FDA label 11a26ba7-6a68-45b7-a82f-3c5e98a4365d

5 WARNINGS AND PRECAUTIONS • Hemodynamic deterioration and ventricular fibrillation if administered to patients with wide complex tachycardia of ventricular origin. ( 5.1 ) • Second-or third-degree AV block. ( 5.2 ) • Heart failure. ( 5.3 ) • Hypotension. ( 5.4 ) 5.1 Hemodynamic Deterioration in Patients with Wide Complex Tachycardia Diltiazem may cause hemodynamic deterioration and ventricular fibrillation if administered to patients with wide complex tachycardia of ventricular origin. Distinguish wide complex QRS tachycardia of supraventricular origin from that of ventricular origin prior to diltiazem administration [see Contraindications ( 4 )]. 5.2 AV Block Diltiazem prolongs AV nodal conduction and refractoriness that may cause second- or third-degree AV block in sinus rhythm. Concomitant use of diltiazem with agents known to affect cardiac conduction may result in additive effects [see Drug Interactions ( 7 )] . If high-degree AV block occurs in sinus rhythm, discontinue diltiazem and institute appropriate supportive measures [see Overdosage ( 10 )]. 5.3 Heart Failure Diltiazem is a negative inotrope and can cause decreased systolic function and heart failure. Do not initiate in patients with acute decompensated heart failure or cardiogenic shock. If heart failure develops during diltiazem treatment, discontinue treatment and treat heart failure appropriately. 5.4 Hypotension Diltiazem can cause symptomatic hypotension. Patients with low blood pressure at baseline and those on concomitant medications that decrease blood pressure, intravascular volume, or myocardial contractility are at increased risk for hypotension.

6 ADVERSE REACTIONS The following adverse reaction rates are based on the use of diltiazem hydrochloride injection in over 400 domestic clinical trial patients with atrial fibrillation/flutter or PSVT under double-blind or open-label conditions. Hypotension was the most commonly reported adverse event during clinical trials, with symptomatic hypotension occurring in 3.2% of patients. Other events reported in a least 1% of the diltiazem-treated patients were injection site reactions (e.g., itching, burning) - 3.9%, vasodilation (flushing) - 1.7%, and arrhythmia (junctional rhythm or isorhythmic dissociation) - 1%. In addition, the following events were reported infrequently (less than 1%): Cardiovascular - Asystole, atrial flutter, AV block first degree, AV block second degree, bradycardia, chest pain, congestive heart failure, sinus pause, sinus node dysfunction, syncope, ventricular arrhythmia, ventricular fibrillation, ventricular tachycardia Dermatologic - Pruritus, sweating Gastrointestinal - Constipation, elevated SGOT or alkaline phosphatase, nausea, vomiting Nervous System - Dizziness, paresthesia Other - Amblyopia, asthenia, dry mouth, dyspnea, edema, headache, Although not observed in clinical trials with diltiazem hydrochloride injection, the following events associated with oral diltiazem may occur: Dermatologic - Erythema multiforme (including Stevens-Johnson syndrome, toxic epidermal necrolysis), exfoliative dermatitis, leukocytoclastic vasculitis, petechiae, photosensitivity, purpura, rash, urticaria Gastrointestinal - Anorexia, diarrhea, dysgeusia, dyspepsia, mild elevations of SGPT and LDH, weight increase Other - Allergic reactions, angioedema (including facial or periorbital edema), CPK elevation, gingival hyperplasia, hemolytic anemia, hyperglycemia, leukopenia, muscle cramps, myopathy, nasal congestion Most common adverse reactions are hypotension, itching and burning at injection site, vasodilation, and arrhythmia. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Exela Pharma Sciences, LLC at 1-888-451-4321, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.