About Amlodipine

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Amlodipine
medicaldialogues.in/generics/amlodipine-2721953
October 2, 2022
Indications, Uses, Dosage, Drugs Interactions,
Side effects Amlodipine Medicine Type
Allopathy Prescription Type Prescription
Required Approval DCGI (Drugs Controller
General of India) Schedule Schedule
H Pharmacological Class Calcium channel
blocker, Therapy Class Antihypertensive,
Innovator name Pfizer Medicals Amlodipine is an
antihypertensive agent belonging to the Calcium
Channel Blocker class. Amlodipine is a Calcium
Channel Blocker used to treat Hypertension and
Angina.
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Amlodipine absorbed slowly and almost completely
from the gastrointestinal tract. Peak plasma
concentrations are achieved 6-12 hours after oral
administration. The estimated bioavailability of
amlodipine is 64-90. Steady-state plasma
amlodipine levels are achieved after 7-8 days of
consecutive daily dosing. Absorption is not
affected by food. The plasma protein binding of
Amlodipine is approximately 98. Amlodipine is
heavily (approximately 90) converted to
inactive metabolites via hepatic breakdown with
10 of the parent compound and 60 of the
metabolites found excreted in the
urine. Amlodipine shows common side effects
swelling of the hands, feet, ankles, or lower
legs, headache, upset stomach, nausea, stomach
pain, dizziness or light-headedness, drowsiness,
excessive tiredness, flushing, etc. Amlodipine is
available in the form of Oral Tablet, Oral
Solution and Oral Suspension. Amlodipine is
available in India, US, UK, Canada, Russia,
China, Japan, Korea, Singapore, and South
Africa. Amlodipine belonging to the Calcium
Channel Blockers acts as an antihypertensive
agent. Mechanism of action on Hypertension Amlod
ipine is considered a peripheral arterial
vasodilator that exerts its action directly on
vascular smooth muscle to lead to a reduction in
peripheral vascular resistance, causing a
decrease in blood pressure. Amlodipine is a
dihydropyridine calcium antagonist (calcium ion
antagonist or slow-channel blocker) that inhibits
the influx of calcium ions into both vascular
smooth muscle and cardiac muscle. Experimental
studies imply that amlodipine binds to both
dihydropyridine and non-dihydropyridine binding
sites, located on cell membranes. The contraction
of cardiac muscle and vascular smooth muscle
are dependent on the movement of extracellular
calcium ions into these cells by specific ion
channels. Amlodipine blocks calcium ion influx
across cell membranes with selectivity. A
stronger effect of amlodipine is exerted on
vascular smooth muscle cells than on cardiac
muscle cells. Direct actions of amlodipine on
vascular smooth muscle result in reduced blood
pressure. Mechanism of action in angina The
exact mechanism by which amlodipine relieves the
symptoms of angina have not been fully
elucidated to this date, however, the mechanism
of action is likely twofold Amlodipine has a
dilating effect on peripheral arterioles,
reducing the total peripheral resistance
(afterload) against which the cardiac muscle
functions. Since the heart rate remains stable
during amlodipine administration, the reduced
work of the heart reduces both myocardial energy
use and oxygen requirements. Dilatation of the
main coronary arteries and coronary arterioles,
both in healthy and ischemic areas, is another
possible mechanism of amlodipine reduction of
blood pressure. The dilatation causes an
increase in myocardial oxygen delivery in
patients experiencing
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coronary artery spasm (Prinz metals or variant
angina) and reduces coronary vasoconstriction
caused by smoking. The Onset of action of
Amlodipine is not clinically established. The
Duration of Action for Amlodipine in the body is
approximately 24 hours. The Tmax was found
within 6-12 hours following the administration of
Amlodipine. Amlodipine is available in the form
of Oral Tablet, Oral Solution and Oral
Suspension. Amlodipine tablet, solution and
suspension taken orally. Usually once a
day. Amlodipine is a medicine used for the
treatment of high blood pressure. This medicine
works by relaxing the blood vessels which make
the blood flow easily, thus lowering the blood
pressure. This will reduce your risk of heart
attack or a stroke by making it easier for your
heart to pump blood around your body. Amlodipine
is an antihypertensive agent belonging to Calcium
Channel Blockers. It inhibits calcium ion from
entering the slow channels or select
voltage-sensitive areas of vascular smooth
muscle and myocardium during depolarization,
producing a relaxation of coronary vascular
smooth muscle and coronary vasodilation
increases myocardial oxygen delivery in patients
with vasospastic angina. Amlodipine directly acts
on vascular smooth muscle to produce peripheral
arterial vasodilation reducing peripheral
vascular resistance and blood pressure. Amlodipi
ne is approved for use in the following clinical
indications HYPERTENSION Amlodipine is
indicated for the treatment of hypertension, to
lower blood pressure. Lowering blood pressure
reduces the risk of fatal and nonfatal
cardiovascular events, primarily strokes and
myocardial infarctions. These benefits have been
seen in controlled trials of antihypertensive
drugs from a wide variety of pharmacologic
classes including Amlodipine. CORONARY ARTERY
DISEASE (CAD) Chronic Stable Angina Amlodipine
is indicated for the symptomatic treatment of
chronic stable angina. Amlodipine may be used
alone or in combination with other antianginal
agents. Vasospastic Angina (Prinz metals Or
Variant Angina) Amlodipine is indicated for the
treatment of confirmed or suspected vasospastic
angina. Amlodipine may be used as monotherapy or
in combination with other antianginal agents.
