Almobest

Almobest

amlodipine

Manufacturer:

Pacific Medical

Distributor:

AA Medical
Full Prescribing Info
Contents
Amlodipine.
Description
Each uncoated tablet contains: Amlodipine Besilate eq. to Amlodipine USP 5 mg.
Action
Amlodipine is a long-action calcium channel blocker (dihydropyridine class) used as an anti-hypertensive and in the treatment of angina.
Pharmacology:
ALMOBEST is a calcium ion influx inhibitor of the dihydropyridine group (slow channel blocker or calcium ion antagonist) and inhibits the transmembrane influx of calcium ions into cardiac and vascular smooth muscle.
The mechanism of the antihypertensive action of ALMOBEST is due to a direct relaxant effect on vascular smooth muscle. The precise mechanism by which ALMOBEST relieves angina has not been fully determined but ALMOBEST reduces total ischaemic burden by the following two actions.
1. ALMOBEST dilates peripheral arterioles and thus, reduces the total peripheral resistance (afterload) against which the heart works. Since the heart rate remains stable, this unloading of the heart reduces myocardial energy consumption and oxygen requirements.
2. The mechanism of action of ALMOBEST also probably involves dilatation of the main coronary arterioles, both in normal and ischaemic regions. This dilatation increases myocardial oxygen delivery in patients with coronary artery spasm (Prinzmetal's or variant angina).
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. Due to the slow onset of action, acute hypotension is not a feature of ALMOBEST administration.
ALMOBEST has not been associated with any adverse metabolic effects or changes in plasma lipids and is suitable for use in patients with asthma, diabetes and gout.
Use in Patients with Heart Failure: Haemodynamic studies and exercise based controlled clinical trails in NYHA Class II-IV heart failure patients have shown that ALMOBEST did not lead to clinical deterioration as measured by exercise tolerance, left ventricular ejection traction and clinical symptomatology. A placebo controlled study (PRAISE) designed to evaluate patients in NYHA III and IV heart failure without clinical symptoms or objective findings suggestive or underlying ischaemic disease, on stable doses of ACE inhibitors, digitals, and diuretics, ALMOBEST had no effect on total cardiovascular mortality. In this same population ALMOBEST was associated with increased reports of pulmonary oedema despite no significant difference in the incidence of worsening heart failure as compared to placebo.
A randomized double-blind morbidity-mortality study called the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trail (ALLHAT) was performed to compare newer drug therapies: "amlodipine 2.5-10 mg/d (calcium channel blocker) or lisinopril 10-40 mg/d (ACE-inhibitor) as first-line therapies to that of the thiazide-diuretic, chlorthalidone 12.5-25 mg/d in mild to moderate hypertension." A total of 33,357 hypertensive patients aged 55 or older were randomized and followed for a mean of 4.9 years. The patients had at least one additional CHD risk factor, including: previous myocardial infarction or stroke, 6 months prior to enrollment, or documentation of other atherosclerotic CVD (over all 51.5%), type 2 diabetes (36.1%), HDL-C 35 mg/Dl (11.6%), left ventricular hypertrophy diagnosed by electrocardiogram or echocardiography (20.9%), current cigarette smoking (21.9%).
The primary endpoint was a composite of fatal CHD or non-fatal myocardial infarction. There was no significant difference in the primary end point between amlodipine-based therapy and chlorthalidone-based therapy: RR 0.98 95% CI [0.90-1.07] p=0.65. Among Secondary Endpoints, the incidence of heart failure (component of a composite combined cardiovascular endpoint) was significantly higher in the amlodipine group as compared to the chlorthalidone group (10.2% vs RR 1.38, 95% CI [1.25-1.52] p <0.001). However, there was no significant difference in all-cause mortality between amlodipine-based therapy and chlorthalidone-based therapy. RR 0.96 95% CI [0.89-1.02] p=0.20.
In a study involving 268 children age 6-17 years with predominantly secondary hypertension, comparison of a 2.5 mg dose, and 5.0 mg dose of amlodipine with placebo, showed that both reduced Systolic Blood Pressure significantly more than placebo. The difference between two doses was not statistically significant.
The long-term effects of amlodipine on growth, puberty and general development have not been studied. The long-term efficacy of amlodipine on therapy in childhood to reduce cardiovascular morbidity and mortality in adulthood has also not been established.
Pharmacokinetics: Absorption, distribution, plasma protein binding: After oral administration of therapeutic doses, amlodipine is well absorbed with peak blood levels between 6-12 hours post dose. Absolute bioavailability has been estimated to be between 64 and 80%. The volume of distribution is approximately 21 l/kg. In vitro studies have shown that approximately 97.5% of circulating amlodipine is bound to plasma proteins.
Biotransformation/elimination: The terminal plasma elimination half-life is about 35-50 hours and is consistent with once daily dosing. Amlodipine is extensively metabolised by the liver to inactive metabolites with 10% of the parent compound and 60% of metabolites excreted in the urine.
Use in the elderly: The time to reach peak plasma concentrations of amlodipine is similar in elderly and younger subjects. Amlodipine clearance tends to be decreased with resulting increases in AUC and elimination half-life in elderly patients. Increases in AUC and elimination half-life in patients with congestive heart failure were as expected for the patient age group studied.
Indications/Uses
Hypertension.
Prophylaxis of chronic stable angina pectoris.
Prinzmetal's (variant) angina when diagnosed by a cardiologist.
In hypertensive patients, ALMOBEST has been used in combination with a thiazide diuretic, alpha blocker, beta-adrenoceptor blocking agent, or an angiotensin converting enzyme inhibitor. For angina, ALMOBEST may be used as monotherapy or in combination with other antianginal drugs in patient with angina that is refractory to nitrates and/or adequate doses of beta blockers.
ALMOBEST is well tolerated in patients with heart failure and a history of hypertension or ischaemic heart disease.
Dosage/Direction for Use
In adult: For both hypertension and angina the usual initial dose is 5 mg ALMOBEST once daily which may be increased to a maximum dose of 10 mg depending on the individual patient's response.
No dose adjustment of ALMOBEST is required upon concomitant administration of thiazide diuretics, beta blockers, and angiotensin-converting enzyme inhibitors.
Use in children: Not recommended.
Use in elderly: ALMOBEST, used at similar doses in elderly or younger patients, is equally well tolerated. Therefore normal dosage regimens are recommended.
Patients with hepatic impairment: See "Precautions".
Patients with renal impairment: Changes in amlodipine plasma concentrations are not correlated with degree of renal impairment, therefore the normal dosage is recommended. Amlodipine is not dialysable.
Overdosage
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.
Administration of activated charcoal to healthy volunteers immediately or up to two hours after ingestion of amlodipine 10 mg has been shown to significantly decrease amlodipine absorption. Gastric lavage may be worthwhile in some cases. Clinically significant hypotension due to ALMOBEST overdosage calls for active cardiovascular support including frequent monitoring of cardiac and respiratory function, elevation of extremities, and attention to circulation fluid volume and urine output. A vasoconstrictor may be helpful in restoring vascular tone and blood pressure, provide that there is no contraindication to its use. Intravenous calcium gluconate may be beneficial in reversing the effects of calcium channel blockade. Since ALMOBEST is highly protein-bound, dialysis is not likely to be of benefit.
Contraindications
ALMOBEST is contraindicated in patients with a known sensitivity to dihydropyridines, amlodipine or any of the excipients.
ALMOBEST should not be used in cardiogenic shock, clinically significant aortic stenosis, unstable angina (excluding Prinzmetal’s angina).
Special Precautions
Use in patients with heart failure: In a long term, placebo controlled study (PRISE-2) of ALMOBEST, in patients with NYHA III and IV heart failure of nonischaemic aetiology, amlodipine was associated with increased reports of pulmonary oedema despite no significant difference in the incidence of worsening heart failure as compared to placebo. See "Pharmacology under Actions".
Use in patients with impaired hepatic function: As with all calcium antagonists, amlodipine's half-life is prolonged in patients with impaired liver function and dosage recommendations have not been established. The drug should therefore be administered with caution in these patients.
There are no data to support the use if ALMOBEST alone, during or within one month of a myocardial infarction.
The safety and efficacy of ALMOBEST in hypertensive crisis has not been established.
Effects on ability to drive and use machines: Clinical experience with ALMOBEST indicates that therapy is unlikely to impair a patient’s ability to drive or use machinery.
Use In Pregnancy & Lactation
Although some dihydropyridine compounds have been found to be teratogenic in animals, data in the rat and rabbit for amlodipine provide no evidence for a teratogenic effect. There is, however, no clinical experience with the preparation in pregnancy or lactation. Accordingly, ALMOBEST should not be administered during pregnancy, or lactation, or to women of childbearing potential unless effective contraception is used.
Adverse Reactions
Adverse events that have been reported in amlodipine trials are categorized as follows, according to system organ class and frequency. Frequencies are defined as: very common (>10%); common (>1%, 10%); uncommon (>0.1%, 1%); rare (>0.01%, 0.1%) and very rare (0.01%). (See table.)

