trandolapril 4 MG Oral Tablet

Brand Name: Trandolapril
  • Substance Name(s):


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, 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.

In the same patients, these reactions did not occur when ACE inhibitors were temporarily withheld, but they reappeared when the ACE inhibitors were inadver­tently readministered.

Anaphylactoid Reactions During Membrane Exposure Anaphylactoid reactions have been reported in patients dialyzed with high-flux membranes and treated concomitantly with an ACE inhibitor.

Anaphylactoid reactions have also been reported in patients undergoing low-density lipoprotein apheresis with dextran sulfate absorption.

Head and Neck Angioedema In controlled trials ACE inhibitors (for which adequate data are available) cause a higher rate of angioedema in black than in non-black patients.

Angioedema of the face, extremities, lips, tongue, glottis, and larynx has been reported in patients treated with ACE inhibitors including trandolapril.

Symptoms suggestive of angioedema or facial edema occurred in 0.13% of trandolapril-treated patients.

Two of the four cases were life-threatening and resolved without treatment or with medication (corticosteroids).

Angioedema associated with laryngeal edema can be fatal.

If laryngeal stridor or angioedema of the face, tongue or glottis occurs, treatment with trandolapril should be discontinued immediately, the patient treated in accordance with accepted medical care and carefully observed until the swelling disappears.

In instances where swelling is confined to the face and lips, the condition generally resolves without treatment; antihistamines may be useful in relieving symptoms.

Where there is involvement of the tongue, glottis, or larynx, likely to cause airway obstruction, emergency therapy, including but not limited to subcutaneous epinephrine solution 1:1,000 (0.3 to 0.5 mL) should be promptly administered.

(See PRECAUTIONS – Information for Patients and ADVERSE REACTIONS .

) Patients receiving coadministration of an ACE inhibitor with an mTOR (mammalian target of rapamycin) inhibitor (e.g., temsirolimus, sirolimus, everolimus) or a neprilysin inhibitor (e.g., sacubitril) may be at increased risk for angioedema.

Intestinal Angioedema Intestinal angioedema has been reported in patients treated with ACE inhibitors.

These patients presented with abdominal pain (with or without nausea or vomiting); in some cases there was no prior history of facial angioedema and C-1 esterase levels were normal.

The angioedema was diagnosed by procedures including abdominal CT scan or ultrasound, or at surgery, and symptoms resolved after stopping the ACE inhibitor.

Intestinal angioedema should be included in the differential diagnosis of patients on ACE inhibitors presenting with abdominal pain.

Hypotension Trandolapril can cause symptomatic hypotension.

Like other ACE inhibitors, trandolapril has only rarely been associated with symptomatic hypotension in uncomplicated hypertensive patients.

Symptomatic hypotension is most likely to occur in patients who have been salt- or volume-depleted as a result of prolonged treatment with diuretics, dietary salt restriction, dialysis, diarrhea, or vomiting.

Volume and/or salt depletion should be corrected before initiating treatment with trandolapril.

(See PRECAUTIONS – Drug Interactions and ADVERSE REACTIONS .) In controlled and uncontrolled studies, hypotension was reported as an adverse event in 0.6% of patients and led to discontinuations in 0.1% of patients.

In patients with concomitant congestive heart failure, with or without associated renal insufficiency, ACE inhibitor therapy may cause excessive hypotension, which may be associated with oliguria or azotemia, and rarely, with acute renal failure and death.

In such patients, trandolapril therapy should be started at the recommended dose under close medical supervision.

These patients should be followed closely during the first 2 weeks of treatment and, thereafter, whenever the dosage of trandolapril or diuretic is increased.


) Care in avoiding hypotension should also be taken in patients with ischemic heart disease, aortic stenosis, or cerebrovascular disease.

If symptomatic hypotension occurs, the patient should be placed in the supine position and, if necessary, normal saline may be administered intravenously.

A transient hypotensive response is not a contraindication to further doses; however, lower doses of trandolapril or reduced concomitant diuretic therapy should be considered.

