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Trandolapril (Monograph)

Brand name: Mavik
Drug class: Angiotensin-Converting Enzyme Inhibitors
- ACE Inhibitors
VA class: CV800
Chemical name: 1-Ethyl ester (2S,3aR,7aS)-1-[(S)-N-[(S)-1-carboxy-3-phenylpropyl] alanyl]hexahydro-2-indolinecarboxylic acid
Molecular formula: C24H34N2O5
CAS number: 87679-37-6

Medically reviewed by Drugs.com on Feb 23, 2024. Written by ASHP.

Warning

  • May cause fetal and neonatal morbidity and mortality if used during pregnancy.1 81 82 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

  • If pregnancy is detected, discontinue trandolapril as soon as possible.1 82

Introduction

Nonsulfhydryl ACE inhibitor.1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17

Uses for Trandolapril

Hypertension

Management of hypertension (alone or in combination with other classes of antihypertensive agents).1 3 5 11 13 14 15 16 17 1200

ACE inhibitors are recommended as one of several preferred agents for the initial management of hypertension according to current evidence-based hypertension guidelines; other preferred options include angiotensin II receptor antagonists, calcium-channel blockers, and thiazide diuretics.501 502 503 504 1200 While there may be individual differences with respect to recommendations for initial drug selection and use in specific patient populations, current evidence indicates that these antihypertensive drug classes all generally produce comparable effects on overall mortality and cardiovascular, cerebrovascular, and renal outcomes.501 502 504 1200 1213

Individualize choice of therapy; consider patient characteristics (e.g., age, ethnicity/race, comorbidities, cardiovascular risk) as well as drug-related factors (e.g., ease of administration, availability, adverse effects, cost).501 502 503 504 515 1200 1201

A 2017 ACC/AHA multidisciplinary hypertension guideline classifies BP in adults into 4 categories: normal, elevated, stage 1 hypertension, and stage 2 hypertension.1200 (See Table 1.)

Source: Whelton PK, Carey RM, Aronow WS et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2018;71:e13-115..

Individuals with SBP and DBP in 2 different categories (e.g., elevated SBP and normal DBP) should be designated as being in the higher BP category (i.e., elevated BP).

Table 1. ACC/AHA BP Classification in Adults1200

Category

SBP (mm Hg)

DBP (mm Hg)

Normal

<120

and

<80

Elevated

120–129

and

<80

Hypertension, Stage 1

130–139

or

80–89

Hypertension, Stage 2

≥140

or

≥90

The goal of hypertension management and prevention is to achieve and maintain optimal control of BP.1200 However, the BP thresholds used to define hypertension, the optimum BP threshold at which to initiate antihypertensive drug therapy, and the ideal target BP values remain controversial.501 503 504 505 506 507 508 515 523 526 530 1200 1201 1207 1209 1222 1223 1229

The 2017 ACC/AHA hypertension guideline generally recommends a target BP goal (i.e., BP to achieve with drug therapy and/or nonpharmacologic intervention) of <130/80 mm Hg in all adults regardless of comorbidities or level of atherosclerotic cardiovascular disease (ASCVD) risk.1200 In addition, an SBP goal of <130 mm Hg is recommended for noninstitutionalized ambulatory patients ≥65 years of age with an average SBP of ≥130 mm Hg.1200 These BP goals are based upon clinical studies demonstrating continuing reduction of cardiovascular risk at progressively lower levels of SBP.1200 1202 1210

Other hypertension guidelines generally have based target BP goals on age and comorbidities.501 504 536 Guidelines such as those issued by the JNC 8 expert panel generally have targeted a BP goal of <140/90 mm Hg regardless of cardiovascular risk and have used higher BP thresholds and target BPs in elderly patients501 504 536 compared with those recommended by the 2017 ACC/AHA hypertension guideline.1200

Some clinicians continue to support previous target BPs recommended by JNC 8 due to concerns about the lack of generalizability of data from some clinical trials (e.g., SPRINT study) used to support the 2017 ACC/AHA hypertension guideline and potential harms (e.g., adverse drug effects, costs of therapy) versus benefits of BP lowering in patients at lower risk of cardiovascular disease.1222 1223 1224 1229

Consider potential benefits of hypertension management and drug cost, adverse effects, and risks associated with the use of multiple antihypertensive drugs when deciding a patient's BP treatment goal.1200 1220

