Monograph: |
S (-) AMLODIPINE
Therapeutic Category:
Calcium channel blocker
Composition:
S-Numlo®-1.25
Each uncoated tablet contains:
S(-) Amlodipine besilate equivalent to
S(-) Amlodipine 1.25 mg
Colour: Yellow Oxide of Iron
S-Numlo® -2.5
Each uncoated tablet contains:
S(-) Amlodipine besilate equivalent to
S(-) Amlodipine 2.5 mg
Colour: Yellow Oxide of Iron
S-Numlo®-5
Each uncoated tablet contains:
S(-) Amlodipine besilate equivalent to
S(-) Amlodipine 5 mg
Colour: Yellow Oxide of Iron
DESCRIPTION
S (-) Amlodipine is the pharmacologically active
isomer of Amlodipine. S (-) Amlodipine is
chemically designated as S(-)3-ethyl-5-methyl-
2-(2-Aminoethoxynnethyl)-4-(2-chlorophenyl)-
1,4-dihydro-6-methyl-3,5-pyridinedicarboxylate
benzenesulphonate. Its empirical formula is :
C2oH25C"P20;FsH.o,swmTamOTecUraT weight
of 567.1
CLINICAL PHARMACOLOGY
Pharmacodynamics:
S (-) Amlodipine, the chirally pure form of
Amlodipine is a calcium channel antagonist
belonging to the dihydropyridine class. The S (-)
isomer of Amlodipine is found to possess greater
pharmacological effects than R (+) Amlodipine.
S (-) Amlodipine is 1000 times more potent than
the R (+) isomer in-binding to the dihydropyridine
receptor. In humans, the dominant effects of
Amlodipine are consequent to vasodilation. S (-)
Amlodipine lowers peripheral vascular resistance
without causing a reflex tachycardia. It is effective
as a once daily dosage in the control of
hypertension.
Pharmacokinetics and Metabolism
Administration o( S(-) Amlodipine 2.5 mg as a
single dose in the fasting state produced maxi-
mum plasma concentration (C ) of 8.30 ± 1.071
ng/ ml in 2.73 ± 0.88 hrs. Amlodipine is
extensively (about 90%) converted to inactive me-
tabolites via hepatic metabolism with 10% of the
parent compound and 60% of the 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.
The mean AUc, value (t= 48 hrs.) of Tablet
S(-)Amlodipine (2.5mg) is 95.33 ± 14.45 ng.hr/
ml. The AUC value is recorded to be 140.91 ±
28.06 ng.hr/ml.The plasma elimination hall life ol
S(-) Amlodipine has been found to be in the range
of 14.62- 68.88 hrs.
INDICATIONS
• Essential Hypertension
• Angina pectoris.
CONTRAINDICATIONS
Hypersensitivity to any of the components of the
formulation.
ADVERSE REACTIONS
On the basis of the clinical data available, no
adverse events have been reported with the use
of S(-)Amlodipine.
DRUG INTERACTIONS
Clinical studies have shown that S(-) Amlodipine
when combined with aspirin, nitrates, beta-
blockers, statins, ACE inhibitors, H-2 blockers, and
Proton Pump Inhibitors produced no drug
interactions.
PRECAUTIONS
No controlled clinical study of S(-)Amlodipine has
been performed in patients with hepatic
impairment and renal impairment. Clinical
studies in patients with normal liver function
have shown that there is no elevation in
the hepatic enzymes with the use of
S(-)Amlodipine. However, caution should be
taken while administering S(-) Amlodipine to
patients with hepatic and renal impairment.
Pregnant Women & Nursing Mothers
There is no data available on the use of S(-)
Amlodipine in pregnant and lactating women,
hence the drug should be administered only when
the potential benefits outweighs the risk to the
patient.
Children
Safety and effectiveness of this product in
children have not been established.
OVERDOSAGE
There are no reported cases of overdosage with
The use of s(-)Amlodipine.
Overdosage with racemic Amlodipine may cause
excessive peripheral vasodilation with marked
hypotension and possibly a reflex tachycardia.
Hence, caution should be taken in case of an over-
dosage with S(-) Amlodipine. If massive overdose
occurs, active cardiac and respiratory monitoring
should be instituted. Frequent blood pressure
measurements should be performed. If hypoten-
sion occurs, cardiovascular support including
elevation of the extremities and the judicious
administration of fluids should be initiated. If
hypotension remains unresponsive to these
conservative measures, administration of vaso-
pressors (such as phenylephrine) should be
considered with attention to the circulating drug.
If massive overdose occurs, gastric lavage should
be employed. As this product is highly plasma
protein bound, hemodialysis is not likely to be of
benefit.
DOSAGE AND ADMINISTRATION
The recommended starting dose of
S(-)Amlodipine in hypertension is 1.25 mg once
daily. The normal recommended dose is 2.5 mg
once a day for the treatment of hypertension.
Based on the clinical response of the patient, the
dose may be enhanced, up to 5 mg once a day.
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