Trandolapril + Verapamil

Trandolapril + Verapamil Should be taken with food.

Hereditary or idiopathic angioedema, history of angioedema associated with previous ACE inhibitor treatment; severe left ventricular dysfunction, hypotension (systolic blood pressure <90 mmHg), cardiogenic shock; sick sinus syndrome or 2nd- or 3rd-degree AV block (unless with a functioning pacemaker); atrial flutter or atrial fibrillation, and an accessory bypass tract (e.g. Wolff-Parkinson-White, Lown-Ganong-Levine syndromes). Pregnancy. Concomitant use with aliskiren-containing agents in patients with diabetes mellitus or renal impairment (GFR <60 mL/min/1.73 m²). Concomitant use with or within 36 hours of switching to or from sacubitril/valsartan. Concomitant administration with flibanserin.

Patient with hypertrophic cardiomyopathy with left ventricular outflow tract obstruction, aortic stenosis, CHF, ischaemic heart disease or cerebrovascular disease; unstented unilateral or bilateral renal artery stenosis; pre-existing salt or volume depletion; risk factors for hyperkalaemia (e.g. diabetes mellitus); collagen vascular disease (e.g. systemic lupus erythematosus or scleroderma); attenuated neuromuscular transmission (e.g. Duchenne muscular dystrophy, myasthenia gravis). Patients undergoing major surgery, haemodialysis with high-flux dialysis membranes, LDL apheresis with dextran sulfate, and desensitisation treatment with hymenoptera venom. Black race. Not suitable for use as initial therapy. Renal and hepatic impairment. Lactation (use not recommended). Concomitant use with mTOR inhibitors (e.g. everolimus, sirolimus, temsirolimus).

Significant: Symptomatic hypotension with or without syncope (usually during initial doses), conduction abnormalities (e.g. 1st-degree AV block, bradycardia); may decrease coronary perfusion leading to ischaemia; dry, hacking, or nonproductive cough; haematologic effects such as neutropenia with myeloid hypoplasia and agranulocytosis, anaemia, thrombocytopenia; elevation of transaminases, hyperkalaemia, deterioration of renal function and/or increased BUN or serum creatinine; reduced neuromuscular transmission. Rarely, angioedema of the face, lips, or intestines.
Cardiac disorders: Chest pain.
Ear and labyrinth disorders: Vertigo.
Gastrointestinal disorders: Constipation, diarrhoea, nausea.
General disorders and administration site conditions: Asthenia, fatigue.
Infections and infestations: Influenza.
Metabolism and nutrition disorders: Hyperlipidaemia.
Musculoskeletal and connective tissue disorders: Arthralgia, limb pain, back pain.
Nervous system disorders: Dizziness, headache.
Respiratory, thoracic and mediastinal disorders: Bronchitis, dyspnoea, URTI.
Skin and subcutaneous tissue disorders: Rash, pruritus.
Vascular disorders: Orthostatic hypotension, flushing.
Potentially Fatal: Anaphylactic/anaphylactoid reactions. Rarely, angioedema of the tongue, glottis or larynx; cholestatic jaundice that may progress to fulminant hepatic necrosis.

PO: D

Correct sodium and/or volume depletion before administration. Monitor blood pressure, heart rate; BUN, serum creatinine, and electrolytes; CBC with differential (periodically, in patients with collagen vascular disease and/or renal impairment). Assess for signs and symptoms of angioedema or cough.

Symptoms: Severe hypotension, bradycardia, AV block and asystole, negative inotropy, shock, stupor, electrolyte disturbance, renal failure, hyperventilation, tachycardia, palpitations, dizziness, anxiety, cough and acute respiratory distress syndrome.

Management: Symptomatic and supportive treatment. Consider gastric lavage and administration of activated charcoal or laxatives to prevent further absorption. May administer dopamine or dobutamine for inotropic support, IV infusion of normal saline solution, or may also consider treatment with IV angiotensin II infusion and/or catecholamines if available. Frequently monitor vital signs, electrolytes, and serum creatinine.

Trandolapril: May increase risk of angioedema with mTOR inhibitors (e.g. everolimus, sirolimus, temsirolimus). May increase risk of hyperkalaemia with potassium-sparing diuretics (e.g. amiloride, spironolactone, triamterene), trimethoprim/sulfamethoxazole, ciclosporin, and heparin. Increased risk of renal impairment with thiazide diuretics and NSAIDs, including COX-2 inhibitors. Increased risk of hypoglycaemia with antidiabetic agents.
Verapamil: Significantly increases the serum levels of flibanserin that may result in severe hypotension and syncope. May increase the serum levels of ivabradine, potentially exacerbating bradycardia and conduction disturbances. May increase plasma levels with CYP3A4 inhibitors (e.g. erythromycin, ritonavir) and cimetidine. May decrease plasma levels with CYP3A4 inducers (e.g. rifampicin). May increase serum levels of cardiac glycosides (e.g. digoxin), immunosuppressants (e.g. ciclosporin, sirolimus, tacrolimus), HMG-CoA reductase inhibitors (e.g. atorvastatin, simvastatin), quinidine, theophylline, and carbamazepine. Additive hypotensive effects with α-blockers (e.g. prazosin, terazosin), diuretics, and other antihypertensive agents. May increase the bioavailability of dabigatran. Concomitant use with direct oral anticoagulants (DOACs) may increase the risk of bleeding. Additive negative effects on heart rate, AV conduction, and/or cardiac contractility with β-blockers. May enhance the effects of neuromuscular blockers. May increase the neurotoxic effect of lithium. May alter the plasma concentrations of phenytoin. May increase clearance with phenobarbital. May decrease the effect of metformin.
Potentially Fatal: Trandolapril: Increased risk of angioedema with neprilysin inhibitors (e.g. sacubitril, racecadotril). Increased risk or frequency of adverse events such as hypotension, hyperkalaemia, and reduced renal function (including acute renal failure) with aliskiren.