Neutropenia/Agranulocytosis Another ACE inhibitor, captopril, has been shown to cause agranulocytosis and bone marrow depression rarely in patients with uncomplicated hypertension, but more frequently in patients with renal impairment, especially if they also have a collagen-vascular disease such as systemic lupus erythematosus or scleroderma.

Available data from clinical trials of trandolapril are insufficient to show that trandolapril does not cause agranulocytosis at similar rates.

As with other ACE inhibitors, periodic monitoring of white blood cell counts in patients with collagen-vascular disease and/or renal disease should be considered.

Hepatic Failure ACE inhibitors rarely have been associated with a syndrome of cholestatic jaundice, fulminant hepatic necrosis, and death.

The mechanism of this syndrome is not understood.

Patients receiving ACE inhibitors who develop jaundice should discontinue the ACE inhibitor and receive appropriate medical follow-up.

Fetal Toxicity Pregnancy Category D Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death.

Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations.

Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death.

When pregnancy is detected, discontinue trandolapril as soon as possible.

These adverse outcomes are usually associated with use of these drugs in the second and third trimester of pregnancy.

Most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents.

Appropriate management of maternal hypertension during pregnancy is important to optimize outcomes for both mother and fetus.

In the unusual case that there is no appropriate alternative to therapy with drugs affecting the renin-angiotensin system for a particular patient, apprise the mother of the potential risk to the fetus.

Perform serial ultrasound examinations to assess the intra-amniotic environment.

If oligohydramnios is observed, discontinue trandolapril, unless it is considered lifesaving for the mother.

Fetal testing may be appropriate, based on the week of pregnancy.

Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury.

Closely observe infants with histories of in utero exposure to trandolapril for hypotension, oliguria, and hyperkalemia.

(See PRECAUTIONS, Pediatric Use .) Doses of 0.8 mg/kg/day (9.4 mg/m 2 /day) in rabbits, 1000 mg/kg/day (7000 mg/m 2 /day) in rats, and 25 mg/kg/day (295 mg/m 2 /day) in cynomolgus monkeys did not produce teratogenic effects.

These doses represent 10 and 3 times (rabbits), 1250 and 2564 times (rats), and 312 and 108 times (monkeys) the maximum projected human dose of 4 mg based on body-weight and body-surface-area, respectively assuming a 50 kg woman.


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.

Closely monitor blood pressure, renal function and electrolytes in patients on trandolapril and other agents that affect the RAS.

Do not co-administer aliskiren with trandolapril in patients with diabetes.

Avoid use of aliskiren with trandolapril in patients with renal impairment (GFR <60 mL/min).

Concomitant Diuretic Therapy As with other ACE inhibitors, patients on diuretics, especially those on recently instituted diuretic therapy, may experience an excessive reduction of blood pressure after initiation of therapy with trandolapril.

The possibility of exacerbation of hypotensive effects with trandolapril may be minimized by either discontinuing the diuretic or cautiously increasing salt intake prior to initiation of treatment with trandolapril.

If it is not possible to discontinue the diuretic, the starting dose of trandolapril should be reduced.


) Agents Increasing Serum Potassium Trandolapril can attenuate potassium loss caused by thiazide diuretics and increase serum potassium when used alone.

Use of potassium-sparing diuretics (spironolactone, triamterene, or amiloride), potassium supplements, or potassium-containing salt substitutes concomitantly with ACE inhibitors can increase the risk of hyperkalemia.

If concomitant use of such agents is indicated, they should be used with caution and with appropriate monitoring of serum potassium.


) Antidiabetic Agents Concomitant use of ACE inhibitors and antidiabetic medicines (insulin or oral hypoglycemic agents) may cause an increased blood glucose lowering effect with greater risk of hypoglycemia.

Lithium Increased serum lithium levels and symptoms of lithium toxicity have been reported in patients receiving concomitant lithium and ACE inhibitor therapy.

These drugs should be coadministered with caution, and frequent monitoring of serum lithium levels is recommended.

If a diuretic is also used, the risk of lithium toxicity may be increased.

