Trandolapril + Verapamil
Indications
Trandolapril + Verapamil is used for:
Hypertension
Adult Dose
Hypertension
Not indicated for initial therapy
Usual dose: Trandolapril 1- 4 mg/verapamil HCl ER 180-240 mg PO qDay
For convenience, patients receiving trandolapril (up to 8 mg) and verapamil (up to 240 mg) in separate tablets, administered qDay, may instead receive tablets of combination containing the same component doses
Clinical trials with combination have explored only qDay dosing
Child Dose
Renal Dose
Renal impairment: This combination product has not been studied in patients with renal or hepatic impairment
Administration
Administer with food
Contra Indications
Hypersensitivity to either component
Second- or third-degree AV block (unless permanent pacemaker in place)
Hypotension (systolic pressure less than 90 mmHg) or cardiogenic shock
Concomitant use with aliskiren in patients with diabetes mellitus
Sick sinus syndrome (unless permanent pacemaker in place)
Patients with atrial flutter or atrial fibrillation and an accessory bypass tract (e.g. Wolff-Parkinson-White, Lown-Ganong-Levine syndromes)
Do not coadminister with aliskiren in patients with diabetes
History of angioedema
Coadministration of neprilysin inhibitors (eg, sacubitril) with ACE inhibitors may increase angioedema risk; do not administer ACE inhibitors within 36 hr of switching to or from sacubitril/valsartan
Severe left ventricular dysfunction
Precautions
Aortic stenosis, hypotension (initially or after dose increases) reported
Persistent progressive dermatologic reactions reported
Avoid taking with grapefruit juice
Use caution in heart failure or compromised ventricular function
Use caution in liver or renal impairment
Use caution and monitor closely if adminstered with concurrent beta blocker therapy
Excessive hypotension may occur if administered with concomitant diuretics, hypovolemia, hyponatremia
Dual blockade of the renin angiotensin system with ARBs, ACE inhibitors, or aliskiren associated with increased risk for hypotension, hyperkalemia, and renal function changes (including acute renal failure) compared to monotherapy
Avoid concomitant use of verapamil and quinidine in patients with hypertrophic cardiomyopathy; may cause significant hypotension
Hemodialysis with high flux membrane and low-density lipoprotein apharesis associated with anaphylactoid reactions
Avoid verapamil in patients with severe left ventricular dysfunction (e.g., ejection fraction < 30%, pulmonary wedge pressure above 20 mmHg, or severe symptoms of cardiac failure) and in patients with any degree of ventricular dysfunction if they are receiving a beta adrenergic blocker
ACE inhibitors may cause excessive hypotension in patients with congestive heart failure
Verapamil may produce a decrease in blood pressure below normal levels which may result in dizziness or symptomatic hypotension
ACE inhibitors rarely associated with syndrome of cholestatic jaundice, fulminant hepatic necrosis, and death; mechanism of this syndrome is not understood; patients receiving ACE inhibitors who develop jaundice should discontinue therapy
Not for administration to patients with paroxysmal and/or chronic atrial fibrillation or atrial flutter and a coexisting accessory AV pathway
Pregnancy-Lactation
Pregnancy Category: C (1st trimester); D (2nd and 3rd trimester)
Lactation: excreted in breast milk, use caution
Interactions
Adverse Effects
Side effects of Trandolapril + Verapamil :
>10%
Verapamil
Headache (1-12 %)
Gingival hyperplasia (≤ 19%)
Constipation (7-12%)
Trandolapril
Hypotension (1-11%)
Dizziness (1-23%)
Increased uric acid (15%)
Cough (2-35%)
1-10%
Verapamil
Dizziness (4%)
Dyspepsia (3%)
Edema (2%)
Fatigue (2%)
Lethargy (3%)
Pain (2%)
Sleep disturbance (1%)
Increased liver enzymes (1%)
Pulmonary edema (2%)
Flushing (1%)
Hypotension (4%)
Nausea (3%)
Trandolapril
Syncope (6%)
Bradycardia (1-5%)
Stroke (3%)
Gastritis (4%)
Diarrhea (1%)
Weakness (3%)
Myalgia (5%)
Mechanism of Action
Trandolapril/verapamil hydrochloride ER combines a slow release formulation of a calcium channel blocker, verapamil hydrochloride, and an immediate release formulation of an angiotensin converting enzyme inhibitor, trandolapril
Trandolapril competitively inhibits angiotensin-converting enzymes resulting in decreased plasma angiotensin II concentrations and consequently, blood pressure may be reduced in part through decreased vasoconstriction, increased renin activity, and decreased aldosterone secretion
Verapamil, a nondihydropyridine calcium-channel blocker, inhibits transmembrane influx of extracellular Ca ions across membranes of myocardial cells and vascular smooth muscle cells, without changing serum calcium concentrations, resulting in inhibition of cardiac and vascular smooth muscle contraction, thereby dilating main coronary and systemic arteries