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.
Hypertension:
Note : For patients who warrant combination therapy (BP >20/10 mm Hg above goal or suboptimal response to initial monotherapy), may use with another appropriate agent (eg, long-acting dihydropyridine calcium channel blocker or thiazide diuretic) (ACC/AHA [Whelton 2018]).
Oral: Initial: 1 mg once daily; evaluate response after ~2 to 4 weeks and titrate dose (eg, increase the daily dose by doubling), as needed, up to 4 mg once daily. If additional BP control is needed, consider combination therapy. Patients with severe asymptomatic hypertension and no signs of acute end organ damage should be evaluated for medication titration within 1 week (ACC/AHA [Whelton 2018]; Mann 2022).
Post–myocardial infarction heart failure or left ventricular dysfunction: Oral: Initial: 1 mg once daily; titrate (as tolerated) toward target dose of 4 mg once daily. If 4 mg dose is not tolerated, patients may continue therapy with the greatest tolerated dose.
Heart failure with reduced ejection fraction (off-label use):
Note : If tolerated, an angiotensin II receptor/neprilysin inhibitor is generally preferred over an angiotensin-converting enzyme inhibitor (ACC/AHA/HFSA [Heidenreich 2022]).
Oral: Initial: 1 mg once daily; may increase dose as tolerated (eg, double the dose) every ~1 to 2 weeks to a target dose of 4 mg once daily (ACC/AHA/HFSA [Heidenreich 2022]).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
CrCl ≥30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling.
CrCl <30 mL/minute: Initial: 0.5 mg once daily; titrate as tolerated to optimal response.
Mild to severe impairment: There are no dosage adjustments provided in the manufacturer's labeling; consider lower doses in patients with hepatic impairment.
Cirrhosis: Initial: 0.5 mg once daily; titrate as tolerated to optimal response. Use with caution, particularly in patients with ascites due to cirrhosis (AASLD [Biggins 2021]; AASLD [Runyon 2013]).
Refer to adult dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Generic: 1 mg, 2 mg, 4 mg
Yes
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Mavik: 0.5 mg, 1 mg, 2 mg, 4 mg
Odrik: 2 mg
Generic: 0.5 mg, 1 mg, 2 mg, 4 mg
Hypertension: Management of hypertension.
Post–myocardial infarction heart failure or left-ventricular dysfunction: Treatment of post–myocardial infarction (MI) heart failure (HF) in patients who are symptomatic from HF within the first few days after sustaining acute MI or post-MI left ventricular dysfunction in stable patients who have evidence of left ventricular systolic dysfunction (identified by wall motion abnormalities)
Heart failure with reduced ejection fraction
Use may be associated with increased blood urea nitrogen and increased serum creatinine, resulting in oliguria and acute kidney injury (AKI). Increases in serum creatinine are expected due to pharmacologic mechanism and generally stabilize within 20% to 30% of the baseline; higher increases may indicate high efferent tone (such as with hypovolemia, congestive heart failure, or renal artery stenosis) (Ref).
Mechanism: Related to pharmacologic action; inhibits efferent arteriolar vasoconstriction, lowering glomerular filtration pressure, which can lead to a reduction in the glomerular filtration rate (GFR). Kidney hypoperfusion from systemic hypotension may also occur (Ref).
Onset: Intermediate; increases in serum creatinine generally occur within 2 weeks of initiation and stabilize within 2 to 4 weeks (Ref). However, more immediate increases can occur in patients with other risk factors for AKI (Ref).
Risk factors:
• Patients with low renal blood flow whose GFR is dependent on efferent arteriolar vasoconstriction by angiotensin II including (Ref):
- Low effective circulating volume (sodium or volume depletion)
- Congestive heart failure
- Hypotension or shock
- Renal artery stenosis
• High dose at initiation (Ref)
• Older patients (Ref)
• Preexisting kidney impairment (Ref)
• Concurrent diuretic and/or nonsteroidal anti-inflammatory drug use (Ref)
Angioedema may occur rarely; edema may manifest in the head and neck (potentially compromising the airway) or the intestine (presenting with abdominal pain). Use is contraindicated in patients with idiopathic or hereditary angioedema or previous angioedema associated with any angiotensin-converting enzyme inhibitors or neprilysin inhibitors (Ref).
