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Trandolapril / Verapamil Hydrochloride

Pronunciation: tran-DOL-a-pril/ver-AP-a-mil HYE-droe-KLOR-ide
Class: Antihypertensive combination

Trade Names

- Tablets, oral trandolapril 1 mg/verapamil 240 mg ER
- Tablets, oral trandolapril 2 mg/verapamil 180 mg ER
- Tablets, oral trandolapril 2 mg/verapamil 240 mg ER
- Tablets, oral trandolapril 4 mg/verapamil 240 mg ER



Reduces formation of the vasopressor hormone angiotensin II by inhibiting ACE, resulting in decreased BP and reduced sodium reabsorption and potassium retention.


Inhibits movement of calcium ions across cell membrane, resulting in depression of mechanical contraction of myocardial and vascular smooth muscle and depression of both impulse formation (automaticity) and conduction velocity.

Indications and Usage

For the treatment of hypertension.


Severe left ventricular dysfunction; hypotension (systolic pressure less than 90 mm Hg) or cardiogenic shock; sick sinus syndrome (except in patients with a functioning artificial ventricular pacemaker); atrial flutter or atrial fibrillation and an accessory bypass tract (eg, Wolff-Parkinson-White, Lown-Ganong-Levine syndromes); history of angioedema related to previous treatment with an ACE inhibitor; hypersensitivity to any component of the product; second- or third-degree AV block (except in patients with a functioning artificial ventricular pacemaker).

Dosage and Administration


PO Patients receiving trandolapril (up to 8 mg) and verapamil (up to 240 mg) in separate tablets administered once a day may instead substitute trandolapril/verapamil containing the same component doses.

Renal function impairment

PO Consider lower doses.

Hepatic function impairment

PO Consider lower doses.

General Advice

  • Administer with food.
  • This fixed-dose combination is not indicated for initial therapy.
  • The combination may be substituted for the titrated components.


Store between 59° and 77°F.

Drug Interactions

No drug interaction studies have been conducted with trandolapril/verapamil and other drugs. The following interactions are based on drug interactions involving each component of the trandolapril/verapamil combination.

Aldosterone blockers (eg, eplerenone)

The risk of serious hyperkalemia may be increased, resulting in cardiac arrhythmias or arrest. Periodic monitoring of serum potassium level is recommended until the effect of the aldosterone blocker is established. Dose reduction of the aldosterone blocker may be necessary to decrease potassium levels.


The risk of hyperkalemia may be increased, particularly in diabetic patients. In addition, concurrent use in diabetic patients may increase the risk of nonfatal stroke, renal complications, and hypotension. Coadministration in diabetic patients is not recommended. Use with caution and closely monitor potassium concentrations.

Angiotensin II receptor antagonists (eg, telmisartan)

Coadministration of angiotensin II receptor antagonists and trandolapril may be associated with an increased risk of renal dysfunction. Consider monotherapy. If trandolapril/verapamil is coadministered with angiotensin II receptor antagonists, monitor renal function and potassium closely.

Antiarrhythmics (eg, disopyramide, dofetilide, dronedarone, flecainide)

Coadministration may have an additive effect on myocardial contractility, AV conduction, and repolarization. Additive negative inotropic effects and prolongation of the AV conduction may occur. Concurrent use with dofetilide is contraindicated. Do not administer disopyramide within 48 h before or 24 h after trandolapril/verapamil.

Antihypertensive agents

Concurrent use may produce additive hypotensive effects.

Barbiturates (eg, phenobarbital)

Concurrent use may increase verapamil Cl, decreasing its pharmacological effect. May need to increase the dose of trandolapril/verapamil during coadministration.

Beta-adrenergic blockers (eg, atenolol)

Therapeutic and toxic effects of both drugs may be increased; hypotension, bradycardia, cardiac failure, and life-threatening cardiac conduction abnormalities may result. Use only with caution.


Verapamil may increase the plasma concentrations of buspirone.


Plasma concentrations and pharmacologic effects of carbamazepine may be increased with coadministration. Toxicity characterized by nausea, vomiting, somnolence, nystagmus, ataxia, and other cerebellar symptoms may occur. Dosage reduction of carbamazepine may be needed during coadministration. When stopping trandolapril/verapamil, consider increasing the dosage of carbamazepine to avoid loss of seizure control.


Sinus bradycardia, AV block, and severe hypotension may occur with coadministration. Monitor patients closely.


An additive or synergistic hypotensive effect with postural syncope may occur when trandolapril is given with clozapine. In addition, clozapine concentrations may be increased. Use with caution. Monitor BP and adjust the dose as needed.