Click on icon to see table/diagram/image
Drug Interactions
ALMOBEST has been safely administered with thiazide diuretics, alpha blockers, beta blockers, angiotensin-converting enzyme inhibitors, long-acting nitrates, sublingual glyceryl trinitrate, non-steroidal anti-inflammatory drugs, antibiotics, and oral hypoglycaemic drugs.
In vitro data from studies with human plasma, indicate that amlodipine has no effect on protein binding of digoxin, phenytoin, warfarin or indomethacin.
Special Studies: Effect of each agents on Amlodipine: Cimetidine: Co-administration of ALMOBEST with cimetidine did not alter the pharmacokinetics of ALOMOBEST.
Grapefruit Juice: Co-administration of 240 ml of grapefruit juice with a single oral dose of ALMOBEST 10 mg in 20 healthy volunteers had no significant effect on the pharmacokinetics of ALMOBEST.
Sildenafil: When ALMOBEST and sildenafil were used in combination, each agent independently exerted its own blood pressure lowering effect.
Caution For Usage
Incompatibilities: None.
Storage
Store below 30°C in a dry place, protected from light.
MIMS Class
Calcium Antagonists
ATC Classification
C08CA01 - amlodipine ; Belongs to the class of dihydropyridine derivative selective calcium-channel blockers with mainly vascular effects. Used in the treatment of cardiovascular diseases.
Presentation/Packing
Tab 5 mg x 10 x 10's.
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