Mechanism: Related to pharmacologic action (ie, increased bradykinin and substance P, vascular permeability, and vasodilation) (Ref).
Onset: Varied; may occur at any time during treatment. Most cases occur within the first week of therapy but may also occur years after therapy (Ref).
Risk factors:
• Black patients (estimated 4- to 5-fold higher risk); the mechanism for this is not completely understood but may be related to genetic variants (Ref)
• Females (Ref)
• Smoking history (Ref)
• Previous history of angioedema (Ref)
• Age >65 years (Ref)
• Seasonal allergies (Ref)
• Concurrent use of mechanistic target of rapamycin (mTOR) inhibitors (eg, everolimus) (Ref)
• Concurrent use of neprilysin inhibitor (contraindicated)
A dry, hacking, nonproductive cough that is typically associated with tickling or scratching in the throat may occur with angiotensin converting enzyme inhibitors (ACEI) in adult and pediatric patients (Ref). Recurrence is likely with rechallenge (Ref). Resolution of cough typically occurs 1 to 4 weeks after ACEI discontinuation but may persist for up to 3 months (Ref).
Mechanism: Various proposed mechanisms. May be related to pharmacologic action (ie, increased bradykinin and substance P, resulting in accumulation in the lungs and bronchoconstriction (Ref).
Onset: Varied; within hours to 4 weeks after initiation but can be delayed for up to 6 months (Ref).
Risk factors:
• Females (Ref)
• Possibly certain genetic variants (some of which may be independent of the bradykinin pathway) (Ref)
Hyperkalemia (elevated serum potassium) may occur on therapy with angiotensin converting enzyme inhibitors (ACEI), including trandolapril (Ref).
Mechanism: Related to pharmacologic action; inhibits formation of circulating angiotensin II, which leads to efferent arteriole vasodilation and subsequent lowering of glomerular filtration rate, which lowers potassium elimination. Additionally, interferes with the generation and release of aldosterone from the adrenal cortex, leading to an impairment of potassium excretion from the kidney (Ref).
Risk factors:
• Disease states associated with hyperkalemia (congestive heart failure, diabetes mellitus, chronic kidney disease) (Ref)
• Concurrent use of medications which cause hyperkalemia (ACEI, angiotensin receptor blockers, spironolactone, nonsteroidal anti-inflammatory drugs, beta blockers, heparin, tacrolimus, cyclosporine) (Ref)
• Acute kidney injury (elevated BUN and/or serum creatinine) (Ref)
• High dietary intake of potassium or concurrent use of potassium supplements (including potassium-containing salt substitutes) (Ref)
• Baseline elevated potassium level (≥5 mmol/L) (Ref)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Frequency ranges include data from hypertension and post-myocardial infarction (post-MI) trials. Higher rates of adverse reactions have generally been noted in post-MI patients.
