>1%:

Cardiovascular: Hypotension (<1% to 11%), bradycardia (<1% to 4.7%), intermittent claudication (3.8%), stroke (3.3%), syncope (5.9%)

Central nervous system: Dizziness (1.3% to 23%), asthenia (3.3%)

Endocrine & metabolic: Elevated uric acid (15%), hyperkalemia (5.3%), hypocalcemia (4.7%)

Gastrointestinal: Dyspepsia (6.4%), gastritis (4.2%)

Neuromuscular & skeletal: Myalgia (4.7%)

Renal: Elevated BUN (9%), elevated serum creatinine (1.1% to 4.7%)

Respiratory: Cough (1.9% to 35%)

<1% (Limited to important or life-threatening): Chest pain, AV block (first-degree), edema, flushing, palpitation, drowsiness, insomnia, paresthesia, vertigo, pruritus, rash, pemphigus, epistaxis, pharyngitis, upper respiratory tract infection, anxiety, impotence, decreased libido, abdominal distension, abdominal pain, constipation, dyspepsia, diarrhea, vomiting, pancreatitis, leukopenia, neutropenia, thrombocytopenia, increased serum creatinine, increased ALT, muscle pain, gout, dyspnea, angioedema, laryngeal edema, symptomatic hypotension, transaminases elevation, increased bilirubin. Worsening of renal function may occur in patients with bilateral renal artery stenosis or in hypovolemic patients. In addition, a syndrome which may include fever, myalgia, arthralgia, interstitial nephritis, vasculitis, rash, eosinophilia and positive ANA, and elevated ESR has been reported with ACE inhibitors.

Alpha1 blockers: Hypotensive effect increased.

Aspirin: The effects of ACE inhibitors may be blunted by aspirin administration, particularly at higher dosages (see Cardiovascular Considerations) and/or increase adverse renal effects.

Diuretics: Hypovolemia due to diuretics may precipitate acute hypotensive events or acute renal failure.

Insulin: Risk of hypoglycemia may be increased.

Lithium: Risk of lithium toxicity may be increased; monitor lithium levels, especially the first 4 weeks of therapy.

Mercaptopurine: Risk of neutropenia may be increased.

NSAIDs: May attenuate hypertensive efficacy; effect has been seen with captopril and may occur with other ACE inhibitors; monitor blood pressure. May increase adverse renal effects.

Potassium-sparing diuretics (amiloride, potassium, spironolactone, triamterene): Increased risk of hyperkalemia.

Potassium supplements may increase the risk of hyperkalemia.

Trimethoprim (high dose) may increase the risk of hyperkalemia.

Onset of action: 1-2 hours

Peak effect: Reduction in blood pressure: 6 hours

Duration: Prolonged; 72 hours after single dose

Absorption: Rapid

Distribution: Trandolaprilat (active metabolite) is very lipophilic in comparison to other ACE inhibitors

Protein binding: 80%

Metabolism: Hepatically hydrolyzed to active metabolite, trandolaprilat

Half-life elimination:

Trandolapril: 6 hours; Trandolaprilat: Effective: 10 hours, Terminal: 24 hours

Elimination: As metabolites in urine;

Time to peak: Parent: 1 hour; Active metabolite trandolaprilat: 4-10 hours

Excretion: Urine (as metabolites)

Clearance: Reduce dose in renal failure; creatinine clearances 30 mL/minute result in accumulation of active metabolite

Hypertension: Initial dose in patients not receiving a diuretic: 1 mg/day (2 mg/day in black patients). Adjust dosage according to the blood pressure response. Make dosage adjustments at intervals of 1 week. Most patients have required dosages of 2-4 mg/day. There is a little experience with doses >8 mg/day. 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 monotherapy, a diuretic may be added.

Usual dose range (JNC 7): 1-4 mg once daily

Heart failure postmyocardial infarction or left ventricular dysfunction postmyocardial infarction: Initial: 1 mg/day; titrate patients (as tolerated) towards the target dose of 4 mg/day. If a 4 mg dose is not tolerated, patients can continue therapy with the greatest tolerated dose.

Dosing adjustment in renal impairment: Clcr 30 mL/minute: Recommended starting dose: 0.5 mg/day.

Dosing adjustment in hepatic impairment: Cirrhosis: Recommended starting dose: 0.5 mg/day.

ACE inhibitor therapy may elicit rapid increases in potassium and creatinine, especially when used in patients with bilateral renal artery stenosis. When ACE inhibition is introduced in patients with pre-existing diuretic therapy who are hypovolemic, the ACE inhibitor may induce acute hypotension. In those patients experiencing cough on an ACE inhibitor, the ACE inhibitor may be discontinued and, if necessary, angiotensin receptor blocker therapy instituted. Concomitant NSAID therapy may attenuate blood pressure control; use of NSAIDs should be avoided or limited, with monitoring of blood pressure control. In the setting of heart failure, NSAID use may be associated with an increased risk for fluid accumulation and edema. Because of the potent teratogenic effects of ACE inhibitors, these drugs should be avoided, if possible, when treating women of childbearing potential not on effective birth control measures.

In the treatment of unstable angina/non-ST-segment elevation MI, ACE inhibitors are recommended when hypertension persists despite treatment with nitroglycerin and a beta-blocker in patients with LV systolic dysfunction or CHF and in ischemic patients with diabetes (Class I). ACE inhibitors are also recommended for all post-ACS individuals (Class IIa).

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