Non-Steroidal Anti-Inflammatory Agents including Selective Cyclooxygenase-2 Inhibitors (COX-2 Inhibitors) In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, co-administration of NSAIDs, including selective COX-2 inhibitors, with ACE inhibitors, including trandolapril, may result in deterioration of renal function, including possible acute renal failure.

These effects are usually reversible.

Monitor renal function periodically in patients receiving trandolapril and NSAID therapy.

The antihypertensive effect of ACE inhibitors, including trandolapril may be attenuated by NSAIDs.

Gold Nitritoid reactions (symptoms include facial flushing, nausea, vomiting and hypotension) have been reported rarely in patients on therapy with injectable gold (sodium aurothiomalate) and concomitant ACE inhibitor therapy including trandolapril.

Mammalian Target of Rapamycin (mTOR) Inhibitors Patients taking concomitant mTOR inhibitor (e.g., temsirolimus, sirolimus, everolimus) therapy may be at increased risk for angioedema (see Warnings – Head and Neck Angioedema).

Neprilysin Inhibitor Patients taking concomitant neprilysin inhibitors (e.g., sacubitril) may be at increased risk for angioedema (see WARNINGS ).

Other No clinically significant pharmacokinetic interaction has been found between trandolaprilat and food, cimetidine, digoxin, or furosemide.

The anticoagulant effect of warfarin was not significantly changed by trandolapril.

The hypotensive effect of certain inhalation anesthetics may be enhanced by ACE inhibitors including trandolapril.

(See PRECAUTIONS-Surgery/Anesthesia .



No data are available with respect to overdosage in humans.

The oral LD 50 of trandolapril in mice was 4875 mg/Kg in males and 3990 mg/Kg in females.

In rats, an oral dose of 5000 mg/Kg caused low mortality (1 male out of 5; 0 females).

In dogs, an oral dose of 1000 mg/Kg did not cause mortality and abnormal clinical signs were not observed.

In humans, the most likely clinical manifestation would be symptoms attributable to severe hypotension.

Symptoms also expected with ACE inhibitors are hypotension, hyperkalemia, and renal failure.

Laboratory determinations of serum levels of trandolapril and its metabolites are not widely available, and such determinations have, in any event, no established role in the management of trandolapril overdose.

No data are available to suggest that physiological maneuvers (e.g., maneuvers to change the pH of the urine) might accelerate elimination of trandolapril and its metabolites.

Trandolaprilat is removed by hemodialysis.

Angiotensin II could presumably serve as a specific antagonist antidote in the setting of trandolapril overdose, but angiotensin II is essentially unavailable outside of scattered research facilities.

Because the hypotensive effect of trandolapril is achieved through vasodilation and effective hypovolemia, it is reasonable to treat trandolapril overdose by infusion of normal saline solution.


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.

= 430.54 Melting Point = 125°C Trandolapril USP is a white or almost white powder that is soluble (>100 mg/mL) in chloroform, dichloromethane, and methanol.

Trandolapril tablets USP contain 1 mg, 2 mg, or 4 mg of trandolapril USP for oral administration.

Each tablet also contains lactose monohydrate, corn starch, croscarmellose sodium, hypromellose, povidone, and sodium stearyl fumarate.

In addition 1 mg and 4 mg tablet also contains ferric oxide red and 2 mg tablet contains ferric oxide yellow.

Chemical Structure


Trandolapril tablets USP are supplied as follows: Trandolapril Tablets USP 1 mg are salmon colored, round, biconvex, uncoated tablets debossed with ‘E’ on upper side of the bisector line on one side and ‘35’ on the other side.

Bottles of 100 NDC 57237-089-01 Trandolapril Tablets USP 2 mg are yellow colored, round, biconvex, uncoated tablets debossed with ‘E’ on one side and ‘36’ on the other side.

Bottles of 100 NDC 57237-090-01 Trandolapril Tablets USP 4 mg are rose colored, round, biconvex, uncoated tablets debossed with ‘E’ on one side and ‘37’ on the other side.

Bottles of 100 NDC 57237-091-01 Dispense in well-closed container with safety closure.

Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].

