Asomex™ 2.5 /5
S (-) Amlodipine Besilate Tablets
For the use of a Registered Medical Practitioner or a Hospital or a Laboratory Only.
Calcium channel blocker.
Each uncoated tablet contains:
S (-) Amlodipine besilate equivalent to S (-) Amlodipine 2.5 mg
Each uncoated tablet contains:
S (-) Amlodipine besilate equivalent to S (-) Amlodipine 5mg
S (-) Amlodipine is the pharmacologically active isomer of Amlodipine. S (-) Amlodipine is chemically designated as S(-)-3-ethyl-5-methyl-2-(2-aminoethoxymethyl)-4-(2-chlorophenyl)-1,4-dihydro-6-methyl-3,5- pyridinedicarboxylate benzenesulphonate. Its empirical formula is: C20H25ClN2O5C6H6O3S with a molecular weight of 567.1
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 dihydropyndine 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 of S (-) Amlodipine 5 mg as a single dose in the fasting state produced maximum plasma concentration (Cmax) of 2.98±0.441 ng/ml in 8.05 ±2.24 hours (Tmax). The mean AUC value (t=196 hours) of S (-) Amlodipine (5mg tablet) was 163.89 ± 42.52 ng.hr/ml. The AUC value was 176.57±44.31 ng.hr/ml. Amlodipine is extensively (about 90%) converted to inactive metabolites via hepatic metabolism with 10% of the parent compound and 60% of the metabolites excreted in the urine. The plasma elimination half-life of S (-) Amlodipine is 44.15 ± 9.915 hours. Significant reduction in systolic and diastolic blood pressure was noted at 15 days of S (-) Amlodipine therapy in one clinical trial using office and 24-hour ambulatory blood pressure monitoring.
• Essential Hypertension
• Angina pectoris
Hypersensitivity to any of the components of the formulation.
On the basis of the clinical data available, following non-serious adverse events with incidence <2% have been reported with the use of S (-) Amlodipine: pedal edema, headache, dizziness, asthenia, somnolence, blushing, chest pain, vomiting, abdominal pain, myalgia, rash, frequent urination, palpitation, fever, presyncopy, difficulty in breathing, tachycardia, cough, cheerlessness, facial puffiness, heavy headedness, worsening of hyperlipidemia, impaired gycemic control, and diarrhea.
Clinical studies have shown that Amlodipine has been safely administered with thiazide diuretics, beta-blockers, angiotensin-converting enzyme inhibitors, long-acting nitrates, sublingual nitroglycerin, digoxin, warfarin, non-steroidal anti-inflammatory drugs, antibiotics, and oral hypoglycemic drugs. Hence no such interactions are expected with S (-) Amlodipine.
The pharmacokinetic studies with fixed dose combinations (FDCs) of S (-) Amlodipine with Atorvastatin, Hydrochlorothiazide, Ramipril, Atenolol and S (-)
Metoprolol reported no any adverse interaction profile. So the above mentioned drugs can be administered with S (- )Amlodipine as co-prescription or in FDC.
Atorvastatin: It has been reported that in patients with hypertension and coexisting hypercholesterolemia, fixed-dose combination (FDC) of S (-) Amlodipine (2.5 mg) and Atorvastatin (10 mg) leads to significant reduction in both systolic and diastolic blood pressure and total cholesterol levels and well tolerated. So Atorvastatin can be co-administrated S (-) Amlodipine, if required clinically.
Beta Blockers: FDC of S (-) Amlodipine with Atenolol and S (-) Amlodipine with S (-) Metoprolol is safe and effective in management of hypertension in clinical practice. Beta blockers can be co-administrated with S (-) Amlodipine, if required clinically.
Angiotensin II Receptor Antagonist: A fixed dose combination (FDC) of S (-) Amlodipine and Losartan is safe and effective when administered once-daily in patients with mild to moderate hypertension. Angiotensin II Receptor antagonists, can be co-administrated with S (-) Amlodipine, if required clinically.
Digoxin: Co-administration of Amlodipine with digoxin reported no change in serum digoxin levels or digoxin renal clearance in normal volunteers. Hence similar effects are expected with S (-) Amlodipine.
Ethanol (alcohol): Single and multiple doses of racemic Amlodipine had reported no significant effect on the pharmacokinetics of ethanol. Hence similar effects are expected with S (-) Amlodipine.
Warfarin: Co-administration of racemic Amlodipine with warfarin reported no change the warfarin prothrombin response time. Similar effects are expected with S (-) Amlodipine.
Nicotine: Not known.
Drug/Laboratory Test Interactions: Not known.
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.
Safety and effectiveness of this product in children have not been established.
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 overdosage with S (-) Amlodipine. If massive overdose occurs, active cardiac and respiratory monitoring should be instituted. Frequent blood pressure measurements should be performed. If hypotension 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 vasopressors (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 normal recommended dose is 2.5 mg once a day. Based on the clinical response of the patient, the dose may be enhanced, up to 5 mg once a day.
Duration of Therapy: S (-) Amlodipine is prescribed as part of therapy for chronic conditions like hypertension and angina. Duration of therapy will be for as long as required and will be decided by treating doctor based on individual response to therapy and tolerability.
Store in a dry place, below 30°C and protect from light.
Blister strip of 10 tablets.
Emcure PHARMACEUTICALS LTD.
Lane No. 3, Phase-II, SIDCO,
Bari-Brahmana, Jammu – 181 133, India.
TM Trade Mark Owners.
Fidson Healthcare Plc
268, lkorodu Road, Obanikoro,