TARKA^® (trandolapril/verapamil HCl ER) Indication and Important Safety Information¹

INDICATION

• TARKA^® (trandolapril/verapamil hydrochloride ER tablets) is indicated for the treatment of hypertension.
• TARKA is not indicated for the initial therapy of hypertension.
• In using TARKA, consideration should be given to the fact that an ACE inhibitor, captopril, has caused agranulocytosis, particularly in patients with renal impairment or collagen vascular disease, and that available data are insufficient to show that trandolapril does not have similar risk.

IMPORTANT SAFETY INFORMATION

• TARKA is contraindicated in patients hypersensitive to any ACE inhibitor or verapamil. Because of the verapamil component, TARKA is contraindicated in: 1) severe left ventricular dysfunction, 2) hypotension (systolic pressure <90 mmHg) or cardiogenic shock, 3) sick sinus syndrome (except in patients with a functioning artificial ventricular pacemaker), 4) second- or third-degree AV block (except in patients with a functioning artificial ventricular pacemaker), 5) atrial flutter or atrial fibrillation and an accessory bypass tract (e.g., Wolff-Parkinson-White, Lown-Ganong-Levine syndromes), and 6) patients taking flibanserin. Because of the trandolapril component, TARKA is contraindicated in patients with a history of angioedema related to previous treatment with an ACE inhibitor.
• TARKA is contraindicated in combination with aliskiren in patients with diabetes; with a neprilysin inhibitor (e.g., sacubitril); and within 36 hours of switching to or from sacubitril/valsartan, a neprilysin inhibitor.
• Verapamil may cause CHF or pulmonary edema. Avoid verapamil in patients with severe left ventricular dysfunction and in patients with any degree of ventricular dysfunction if they are receiving a beta adrenergic blocker. In patients with CHF, trandolapril may cause excessive hypotension, which may be associated with oliguria or azotemia, and, rarely, with acute renal failure and death.
• Verapamil and trandolapril may produce dizziness or symptomatic hypotension. Lower doses of verapamil and/or trandolapril or reduced concomitant diuretic therapy should be considered.
• Use of a moderate CYP3A4 inhibitor such as verapamil with flibanserin significantly increases flibanserin concentrations, which can lead to severe hypotension and syncope. Discontinue TARKA at least 2 weeks prior to starting flibanserin and do not administer TARKA within 2 days of discontinuing flibanserin.
• Monitor liver function periodically, as TARKA can increase liver enzymes. ACE inhibitors rarely have been associated with a syndrome of cholestatic jaundice, fulminant hepatic necrosis, and death; patients who develop jaundice should discontinue the ACE inhibitor and receive appropriate medical follow-up.
• Verapamil may lead to asymptomatic first-degree AV block and transient bradycardia. Reduce the dose or discontinue verapamil if marked first-degree AV block or progressive development to second- or third-degree AV block occurs.
• Pulmonary edema, severe hypotension, sinus bradycardia, second-degree AV block, and sinus arrest have occurred in patients with hypertrophic cardiomyopathy (IHSS) who received verapamil at doses up to 720 mg/day. Most adverse effects responded well to dose reduction and only rarely did verapamil have to be discontinued.
• Trandolapril may cause anaphylactoid reactions. A possibly related reaction, angioedema of the face, extremities, lips, tongue, glottis, and larynx, has occurred. Angioedema associated with laryngeal edema can be fatal. If laryngeal stridor or angioedema of the face, tongue, or glottis occurs, discontinue TARKA immediately, treat the patient in accordance with accepted medical care, and carefully observe until the swelling disappears. Where there is involvement of the tongue, glottis, or larynx likely to cause airway obstruction, emergency therapy, including but not limited to subcutaneous epinephrine solution 1:1,000 (0.3-0.5 mL), should be promptly administered. Concomitant use of TARKA with an mTOR (mammalian target of rapamycin) inhibitor (e.g., temsirolimus, sirolimus, everolimus) or a neprilysin inhibitor (e.g., sacubitril) may increase the risk for angioedema.
• TARKA may cause agranulocytosis. Monitor white blood cell counts periodically in patients with collagen vascular disease and/or renal disease.
• Administer verapamil cautiously to patients with impaired hepatic or renal function. Approximately 30% of the dose given to patients with normal liver function should be administered to patients with severe liver dysfunction. Monitor patients with impaired hepatic or renal function for signs of excessive pharmacologic effects. Evaluation of hypertensive patients should always include assessment of renal function.
• Verapamil decreases neuromuscular transmission in patients with Duchenne’s muscular dystrophy and prolongs recovery from the neuromuscular blocking agent vecuronium; decreased doses of verapamil may be required in patients with attenuated neuromuscular transmission.
• Hyperkalemia and cough have occurred with use of verapamil or trandolapril.
• Clinically significant interactions have been reported with inhibitors of CYP3A4 (e.g., erythromycin, ritonavir), causing elevation of plasma levels of verapamil, while inducers (e.g., rifampin) have caused a lowering of plasma levels of verapamil. Therefore, patients receiving inhibitors or inducers of the CYP450 system should be monitored for drug interactions. TARKA should be used with caution with certain other medications, including digoxin. Please see full Prescribing Information for a complete list of drug interactions.
• The use of HMG-CoA reductase inhibitors that are CYP3A4 substrates (e.g., simvastatin) in combination with verapamil has been associated with reports of myopathy/rhabdomyolysis. Lower starting and maintenance doses may be required, as verapamil may increase the plasma concentrations of these drugs.
• In patients who are elderly, volume-depleted, or with compromised renal function, co-administration of NSAIDs or COX-2 inhibitors with ACE inhibitors, including trandolapril, may result in deterioration of renal function, including possible acute renal failure. Monitor renal function periodically in patients receiving trandolapril and NSAID or COX-2 therapy.
• Closely monitor blood pressure, renal function, and electrolytes in patients concomitantly receiving trandolapril with other agents that affect the renin-angiotensin system (RAS). However, in general, avoid combined use of RAS inhibitors.
• TARKA should not be administered to nursing mothers.
• Adverse events reported (≥1% and more than placebo) in clinical trials included AV block first degree, bradycardia, bronchitis, chest pain, constipation, cough, diarrhea, dizziness, dyspnea, fatigue, increased liver enzymes, nausea, pain (extremities), pain (joints).

Reference: 1. TARKA [package insert]. North Chicago, IL: AbbVie Inc.

Please see full Prescribing Information, including BOXED WARNING about use in pregnancy.

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