Lodiben

Uses

This is used for the treatment of hypertension.

Lodiben is also used to associated treatment for these conditions: Anginal Pain, Cardiovascular Events, Chronic Stable Angina Pectoris, Coronary Artery Disease (CAD), High Blood Pressure (Hypertension), Homozygous Familial Hypercholesterolemia, Hypertension,Essential, Mixed Dyslipidemias, Primary Hypercholesterolemia, Vasospastic Angina

How Lodiben works

Mechanism of action on blood pressure

Amlodipine is considered a peripheral arterial vasodilator that exerts its action directly on vascular smooth muscle to lead to a reduction in peripheral vascular resistance, causing a decrease in blood pressure. Amlodipine is a dihydropyridine calcium antagonist (calcium ion antagonist or slow-channel blocker) that inhibits the influx of calcium ions into both vascular smooth muscle and cardiac muscle. Experimental studies imply that amlodipine binds to both dihydropyridine and nondihydropyridine binding sites, located on cell membranes. The contraction of cardiac muscle and vascular smooth muscle are dependent on the movement of extracellular calcium ions into these cells by specific ion channels. Amlodipine blocks calcium ion influx across cell membranes with selectivity. A stronger effect of amlodipine is exerted on vascular smooth muscle cells than on cardiac muscle cells . Direct actions of amlodipine on vascular smooth muscle result in reduced blood pressure .

Mechanism of action in angina

The exact mechanism by which amlodipine relieves the symptoms of angina have not been fully elucidated to this date, however, the mechanism of action is likely twofold:

Amlodipine has a dilating effect on peripheral arterioles, reducing the total peripheral resistance (afterload) against which the cardiac muscle functions. Since the heart rate remains stable during amlodipine administration, the reduced work of the heart reduces both myocardial energy use and oxygen requirements .

Dilatation of the main coronary arteries and coronary arterioles, both in healthy and ischemic areas, is another possible mechanism of amlodipine reduction of blood pressure. The dilatation causes an increase in myocardial oxygen delivery in patients experiencing coronary artery spasm (Prinzmetal's or variant angina) and reduces coronary vasoconstriction caused by smoking .

Dosage

Lodiben dosage

Amlodipine is an effective treatment of hypertension in once-daily doses of 2.5-10 mg while benazepril is effective in doses of 10-80 mg. In clinical trials of amlodipine/benazepril combination therapy using amlodipine doses of 2.5-5 mg and benazepril doses of 10-20 mg, the antihypertensive effects increased with increasing dose of amlodipine in all patient groups, and the effects increased with increasing dose of benazepril in non black groups.

Side Effects

Cough Headache, Dizziness, and Edema. Other side effects considered possibly or probably related to the drug are: Angioedema, Asthenia and fatigue, Insomnia, nervousness, anxiety, tremor, and decreased libido, Dry mouth, nausea, abdominal pain, constipation, diarrhea, dyspepsia, and esophagitis, Hypokalemia, Back pain, musculoskeletal pain, cramps, impotence, polyuria etc.

Toxicity

Acute oral toxicity (LD50): 37 mg/kg (mouse) .

Overdose

An overdose of amlodipine could result in a high degree of peripheral vasodilatation with a possibility of reflex tachycardia. Significant and prolonged hypotension leading to shock and fatal outcomes have been reported .

Carcinogenesis, mutagenesis, impairment of fertility

Rats and mice treated with amlodipine maleate in the diet on a long-term basis for up to 2 years demonstrated no evidence of a carcinogenic effect of the drug. For the mouse, the highest dose was comparable to the maximum recommended human dose of 10 mg amlodipine per day. For the rat, the highest dose was measured to be about twice the maximum recommended human dose .

Mutagenicity studies using amlodipine maleate showed no drug-related gene or chromosomal effects .

There was no impact on the fertility of rats given oral amlodipine maleate (males for 64 days and females for 14 days before mating) at doses up to 10 mg amlodipine/kg/day (8 times the maximum recommended human dose) .

