COMPOSITION
Each film coated tablet contains:
Levocetirizine dihydrochloride ………… 5 mg
Other ingredients:
Microcrystalline cellulose, croscarmellose sodium, colloidal anhydrous silica, magnesium stearate, opadry II 85G51300 green & purified water.
DESCRIPTION
Green colored, film coated, round, biconvex tablets plain on both side.

INDICATIONS:
Hypertension and chronic stable angina pectoris.
DOSAGE AND ADMINISTRATION: Adults: For both hypertension and angina, the usual initial dose is 2.5 mg S(-) Amlodipine once daily which may be increased to a maximum dose of 5 mg depending on the individual patient’s response.
Elderly patients:
S(-) Amlodipine used at similar doses in elderly or younger patients is equally well tolerated. Normal dosage regimens are recommended in the elderly, but increase of the dosage should take place with care.
Patients with renal impairment:
Changes in S(-) Amlodipine plasma concentrations are not correlated with degree of renal impairment, therefore the normal dosage is recommended. S(-) Amlodipine is not dialyzable.
Patients with hepatic impairment:
Dosage recommendations have not been established in patients with mild to moderate hepatic impairment; therefore dose selection should be cautious and should start at the lower end of the dosing range. The pharmacokinetics of S(-) Amlodipine have not been studied in severe hepatic impairment. S(-) Amlodipine should be initiated at the lowest dose and titrated slowly in patients with severe hepatic impairment.
Mode of administration:
Oral administration.

UNDESIRABLE EFFECTS
On the basis of clinical data, only minor side effects have been reported with the use of S(-) Amlodipine.
These side effects included vertigo, tachycardia, cough, headache, fever, mild difficulty in breathing and edema. Adverse events were of mild in nature and no serious adverse events were reported.
In a postmarketing surveillance study, S(-) Amlodipine (2.5/5 mg) was found to be well tolerated (n = 1859) in patients with hypertension. Out of 314 patients, who reported peripheral edema with conventional amlodipine were switched over to S(-) Amlodipine and edema was resolved in 310 patients (98.72%) at the end of 4 weeks. Only in 4 patients, edema was sustained. Only 30 patients (out of 1859) reported side effects.

INTERACTIONS WITH OTHER MEDICINAL PRODUCTS:
CYP3A4 inhibitors:
Concomitant use of S(-) Amlodipine with strong or moderate CYP3A4 inhibitors (protease inhibitors, azole antifungals, macrolides like erythromycin or clarithromycin, verapamil or diltiazem) may give rise to significant increase in amlodipine exposure. The clinical translation of these PK variations may be more pronounced in the elderly. Clinical monitoring and dose adjustment may thus be required. CYP3A4 inducers: There is no data available regarding the effect of CYP3A4 inducers on S(-) Amlodipine. The concomitant use of CYP3A4 inducers (e.g., rifampicin, hypericum perforatum) may give a lower plasma concentration of S(-) Amlodipine. S(-) Amlodipine should be used with caution together with CYP3A4 inducers.
Administration of S(-) Amlodipine with grapefruit or grapefruit juice is not recommended as bioavailability may be increased in some patients resulting in increased blood pressure lowering effects.
Dantrolene (infusion): In animals, lethal ventricular fibrillation and cardiovascular collapse are observed in association with hyperkalemia after administration of verapamil and dantrolene I.V. Due to risk of hyperkalemia, it is recommended that the co administration of calcium channel blockers such as S(-) Amlodipine be avoided in patients susceptible to malignant hyperthermia and in the management of malignant hyperthermia. Effects of S(-) Amlodipine on other medicinal products: The blood pressure lowering effects of S(-) Amlodipine adds to the blood pressurelowering effects of other medicinal products with antihypertensive properties.
Simvastatin: Limit the dose of simvastatin in patients on S-amlodipine to 20 mg daily.

SPECIAL WARNINGS AND PRECAUTIONS FOR USE:
The safety and efficacy of S(-) Amlodipine in hypertensive crisis has not been established.
Patients with cardiac failure:
Patients with heart failure should be treated with caution. Calcium channel blockers, including S(-) Amlodipine, should be used with caution in patients with congestive heart failure, as they may increase the risk of future cardiovascular events and mortality.
Use in patients with impaired hepatic function:
The half-life of S(-) Amlodipine is prolonged and AUC values are higher in patients with impaired liver function; dosage recommendations have not been established. S(-) Amlodipine should therefore be initiated at the lower end of the dosing range and caution should be used, both on initial treatment and when increasing the dose. Slow dose titration and careful monitoring may be required in patients with severe hepatic impairment.
Use in elderly patients:
In the elderly increase of the dosage should take place with care.
Use in renal failure:
S(-) Amlodipine may be used in such patients at normal doses. Changes in S(-) Amlodipine plasma concentrations are not correlated with degree of renal impairment. S(-) Amlodipine is not dialyzable.