>10%:
Cardiovascular: Hypotension (≤11%; can be symptomatic hypotension)
Endocrine & metabolic: Increased uric acid (15%)
Nervous system: Dizziness (1% to 23%)
Respiratory: Cough (2% to 35%)
Drug (Trandolapril) |
Placebo |
Indication |
Number of Patients (Trandolapril) |
Number of Patients (Placebo) |
---|---|---|---|---|
2% |
0.4% |
Hypertension |
832 |
237 |
35% |
22% |
Left ventricular dysfunction post-myocardial infarction |
876 |
873 |
1% to 10%:
Cardiovascular: Bradycardia (≤5%), cardiogenic shock (4%), intermittent claudication (4%), syncope (6%)
Endocrine & metabolic: Hyperkalemia (5%; serum potassium >6 mEq/L: <1%) (table 1) , hypocalcemia (5%)
Drug (Trandolapril) |
Placebo |
Indication |
Number of Patients (Trandolapril) |
Number of Patients (Placebo) |
Comments |
---|---|---|---|---|---|
0.4% |
N/A |
Hypertension |
N/A |
N/A |
Serum potassium >6 mEq/L |
5% |
3% |
Left ventricular dysfunction post-myocardial infarction |
876 |
873 |
N/A |
Gastrointestinal: Diarrhea (≤1%)
Neuromuscular & skeletal: Myalgia (5%)
Renal: Increased blood urea nitrogen (≤9% (table 2) ), increased serum creatinine (1% to 5%) (table 3)
Drug (Trandolapril) |
Comparator (Trandolapril + Calcium Ion Antagonist + Diuretic) |
Placebo |
Indication |
Number of Patients (Trandolapril) |
Number of Patients (Placebo) |
---|---|---|---|---|---|
9% |
N/A |
8% |
Left ventricular dysfunction post-myocardial infarction |
876 |
873 |
0.6% |
1% |
N/A |
N/A |
N/A |
N/A |
Drug (Trandolapril) |
Comparator (Trandolapril + Calcium Ion Antagonist + Diuretic) |
Placebo |
Indication |
Number of Patients (Trandolapril) |
Number of Patients (Placebo) |
---|---|---|---|---|---|
5% |
N/A |
2% |
Left ventricular dysfunction post-myocardial infarction |
876 |
873 |
1% |
7% |
N/A |
N/A |
N/A |
N/A |
<1%:
Cardiovascular: Chest pain, edema, first degree atrioventricular block, flushing, palpitations
Dermatologic: Pemphigus, pruritus, skin rash
Endocrine & metabolic: Decreased libido, gout
Gastrointestinal: Abdominal cramps, abdominal distention, abdominal pain, constipation, dyspepsia, nausea, vomiting
Genitourinary: Impotence
Hematologic & oncologic: Decreased neutrophils, leukopenia
Hepatic: Increased serum bilirubin, increased serum transaminases (including increased serum alanine aminotransferase and increased serum aspartate aminotransferase)
Nervous system: Anxiety, drowsiness, insomnia, paresthesia, vertigo
Neuromuscular & skeletal: Limb pain, muscle cramps
Respiratory: Dyspnea, epistaxis, pharyngitis, upper respiratory tract infection
Postmarketing:
Cardiovascular: Acute myocardial infarction, angina pectoris, cardiac arrhythmia, cardiac failure, ischemic heart disease, tachycardia, transient ischemic attacks, ventricular tachycardia
Dermatologic: Alopecia, diaphoresis, psoriasis (Song 2021), Stevens-Johnson syndrome, toxic epidermal necrolysis
Endocrine & metabolic: Hyponatremia
Gastrointestinal: Pancreatitis, xerostomia
Hematologic & oncologic: Agranulocytosis, pancytopenia, thrombocytopenia
Hepatic: Hepatitis, jaundice
Hypersensitivity: Angioedema
Nervous system: Cerebral hemorrhage, depression, hallucination, malaise
Renal: Acute kidney injury
Respiratory: Bronchitis
Miscellaneous: Fever
Hypersensitivity to trandolapril or any component of the formulation; coadministration with aliskiren in patients with diabetes; hereditary/idiopathic angioedema; history of angioedema related to previous treatment with an ACE inhibitor; coadministration with or within 36 hours of switching to or from a neprilysin inhibitor (eg, sacubitril).
Documentation of allergenic cross-reactivity for Angiotensin-Converting Enzyme Inhibitors is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.
Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to other ACE inhibitors; women who are pregnant, planning to become pregnant, or women of childbearing potential and not using adequate contraception; breastfeeding; hypotensive or hemodynamically unstable states; hemodynamically significant bilateral artery stenosis or severe artery stenosis of a solitary functioning kidney; concomitant use with sacubitril/valsartan; concomitant use with ACE inhibitors, angiotensin receptor blockers (ARBs) or aliskiren-containing medications in patients with type 1 or 2 diabetes mellitus, moderate to severe kidney impairment (GFR <60 mL/minute/1.73 m2), hyperkalemia (>5 mMol/L) or with heart failure who are hypotensive; hereditary problems of galactose intolerance, congenital lactase deficiency or glucose-galactose malabsorption.