For decisions regarding when to initiate drug therapy (BP threshold), the 2017 ACC/AHA hypertension guideline incorporates underlying cardiovascular risk factors.1200 1207 ASCVD risk assessment is recommended by ACC/AHA for all adults with hypertension.1200

ACC/AHA currently recommend initiation of antihypertensive drug therapy in addition to lifestyle/behavioral modifications at an SBP ≥140 mm Hg or DBP ≥90 mm Hg in adults who have no history of cardiovascular disease (i.e., primary prevention) and a low ASCVD risk (10-year risk <10%).1200

For secondary prevention in adults with known cardiovascular disease or for primary prevention in those at higher risk for ASCVD (10-year risk ≥10%), ACC/AHA recommend initiation of antihypertensive drug therapy at an average SBP ≥130 mm Hg or an average DBP ≥80 mm Hg.1200

Adults with hypertension and diabetes mellitus, chronic kidney disease (CKD), or age ≥65 years are assumed to be at high risk for cardiovascular disease; ACC/AHA state that such patients should have antihypertensive drug therapy initiated at a BP ≥130/80 mm Hg.1200 Individualize drug therapy in patients with hypertension and underlying cardiovascular or other risk factors.502 1200

In stage 1 hypertension, experts state that it is reasonable to initiate drug therapy using the stepped-care approach in which one drug is initiated and titrated and other drugs are added sequentially to achieve the target BP.1200 Initiation of antihypertensive therapy with 2 first-line agents from different pharmacologic classes recommended in adults with stage 2 hypertension and average BP >20/10 mm Hg above BP goal.1200

Black hypertensive patients generally tend to respond better to monotherapy with calcium-channel blockers or thiazide diuretics than to ACE inhibitors.24 56 57 79 80 501 504 1200 However, the combination of an ACE inhibitor or an angiotensin II receptor antagonist with a calcium-channel blocker or thiazide diuretic produces similar BP lowering in black patients as in other racial groups.1200

ACE inhibitors may be preferred in hypertensive patients with heart failure, ischemic heart disease, diabetes mellitus, CKD, or cerebrovascular disease or post-MI.501 502 504 523 524 525 526 527 534 535 536 543 1200 1214 1215

Heart Failure or Left Ventricular Dysfunction After Acute MI

Reduction of the risk of mortality (mainly cardiovascular mortality) and risk of heart failure-associated hospitalization following MI in hemodynamically stable patients who have evidence of left ventricular systolic dysfunction or who have demonstrated clinical signs of heart failure within a few days following acute MI.1 32 524

Expert guidelines recommend initiation of an oral ACE inhibitor within the first 24 hours of acute MI in patients with an anterior infarct, heart failure, or ejection fraction ≤40% who do not have any contraindications (e.g., hypotension, shock, renal dysfunction).527 Use with caution (and with gradual upward titration) during initial postinfarction period because of the possibility of hypotension or renal dysfunction.527 1100

Continue therapy indefinitely in patients with left ventricular dysfunction or other compelling indications (e.g., hypertension, diabetes mellitus, CKD).525 1100

Heart Failure

Management of heart failure† [off-label], usually in conjunction with other agents such as cardiac glycosides, diuretics, and β-adrenergic blocking agents (β-blockers).60 61 62 63 64 524 800

Some evidence indicates that therapy with an ACE inhibitor (enalapril) may be less effective than angiotensin receptor-neprilysin inhibitor (ARNI) therapy (e.g., sacubitril/valsartan) in reducing cardiovascular death and heart failure-related hospitalization.702 800

ACCF, AHA, and the Heart Failure Society of America (HFSA) recommend that patients with chronic symptomatic heart failure and reduced left ventricular ejection fraction (LVEF) (NYHA class II or III) who are able to tolerate an ACE inhibitor or angiotensin II receptor antagonist be switched to therapy containing an ARNI to further reduce morbidity and mortality.800

Diabetic Nephropathy

A recommended agent in the management of patients with diabetes mellitus and persistent albuminuria† [off-label] who have modestly elevated (30–300 mg/24 hours) or higher (>300 mg/24 hours) levels of urinary albumin excretion; slows rate of progression of renal disease in such patients.74 75 76 77 78 535 536 1232

Trandolapril Dosage and Administration

General

BP Monitoring and Treatment Goals

Administration

Oral Administration

Administer orally once or twice daily.1

Administer trandolapril/verapamil fixed combination with food;29 manufacturer makes no specific recommendation regarding administration of trandolapril with meals.1

Dosage

In patients currently receiving diuretic therapy, discontinue diuretic or cautiously increase salt intake prior to initiating trandolapril.600 If diuretic cannot be discontinued, initiate trandolapril at a reduced dosage.600 (See Hypotension under Cautions and see the individual dosage sections in Dosage and Administration.)