FERTILITY, PREGNANCY AND LACTATION:
Pregnancy: The safety of S(-) Amlodipine in human pregnancy has not been established.
Use in pregnancy is only recommended when there is no safer alternative and when the disease itself carries greater risk for the mother and foetus. Lactation: It is not known whether S(-) Amlodipine is excreted in breast milk. A decision on whether to continue/discontinue breast-feeding or to continue/discontinue therapy with S(-) Amlodipine should be made taking into account the benefit of breast-feeding to the child and the benefit of S(-) Amlodipine therapy to the mother.
Fertility: Reversible biochemical changes in the head of spermatozoa have been reported in some patients treated by calcium channel blockers. Clinical data are insufficient regarding the potential effect of S(-) Amlodipine on fertility.
EFFECTS ON ABILITY TO DRIVE AND USE MACHINES:
S(-) Amlodipine can have minor or moderate influence on the ability to drive and use machines. If patients taking S(-) Amlodipine suffer from dizziness, headache, fatigue or nausea the ability to react may be impaired. Caution is recommended especially at the start of treatment.

OVERDOSE AND TREATMENT
In humans, experience with intentional overdose is limited.
Symptoms:
Available data suggest that gross overdosage could result in excessive peripheral vasodilatation and possibly reflex tachycardia. Marked and probably prolonged systemic hypotension up to and including shock with fatal outcome have been reported in amlodipine which can be applicable to S(-) Amlodipine as well.
Treatment:
Clinically significant hypotension due to S(-) Amlodipine overdosage calls for active cardiovascular support including frequent monitoring of cardiac and respiratory function, elevation of extremities and attention to circulating fluid volume and urine output.
A vasoconstrictor may be helpful in restoring vascular tone and blood pressure, provided that there is no contraindication to its use. Intravenous calcium gluconate may be beneficial in reversing the effects of calcium channel blockade.
Gastric lavage may be worthwhile in some cases.
Since S(-) Amlodipine is highly protein-bound, dialysis is not likely to be of benefit.

CONTRAINDICATIONS:
S(-) Amlodipine is contraindicated in patients with:
– hypersensitivity to dihydropyridine derivatives, amlodipine or any of the excipients
– severe hypotension
– shock (including cardiogenic shock)
– obstruction of the outflow tract of the left ventricle (e.g. high grade aortic stenosis)
– haemodynamically unstable heart failure after acute myocardial infarction

Pharmaceutical Form: Tablets
PHARMACOLOGICAL PROPERTIES:
Pharmacotherapeutic group:
Selective calcium channel blockers with mainly vascular effects – Dihydropyridine derivatives
ATC Code: C08CA01
Pharmacodynamics:
S(-) Amlodipine is a pharmacologically active enantiomer of amlodipine. S(-) Amlodipine is an allosteric modulator and acts on the L-type of calcium channels. Receptor binding studies have shown that out of the two forms only the (S)-enantiomer of amlodipine binds to and blocks L-type calcium channels whereas the (R)-enantiomer has no activity on these channels.
The mechanism of the antihypertensive action of S(-) Amlodipine is due to a direct relaxant effect on vascular smooth muscle.
The precise mechanism by which S(-) Amlodipine relieves angina has not been fully determined but the following two actions play a role:
1. Decreases peripheral resistance by arteriolar vasodilatation leading to the reduction in oxygen requirement and energy consumption of cardiac smooth muscles.
2. Decreases coronary vascular resistance and can lead to an increase in coronary blood flow.
In patients with hypertension, once daily dosing provides clinically significant reductions of blood pressure (in both supine and standing positions) throughout the 24 hour interval.
In patients with angina, once daily administration of amlodipine increases total exercise time, the delay of occurrence of anginal attack and the delay of the occurrence of a 1-mm ST interval. Amlodipine decreases both angina attack frequency and glyceryl trinitrate tablet consumption.
Pharmacokinetics:
Absorption/Distribution:
Administration of S(-) Amlodipine (2.5 mg) as a single dose gives maximum plasma concentration (C ) of 8.3 to 9.3 ng/mL max in 2 to 3 hrs (T ). S(-) Amlodipine shows approximately 93% plasma protein binding in hypertensive patients. The mean AUC value (t = 48 hrs) of S(-) max 0-t Amlodipine tablets (2.5 mg) is 95±14 ng.hr/mL.
Metabolism/Elimination:
S(-) 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 has been found to be 31±13 hrs.

STORAGE CONDITION:
Store below 30°C .
Keep all medicines out of reach of children.
DOSAGE FORMS AND PACKAGING AVAILABLE:
Amber PVC/PVDC-Alu blister of 14 tablets. 2 or 10 blisters are in a carton box.
NAME AND ADDRESS OF MANUFACTURER:
Kusum Healthcare Pvt. Ltd.
SP 289(A), RIICO Indl. Area,
Chopanki, Bhiwadi (Rajasthan), India
DATE OF REVISION OF PACKAGE INSERT:
Not Applicable
Sampine Tablets 2.5 mg – MM Reg. No.: 1812AA 7084
Sampine Tab 2.5/5 mg/MY/F Sampine Tablets 5 mg – MM Reg. No.: 1812AA 7083