Plasma concentrations of colchicine may be increased and colchicine toxicity may occur. Use with caution. The recommended colchicine dose for the treatment of a gout flare in patients taking trandolapril/verapamil is 1.2 mg for 1 dose. Ensure that a 3-day lapse occurs before subsequent colchicine administration. Max dose of colchicine for the treatment of familial Mediterranean fever in patients receiving trandolapril/verapamil is 1.2 mg daily.

Cyclooxygenase 2 inhibitors (eg, celecoxib), NSAIDs (eg, indomethacin)

The hypotensive effects of trandolapril/verapamil may be reduced. In addition, nephrotoxicity, including hyperkalemia, associated with both drugs may be increased. Monitor BP and renal function periodically.


Pharmacologic effects and plasma concentrations of dabigatran may be increased. However, in patients receiving dabigatran for venous thromboembolism prophylaxis following knee or hip arthroplasty, adjust the dabigatran dose to 150 mg daily in patients who are receiving concomitant therapy with trandolapril/verapamil.


Long-term verapamil therapy can increase serum digoxin levels by 50% to 75% during the first week of therapy. Elevated digoxin serum levels, toxicity characterized by GI and neuropsychiatric symptoms, and cardiac arrhythmias could occur in some patients. Carefully monitor digoxin levels. Dosage reduction of digoxin may be needed during coadministration.


Concurrent use may increase doxorubicin concentrations.


Fingolimod-related bradycardia may be increased by coadministration; negative chronotropic effects of both drugs may be additive. Carefully monitor patients during initiation of therapy.

Gold salts (eg, sodium aurothiomalate)

The risk of gold salt–induced nitritoid reactions, characterized by flushing, sweating, dizziness, nausea, malaise, weakness, and hypotension, may be increased. Closely observe patients for signs and symptoms of nitritoid reactions.

HMG-CoA reductase inhibitors (eg, atorvastatin, lovastatin, simvastatin)

Plasma concentrations and pharmacologic effects of HMG-CoA reductase inhibitors may be increased by verapamil. Toxicity, characterized by muscle injury, may occur. Additionally, limited data indicate that atorvastatin and lovastatin may cause an increased exposure to verapamil. Close clinical monitoring for signs of myopathy is indicated with coadministration. Limit the dose of simvastatin to 10 mg daily and lovastatin to 40 mg daily when coadministered with trandolapril/verapamil. Also monitor patients for an increased effect of trandolapril/verapamil when administered with atorvastatin or lovastatin.

Immunosuppressive agents (eg, cyclosporine, sirolimus, tacrolimus)

Plasma concentrations and pharmacologic effects of immunosuppressive agents may be increased. Beneficial and adverse effects may occur. In addition, acute renal failure has been reported with cyclosporine administration. Monitor graft status and cyclosporine concentrations. Consider decreasing the dosage of cyclosporine during coadministration.

Insulin, sulfonylureas (eg, glyburide)

Verapamil may increase the concentrations of glyburide. The risk of hypoglycemia may be increased. Monitor blood glucose and observe the patient for symptoms of hypoglycemia. Adjust the sulfonylurea dose as needed.

Iron salts, parenteral (eg, iron dextran)

The risk of adverse reactions to parenteral iron (eg, arthralgia, fever) may be increased. If these agents must be used concurrently, monitor the patient closely.


Plasma concentrations and pharmacologic effects of ivacaftor may be increased. A reduction in the dosage of ivacaftor to 150 mg once daily is recommended in patients receiving trandolapril/verapamil.


Lithium serum concentrations may be elevated, increasing the pharmacologic effects and risk of toxicity (eg, neurotoxicity). In addition, severe sinus bradycardia and reduced lithium serum concentrations with worsening of manic-depressive symptoms have been reported. Monitor lithium concentrations and adjust the dose as necessary.

Loop diuretics (eg, furosemide)

The effect of the loop diuretic may be decreased or increased. In addition, coadministration may cause more acute renal dysfunction than trandolapril/verapamil alone. If fluid and sodium retention occurs, consider increasing the dosage of the loop diuretic. If renal function deteriorates, stop both agents.


Plasma concentrations and pharmacologic effects of lurasidone may be increased. The dose of lurasidone should not exceed 40 mg/day in patients receiving trandolapril/verapamil.

