time.
Drug/laboratory Test Interactions: None known.
Pregnancy: Category C. Amlodipine has been shown to prolong both the
gestation period and the duration of labor in rats, at this dose. There are no
adequate, and well-controlled studies in pregnant women-Amlodipine should be
used during pregnancy only if the potential benefit justifies the potential risk to
Nursing Mothers: it is not known whether amlodipine is excreted in human
milk. In the absence of this information, it is recommended that nursing be
discontinued while amlodipine is administered.
Pediatric Use: The effect of amlodipine on blood pressure in patients less than 6
years of age is not known,
Geriatric Use: In general, dose selection for an Iderly patient should be
cautious, usually starting at the low end of the dosing range, reflecting the
greater frequency of decreased hepatic, renal, or Cardiac function, and of
concomitant disease or other drug therapy. Elderly patients have decreased
clearance of amlodipine With a resulting increase of AUC of approximately 40 -
60%, and a lower initial dose may be required (see DOSAGE AND ADMINISTRA-
Adverse Reactions:
The following events occurred in •z but so. of patients in controlled clinical
trials or under conditions of open trials or marketing experience where a causal
relationship is uncertain; they are listed to alert the physician to a possible
Cardiovascular: arrhythmia (including ventricular tachycardia and atrial
fibrillation), bradycardia, chest pain, hypotension, ischemia, syncope,
tachycardia, postural dizziness, postural hypotension, xpsculitis.
Central and Peripheral Nervous System: hypoesthesa, neuropathy peripheral,
paresthesia, tremor, vertigo.
Gastrointestinal: anorexia, constipation, dyspepsia, dysphagia, diarrhea,
flatulence, pancreatitis, vomiting, gingival hyperplasia.
General: allergic reaction, asthenia, back pain, hot fluShes, malaise, pain, rigors,
weight gain, weight decrease.
Musculoskeletal System: arthralgia, arthrosis, muscle cramps, myaigia.
Psychiatric: sexual dysfunction (male and female), insomnia, nervousness,
depression. abnormal dreams, anxiety, depersonalization.
Respiratory System: dyspnea, epistaxis.
Skin and Appendages: angioedema, erythema multiforme, pruritus, rash, rash
erythematous, rash maculopapular.
Special Senses: abnormal vision, conjunctivitis, diplopia, eye pain, tinnitus.
Urinary System: micturition frequency, micturition disorder, nocturia.
Autonomic Nervous System: dry mouth, sweating increased.
Metabolic and Nutritional: hyperglycemia, thirst.
Hemopoietic: leukopenia, purpura, thrombocytopenia.
These events occurred in less than 1% in placebo-controlled trials, but the
incidence of these side effects was between 1% and 2% in all multiple dose
The following events occurred in 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.
Other reactions occurred sporadically and cannot be distinguished from
medications or concurrent disease states such as myocardial infarction and
Arnlodipjne therapy has not been associated with clinically significant changes in
routine laboratory tests. No clinically relevant changes were noted in serum
potassium, serum glucose, total triglycerides, total cholesterol, HDL cholesterol,
uric acid, blood urea nitrogen, or creatinine,
Postmarketing Experience:
Because these reactions are reported voluntarily from a population of uncertain
size, it is not always possible to reliably estimate thei( frequency or establish a
causal relationship to drug exposure,
The following postmarketing event has been reported infrequently where a
causal relationship is uncertain: gynecomastia. In postmarketing experience,
jaundice and hepatic enzyme elevations (mostly consistent with cholestasis or
hepatitis), in some cases severe enough to require hospitalization, have been
reported in association with use of amlodipine.
Amlodipine has been used safely in patients with chronic obstructive pulmonary
disease, well-compensated congestive heart failure, coronary artery disease,
peripheral vascular disease, diabetes mellitus, and abnormal lipid profiles.
Single oral doses of 40 mg/kg and 100 mg/kg in mice nd rats, respectively, 
s caused a marked 
caused deaths. A single oral dose of 4 mg/kg or higher in 
peripheral vasodilatation and hypotension. 