Verapamil: May increase blood levels and prolong the intoxicating effects of alcohol. May increase serum levels with grapefruit juice. May decrease serum levels with St. John's wort.

Trandolapril: May result in a false-negative aldosterone-to-renin ratio (ARR).
Verapamil: May cause false-positive result in urine detection of methadone.

Description:
Overview: Trandolapril and verapamil combination works with complementary mechanisms to produce additive antihypertensive effects.
Trandolapril is a long-acting, highly lipophilic non-sulfhydryl-containing angiotensin converting enzyme (ACE) inhibitor.
Verapamil is a phenylalkylamine calcium channel blocker.
Mechanism of Action: Trandolapril is hepatically hydrolysed to trandolaprilat, its active metabolite. Trandolaprilat competes with angiotensin I for its binding site on the angiotensin-converting enzyme (ACE), thereby inhibiting the conversion of angiotensin I to angiotensin II. This results in reduced plasma levels of angiotensin II, a potent vasoconstrictor, leading to decreased blood pressure and reduced aldosterone secretion, with a subsequent reduction in sodium and water retention.
Verapamil inhibits the influx of calcium ions across the cell membrane of arterial smooth muscle and within conductile and contractile myocardial cells. This leads to reduced myocardial contractility, suppression of the formation and propagation of cardiac electrical impulses, and decreased coronary and systemic vascular tone.
Pharmacodynamics: Trandolapril causes arterial vasodilation, resulting in a reduction in total peripheral vascular resistance. In hypertensive patients, both standing and supine blood pressure are reduced with little or no change in heart rate, stroke volume, or cardiac output. As an antihypertensive, trandolapril reduces left ventricular hypertrophy and does not exacerbate insulin resistance or hyperlipidaemia, and does not induce sexual dysfunction. Verapamil exerts antihypertensive effects primarily by decreasing systemic vascular resistance, usually without causing orthostatic hypotension or reflex tachycardia. Inhibition of vascular smooth muscle contraction leads to dilation of coronary and systemic arteries, increasing myocardial oxygen delivery and reducing afterload. By slowing calcium influx, verapamil prolongs the effective refractory period in the AV node, prolongs the ECG PR interval, and slows AV conduction and heart rate. It also exerts favourable effects on left ventricular hypertrophy and does not worsen insulin resistance or adversely affect lipid profiles.
Pharmacokinetics:
Absorption: Trandolapril: Bioavailability: Approx 70% (trandolaprilat); approx 10% (trandolapril). Time to peak plasma concentration: 4-10 hours (trandolaprilat); approx 1 hour (trandolapril).
Verapamil: Well absorbed orally (>90%). Bioavailability: 20-35%. Time to peak plasma concentration: 4-15 hours.
Distribution: Trandolapril: Volume of distribution: Approx 18 L. Plasma protein binding: 65-94% (trandolaprilat); approx 80% (trandolapril).
Verapamil: Crosses the placenta and enters breast milk. Volume of distribution: 3.89 L/kg. Plasma protein binding: Approx 90%.
Metabolism: Trandolapril: Metabolised in the liver into trandolaprilat (active metabolite) and some inactive metabolites.
Verapamil: Extensively metabolised in the liver by multiple CYP isoenzymes to form at least 12 metabolites, including norverapamil (primary active metabolite).
Excretion: Trandolapril: Via urine (approx 33% as trandolaprilat and trandolapril); faeces (approx 66%). Elimination half-life: Approx 6 hours (trandolapril); 22.5 hours (trandolaprilat).
Verapamil: Via urine (approx 70% as metabolites, 3-4% as unchanged drug); faeces (≥16%). Elimination half-life: Approx 12 hours.

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 5484727, Trandolapril. https://pubchem.ncbi.nlm.nih.gov/compound/Trandolapril. Accessed Dec. 18, 2025.

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 2520, Verapamil. https://pubchem.ncbi.nlm.nih.gov/compound/Verapamil. Accessed Dec. 18, 2025.

Store between 20-25°C.

ACE Inhibitors/Direct Renin Inhibitors / Calcium Antagonists

C09BB10 - trandolapril and verapamil ; Belongs to the class of ACE inhibitors and calcium channel blockers. Used in the treatment of cardiovascular diseases.

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