Adults

Hypertension
Trandolapril Therapy
Oral

Initially, 2 mg once daily in black patients and 1 mg once daily in patients of other races as monotherapy.600 Adjust dosage based on BP response, usually at intervals of ≥1 week.600

In patients currently receiving diuretic therapy, discontinue diuretic, if possible, 2–3 days before initiating trandolapril.600 May resume diuretic therapy if BP not controlled adequately with trandolapril alone.600 If diuretic cannot be discontinued, initiate trandolapril therapy at 0.5 mg once daily under close medical supervision for several hours until BP has stabilized.600

Usual maintenance dosage: Manufacturer states 2–4 mg once daily.600 Some experts state 1–4 mg once daily.1200

If 4 mg once daily does not adequately control BP, consider administering drug in 2 divided doses.28 600

Limited clinical experience with dosages >8 mg daily.600

Trandolapril/Verapamil Fixed-combination Therapy
Oral

Manufacturer states fixed-combination preparation should not be used for initial antihypertensive therapy.601

May be used after adequate response is not achieved with trandolapril or verapamil monotherapy.601

May be initiated in patients who experience dose-limiting adverse effects with either trandolapril or verapamil monotherapy.601

For patients receiving verapamil (up to 240 mg) and trandolapril (up to 8 mg) in separate tablets once daily, replacement with the fixed combination can be attempted using tablets containing the same component doses.29

Heart Failure or Left Ventricular Dysfunction After Acute MI
Oral

Manufacturer recommends initial dose of 1 mg.1 32 524 602

Some experts recommend initiation of therapy within the first 24 hours of MI with a test dose of 0.5 mg.527

Following initial dose, titrate as tolerated to a target dosage of 4 mg once daily; if 4 mg once daily is not tolerated, may continue therapy at the highest tolerated dosage.1 524 602

Prescribing Limits

Adults

Hypertension
Oral

Limited clinical experience with dosages >8 mg daily.600

Heart Failure† [off-label]
Oral

ACCF and AHA recommend maximum dosage of 4 mg once daily.524

Special Populations

Hepatic Impairment

Hypertension
Oral

Reduced initial dosage (0.5 mg once daily) recommended in patients with hepatic cirrhosis;1 16 titrate subsequent dosage according to BP response.1

Heart Failure or Left Ventricular Dysfunction after Acute MI
Oral

Reduced initial dosage (0.5 mg once daily) recommended in patients with hepatic cirrhosis;1 16 titrate subsequent dosage as tolerated according to response.1

Renal Impairment

Hypertension
Oral

Reduced initial dosage (0.5 mg once daily) recommended in patients with severe renal impairment (Clcr <30 mL/minute);1 3 4 16 17 titrate subsequent dosage according to BP response.1

Heart Failure or Left Ventricular Dysfunction after Acute MI
Oral

Reduced initial dosage (0.5 mg once daily) recommended in patients with severe renal impairment (Clcr <30 mL/minute); titrate subsequent dosage as tolerated according to response.1

Detailed Trandolapril dosage information

Cautions for Trandolapril

Contraindications

Warnings/Precautions

Warnings

Hypotension

Possible symptomatic hypotension, particularly in volume- and/or salt-depleted patients (e.g., those treated with diuretics or undergoing dialysis, patients with diarrhea or vomiting).1 Risk of marked hypotension, sometimes associated with oliguria, azotemia, and rarely, death in patients with heart failure with or without associated renal insufficiency.1

Hypotension may occur in patients undergoing surgery or during anesthesia with agents that produce hypotension; recommended treatment is fluid volume expansion.1

To minimize potential for hypotension, consider recent antihypertensive therapy, extent of BP elevation, sodium intake, fluid status, and other clinical conditions.1 May minimize potential for hypotension by correcting volume and/or salt depletion prior to initiating trandolapril therapy.1 (See Dosage under Dosage and Administration.)