Concerns related to adverse reactions:
• Cholestatic jaundice: A rare toxicity associated with angiotensin-converting enzyme (ACE) inhibitors includes cholestatic jaundice, although there are no published reports with trandolapril.
• Hypersensitivity reactions: Anaphylaxis/nonimmune anaphylaxis can occur with ACE inhibitors. Severe nonimmune anaphylaxis may be seen during hemodialysis (eg, CVVHD) with high-flux dialysis membranes (eg, AN69), and rarely, during low density lipoprotein apheresis with dextran sulfate cellulose. Rare cases of nonimmune anaphylaxis have been reported in patients undergoing sensitization treatment with hymenoptera (bee, wasp) venom while receiving ACE inhibitors.
• Hypotension/syncope: Symptomatic hypotension with or without syncope can occur with ACE inhibitors (usually with the first several doses); effects are most often observed in volume-depleted patients; correct volume depletion prior to initiation; close monitoring of patient is required especially with initial dosing and dosing increases; blood pressure must be lowered at a rate appropriate for the patient's clinical condition. Although dose reduction may be necessary, hypotension is not a reason for discontinuation of future ACE inhibitor use especially in patients with heart failure where a reduction in systolic blood pressure is a desirable observation.
Disease-related concerns:
• Aortic stenosis: Use with caution in patients with aortic stenosis; may reduce coronary perfusion resulting in ischemia.
• Ascites: Generally, avoid use in patients with ascites due to cirrhosis or refractory ascites; if use cannot be avoided in patients with ascites due to cirrhosis, monitor BP and kidney function carefully to avoid rapid development of kidney failure (AASLD [Runyon 2013]).
• Cardiovascular disease: Initiation of therapy in patients with ischemic heart disease or cerebrovascular disease warrants close observation due to the potential consequences posed by falling blood pressure (eg, MI, stroke). Fluid replacement, if needed, may restore blood pressure; therapy may then be resumed. Discontinue therapy in patients whose hypotension recurs.
• Hepatic impairment: Use with caution in patients with hepatic impairment; dosage adjustment recommended in patients with cirrhosis and lower doses should be considered in patients with hepatic impairment.
• Hypertrophic cardiomyopathy with left ventricular outflow tract obstruction: Use with caution in patients with hypertrophic cardiomyopathy and left ventricular outflow tract obstruction since reduction in afterload may worsen symptoms associated with this condition (AHA/ACC [Ommen 2020]).
• Kidney impairment: Use with caution in patients with kidney impairment; dosage adjustment may be required. Avoid rapid dosage escalation, which may lead to further kidney impairment.
Special populations:
• Race/Ethnicity: In Black patients, the BP-lowering effects of ACE inhibitors may be less pronounced. The exact mechanism is not known; differences in the renin-angiotensin-aldosterone system, low renin levels, and salt sensitivity more commonly found in Black patients may contribute (Brewster 2013; Helmer 2018).
• Surgical patients: In patients on chronic ACE inhibitor therapy, intraoperative hypotension may occur with induction and maintenance of general anesthesia; use with caution before, during, or immediately after major surgery. Cardiopulmonary bypass, intraoperative blood loss, or vasodilating anesthesia increases endogenous renin release. Use of ACE inhibitors perioperatively will blunt angiotensin II formation and may result in hypotension. However, discontinuation of therapy prior to surgery is controversial. If continued preoperatively, avoidance of hypotensive agents during surgery is prudent (Hillis 2011). Based on current research and clinical guidelines in patients undergoing non-cardiac surgery, continuing ACE inhibitors is reasonable in the perioperative period. If ACE inhibitors are held before surgery, it is reasonable to restart postoperatively as soon as clinically feasible (ACC/AHA [Fleisher 2014]).