Macrolide and ketolide antibiotics (eg, clarithromycin, erythromycin, telithromycin)

Inhibition of CYP3A4 isoenzymes by the macrolides may decrease the metabolic elimination of trandolapril/verapamil, increasing its pharmacologic effects. Hypotension, bradyarrhythmias, and lactic acidosis have been observed. In addition, concurrent use may increase the risk of AV block and hypotension. Avoid concurrent use with erythromycin.

Mammalian target of rapamycin inhibitors (eg, everolimus)

The risk of angioedema may be increased during coadministration. Pharmacologic effects and plasma concentrations of everolimus may be increased. Reduce the dose of everolimus to 2.5 mg daily during concomitant therapy with trandolapril/verapamil if coadministration cannot be avoided. A dose increase to 5 mg may be considered depending on patient tolerance. The everolimus dose can be returned to the dose used prior to initiation of trandolapril/verapamil 2 to 3 days after trandolapril/verapamil is discontinued. Monitor everolimus concentrations carefully during dose adjustments.


Verapamil may increase the plasma concentrations of midazolam.

Narcotic analgesics (eg, fentanyl)

Concurrent use may increase plasma concentrations of narcotic analgesics, increasing the potential for enhanced pharmacologic effects and toxicity. Monitor patients carefully during coadministration.

Nondepolarizing muscle relaxants (eg, vecuronium)

The neuromuscular blocking effects may be increased during coadministration. Excessive respiratory depression with periods of prolonged apnea may occur. Use this combination with caution and only when necessary.


An additive or synergistic effect, resulting in profound hypotension, may occur. Use with caution. Consider starting with a low dose of pergolide. Closely monitor BP.

Phenothiazines (eg, chlorpromazine)

An additive or synergistic hypotensive effect with postural syncope may occur when trandolapril is used with a phenothiazine. Use with caution.

Potassium preparations (eg, potassium chloride, potassium-sparing diuretics [eg, amiloride]), salt substitutes containing potassium

The risk of hyperkalemia may be increased. If these agents are coadministered, use with caution. Frequently monitor serum potassium and adjust the dose of either drug as needed.

Protease inhibitors (eg, ritonavir)

Concentrations of verapamil may be increased.


Pharmacologic effects of quinidine may be increased. This combination may produce marked hypotension. Avoid concurrent use. May need a 20% to 50% lower dose of quinidine during coadministration.

Quinazolines (eg, prazosin)

Concurrent use may decrease the first-pass elimination of prazosin and substantially increase its hypotensive effects. Careful dosage titration is recommended.


Plasma concentrations and pharmacologic effects of ranolazine may be increased. Limit the dosage of ranolazine to 500 mg twice daily. Close clinical monitoring for signs of ranolazine-related toxicity, including QT-interval prolongation, is indicated during coadministration.

Rifamycins (eg, rifampin)

Plasma concentrations and pharmacologic effects of verapamil may be decreased. Larger dosages of trandolapril/verapamil may be needed during coadministration.

Salicylates (eg, aspirin)

The hypotensive and vasodilator effects of trandolapril may be reduced. A decrease in the salicylate dose may avoid the interaction.

Serotonin 5-HT 1 receptor agonist (eg, almotriptan, eletriptan)

Plasma concentrations of serotonin 5-HT 1 receptor agonists may be increased.

St. John's wort

Plasma concentrations and pharmacologic effects of verapamil may be decreased when coadministered with St. John's wort. Avoid concurrent use.


Verapamil may inhibit the Cl and increase the plasma levels of theophylline.

Thiazide diuretics (eg, hydrochlorothiazide)

The risk of renal failure may be increased with coadministration. Monitor renal function, especially in elderly patients and patients with impaired renal function.


The pharmacologic effects of trandolapril may be increased, possibly resulting in severe hypotension. Use with caution and closely monitor BP.

Tricyclic antidepressants (eg, imipramine)

The bioavailability of tricyclic antidepressants may be increased with coadministration. Cardiac dysrhythmic effects may be additive. Monitor the tricyclic antidepressant serum concentration.


The risk of serious hyperkalemia may be increased, resulting in cardiac arrhythmias or arrest. Closely monitor the serum potassium level and clinical response of the patient.

Vasopressin receptor antagonists (eg, tolvaptan)

Plasma concentrations and pharmacologic effects of vasopressin receptor antagonists may be increased. Avoid coadministration.

Adverse Reactions


First-degree AV block (4%); bradycardia, chest pain (2%); hypotension (1%).


Headache (9%); dizziness, fatigue (3%).


Constipation (3%); diarrhea, nausea (2%).

