Active ingredient: Trandolapril - Brands, Medical Use, Clinical Data

Brands, Medical Use, Clinical Data

Drug Category

• Angiotensin-Converting Enzyme Inhibitors
• Antihypertensive Agents

Dosage Forms

• Capsule
• Tablets (1 mg, 2 mg, or 4 mg of trandolapril for oral administration)

Brands / Synonyms

Mavik; Tarka; Trandolaprilum [Latin]

Indications

For the treatment of hypertension.

Pharmacology

Trandolapril is the ethyl ester prodrug of a nonsulfhydryl angiotensin converting enzyme (ACE) inhibitor, trandolaprilat. Trandolapril is deesterified to the diacid metabolite, trandolaprilat, which is approximately eight times more active as an inhibitor of ACE activity. ACE is a peptidyl dipeptidase that catalyzes the conversion of angiotensin I to the vasoconstrictor, angiotensin II. Angiotensin II is a potent peripheral vasoconstrictor that also stimulates secretion of aldosterone by the adrenal cortex and provides negative feedback for renin secretion.

Mechanism of Action

The effect of trandolapril in hypertension appears to result primarily from the inhibition of circulating and tissue ACE activity thereby reducing angiotensin II formation, decreasing vasoconstriction, decreasing aldosterone secretion, and increasing plasma renin. Decreased aldosterone secretion leads to diuresis, natriuresis, and a small increase of serum potassium.

Absorption

Absolute bioavailability after oral administration of trandolapril is about 10% as trandolapril and 70% as trandolaprilat. Food slows absorption of trandolapril, but does not affect the area under the plasma concentration–time curve (AUC) or peak plasma concentration (C_max) of trandolaprilat or C_max of trandolapril.

Toxicity

No data are available with respect to overdosage in humans. The oral LD₅₀ of trandolapril in mice was 4875 mg/Kg in males and 3990 mg/Kg in females. In rats, an oral dose of 5000 mg/Kg caused low mortality (1 male out of 5; 0 females). In dogs, an oral dose of 1000 mg/Kg did not cause mortality and abnormal clinical signs were not observed. In humans the most likely clinical manifestation would be symptoms attributable to severe hypotension.

Biotrnasformation / Drug Metabolism

Cleavage of the ester group of trandolapril, primarily in the liver, is responsible for conversion to trandolaprilat, the active metabolite. Seven other metabolites, resulting primarily from glucuronidation or de-esterification, have been identified.

Contraindications

MAVIK is contraindicated in patients who are hypersensitive to this product and in patients with a history of angioedema related to previous treatment with an ACE inhibitor.

Drug Interactions

Concomitant diuretic therapy:

As with other ACE inhibitors, patients on diuretics, especially those on recently instituted diuretic therapy, may experience an excessive reduction of blood pressure after initiation of therapy with MAVIK. The possibility of exacerbation of hypoten-sive effects with MAVIK may be minimized by either discontinuing the diuretic or cautiously increasing salt intake prior to initiation of treatment with MAVIK. If it is not possible to discontinue the diuretic, the starting dose of trandolapril should be reduced.

Agents increasing serum potassium:

Trandolapril can attenuate potassium loss caused by thiazide diuretics and increase serum potassium when used alone. Use of potassium-sparing diuretics (spironolactone, triamterene, or amiloride), potassium supplements, or potassium-containing salt substitutes concomitantly with ACE inhibitors can increase the risk of hyperkalemia. If concomitant use of such agents is indicated, they should be used with caution and with appropriate monitoring of serum potassium.

Lithium:

Increased serum lithium levels and symptoms of lithium toxicity have been reported in patients receiving concomitant lithium and ACE inhibitor therapy. These drugs should be coadministered with caution, and frequent monitoring of serum lithium levels is recommended. If a diuretic is also used, the risk of lithium toxicity may be increased.

Other:

No clinically significant interaction has been found between trandolaprilat and food, cimetidine, digoxin, or furosemide. The anticoagulant effect of warfarin was not significantly changed by trandolapril.