Trandolapril

Hypertension Trandolapril tablets are indicated for the treatment of hypertension. It 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 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 infarction. Administration of trandolapril to Caucasian patients has been shown to decrease the risk of death (principally cardiovascular death) and to decrease the risk of heart failure-related hospitalization.

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. Decreased aldosterone secretion leads to diuresis, natriuresis, and a small increase of serum potassium.

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. If blood pressure is not adequately controlled with trandolapril tablets monotherapy, a diuretic may be added. In patients who are currently being treated with a diuretic, symptomatic hypotension occasionally can occur following the initial dose of trandolapril tablets.

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 tablets in patients with diabetes. Trandolapril tablets are contraindicated in combination with a neprilysin inhibitor (e.g., sacubitril). Do not administer trandolapril tablets within 36 hours of switching to or from sacubitril/valsartan, a neprilysin inhibitor.

Boxed warning (fetal toxicity): When pregnancy is detected, discontinue trandolapril tablets as soon as possible. Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus. Anaphylactoid and Possibly Related Reactions Presumably because angiotensin converting enzyme inhibitors affect the metabolism of eicosanoids and polypeptides, including endogenous bradykinin, patients receiving ACE inhibitors, including trandolapril tablets, may be subject to a variety of adverse reactions, some of them serious. Anaphylactoid Reactions During Desensitization Two patients undergoing desensitizing treatment with hymenoptera venom while receiving ACE inhibitors sustained life-threatening anaphylactoid reactions.

The safety experience in U.S. placebo-controlled trials included 1069 hypertensive patients, of whom 832 received trandolapril tablets. Nearly 200 hypertensive patients received trandolapril tablets 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 tablets. Adverse events considered at least possibly related to treatment occurring in 1% of trandolapril tablets-treated patients and more common on trandolapril tablets than placebo, pooled for all doses, are shown below, together with the frequency of discontinuation of treatment because of these events. ADVERSE EVENTS IN PLACEBO-CONTROLLED HYPERTENSION TRIALS Occurring at 1 % or greater TRANDOLAPRIL TABLETS ( N = 832 ) % Incidence (% Discontinuance ) PLACEBO ( N = 237 ) % Incidence (% Discontinuance ) Cough 1.9 0.4. Dizziness 1.3 0.4. Diarrhea 1.0 0.4.

Trandolapril did not affect the plasma concentration (pre-dose and 2 hours post-dose) of oral digoxin (0.25 mg). Coadministration of trandolapril and cimetidine led to an increase of about 44% in C max for trandolapril, but no difference in the pharmacokinetics of trandolaprilat or in ACE inhibition. Coadministration of trandolapril and furosemide led to an increase of about 25% in the renal clearance of trandolaprilat, but no effect was seen on the pharmacokinetics of furosemide or trandolaprilat or on ACE inhibition. 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.

Store at 20° to 25°C (68° to 77°F).