trandolapril/verapamil (Rx)

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Brand and Other Names:Tarka

Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

trandolapril/verapamil

tablet

  • 2mg/180mg
  • 1mg/240mg
  • 2mg/240mg
  • 4mg/240mg

Combines an immediate-release formulation of an angiotensin converting enzyme inhibitor, trandolapril and a slow-release formulation of a calcium channel blocker, verapamil hydrochloride

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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

Renal Impairment

CrCl < 30 mL/min: Adjust regimen

Hepatic Impairment

Not studied

Administration

Administer with food

Tablets contain verapamil hydrochloride as a controlled release formulation and trandolapril as an immediate release formulation

<18 years: Safety/efficacy not established

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Interactions

Interaction Checker

and trandolapril/verapamil

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

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            Adverse Effects

            >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%)

            < 1%

            Trandolapril

            • Angioedema
            • ARF if renal artery stenosis
            • Cough

            Verapamil

            • Abdominal discomfort
            • Arthralgia
            • Extrapyramidal symptoms
            • Gastrointestinal distress
            • Hyperkeratosis
            • Gynecomastia
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            Warnings

            Black Box Warnings

            Trandolapril: Discontinue as soon as possible when pregnancy is detected; affects renin-angiotensin system causing oligohydramnios, which may result in fetal injury and/or death

            Contraindications

            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)

            Pregnancy (2nd and 3rd trimesters): significant risk of fetal and neonatal morbidity and mortality

            Do not coadminister with aliskiren in patients with diabetes

            History of angioedema

            Severe left ventricular dysfunction

            Cautions

            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

            Reduce dose if marked first-degree block or progressive development to second-or third-degree AV block; in rare instances, discontinuation of verapamil HCl and institution of appropriate therapy depending upon clinical situation may be necessary

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

            Discontinue immediately if If laryngeal stridor or angioedema of the face, tongue or glottis occurs

            Administration of other ACE inhibitors have been associated with 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; consider periodic monitoring of white blood cell counts in patients with collagen-vascular disease and/or renal disease

            Acceleration of ventricular rate and/or ventricular fibrillation has been reported in patients with atrial flutter or atrial fibrillation and a coexisting accessory AV pathway

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            Pregnancy & Lactation

            Pregnancy Category: C (1st trimester); D (2nd and 3rd trimester)

            Lactation: excreted in breast milk, use caution

            Pregnancy Categories

            A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA:Information not available.

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            Pharmacology

            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

            Pharmacokinetics

            Trandolapril

            • Half-life: 6 (trandolapril); 22.5 hr (trandolaprilat)
            • Onset: 1-2 hr
            • Duration: 72 hr
            • Vd: 18 L
            • Peak plasma time: 1 hr (trandolapril); 4-10 hr (trandolaprilat)
            • Bioavailability: 10% (trandolapril); 70% (trandolaprilat)
            • Protein bound: 80% (trandolapril); 65-94% (trandolaprilat)
            • Metabolism: Liver, undergoes hepatic biotransformation to trandolaprilat
            • Metabolites: Trandolaprilat (active)
            • Clearance: 52 L/hr (total body); 1-4 L/hr (renal)
            • Excretion: Urine 33%, feces 66%
            • Dialyzable: Yes

            Verapamil

            • Half-life: 4-12 hr (parent drug); 6-10 hr (norverapamil); increases to 14-16 hr in liver disease patients (norverapamil)
            • Bioavailability: 20-35%
            • Onset: 1-2 hr (peak effect)
            • Duration: 6-8 hr (PO); 10-20 min (IV)
            • Vd: 3.9 L/kg
            • Peak plasma time: 1-2 hr (immediate release); 11 hr (extended release); 4-5 hr (delayed release); 5-9 hr (sustained release)
            • Protein bound: 90%
            • Metabolism: Liver via P450 enzyme CYP3A4
            • Metabolites: Norverapamil (active)
            • Clearance: 0.5-1 L/kg
            • Excretion: Urine (70%); feces (16%)
            • Dialyzable: HD No
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            Formulary

            FormularyPatient Discounts

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            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
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            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
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