Initiate therapy in patients with heart failure (with or without associated renal insufficiency) under close medical supervision; monitor closely for first 2 weeks following initiation of trandolapril or any increase in trandolapril or diuretic dosage.1

Take care to avoid hypotension in patients with ischemic heart disease, aortic stenosis, or cerebrovascular disease.1

If symptomatic hypotension occurs, place patient in supine position and, if necessary, administer IV infusion of 0.9% sodium chloride injection.1 Transient hypotension is not a contraindication to additional doses; however, consider reinitiating therapy at reduced doses of trandolapril and/or diuretic.1

Fetal/Neonatal Morbidity and Mortality

Possible fetal and neonatal morbidity and mortality when used during pregnancy.1 21 22 23 24 30 81 82 (See Boxed Warning.) Such potential risks occur throughout pregnancy, especially during the second and third trimesters.82

Also may increase the risk of major congenital malformations when administered during the first trimester of pregnancy.81 82

Discontinue as soon as possible when pregnancy is detected, unless continued use is considered lifesaving.82 Nearly all women can be transferred successfully to alternative therapy for the remainder of their pregnancy.1 21

Potential neonatal effects include skull hypoplasia, anuria, hypotension, renal failure, and death.603 Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations.603

Hepatic Effects

Clinical syndrome that usually is manifested initially by cholestatic jaundice and may progress to fulminant hepatic necrosis (occasionally fatal) reported rarely with ACE inhibitors.1 29

If jaundice or marked elevation of liver enzymes occurs, discontinue drug and monitor patient.1 29

Hematologic Effects

Neutropenia and agranulocytosis reported with captopril; risk of neutropenia appears to depend principally on presence of renal impairment and presence of collagen vascular disease (e.g., systemic lupus erythematosus, scleroderma); risk with trandolapril is unknown.1

Consider monitoring leukocytes in patients with collagen vascular disease, especially if renal impairment exists.1 29

Sensitivity Reactions

Anaphylactoid reactions and/or head and neck angioedema possible; angioedema associated with laryngeal edema may be fatal.1 29 Concomitant use of an ACE inhibitor and a mammalian target of rapamycin (mTOR) inhibitor or neprilysin inhibitor (e.g., sacubitril) may increase the risk of angioedema.603 If angioedema occurs, promptly discontinue trandolapril and observe patient until swelling disappears.1 Immediate medical intervention (e.g., epinephrine) for involvement of tongue, glottis, or larynx.1 29

Intestinal angioedema possible; consider in differential diagnosis of patients who develop abdominal pain.1

Anaphylactoid reactions reported in patients receiving ACE inhibitors while undergoing LDL apheresis with dextran sulfate absorption or following initiation of hemodialysis that utilized high-flux membrane.1 29

Life-threatening anaphylactoid reactions reported in at least 2 patients receiving ACE inhibitors while undergoing desensitization treatment with hymenoptera venom.1 29

Contraindicated in patients with a history of angioedema associated with ACE inhibitors.1

General Precautions

Renal Effects

Transient increases in BUN and Scr possible, especially in patients with preexisting renal impairment or those receiving concomitant diuretic therapy.1 Possible increases in BUN and Scr in patients with unilateral or bilateral renal artery stenosis; generally reversible following discontinuance of ACE inhibitor and/or diuretic.1 29

Possible oliguria, progressive azotemia, and rarely, acute renal failure and/or death in patients with severe heart failure.1

Closely monitor renal function following initiation of therapy in hypertensive patients with unilateral or bilateral renal artery stenosis.1 29 Some patients may require dosage reduction or discontinuance of ACE inhibitor and/or diuretic.1

Hyperkalemia

Possible hyperkalemia, especially in patients with renal impairment or diabetes mellitus and those receiving drugs that can increase serum potassium concentration (e.g., potassium-sparing diuretics, potassium supplements, potassium-containing salt substitutes).1 (See Specific Drugs under Interactions.)

Monitor serum potassium concentration carefully in these patients.1

Cough

Persistent and nonproductive cough; resolves after drug discontinuance.1

Specific Populations

Pregnancy

Category D.603

Can cause fetal and neonatal morbidity and mortality when administered to a pregnant woman.603 (See Boxed Warning.)

Lactation

Distributed into milk in rats.1 Use not recommended.1

Pediatric Use

If oliguria or hypotension occurs in neonates with a history of in utero exposure to trandolapril, support BP and renal function; exchange transfusions or dialysis may be required.603

Safety and efficacy not established.1

Geriatric Use

No substantial differences in safety and efficacy relative to younger adults; however, possibility exists of greater sensitivity to the drug in some geriatric individuals.1

Hepatic Impairment

Consider dosage reduction.1 (See Hepatic Impairment under Dosage and Administration.)