Lab Tests

Increased liver enzymes (3%); hyperkalemia, serum creatinine increase (1%); decreased platelets, neutrophils, lymphocytes, and WBC; elevated bilirubin; hyponatremia.


Back pain, joint pain (2%); pain in extremities (1%).


Cough, upper respiratory tract infection (5%); bronchitis, upper respiratory tract congestion (2%); dyspnea (1%).


Edema (1%); angioedema.



When pregnancy is detected, discontinue therapy as soon as possible. Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus.


Periodic monitoring of liver and renal function is recommended. Periodically monitor WBC in patients with collagen vascular disease and/or renal disease. Monitor for abnormal prolongation of the PR interval or other signs of excessive pharmacologic effects in patients with hepatic and/or renal impairment.


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 therapy as soon as possible.


Verapamil is excreted in human breast milk. Radiolabeled trandolapril or its metabolites are secreted in rat milk. Do not administer to breast-feeding mothers.


Safety and efficacy not established.


Greater sensitivity compared with younger patients should be considered.


Anaphylactoid reactions have been reported.

Renal Function

In studies of ACE inhibitors in patients with unilateral or bilateral renal artery stenosis, increases in serum creatinine or BUN have been reported.

Hepatic Function

Use with caution.


ACE inhibitors, including trandolapril, may cause angioedema of the face, extremities, lips, tongue, glottis, and larynx.

Cardiac effects

Verapamil may be associated with a variety of cardiac conduction abnormalities, including first-, second-, or third-degree AV block, bradycardia, asystole, severe hypotension, nodal escape rhythms, PR prolongation, and ventricular tachycardia in patients with atrial flutter/fibrillation and Wolff-Parkinson-White syndrome caused by antegrade conduction.


Persistent nonproductive cough has been reported with all ACE inhibitors.

Heart failure

Verapamil can cause CHF or pulmonary edema and should be avoided in patients with severe left ventricular dysfunction or any degree of ventricular dysfunction if they are receiving a beta-adrenergic blocker. Trandolapril may cause excessive hypotension in patients with CHF.

Hematologic effects

Agranulocytosis and bone marrow depression may occur with trandolapril; risk appears greatest in patients with renal dysfunction or collagen vascular disease.

Hepatic effects

Elevations of transaminases with and without concomitant elevations in alkaline phosphatase and bilirubin have been reported for verapamil. In addition, ACE inhibitors have been associated with a syndrome of cholestatic jaundice, fulminant hepatic necrosis, and death.


May occur.

Hypertrophic cardiomyopathy

Serious adverse effects were seen in patients with hypertrophic cardiomyopathy who received verapamil.


May occur, especially in patients who are salt- or volume-depleted, as a result of dialysis, prolonged diuretic therapy, dietary salt restriction, diarrhea, or vomiting. Correct volume and salt depletion before initiating therapy.

Neuromuscular transmission

It may be necessary to reduce the dose of verapamil in patients with attenuated neuromuscular transmission.

Renal effects

As a consequence of inhibiting the renin-angiotensin-aldosterone system, changes in renal function may be anticipated in susceptible individuals. In patients whose renal function may depend on the activity of the renin-angiotensin-aldosterone system (eg, patients with severe CHF), treatment with ACE inhibitors has been associated with oliguria or progressive azotemia and, rarely, acute renal failure and/or death. In addition, increases in BUN and serum creatinine may occur.


In patients undergoing surgery, or during anesthesia with agents that produce hypotension, trandolapril will block the angiotensin II formation that could otherwise occur secondary to compensatory renin release.



Pronounced hypotension, bradycardia and conduction system abnormalities, symptoms secondary to hypoperfusion (eg, metabolic acidosis, hyperglycemia, hyperkalemia, renal dysfunction, convulsions).

Patient Information

  • Tell female patients of childbearing age about the consequences of exposure to trandolapril/verapamil during pregnancy. Discuss treatment options with women planning to become pregnant. Advise patients to report pregnancies to their health care provider as soon as possible.
  • Instruct patients to stop taking the drug and immediately report any of the following symptoms to their health care provider: fainting; swelling of the face, lips, eyelids, or tongue; difficulty breathing; yellowing of the skin or eyes.
  • Instruct patients to inform their health care provider if a persistent cough or bothersome constipation develop while taking this medication.
  • Caution patients not to take any prescription or OTC medications, potassium-containing salt substitutes, potassium supplements, or dietary supplements unless advised by their health care provider.
  • Caution patients that inadequate fluid intake, excessive perspiration, diarrhea, or vomiting can lead to an excessive fall in BP, resulting in light-headedness or fainting.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.