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Angiographically Documented CAD In patients with
recently documented CAD by angiography and
without heart failure or an ejection fraction
lt40, Amlodipine is indicated to reduce the risk
of hospitalization for angina and to reduce the
risk of a coronary revascularization
procedure. Hypertension Adult Dose Initial
dose 5 mg orally once a day Maintenance dose 5
to 10 mg orally once a day Maximum dose 10
mg/day Pediatric Dose (6 to 17
years) Maintenance dose 2.5 to 5 mg orally once
a day Maximum dose 5 mg/day Pediatric dose (lt6
years) Limited data available Oral Initial
0.1 mg/kg/dose once daily titrate based on
clinical response. Maximum daily dose 0.6
mg/kg/day or 5 mg/day Geriatric Dose Initial
dose 2.5 mg orally once a day Maintenance dose
2.5 to 10 mg orally once a day Maximum dose 10
mg/day Angina Pectoris Adult Dose Maintenance
dose 5 to 10 mg orally once a day Maximum dose
10 mg/day Geriatric Dose Initial dose 5 mg
orally once a day Maintenance dose 5 to 10 mg
orally once a day
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Maximum dose 10 mg/day Coronary Artery
Disease Maintenance dose 5 to 10 mg orally once
a day Maximum dose 10 mg/day Amlodipine is
available in various strengths as 2.5mg, 5mg,
10mg and 1mg/mL(150mL). Amlodipine is available
in the form of Oral Tablet, Oral Solution and
Oral Suspension. Avoid grapefruit juice while
taking Amlodipine. Amlodipine is contraindicated
in patients with known sensitivity towards
Amlodipine. Hypotension 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 Amlodipine,
particularly in patients with severe obstructive
coronary artery disease. Patients with Hepatic
Failure Because Amlodipine is extensively
metabolized by the liver and the plasma
elimination half-life (t 1/2) is 56 hours in
patients Alcohol Warning No information is
available. Breast Feeding Warning 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. Pregnancy
Warning Pregnancy category C Animal reproduction
studies have shown an adverse effect on the
fetus and there are no adequate and
well-controlled studies in humans, but potential
benefits may warrant use of the drug in pregnant
women despite potential risks. Food Warning
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Avoid grapefruit juice while taking
Amlodipine. Common Adverse effects Peripheral
edema, Flushing, palpitations, Pruritus, skin
rash, Abdominal pain, nausea, Male sexual
disorder, Asthenia, dizziness, drowsiness, Muscle
cramps, Dyspnea. Rare Adverse effects Peripheral
ischemia, sinus tachycardia, syncope,
vasculitis, Diaphoresis, erythema multiforme, Hot
flash, hyperglycemia, weight gain, weight loss,
Anorexia, constipation, dysphagia, flatulence,
gingival hyperplasia, pancreatitis, vomiting,
xerostomia, Difficulty in micturition, female
sexual disorder, nocturia, urinary frequency,
Leukopenia, purpuric disease, thrombocytopenia,
Angioedema, hypersensitivity reaction, Abnormal
dreams, anxiety, depersonalization, depression,
hypoesthesia, insomnia, malaise, pain,
paresthesia, peripheral neuropathy, rigors,
tremor, vertigo, Arthralgia, back pain, myalgia,
osteoarthritis, Conjunctivitis, diplopia, eye
pain, Tinnitus, Epistaxis. CYP3A
Inhibitors Co-administration with CYP3A
inhibitors (moderate and strong) results in
increased systemic exposure to amlodipine and may
require dose reduction. Monitor for symptoms of
hypotension and edema when amlodipine is
co-administered with CYP3A inhibitors to
determine the need for dose adjustment. CYP3A
Inducers No information is available on the
quantitative effects of CYP3A inducers on
amlodipine. Blood pressure should be closely
monitored when amlodipine is co-administered with
CYP3A inducers. Sildenafil Monitor for
hypotension when sildenafil is co-administered
with amlodipine. Simvastatin Co-administration
of simvastatin with amlodipine increases the
systemic exposure of simvastatin. Limit the dose
of simvastatin in patients on amlodipine to 20 mg
daily. Immunosuppressants Amlodipine may
increase the systemic exposure of cyclosporine or
tacrolimus when co- administered. Frequent
monitoring of trough blood levels of cyclosporine
and tacrolimus is recommended and adjust the
dose when appropriate. The common side effects
of Amlodipine include the following Common
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Swelling of the hands, feet, ankles, or lower
legs, headache, upset stomach, nausea, stomach
pain, dizziness or light-headedness, drowsiness,
excessive tiredness, flushing. Rare More
frequent or more severe chest pain, rapid,
pounding, or irregular heartbeat,
fainting. Pregnancy Pregnancy Category C 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 the fetus. No evidence of
teratogenicity or other embryo/fetal toxicity was
found when pregnant rats and rabbits were
treated orally with amlodipine maleate at doses
up to 10 mg amlodipine/kg/day (respectively, 8
times2 and 23 times2 the maximum recommended
human dose of 10 mg on a mg/m2 basis) during
their respective periods of major organogenesis.
