Overview
DESCRIPTION Trandolapril is the ethyl ester prodrug of a nonsulfhydryl angiotensin converting enzyme (ACE) inhibitor, trandolaprilat. Trandolapril is chemically described as (2S,3aR,7aS)-1-[(S)-N-[(S)-1-Carboxy-3-phenylpropyl]alanyl] hexahydro-2-indolinecarboxylic acid, 1-ethyl ester. Its molecular formula is C 24 H 34 N 2 O 5 and its structural formula is M.W. = 430.
Mechanism of Action
CLINICAL PHARMACOLOGY Mechanism of Action 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. 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.
Indications
- INDICATIONS AND USAGE Hypertension Trandolapril tablets USP are indicated for the treatment of hypertension. They may be used alone or in combination with other antihypertensive medication such as hydrochlorothiazide. Heart Failure Post Myocardial Infarction or Left-Ventricular Dysfunction Post Myocardial Infarction Trandolapril tablets USP are indicated in stable patients who have evidence of left-ventricular systolic dysfunction (identified by wall motion abnormalities) or who are symptomatic from congestive heart failure within the first few days after sustaining acute myocardial...
Common Doses
- 1 mg
- 2 mg
- 4 mg
- 8 mg
Dosage
DOSAGE AND ADMINISTRATION Hypertension The recommended initial dosage of trandolapril tablets for patients not receiving a diuretic is 1 mg once daily in non-black patients and 2 mg in black patients. Dosage should be adjusted according to the blood pressure response. Generally, dosage adjustments should be made at intervals of at least 1 week. Most patients have required dosages of 2 to 4 mg once daily. There is little clinical experience with doses above 8 mg. Patients inadequately treated with once-daily dosing at 4 mg may be treated with twice-daily dosing.
Black Box Warning
WARNING: FETAL TOXICITY When pregnancy is detected, discontinue trandolapril as soon as possible. Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus. (See WARNINGS: Fetal Toxicity .)
Contraindications
- CONTRAINDICATIONS Trandolapril tablets are contraindicated in patients who are hypersensitive to this product, in patients with hereditary/idiopathic angioedema and in patients with a history of angioedema related to previous treatment with an ACE inhibitor. Do not co-administer aliskiren with trandolapril in patients with diabetes (see PRECAUTIONS, Drug Interactions ). Trandolapril tablets are contraindicated in combination with a neprilysin inhibitor (e.g., sacubitril).
Side Effects
- ADVERSE REACTIONS The safety experience in U.S. placebo-controlled trials included 1069 hypertensive patients, of whom 832 received trandolapril. Nearly 200 hypertensive patients received trandolapril for over one year in open-label trials. In controlled trials, withdrawals for adverse events were 2.1% on placebo and 1.4% on trandolapril. Adverse events considered at least possibly related to treatment occurring in 1% of trandolapril-treated patients and more common on trandolapril than placebo, pooled for all doses, are shown below, together with the frequency of discontinuation of treatment...
Interactions
- Drug Interactions Dual Blockade of the Renin-Angiotensin System (RAS) Dual blockade of the RAS with angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy. Most patients receiving the combination of two RAS inhibitors do not obtain any additional benefit compared to monotherapy. In general, avoid combined use of RAS inhibitors.