DILTIAZEM HYDROCHLORIDE

DILTIAZEM HYDROCHLORIDE- diltiazem hydrochloride injection, solution
Exela Pharma Sciences,LLC

1 INDICATIONS AND USAGE

1.1 Atrial Fibrillation or Atrial Flutter

Diltiazem Hydrochloride in Dextrose Injection is indicated for the temporary control of rapid ventricular rate in atrial fibrillation or atrial flutter.

1.2 Paroxysmal Supraventricular Tachycardia

Diltiazem Hydrochloride in Dextrose Injection is indicated for rapid conversion of paroxysmal supraventricular tachycardias (PSVT) to sinus rhythm.

2 DOSAGE AND ADMINISTRATION

2.1 General Considerations

Administer intravenous diltiazem in a setting with continuous monitoring of the ECG and frequent measurement of blood pressure. A defibrillator and emergency equipment should be readily available.

2.2 Intravenous Single Injections (Bolus)

Withdraw the bolus volume from the diltiazem hydrochloride infusion bag and administer it over 2 minutes. The initial dose of diltiazem hydrochloride should be 0.25 mg/kg actual body weight as a bolus administered over 2 minutes (20 mg is a reasonable dose for the average patient). If response is inadequate, a second dose may be administered after 15 minutes. The second bolus dose of diltiazem hydrochloride should be 0.35 mg/kg actual body weight administered over 2 minutes (25 mg is a reasonable dose for the average patient). Subsequent intravenous bolus doses should be individualized for each patient. Patients with low body weight should be dosed on a mg/kg basis.

2.3 Continuous Intravenous Infusion

Immediately following bolus, the recommended initial infusion rate of diltiazem hydrochloride is 5 mg/hour. Adjust the infusion rate in 5 mg/hour increments up to a maximum of 15 mg/hour as needed to achieve satisfactory rate control. Infusions longer than 24 hours have not been studied. Patients should generally be transitioned to other antiarrhythmic agents within 24 hours [see Clinical Studies (14)].

2.4 Physical Incompatibilities

Do not mix diltiazem hydrochloride with any other drugs in the same container. If possible, use a dedicated line for diltiazem hydrochloride.

Diltiazem Hydrochloride has demonstrated physical incompatibilities with acetazolamide, acyclovir, aminophylline, ampicillin, ampicillin sodium/sulbactam sodium, cefamandole, cefoperazone, diazepam, furosemide, hydrocortisone sodium succinate, insulin (regular: 100 units/mL), methylprednisolone sodium succinate, mezlocillin, nafcillin, phenytoin, rifampin, and sodium bicarbonate.

3 DOSAGE FORMS AND STRENGTHS

Injection: Clear, colorless solution in a single-dose bag for intravenous use.

125 mg/125 mL (1 mg/mL)

250 mg /250 mL (1 mg/mL)

4 CONTRAINDICATIONS

Diltiazem Hydrochloride Injection is contraindicated in:

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Patients with sick sinus syndrome except in the presence of a functioning ventricular pacemaker.

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Patients with second- or third-degree AV block except in the presence of a functioning ventricular pacemaker.

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Patients with severe hypotension or cardiogenic shock.

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Patients who have demonstrated hypersensitivity to the drug.

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Intravenous diltiazem and intravenous beta-blockers should not be administered together or in close proximity (within a few hours).

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Patients with atrial fibrillation or atrial flutter associated with an accessory bypass tract such as in WPW syndrome or short PR syndrome.
As with other agents which slow AV nodal conduction and do not prolong the refractoriness of the accessory pathway (e.g., verapamil, digoxin), in rare instances patients in atrial fibrillation or atrial flutter associated with an accessory bypass tract may experience a potentially life-threatening increase in heart rate accompanied by hypotension when treated with diltiazem hydrochloride injection. As such, the initial use of diltiazem hydrochloride injection should be, if possible, in a setting where monitoring and resuscitation capabilities, including DC cardioversion/defibrillation, are present [see Overdosage (10)]. Once familiarity of the patient’s response is established, use in an office setting may be acceptable.

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Patients with ventricular tachycardia. Administration of other calcium channel blockers to patients with wide complex tachycardia (QRS ≥ 0.12 seconds) has resulted in hemodynamic deterioration and ventricular fibrillation. It is important that an accurate pretreatment diagnosis distinguish wide complex QRS tachycardia of supraventricular origin from that of ventricular origin prior to administration of diltiazem hydrochloride injection.

5 WARNINGS AND PRECAUTIONS

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