However, litter size was significantly decreased
(by about 50) and the number of intrauterine
deaths was significantly increased (about 5-fold)
in rats receiving amlodipine maleate at a dose
equivalent to 10 mg amlodipine/kg/day for 14
days before mating and throughout mating and
gestation. Amlodipine maleate has been shown to
prolong both the gestation period and the
duration of labor in rats at this dose. 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 Effect of
Amlodipine on blood pressure in patients less
than 6 years of age is not known. Geriatric
Use Clinical studies of Amlodipine did not
include sufficient numbers of subjects aged 65
and over to determine whether they respond
differently from younger subjects. Other reported
clinical experience has not identified
differences in responses between the elderly and
younger patients. In general, dose selection for
an elderly 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 4060, and a lower initial dose
may be required. Overdosage might be expected to
cause excessive peripheral vasodilation
with marked hypotension and possibly a reflex
tachycardia. In humans, experience with
intentional overdosage of Amlodipine is limited.
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Single oral doses of amlodipine maleate
equivalent to 40 mg amlodipine/kg and 100 mg
amlodipine/kg in mice and rats, respectively,
caused deaths. Single oral amlodipine maleate
doses equivalent to 4 or more mg amlodipine/kg or
higher in dogs (11 or more times the maximum
recommended human dose on a mg/m2 basis) caused
a marked peripheral vasodilation and
hypotension. If massive overdose should occur,
initiate active cardiac and respiratory
monitoring. Frequent blood pressure measurements
are essential. Should hypotension occur, provide
cardiovascular support including elevation of the
extremities and the judicious administration of
fluids. If hypotension remains unresponsive to
these conservative measures, consider
administration of vasopressors (such as
phenylephrine) with attention to circulating
volume and urine output. As Amlodipine is highly
protein bound, hemodialysis is not likely to be
of benefit. Pharmacodynamic Amlodipine has a
strong affinity for cell membranes, modulating
calcium influx by inhibiting selected membrane
calcium channels. This drug's unique binding
properties allow for its long-acting action and
less frequent dosing regimen. Pharmacokinetics
Absorption Amlodipine absorbed slowly and almost
completely from the gastrointestinal tract. Peak
plasma concentrations are achieved 6-12 hours
after oral administration. The estimated
bioavailability of amlodipine is 64-90.
Steady-state plasma amlodipine levels are
achieved after 7-8 days of consecutive daily
dosing. Absorption is not affected by
food. Distribution The plasma protein binding
of Amlodipine is approximately 98. Metabolism
and Excretion Amlodipine is heavily
(approximately 90) converted to inactive
metabolites via hepatic breakdown with 10 of
the parent compound and 60 of the metabolites
found excreted in the urine. Ex vivo studies
have shown that about 93 of the circulating drug
is bound to plasma proteins in hypertensive
patients. Characteristics that add to
amlodipine's unique pharmacologic profile
include nearly complete absorption, late-peak
plasma concentrations, high bioavailability, and
slow hepatic breakdown. Approximately 10 of a
given dose is excreted in the urine. There are
some clinical studies of the drug Amlodipine
mentioned below 1. Levine CB, Fahrbach KR, Frame
D, Connelly JE, Estok RP, Stone LR, Ludensky V.
Effect of amlodipine on systolic blood pressure.
Clinical therapeutics. 2003 Jan 125(1)35-57.
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• Pitt B, Byington RP, Furberg CD, Hunninghake DB,
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• Burges RA, Dodd MG, Gardiner DG. Pharmacologic
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• https//www.accessdata.fda.gov/drugsatfda_docs/lab
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  https//go.drugbank.com/drugs/DB00381
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• Jyoti Suthar
• Jyoti is a Post graduate in Pharmaceutics ( M
  Pharm) She did her graduation ( B Pharm) From
  SSR COLLEGE OF PHARMACY And
• thereafter did her M Pharm specialized in
  Pharmaceutics from SSR COLLEGE OF PHARMACY
• Dr JUHI SINGLA
• Dr JUHI SINGLA has completed her MBBS from Eras
  Lucknow Medical college and done MD pharmacology
  from SGT UNIVERSITY
• Gurgaon. She can be contacted at
  editorial_at_medicaldialogues.in. Contact no.
  011-43720751