Overdosage might be expected to cause excessive peripheral vasodilatation with 
marked hypotension and possibly a reflex tachycardia. Inl humans, experience 
with intentional over dosage of Regcor is limited: Reports of intentional 
overdosage include a patient who ingested 250 mg and was asymptomatic and 
was not hospitalized; another (120 mg) was hospitalized, underwent gastric 
lavage and remained normotensive; the third (105 mg) washospitalized and had 
hypotension (90/50 mmHg) which normalized following blasma expansion. A 
patient who took 70 mg amlodipine and an unknown quantity of benzodiazepine 
in a suicide attempt developed shock which was refractory to treatment and died 
the following day with.abnorrnally high benzodiazepine plasma concentration, A 
case of accidental drug overdose has been documented in 19 month-old male 
who ingested 30 mg amlodlpine (about 2 mg/kg). 
During the emergency room presentation, vital signs ere stable with no 
evidence of hypotension, but a heart rate of 180 bpm. Ipecac was administered 
3.5 hours after ingestion and on subsequent observation (ovemight) no sequelae 
were noted. 
If massive overdose should occur, active cardiac and respiratory monitoring 
should be instituted. Frequent blood pressure measurements are essential. 
Should hypotension occur, cardiovascular support including elevation of the 
extremities and the judicious administration of fluids should be initiated. If 
hypotension remains unresponsive to these conservative measures. administra- 
tion of vasopressors (such as phenylephrine) should be conSidered with attention 
to circulating volume and urine output. Intravenous calcium gluconate may help 
to reverse the effects of calcium entry blockade. As Regcor is highly protein 
bound, hemodialysis is not likely to be of benefit. 
Dosage And Administration: 
Adults: The usual initial antihypertensive oral dose of Regcor is 5 mg once daily 
with a maximum dose of 10 mg once daily. Small, fragile, or elderly individuals, 
or patients with hepatic insufficiency may be started on 2.5 mg once daily and 
this dose may be used when adding Regcor to other antihypertensive therapy. 
In general, titration 
Dosage should be adjusted according to each patient's n 
should proceed over 7 to 14 days so that the physician can fully assess the 
patient's response to each dose level. Titration may proceed more rapidly, 
however, if clinically warranted, provided the patient is assessed frequently. 
The recommended dose for chronic stable or vasospastic angina is 5-10 mg, with 
the lower dose suggested in the elderly and in patients with hepatic insufficiency. 
Most patients will require 10 mg for adequate effect. See ADVRSE REACTIONS 
section for Information related to dosage and side effects. 
Children: The effective antihypertensive oral dose in pediatric patients ages 6-17 
years is 2.5 mg to 5 mg once daily. Doses in excess of 5 mg daily have not been 
studied in pediatric patients. See CLINICAL PHARMACOLOGY. 
Coadministration with other antihypertensive and/or Antianginal drugs: 
Regcor has been safely administered with thiazides, ACE inhibitiors, beta- 
blockers, long-acting nitrates, and/or sublingual nitroglycerin. 
Store in a dry place at temperature not exceeding 300C. 
Keep out of reach of children. 
How supplied: 
Regcor 5 mg Tablets: Carton box containing I (AL/PVC) strip of 10 tablets and 
an inner leaflet. 
Regcor 10 mg Tablets: Carton box containing 1 (AL/PVC) ytrip of 10 tablets and 
an inner leaflet. 
Date of revision: 
December 2010. 
This is a Medicament. 
•Medicarnent is a prodiEt which affects your health, aru its consumptbn antrary to instr'Ætions 
is dangerous for you. 
•Folbw strictb•y the doctor's tie method of use, instrudkns of the pharmacist 
who sold nEdicament. 
•The doctor and the pharmacist are in me"v, its benefits arri risks. 
•Do not intermpt the period treatment prescrbed by yourself. 
•Do rwt repeat the same prescription without consulting ywr 
•Keep rnedcires out 0t the reach Of Olikiren, 
56 g/m2 11B 500 PAM 001 
PMS: Black C. 17 X 21 CM 
E. 1. P. 1. CO.