Amlodipine 10mg tab

(1) ROUTE OF ADMINISTRATION

Oral

DOSAGE AND ADMINISTRATION
Hypertension
Initial dose of 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 amlodipine to other anti-hypertensive therapy.
Chronic, stable or vasospastic angina
5-10 mg with a lower dose (2.5 mg) in the elderly and in patients with hepatic insufficiency.

Co-administration with other antihypertensives and/or antianginal drugs
Amlodipine has been safely administered with thiazides, ACE inhibitors, beta-blockers, long acting nitrates and/or sublingual nitroglycerin.

(ii) THERAPEUTIC / DIAGNOSTIC CLAIMS

Health 2000 amlodipine 10mg tablets are indicated for hypertension, chronic stable angina and vasospastic angina (Prinzmetal's or variant angina). Health 2000 amlodipine 10mg tablets may be used as monotherapy or in combination with other antihypertensive or antianginal drugs.

(iii) DESCRIPTION OF DOSAGE FORM

Amlodipine is dihydropyridine calcium antagonist that inhibits the transmembranous influx of calcium ions into vascular smooth muscleand cardiac muscle. It is more selective for the blood vessel compared to the myocardium. The drug provides 24-hour control of hypertension and angina pectoris.

(iv) CONTRAINDICATIONS

Amlodipine is contraindicated in patients with known hypersensitivity to Amlodipine.

WARNING AND PRECAUTIONS
DRUG INTERACTIONS
Digoxin: Amlodipine with digoxin did not change serum digoxin levels or digoxin renal clearance in normal volunteers.
Cimetidine: Co-administration with cimetidine did not alter the pharmacokinetics of Amlodipine.
Warfarin: Co-administration with warfarin did not change the warfarin prothrombin response time.
In clinical trials, 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.
PREGNANCY
Amlodipine should be used during pregnancy only if the potential benefit justifies the potential risk to the foetus.
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.
PAEDIATRIC USE
Safety and effectiveness of Amlodipine in children have not been established.
PATIENTS WITH HEPATIC FAILURE
Amlodipine is extensively metabolised by the liver and the plasma elimination half-life is prolonged in patients with impaired hepatic function. Caution should be exercised when administering Amlodipine to patients with severe hepatic impairment (See also Dosage and Administration).
BETA-BLOCKER WITHDRAWAL
Amlodipine 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.
OTHERS
Rarely patients, particularly those with severe obstructive coronary artery disease, have developed increased frequency, duration and/or severity of angina or acute myocardial infarction on starting calcium channel blocker therapy or at the time of dosage increase. The mechanism of this effect has not been elucidated.
Since the vasodilation induced by Amlodipine is gradual in onset, acute hypotension has rarely been reported after oral administration of Amlodipine. Nonetheless, caution should be exercised when administering Amlodipine as with any other peripheral vasodilator particularly in patients with severe aortic stenosis.
All calcium channel blockers should be used with caution in patients with heart failure.

(v) SIDE EFFECTS

Amlodipine is well tolerated. Side effects include headache, edema, fatigue, somnolence, nausea, abdominal pain, flushing, palpitations and dizziness.
Less commonly observed are pruritus, rash, dyspnea, asthenia, muscle cramps and dyspepsia. Rarely, myocardial infarction and chest pain have been reported.

(vi) TOXIC EFFECTS

TERATOGENICITY

No evidence of teratogenicity or other embryo/fetal toxicity was found when pregnant rats or rabbits were treated orally with up to 10 mg/kg amlodipine (respectively 8 times* and 23 times* the maximum recommended human dose of 10 mg on a mg/m 2 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 administered 10 mg/kg amlodipine for 14 days before mating and throughout mating and gestation. 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 the fetus.
*Based on patient weight of 50 kg.

CARCINOGENICITY & MUTAGENICITY

Rats and mice treated with amlodipine in the diet for two years, at concentrations calculated to provide daily dosage levels of 0.5, 1.25, and 2.5 mg/kg/day showed no evidence of carcinogenicity. The highest dose (for mice, similar to, and for rats twice* the maximum recommended clinical dose of 10 mg on a mg/m 2 basis) was close to the maximum tolerated dose for mice but not for rats. Mutagenicity studies revealed no drug related effects at either the gene or chromosome levels.

There was no effect on the fertility of rats treated with amlodipine (males for 64 days and females 14 days prior to mating) at doses up to 10 mg/kg/day (8 times* the maximum recommended human dose of 10 mg on a mg/m 2 basis