Brand Names

MAVIK
TARKA
TRANDOLAPRIL
TRANDOLAPRIL AND VERAPAMIL HYDROCHLORIDE

Boxed Warning

• When pregnancy is detected, discontinue trandolapril and verapamil hydrochloride extended-release tablets as soon as possible. • Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus (see WARNINGS: Fetal Toxicity).

Indications and Usage

Trandolapril and verapamil hydrochloride extended-release tablets are indicated for the treatment of hypertension. This fixed combination drug is not indicated for the initial therapy of hypertension (see DOSAGE AND ADMINISTRATION ). In using trandolapril and verapamil hydrochloride extended-release tablets, consideration should be given to the fact that an angiotensin converting enzyme 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 (see WARNINGS - Neutropenia/Agranulocytosis ).

Dosage and Administration

The recommended usual dosage range of trandolapril for hypertension is 1 to 4 mg per day administered in a single dose or two divided doses. The recommended usual dosage range of verapamil hydrochloride sustained-release tablets for hypertension is 120 to 480 mg per day administered in a single dose or two divided doses. The hazards (see WARNINGS ) of trandolapril are generally independent of dose; those of verapamil are a mixture of dose-dependent phenomena (primarily dizziness, AV block, constipation) and dose-independent phenomena, the former much more common than the latter. Therapy with any combination of trandolapril and verapamil will thus be associated with both sets of dose-independent hazards. The dose-dependent side effects of verapamil have not been shown to be decreased by the addition of trandolapril nor vice versa. Rarely, the dose-independent hazards of trandolapril are serious. To minimize dose-independent hazards, it is usually appropriate to begin therapy with trandolapril and verapamil hydrochloride extended-release tablets only after a patient has either (a) failed to achieve the desired antihypertensive effect with one or the other monotherapy at its respective maximally recommended dose and shortest dosing interval, or (b) the dose of one or the other monotherapy cannot be increased further because of dose-limiting side effects. Clinical trials with trandolapril and verapamil hydrochloride extended-release tablets have explored only once-a-day doses. The antihypertensive effect and or adverse effects of adding 4 mg of trandolapril once-a-day to a dose of 240 mg verapamil hydrochloride sustained-release tablets administered twice-a-day has not been studied, nor have the effects of adding as little of 180 mg verapamil hydrochloride sustained-release tablets to 2 mg trandolapril administered twice-a-day been evaluated. Over the dose range of verapamil hydrochloride sustained-release tablets 120 to 240 mg once-a-day and trandolapril 0.5 to 8 mg on

Contraindications

Trandolapril and verapamil hydrochloride extended-release tablets are contraindicated in patients who are hypersensitive to any ACE inhibitor or verapamil. Because of the verapamil component, trandolapril and verapamil hydrochloride extended-release tablets are contraindicated in: 1.Severe left ventricular dysfunction (see WARNINGS ). 2.Hypotension (systolic pressure less than 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.Patients with atrial flutter or atrial fibrillation and an accessory bypass tract (e.g. Wolff-Parkinson-White, Lown-Ganong-Levine syndromes) (see WARNINGS ). 6.Patients taking flibanserin (see PRECAUTIONS - Drug Interactions ). Because of the trandolapril component, trandolapril and verapamil hydrochloride extended-release tablets are contraindicated in patients with a history of angioedema related to previous treatment with an angiotensin converting enzyme (ACE) inhibitor. Do not co-administer aliskiren with trandolapril and verapamil hydrochloride extended-release tablets in patients with diabetes (see PRECAUTIONS - Drug Interactions ). Trandolapril and verapamil hydrochloride extended-release tablets are contraindicated in combination with a neprilysin inhibitor (e.g., sacubitril). Do not administer trandolapril and verapamil hydrochloride extended-release tablets within 36 hours of switching to or from sacubitril/valsartan, a neprilysin inhibitor (see WARNINGS ).

Adverse Reactions

Trandolapril and verapamil hydrochloride extended-release tablets have been evaluated in over 1,957 subjects and patients. Of these, 541 patients, including 23% elderly patients, participated in U.S. controlled clinical trials, and 251 were studied in foreign controlled clinical trials. In clinical trials with trandolapril and verapamil hydrochloride extended-release tablets, no adverse experiences peculiar to this combination drug have been observed. Adverse experiences that have occurred have been limited to those that have been previously reported with verapamil or trandolapril. Trandolapril and verapamil hydrochloride extended-release tablets have been evaluated for long-term safety in 272 patients treated for 1 year or more. Adverse experiences were usually mild and transient. Discontinuation of therapy because of adverse events in U.S. placebo-controlled hypertension studies was required in 2.6% and 1.9% of patients treated with trandolapril and verapamil hydrochloride extended-release tablets and placebo, respectively. Adverse experiences occurring in 1% or more of the 541 patients in placebo-controlled hypertension trials who were treated with a range of trandolapril (0.5 to 8 mg) and verapamil (120 to 240 mg) combinations are shown below. ADVERSE EVENTS OCCURRING IN ≥ 1% OF TRANDOLAPRIL AND VERAPAMIL HYDROCHLORIDE EXTENDED-RELEASE TABLETS PATIENTS IN U.S. PLACEBO-CONTROLLED TRIALS Trandolapril and Verapamil Hydrochloride Extended-Release Tablets (N = 541) % Incidence (% Discontinuance) PLACEBO (N = 206) % Incidence (% Discontinuance) AV Block First Degree 3.9 (0.2) 0.5 (0) Bradycardia 1.8 (0) 0 (0) Bronchitis 1.5 (0) 0.5 (0) Chest Pain 2.2 (0) 1 (0) Constipation 3.3 (0) 1 (0) Cough 4.6 (0) 2.4 (0) Diarrhea 1.5 (0.2) 1 (0) Dizziness 3.1 (0) 1.9 (0.5) Dyspnea 1.3 (0.4) 0 (0) Edema 1.3 (0) 2.4 (0) Fatigue 2.8 (0.4) 2.4 (0) Headache(s)+ 8.9 (0) 9.7 (0.5) Increased Liver Enzymes* 2.8 (0.2) 1 (0) Nausea 1.5 (0.2) 0.5 (0) Pain Extremity(ies) 1.1 (0.2) 0.5 (0) Pain

Drug Interactions

In vitro metabolic studies indicate that verapamil is metabolized by cytochrome P450 including CYP3A4, CYP1A2, CYP2C8, CYP2C9 and CYP2C18. Verapamil has been shown to be an inhibitor of CYP3A4 enzymes and P-glycoprotein (P-gp). Clinically significant interactions have been reported with inhibitors of CYP3A4 (e.g. erythromycin, ritonavir) causing elevation of plasma levels of verapamil while inducers of CYP3A4 (e.g. rifampin) have caused a lowering of plasma levels of verapamil. Therefore, patients receiving inhibitors or inducers of the cytochrome P450 system should be monitored for drug interactions.

Overdosage

No specific information is available on the treatment of overdosage with trandolapril and verapamil hydrochloride extended-release tablets.

⚠ Caution

Medical Disclaimer: This information is for educational purposes only. Always consult a healthcare professional before taking any medication.