Trandolapril + Verapamil


Concise Prescribing Info
Indications/Uses
Hypertension.
Dosage/Direction for Use
Adult : PO Each extended-release tab contains trandolapril (mg)/verapamil (mg): 1/240, 2/180, 2/240, 4/240: 1 tab once daily. Dose is individualised based on patient’s current regimen, effectiveness, and tolerability. Max: trandolapril 4 mg and verapamil 240 mg daily.
Dosage Details
Oral
Hypertension
Adult: Available preparations:
Extended-release tab:
Trandolapril 1 mg and verapamil 240 mg
Trandolapril 2 mg and verapamil 180 mg
Trandolapril 2 mg and verapamil 240 mg
Trandolapril 4 mg and verapamil 240 mg
1 tab once daily. Dose is individualised based on patient’s current regimen, effectiveness, and tolerability. Max: trandolapril 4 mg and verapamil 240 mg daily.
Administration
Should be taken with food.
Contraindications
Cardiogenic shock, hypotension (systolic blood pressure <90 mm Hg), heart failure, 2nd- or 3rd-degree AV block (unless pacemaker is fitted), sick-sinus syndrome, tachycardia, severe left ventricular dysfunction, atrial flutter or atrial fibrillation, accessory bypass tract (e.g. Wolff-Parkinson-White, Lown-Ganong-Levine syndromes), hereditary/idiopathic angioedema, history of angioedema related to previous ACE inhibitor treatment. Pregnancy, lactation. Concomitant use with aliskiren in patient with diabetes mellitus or renal impairment. Concomitant use with neprilysin inhibitor (e.g. sacubitril).
Special Precautions
Patient with aortic stenosis, bradycardia or 1st-degree AV block, attenuated neuromuscular transmission, collagen vascular disease, ischaemic heart disease, cerebrovascular disease, hypertrophic cardiomyopathy, unstented unilateral or bilateral renal artery stenosis. Patients on haemodialysis and dietary salt restriction. Renal and hepatic impairment.
Adverse Reactions
Significant: Hypotension with or without syncope, cerebrovascular accident, conduction abnormalities (e.g. 1st-degree AV block, bradycardia), cough, neutropaenia with myeloid hypoplasia, agranulocytosis, anaemia, thrombocytopaenia, elevated transaminases, hyperkalaemia, increased BUN and serum creatinine, proteinuria, taste disturbance. Rarely, rash, photosensitivity.
Gastrointestinal disorders: Constipation, nausea.
General disorders and administration site conditions: Chest pain, fatigue.
Infections and infestations: Influenza.
Metabolism and nutrition disorders: Hyperlipidaemia, peripheral oedema.
Musculoskeletal and connective tissue disorders: Back pain, joint pain, pain in extremities.
Nervous system disorders: Dizziness, headache, dyspnoea.
Respiratory, thoracic and mediastinal disorders: Upper respiratory tract infection and congestion, bronchitis.
Potentially Fatal: Anaphylactic reactions, angioedema, hepatotoxicity (e.g. fulminant hepatic necrosis).
Patient Counseling Information
This drug may cause hypotension, if affected, do not drive or operate machinery.
MonitoringParameters
Monitor blood pressure, heartrate, BUN, serum creatinine, electrolytes, and CBC with differential periodically.
Overdosage
Symptoms: Severe hypotension, bradycardia, AV block and asystole, negative inotropy, shock, stupor, electrolyte disturbance, renal failure, tachycardia, palpitations, dizziness, anxiety and cough. Management: Supportive treatment. Consider gastric lavage and administer activated charcoal. May administer dopamine or dobutamine for inotropic support; IV angiotensin II infusion or catecholamines for hypotension. Maintain adequate circulation volume with plasma replacements.
Drug Interactions
Trandolapril: Additive hyperkalaemic effect with K-sparing diuretics, K-containing salt substitutes and supplements. May increase serum levels and toxicity of lithium. May increase hypoglycaemic effect of antidiabetics. Increased risk of renal function deterioration with NSAIDs.
Verapamil: May increase plasma level with CYP3A4 inhibitors (e.g. erythromycin, ritonavir), cimetidine. May decrease plasma level with CYP3A4 inducers (e.g. rifampicin), phenobarbital, sulfinpyrazone. Increased risk of bleeding with aspirin. May increase bradycardic and hypotensive effect with telithromycin. Increased AV blocking effect with clonidine. May increase plasma level of cardiac glycosides (e.g. digoxin, digitoxin), β-blockers (e.g. propranolol, metoprolol), α-blockers (e.g. terazosin, prazosin), immunosuppressants (e.g. sirolimus, ciclosporin, tacrolimus, everolimus), lipid lowering agents (e.g. simvastatin, atorvastatin), colchicines, quinidine, carbamazepine, imipramine, glibenclamide, doxorubicin, midazolam, buspirone, almotriptan, theophylline. May potentiate hypotensive effect with diuretics, antihypertensives, vasodilators. May increase neurotoxic effect of lithium.
Potentially Fatal: Increased risk of hypotension, hyperkalaemia, and changes in renal function (including acute renal failure) with aliskiren in diabetic patients. Increased risk of angioedema with sacubitril and racedotril.
Food Interaction
May increase blood ethanol levels. May increase plasma level of verapamil with grapefruit juice.
Action
Description: Trandolapril, a prodrug of trandolaprilat, competitively inhibits ACE from converting angiotensin I to angiotensin II (a potent vasoconstrictor) resulting in increased plasma renin activity and reduced aldosterone (a hormone that causes water and Na retention) secretion. This promotes vasodilation and BP reduction.
Verapamil inhibits entry of Ca ions into the slow channels or select voltage-sensitive areas of vascular smooth muscle and myocardium during depolarisation. It relaxes coronary vascular smooth muscle and coronary vasodilation, increases myocardial oxygen delivery, and slows automaticity and AV node conduction.
Onset: Trandolapril: 1-2 hours.
Verapamil: Within 1-2 hours (oral); 3-5 minutes (IV).
Duration: Verapamil: 6-8 hours (oral); 0.5-6 hours (IV).
Pharmacokinetics:
Absorption: Trandolapril: Rapidly absorbed from the gastrointestinal tract. Bioavailability: Approx 70% (trandolaprilat); approx 10% (trandolapril). Time to peak plasma concentrations: 4-10 hours (trandolaprilat).
Verapamil: Well absorbed from the gastrointestinal tract. Bioavailability: 20-35% (oral). Time to peak plasma concentration: 1-2 hours (oral).
Distribution: Trandolapril: Volume of distribution: Approx 18 L. Plasma protein binding: >80% (trandolapril); 65-94% (trandolaprilat).
Verapamil: Crosses the placenta; enters breast milk. Volume of distribution: 3.89 L/kg. Plasma protein binding: Approx 90%.
Metabolism: Trandolapril: Metabolised in the liver via hydrolysis to its active metabolite, trandolaprilat and to some inactive metabolites.
Verapamil: Extensively metabolised in the liver by CYP isoenzymes to its primary metabolite, norverapamil, and to at least 12 metabolites.
Excretion: Trandolapril: Via urine (approx 33%); faeces (approx 66%). Elimination half-life: Approx 6 hours (trandolapril); 22.5 hours (trandolaprilat).
Verapamil: Mainly via urine (approx 70% as metabolites, 3-4% as unchanged drug); faeces (approx 16%). Elimination half-life: Approx 12 hours (extended-release).
Chemical Structure