Distributed by: Rising Health, LLC Saddle Brook, NJ 07663 Made in India Code: TS/DRUGS/19/1993 Revised: 01/2018


Geriatric Use In placebo-controlled studies of trandolapril, 31.1% of patients were 60 years and older, 20.1% were 65 years and older, and 2.3% were 75 years and older.

No overall differences in effectiveness or safety were observed between these patients and younger patients.

(Greater sensitivity of some older individual patients cannot be ruled out.)


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 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 (see CLINICAL PHARMACOLOGY -Heart Failure or Left-Ventricular Dysfunction Post Myocardial Infarction for details of the survival trial).


Pediatric Use Neonates with a history of in utero exposure to trandolapril If oliguria or hypotension occurs, direct attention toward support of blood pressure and renal perfusion.

Exchange transfusions or dialysis may be required as a means of reversing hypotension and/or substituting for disordered renal function.

The safety and effectiveness of trandolapril in pediatric patients have not been established.


Nursing Mothers Radiolabeled trandolapril or its metabolites are secreted in rat milk.

Trandolapril should not be administered to nursing mothers.


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 .)


Information for Patients Angioedema Angioedema, including laryngeal edema, may occur at any time during treatment with ACE inhibitors, including trandolapril.

Patients should be so advised and told to report immediately any signs or symptoms suggesting angioedema (swelling of face, extremities, eyes, lips, tongue, difficulty in swallowing or breathing) and to stop taking the drug until they have consulted with their physician.


) Symptomatic Hypotension Patients should be cautioned that light-headedness can occur, especially during the first days of trandolapril therapy, and should be reported to a physician.

If actual syncope occurs, patients should be told to stop taking the drug until they have consulted with their physician.

(See WARNINGS .) All patients should be cautioned that inadequate fluid intake, excessive perspiration, diarrhea, or vomiting, resulting in reduced fluid volume, may precipitate an excessive fall in blood pressure with the same consequences of light-headedness and possible syncope.

Patients planning to undergo any surgery and/or anesthesia should be told to inform their physician that they are taking an ACE inhibitor that has a long duration of action.

Hyperkalemia Patients should be told not to use potassium supplements or salt substitutes containing potassium without consulting their physician.


) Neutropenia Patients should be told to report promptly any indication of infection (e.g., sore throat, fever) which could be a sign of neutropenia.

Pregnancy Female patients of childbearing age should be told about the consequences of exposure to trandolapril during pregnancy.

Discuss treatment options with women planning to become pregnant.

Patients should be asked to report pregnancies to their physicians as soon as possible.

NOTE: As with many other drugs, certain advice to patients being treated with trandolapril is warranted.

This information is intended to aid in the safe and effective use of this medication.

It is not a disclosure of all possible adverse or intended effects.


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.

To reduce the likelihood of hypotension, the diuretic should, if possible, be discontinued two to three days prior to beginning therapy with trandolapril tablets.


) Then, if blood pressure is not controlled with trandolapril tablets alone, diuretic therapy should be resumed.

If the diuretic cannot be discontinued, an initial dose of 0.5 mg trandolapril tablets should be used with careful medical supervision for several hours until blood pressure has stabilized.

The dosage should subsequently be titrated (as described above) to the optimal response.

(See WARNINGS , PRECAUTIONS and Drug Interactions .

) Concomitant administration of trandolapril tablets with potassium supplements, potassium salt substitutes, or potassium sparing diuretics can lead to increases of serum potassium.


) Heart Failure Post Myocardial Infarction or Left-Ventricular Dysfunction Post Myocardial Infarction The recommended starting dose is 1 mg, once daily.

Following the initial dose, all patients should be titrated (as tolerated) toward a target dose of 4 mg, once daily.

If a 4 mg dose is not tolerated, patients can continue therapy with the greatest tolerated dose.

Dosage Adjustment in Renal Impairment or Hepatic Cirrhosis For patients with a creatinine clearance <30 mL/min.

or with hepatic cirrhosis, the recommended starting dose, based on clinical and pharmacokinetic data, is 0.5 mg daily.

Patients should subsequently have their dosage titrated (as described above) to the optimal response.