Renal Impairment

Deterioration of renal function may occur.1 (See Renal Effects under Cautions.)

Initial dosage adjustment recommended in patients with Clcr <30 mL/minute.1 (See Renal Impairment under Dosage and Administration.)

Black Patients

BP reduction may be smaller in black patients compared with patients of other races.24 25 56 57 (See Hypertension under Uses.)

Higher incidence of angioedema reported with ACE inhibitors in black patients compared with other races.1 57 1200

Common Adverse Effects

Patients with hypertension: Cough, dizziness, diarrhea.1

Patients with left ventricular dysfunction after acute MI: Cough, dizziness, hypotension, elevated serum uric acid concentrations, elevated BUN, percutaneous transluminal coronary angioplasty (PTCA) or CABG, dyspepsia, syncope, hyperkalemia.1

Drug Interactions

Specific Drugs

Drug

Interaction

Comments

Aliskiren

Increased risk of renal impairment (including acute renal failure), hyperkalemia, and hypotension603

Dual blockade of renin-angiotensin system provides no additional benefit over monotherapy in most patients603

Monitor BP, renal function, and electrolytes if used concomitantly550 603

Concomitant use contraindicated in patients with diabetes mellitus; avoid concomitant use in patients with GFR <60 mL/minute per 1.73 m2550 603

Angiotensin II receptor antagonists

Increased risk of renal impairment (including acute renal failure), hyperkalemia, and hypotension603

Dual blockade of renin-angiotensin system provides no additional benefit over monotherapy in most patients603

Generally, avoid concomitant use; monitor BP, renal function, and electrolytes if used concomitantly603

Antidiabetic agents, oral

May increase blood glucose-lowering effect and increase risk of hypoglycemia603

Cimetidine

Possible increase in plasma trandolapril concentrations but no change in plasma trandolaprilat concentrations and no change in ACE inhibition1

Digoxin

Pharmacokinetic interaction unlikely1

Diuretics

Increased hypotensive effect1

If possible, discontinue diuretic before initiating trandolapril1 (see Dosage under Dosage and Administration)

Diuretics, potassium-sparing (amiloride, spironolactone, triamterene)

Enhanced hyperkalemic effect1

Use with caution; monitor serum potassium concentrations frequently1

Gold

Nitroid reactions reported rarely in patients receiving concomitant therapy with sodium aurothiomalate and an ACE inhibitor603

Insulin

May increase blood glucose-lowering effect and increase risk of hypoglycemia603

Lithium

Increased serum lithium concentrations; possible toxicity1

Use with caution; monitor serum lithium concentrations frequently1

mTor inhibitors (e.g., everolimus, sirolimus, temsirolimus)

Increased risk of angioedema603

Monitor for signs of angioedema603

Neprilysin inhibitors (e.g., sacubitril)

Increased risk of angioedema603

Concomitant use contraindicated; do not administer trandolapril within 36 hours of switching to or from a neprilysin inhibitor603

Nifedipine

Pharmacokinetic interaction unlikely29

NSAIAs (including COX-2 inhibitors)

May result in deterioration of renal function, including possible renal failure, in geriatric patients, volume-depleted patients, or patients with compromised renal function;603 effects usually reversible603

Monitor renal function periodically603

Potassium supplements or potassium-containing salt substitutes

Enhanced hyperkalemic effect1

Use with caution; monitor serum potassium concentrations frequently1

Warfarin

Pharmacologic interaction unlikely1
Trandolapril drug interactions (more detail)

Trandolapril Pharmacokinetics

Absorption

Bioavailability

Prodrug;2 9 has little pharmacologic activity until hydrolyzed to trandolaprilat.1 3 4 5 7 12 16 17 Absolute bioavailability following oral administration of trandolapril is about 10% as trandolapril and 70% as trandolaprilat.1

Peak concentrations of trandolapril and trandolaprilat are achieved within 1 and 4–10 hours, respectively, following administration in fasted state.1

Onset

A single 2-mg dose results in approximately 70–85% inhibition of plasma ACE activity at 4 hours after administration.1

During chronic therapy, maximum antihypertensive effect with any dosage is achieved within 1 week.1

Duration

Following a single 2-mg dose, inhibition of plasma ACE activity declines by about 10% at 24 hours and by about one-half after 8 days.1

Food

Food decreases rate of absorption but does not affect extent of absorption or peak plasma concentration.1

Special Populations

In patients with mild to moderate alcoholic cirrhosis, plasma trandolapril and trandolaprilat concentrations are increased approximately 9- and 2-fold, respectively.1