Chemical Structure Image
Trandolapril

Source: National Center for Biotechnology Information. PubChem Database. Trandolapril, CID=5484727, https://pubchem.ncbi.nlm.nih.gov/compound/Trandolapril (accessed on Jan. 23, 2020)


Chemical Structure Image
Verapamil

Source: National Center for Biotechnology Information. PubChem Database. Verapamil, CID=2520, https://pubchem.ncbi.nlm.nih.gov/compound/Verapamil (accessed on Jan. 23, 2020)

Storage
Store between 15-25°C.
ATC Classification
C09BB10 - trandolapril and verapamil ; Belongs to the class of ACE inhibitors and calcium channel blockers. Used in the treatment of cardiovascular diseases.
References
Anon. Trandolapril and Verapamil. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 05/03/2018.

Anon. Trandolapril. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 05/03/2018.

Anon. Verapamil. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 05/03/2018.

Buckingham R (ed). Trandolapril. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 05/03/2018.

Buckingham R (ed). Verapamil Hydrochloride. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 05/03/2018.

McEvoy GK, Snow EK, Miller J et al (eds). Trandolapril. AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com. Accessed 05/03/2018.

McEvoy GK, Snow EK, Miller J et al (eds). Verapamil Hydrochloride. AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com. Accessed 05/03/2018.

Trandolapril and Verapamil Hydrochloride ER Film-Coated, Extended Release (Greenstone LLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 05/03/2018.

Disclaimer: This information is independently developed by MIMS based on Trandolapril + Verapamil from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2020 MIMS. All rights reserved. Powered by MIMS.com
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