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Aliskiren: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Aliskiren may enhance the hypotensive effect of Angiotensin-Converting Enzyme Inhibitors. Aliskiren may enhance the nephrotoxic effect of Angiotensin-Converting Enzyme Inhibitors. Management: Aliskiren use with ACEIs or ARBs in patients with diabetes is contraindicated. Combined use in other patients should be avoided, particularly when CrCl is less than 60 mL/min. If combined, monitor potassium, creatinine, and blood pressure closely. Risk D: Consider therapy modification
Allopurinol: Angiotensin-Converting Enzyme Inhibitors may enhance the potential for allergic or hypersensitivity reactions to Allopurinol. Risk C: Monitor therapy
Alteplase: Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Alteplase. Specifically, the risk for angioedema may be increased. Risk C: Monitor therapy
Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Risk D: Consider therapy modification
Amphetamines: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy
Angiotensin II: Angiotensin-Converting Enzyme Inhibitors may enhance the therapeutic effect of Angiotensin II. Risk C: Monitor therapy
Angiotensin II Receptor Blockers: May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Angiotensin II Receptor Blockers may increase the serum concentration of Angiotensin-Converting Enzyme Inhibitors. Management: Use of telmisartan and ramipril is not recommended. It is not clear if any other combination of an ACE inhibitor and an ARB would be any safer. Consider alternatives when possible. Monitor blood pressure, renal function, and potassium if combined. Risk D: Consider therapy modification
Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor therapy
Aprotinin: May diminish the antihypertensive effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
AzaTHIOprine: Angiotensin-Converting Enzyme Inhibitors may enhance the myelosuppressive effect of AzaTHIOprine. Risk C: Monitor therapy
Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Brigatinib: May diminish the antihypertensive effect of Antihypertensive Agents. Brigatinib may enhance the bradycardic effect of Antihypertensive Agents. Risk C: Monitor therapy
Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Bromperidol: May diminish the hypotensive effect of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Risk X: Avoid combination
Dapoxetine: May enhance the orthostatic hypotensive effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
Dexmethylphenidate: May diminish the therapeutic effect of Antihypertensive Agents. Risk C: Monitor therapy
Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Dipeptidyl Peptidase-IV Inhibitors: May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Specifically, the risk of angioedema may be increased. Risk C: Monitor therapy
Drospirenone-Containing Products: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Risk C: Monitor therapy
Eplerenone: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
Everolimus: May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Specifically, the risk of angioedema may be increased. Risk C: Monitor therapy
Ferric Gluconate: Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Ferric Gluconate. Risk C: Monitor therapy
Ferric Hydroxide Polymaltose Complex: Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Ferric Hydroxide Polymaltose Complex. Specifically, the risk for angioedema or allergic reactions may be increased. Risk C: Monitor therapy
Finerenone: Angiotensin-Converting Enzyme Inhibitors may enhance the hyperkalemic effect of Finerenone. Risk C: Monitor therapy
Flunarizine: May enhance the therapeutic effect of Antihypertensive Agents. Risk C: Monitor therapy
Gelatin (Succinylated): Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Gelatin (Succinylated). Specifically, the risk of a paradoxical hypotensive reaction may be increased. Risk C: Monitor therapy
Gold Sodium Thiomalate: Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Gold Sodium Thiomalate. This combination may increase the risk of developing a nitritoid reaction. Risk C: Monitor therapy
Grass Pollen Allergen Extract (5 Grass Extract): Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Grass Pollen Allergen Extract (5 Grass Extract). Specifically, ACE inhibitors may increase the risk of severe allergic reaction to Grass Pollen Allergen Extract (5 Grass Extract). Risk X: Avoid combination
Heparin: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
Heparins (Low Molecular Weight): May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
Herbal Products with Blood Pressure Increasing Effects: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy
Herbal Products with Blood Pressure Lowering Effects: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy
Icatibant: May diminish the antihypertensive effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
Iron Dextran Complex: Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Iron Dextran Complex. Specifically, patients receiving an ACE inhibitor may be at an increased risk for anaphylactic-type reactions. Risk C: Monitor therapy
Lanthanum: May decrease the serum concentration of Angiotensin-Converting Enzyme Inhibitors. Management: Administer angiotensin-converting enzyme inhibitors at least two hours before or after lanthanum. Risk D: Consider therapy modification
Levodopa-Containing Products: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products. Risk C: Monitor therapy
Lithium: Angiotensin-Converting Enzyme Inhibitors may increase the serum concentration of Lithium. Management: Lithium dosage reductions will likely be needed following the addition of an ACE inhibitor. Monitor for increased concentrations/toxic effects of lithium if an ACE inhibitor is initiated/dose increased, or if switching between ACE inhibitors. Risk D: Consider therapy modification
Loop Diuretics: May enhance the hypotensive effect of Angiotensin-Converting Enzyme Inhibitors. Loop Diuretics may enhance the nephrotoxic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Methylphenidate: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy
Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nicorandil: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the combination may result in a significant decrease in renal function. Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents (Topical): May diminish the therapeutic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Risk D: Consider therapy modification
Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Potassium Salts: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
Potassium-Sparing Diuretics: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
Pregabalin: Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Pregabalin. Specifically, the risk of angioedema may be increased. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Racecadotril: May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Specifically, the risk for angioedema may be increased with this combination. Risk C: Monitor therapy
Ranolazine: May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
Sacubitril: Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Sacubitril. Specifically, the risk of angioedema may be increased with this combination. Risk X: Avoid combination
Salicylates: May enhance the nephrotoxic effect of Angiotensin-Converting Enzyme Inhibitors. Salicylates may diminish the therapeutic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
Sirolimus Products: May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Specifically, the risk for angioedema may be increased. Risk C: Monitor therapy
Sodium Phosphates: Angiotensin-Converting Enzyme Inhibitors may enhance the nephrotoxic effect of Sodium Phosphates. Specifically, the risk of acute phosphate nephropathy may be enhanced. Risk C: Monitor therapy
Tacrolimus (Systemic): Angiotensin-Converting Enzyme Inhibitors may enhance the hyperkalemic effect of Tacrolimus (Systemic). Risk C: Monitor therapy
Temsirolimus: May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Specifically, the risk of angioedema may be increased. Risk C: Monitor therapy
Thiazide and Thiazide-Like Diuretics: May enhance the hypotensive effect of Angiotensin-Converting Enzyme Inhibitors. Thiazide and Thiazide-Like Diuretics may enhance the nephrotoxic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
Tolvaptan: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
Trimethoprim: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
Urapidil: May interact via an unknown mechanism with Angiotensin-Converting Enzyme Inhibitors. Management: Avoid concomitant use of urapidil and angiotensin-converting enzyme (ACE) inhibitors. Risk D: Consider therapy modification
Urokinase: May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Specifically, the risk of angioedema may be increased. Risk C: Monitor therapy
Avoid use of angiotensin-converting enzyme (ACE) inhibitor therapy in patients who may become pregnant and who are not using effective contraception (ADA 2021).
ACE inhibitors should generally be avoided for the treatment of hypertension in patients planning to become pregnant; use should only be considered for cases of hypertension refractory to other medications (ACOG 203 2019).
Exposure to an angiotensin-converting enzyme (ACE) inhibitor during the first trimester of pregnancy may be associated with an increased risk of fetal malformations (ACOG 203 2019; ESC [Regitz-Zagrosek 2018]); however, outcomes observed may also be influenced by maternal disease (ACC/AHA [Whelton 2018]).