In patients with Clcr <30 mL/minute, plasma trandolapril and trandolaprilat concentrations are increased approximately 2-fold.1

Distribution

Extent

Distributed into milk in rats.1

Plasma Protein Binding

Trandolapril: 80% (independent of concentration).1

Trandolaprilat: Concentration-dependent binding (65% at 1000 ng/mL and 94% at 0.1 ng/mL).1

Elimination

Metabolism

Metabolized in the liver3 4 8 17 to an active metabolite, trandolaprilat.1 3 4 5 6 12 16 17 At least 7 other metabolites, principally glucuronide conjugates or de-esterification products, have been identified.1

Elimination Route

Eliminated in urine (33%), principally as trandolaprilat, and in feces (66%).1

Half-life

Elimination half-life of trandolapril: 6 hours.603

Effective half-life of trandolaprilat: 22.5 hours.603

Stability

Storage

Oral

Tablets

20–25°C.1

Actions

Advice to Patients

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Trandolapril

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

1 mg*

Mavik (scored)

AbbVie

Trandolapril Tablets

2 mg*

Mavik

AbbVie

Trandolapril Tablets

4 mg*

Mavik

AbbVie

Trandolapril Tablets
Trandolapril Combinations

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, extended-release core (containing verapamil hydrochloride 240 mg), film-coated

1 mg with Verapamil Hydrochloride 240 mg

Tarka

AbbVie

Tablets, extended-release core (containing verapamil hydrochloride 180 mg), film-coated

2 mg with Verapamil Hydrochloride 180 mg

Tarka

AbbVie

Tablets, extended-release core (containing verapamil hydrochloride 240 mg), film-coated

2 mg with Verapamil Hydrochloride 240 mg

Tarka

AbbVie

Tablets, extended-release core (containing verapamil hydrochloride 240 mg), film-coated

4 mg with Verapamil Hydrochloride 240 mg

Tarka

AbbVie

AHFS DI Essentials™. © Copyright 2024, Selected Revisions March 4, 2019. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Off-label: Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

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14. Meyer BH, Pauly NC, for the Investigator Study Group. Double-blind comparison of the efficacy and safety of trandolapril 2 mg and hydrochlorothiazide 25 mg in patients with mild- to-moderate essential hypertension. J Cardiovasc Pharmacol. 1994; 23(Suppl 4):S77-80.

15. Steiner G, Pauly NC, for the Investigator Study Group. Comparison of the efficacy and safety of trandolapril and nifedipine SR in mild-to-moderate hypertension. J Cardiovasc Pharmacol. 1994; 23(Suppl 4):S81-5.

16. Wiseman LR, McTavish D. Trandolapril: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in essential hypertension. Drugs. 1994; 48:71-90. http://www.ncbi.nlm.nih.gov/pubmed/7525196?dopt=AbstractPlus

17. Duc LNC, Brunner HR. Trandolapril in hypertension: overview of a new angiotensin-converting enzyme inhibitor. Am J Cardiol. 1992; 70:27-34D.

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20. Anon. Drugs for hypertension. Med Lett Drugs Ther. 1984; 26:107-12. http://www.ncbi.nlm.nih.gov/pubmed/6150424?dopt=AbstractPlus

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22. Shotan A, Widerhorn J, Hurst A et al. Risks of angiotensin-converting enzyme inhibition during pregnancy: experimental and clinical evidence, potential mechanisms, and recommendations for use. Am J Med. 1994; 96:451-6. http://www.ncbi.nlm.nih.gov/pubmed/8192177?dopt=AbstractPlus

23. Piper JM, Ray WA, Rosa FW. Pregnancy outcome following exposure to angiotensin-converting enzyme inhibitors. Obstet Gynecol. 1992; 80:429-32. http://www.ncbi.nlm.nih.gov/pubmed/1495700?dopt=AbstractPlus

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26. Holland OB, Kuhnert L, Campbell WB et al. Synergistic effect of captopril with hydrochlorothiazide for the treatment of low-renin hypertensive black patients. Hypertension. 1983; 5:235-9. http://www.ncbi.nlm.nih.gov/pubmed/6337951?dopt=AbstractPlus

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28. Knoll Pharmaceutical, Parsippany, NJ: Personal communication.

29. Abbott Laboratories. Tarka (trandolapril/verapamil) tablets prescribing information. North Chicago, IL; 2003 Jul.

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