Use in pregnancy

The safety of amlodipine in human pregnancy or lactation has not been proven. Amlodipine is therefore considered a pregnancy category C drug . Use amlodipine only if the potential benefit justifies the potential risk .

Use in nursing

Discontinue when administering amlodipine .

Precaution

Impaired Renal Function: Amlodipine & Benazepril should be used with cautionin patients with severe renal disease.

Hyperkalemia: This may occur in only a few patients but generallyare reversible.

Patients With Hepatic Failure: Since Amlodipine is extensively metabolized by the liver and the plasma elimination half-life (t½) is 56 hours in patients with impaired hepatic function, caution should be exercised when administering Amlodipine & Benazepril to patients with severe hepatic impairment.

Cough: ACE inhibitor-induced cough should be considered in the differential diagnosis of cough.

Surgery/Anesthesia: In patients undergoing surgery or during anesthesia with agents that produce hypotension, Benazepril will block the angiotensin II formation that could otherwise occur secondary to compensatory renin release. Hypotension that occurs as a result of this mechanism can be corrected by volume expansion.

Carcinogenesis, Mutagenesis, Impairment of Fertility: No evidence of carcinogenicity, mutagenicity or impairment of fertility was found when the Benazepril/Amlodipine combination were given orally.

Interaction

Diuretics: Patients on diuretics may occasionally experience an excessive reduction of blood pressure after initiation of therapy with Amlodipine and Benazepril. Potassium-sparing diuretics (e.g. spironolactone) or potassium supplements can increase the risk of hyperkalemia.

Lithium: Increased serum lithium level and symptoms of lithium toxicity have been reported in patients receiving ACE inhibitors during therapy with lithium.

Volume of Distribution

21 L/kg , .

Elimination Route

Amlodipine absorbed slowly and almost completely from the gastrointestinal tract. Peak plasma concentrations are achieved 6-12 hours after oral administration. The estimated bioavailability of amlodipine is 64-90%. Steady-state plasma amlodipine levels are achieved after 7-8 days of consecutive daily dosing. Absorption is not affected by food .

Half Life

The terminal elimination half-life of about 30–50 hours .

Plasma elimination half-life is 56 hours in patients with impaired hepatic function, titrate slowly when administering this drug to patients with severe hepatic impairment .

Clearance

Total body clearance (CL) has been calculated as 7 ± 1.3 ml/min/kg (0.42 ± 0.078 L/ h/kg) in healthy volunteers , .

Elderly patients show a reduced clearance of amlodipine with an AUC (area under the curve) increase of about 40–60%, and a lower initial dose may be required .

Elimination Route

Elimination from the plasma occurs in a biphasic with a terminal elimination half-life of about 30–50 hours. Steady-state plasma levels of amlodipine are reached after 7-8 days of consecutive daily dosing . Amlodipine is 10% excreted as unchanged drug in the urine. Amlodipine can be initiated at normal doses in patients diagnosed with renal failure , .

Pregnancy & Breastfeeding use

Pregnancy: Categories C (first trimester) and D (second and third trimesters).

Nursing Mothers: Minimal amounts of unchanged benazepril and of benazeprilat are excreted into the breast milk of lactating women treated with benazepril, so that a newborn child ingesting nothing but breast milk would receive less than 0.1% of the maternal doses of benazepril and benazeprilat. 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 this combination is administered.

Contraindication

Amlodipine besylate and Benazepril hydrochloride combination is contraindicated in patients who are hypersensitive to benazepril, to any other ACE inhibitor, or to amlodipine.

Special Warning

Pediatric Use: Safety and effectiveness in pediatric patients have not been established.

Geriatric Use: Clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Acute Overdose

Human overdoses with any combination of Amlodipine and Benazepril have not been reported. In scattered reports of human overdoses with Benazepril and other ACE inhibitors, there are no reports of death.

Storage Condition

Store at 25°C, protect from moisture. Keep out of reach of children.

Innovators Monograph

You find simplified version here Lodiben