[US Boxed Warning]: Drugs that act on the renin-angiotensin system can cause injury and death to the developing fetus. Discontinue as soon as possible once pregnancy is detected. Drugs that act on the renin-angiotensin system are associated with oligohydramnios. Oligohydramnios, due to decreased fetal kidney function, may lead to fetal lung hypoplasia and skeletal malformations. The use of these drugs in pregnancy is also associated with anuria, hypotension, kidney failure, skull hypoplasia, and death in the fetus/neonate. Infants exposed to an ACE inhibitor in utero should be monitored for hyperkalemia, hypotension, and oliguria. Oligohydramnios may not appear until after irreversible fetal injury has occurred. Exchange transfusions or dialysis may be required to reverse hypotension or improve kidney function, although data related to the effectiveness in neonates is limited.
Chronic maternal hypertension is also associated with adverse events in the fetus/infant. Chronic maternal hypertension may increase the risk of birth defects, low birth weight, premature delivery, stillbirth, and neonatal death. Actual fetal/neonatal risks may be related to duration and severity of maternal hypertension. Untreated chronic hypertension may also increase the risks of adverse maternal outcomes, including gestational diabetes, preeclampsia, delivery complications, stroke, and myocardial infarction (ACOG 203 2019).
When treatment of hypertension in pregnancy is indicated, ACE inhibitors should generally be avoided due to their adverse fetal events; use in pregnant women should only be considered for cases of hypertension refractory to other medications (ACOG 203 2019). ACE inhibitors are not recommended for the treatment of heart failure in pregnancy (Regitz-Zagrosek [ESC 2018]).
It is not known if trandolapril is present in breast milk. Breastfeeding is not recommended by the manufacturer.
Use potassium-containing salt substitutes cautiously in patients with diabetes, kidney impairment, or those maintained on potassium supplements or potassium-sparing diuretics.
BP; BUN, serum creatinine and electrolytes (including potassium, especially in patients on concomitant potassium-sparing diuretics, potassium supplements, and/or potassium-containing salts); if patient has collagen vascular disease and/or kidney impairment, periodically monitor CBC with differential. If angioedema is suspected, assess risk of airway obstruction (eg, involvement of tongue, glottis, larynx, and/or history of airway surgery).
BP goals: May vary depending on clinical condition, different clinical practice guidelines, and expert opinion. Refer to clinical practice guidelines for specific treatment goals.
Trandolapril is an ACE inhibitor which prevents the formation of angiotensin II from angiotensin I. Trandolapril must undergo enzymatic hydrolysis, mainly in liver, to its biologically active metabolite, trandolaprilat. A CNS mechanism may also be involved in the hypotensive effect as angiotensin II increases adrenergic outflow from the CNS. Vasoactive kallikreins may be decreased in conversion to active hormones by ACE inhibitors, thus reducing blood pressure.
Absorption: Slowed with food
Distribution: Trandolapril: ~18 L
Protein binding: Trandolapril: ~80%; Trandolaprilat: 65% to 94% (concentration dependent)
Metabolism: Hepatically hydrolyzed to active metabolite, trandolaprilat and at least 7 other metabolites
Bioavailability: Trandolapril: ~10%; Trandolaprilat: ~70%
Half-life elimination: Trandolapril: ~6 hours; Trandolaprilat: Effective: 22.5 hours
Time to peak: Trandolapril: ~1 hour; Trandolaprilat: 4 to 10 hours
Excretion: Urine (~33% as trandolapril and trandolaprilat); feces (~66%)
Renal clearance: 1 to 4 L/hour (dose dependent); reduced in renal impairment
Altered kidney function: Plasma trandolapril and trandolaprilat are approximately 2-fold greater and renal Cl is decreased ~85% in patients with CrCl <30 mL/minute and in hemodialysis patients.
Hepatic function impairment: In patients with mild to moderate alcoholic cirrhosis, plasma concentrations of trandolapril and trandolaprilat were 9- and 2-fold greater, respectively, but inhibition of ACE activity was not affected.
Older adult: Plasma concentration of trandolapril is increased.
Tablets (Trandolapril Oral)
1 mg (per each): $1.21 - $1.24
2 mg (per each): $1.21 - $1.24
4 mg (per each): $1.21 - $1.24
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