Dilution Cardizem ® -diltiazem

DILTIAZEM (CARDIZEM ®)

The authors make no claims of the accuracy of the information contained herein; and these suggested doses and/or guidelines are not a substitute for clinical judgment. Neither GlobalRPh Inc. nor any other party involved in the preparation of this document shall be liable for any special, consequential, or exemplary damages resulting in whole or part from any user's use of or reliance upon this material. PLEASE READ THE DISCLAIMER CAREFULLY BEFORE ACCESSING OR USING THIS SITE. BY ACCESSING OR USING THIS SITE, YOU AGREE TO BE BOUND BY THE TERMS AND CONDITIONS SET FORTH IN THE DISCLAIMER.

Usual Diluents

D5W, NS

Standard Dilutions [Amount of drug] [Infusion volume] [Infusion rate]

---Final Concentration 1 mg/ml ---
Diltiazem hydrochloride Solution (5 mg/mL)
[125 mg (25 ml)/ 100 ml] [Titrate]
[Total volume = 125 ml]

-----------------------------------------

Diltiazem hydrochloride powder, for solution (100mg vials)
[100mg / 100 ml] [Titrate]
[Total volume = 100 ml]

The vials contain sterile diltiazem hydrochloride, USP, 100 mg and mannitol, USP, 75 mg base for reconstitution in the ADD-Vantage®Flexible Diluent Container containing 5% dextrose injection or 0.9% sodium chloride injection.

Note: if the ADD-Vantage®Flexible containers are not available use the following steps:

remove the breakaway vial cap and the vial port cover from the 100mg vial.
withdraw 5 to 10 ml from a 100mL bag of D5W or NS
Swirl the container to dissolve the diltiazem hcl powder [MAINTAINING STRICT ASEPTIC TECHIQUE IS CRITICAL].
Withdraw the contents and inject into the 100mL bag and use within 24 hours.

Stability / Miscellaneous

ASHP® Injectable Drug Information™. 2021 Edition. A Comprehensive Guide to Compatibility and Stability.
DOI: https://doi.org/10.37573/9781585286850

Diltiazem hydrochloride 1 g/L (1 mg/mL) in dextrose 5% and in sodium chloride 0.9% was evaluated for loss due to sorption to a variety of polymer container types compared to glass containers. No significant loss due to sorption was found at 21°C after 48 hours of contact time to PVC and polyethylene containers and 24 hours of contact time to polyamide containers.

Stability data:

Drug

Stability
Refrigerated

Stability
Room Temp.

Reconstituted
Vial/Powder

Notes

Diltiazem - Cardizem

Store under refrigeration 2° to 8°C (36° to 46°F).

Stable in the following parenteral solutions for at least 24 hours when stored in glass or polyvinylchloride (PVC) bags under refrigeration 2° to 8°C (36° to 46°F).
dextrose (5%) injection USP
sodium chloride (0.9%) injection USP
dextrose (5%) and sodium chloride (0.45%) injection USP

May be stored at room temperature for up to 1 month. Destroy after 1 month at room temperature.

Stable in the following parenteral solutions for at least 24 hours when stored in glass or polyvinylchloride (PVC) bags at controlled room temperature 15° to 30°C (59° to 86°F) dextrose (5%) injection USP
sodium chloride (0.9%) injection USP
dextrose (5%) and sodium chloride (0.45%) injection USP

Solution

Parental drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.

Do not freeze.

Diltiazem hydrochloride injection was found to be physically compatible and chemically stable in the following parenteral solutions for at least 24 hours when stored in glass or polyvinylchloride (PVC) bags at controlled room temperature 20 to 25°C (68 to 77°F) [see USP] or under refrigeration 2 to 8°C (36 to 46°F).

• dextrose (5%) injection USP
• sodium chloride (0.9%) injection USP
• dextrose (5%) and sodium chloride (0.45%) injection USP
Label: Refrigerate/ concentration= 1 mg/ ml.

DOSAGE AND ADMINISTRATION
Direct Intravenous Single Injections (Bolus)
The initial dose of Diltiazem Hydrochloride Injection 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 injection 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 weights should be dosed on a mg/kg basis. Some patients may respond to an initial dose of 0.15 mg/kg, although duration of action may be shorter. Experience with this dose is limited.

Continuous Intravenous Infusion
For continued reduction of the heart rate (up to 24 hours) in patients with atrial fibrillation or atrial flutter, an intravenous infusion of diltiazem hydrochloride may be administered. Immediately following bolus administration of 20 mg (0.25 mg/kg) or 25 mg (0.35 mg/kg) diltiazem hydrochloride injection and reduction of heart rate, begin an intravenous infusion of diltiazem hydrochloride. The recommended initial infusion rate of diltiazem hydrochloride is 10 mg/h. Some patients may maintain response to an initial rate of 5 mg/h. The infusion rate may be increased in 5 mg/h increments up to 15 mg/h as needed, if further reduction in heart rate is required. The infusion may be maintained for up to 24 hours.

Diltiazem shows dose-dependent, non-linear pharmacokinetics. Duration of infusion longer than 24 hours and infusion rates greater than 15 mg/h have not been studied. Therefore, infusion duration exceeding 24 hours and infusion rates exceeding 15 mg/h are not recommended.

Dilution: To prepare diltiazem hydrochloride injection for continuous intravenous infusion aseptically transfer the appropriate quantity (see chart) of diltiazem hydrochloride injection to the desired volume of either Normal Saline, D5W, or D5W/0.45% NaCl. Mix thoroughly. Use within 24 hours. Keep refrigerated until use.

Diluent Volume	Quantity of Diltiazem HCl Injection to Add	Final Concentration	Administration Dose*	Infusion Rate
100 mL	125 mg (25 mL) Final Volume 125 mL	1 mg/mL	10 mg/h 15 mg/h	10 mL/h 15 mL/h
250 mL	250 mg (50 mL) Final Volume 300 mL	0.83 mg/mL	10 mg/h 15 mg/h	12 mL/h 18 mL/h
500 mL	250 mg (50 mL)	0.45 mg/mL	10 mg/h	22 mL/h
500 mL	Final Volume 550 mL		15 mg/h	33 mL/h

*5 mg/h may be appropriate for some patients.

Compatibility:
Diltiazem hydrochloride injection was tested for compatibility with three commonly used intravenous fluids at a maximal concentration of 1 mg diltiazem hydrochloride per milliliter. Diltiazem hydrochloride injection was found to be physically compatible and chemically stable in the following parenteral solutions for at least 24 hours when stored in glass or polyvinylchloride (PVC) bags at controlled room temperature 20 to 25°C (68 to 77°F) [see USP] or under refrigeration 2 to 8°C (36 to 46°F).

• dextrose (5%) injection USP
• sodium chloride (0.9%) injection USP
• dextrose (5%) and sodium chloride (0.45%) injection USP

Physical Incompatibilities:
Because of potential physical incompatibilities, it is recommended that diltiazem hydrochloride not be mixed with any other drugs in the same container. If possible, it is recommended that diltiazem hydrochloride not be coinfused in the same intravenous line. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.

Diltiazem Hydrochloride. Physical incompatibilities (precipitate formation or cloudiness) were observed when diltiazem hydrochloride was infused in the same intravenous line with the following drugs: 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.

Transition to Further Antiarrhythmic Therapy:
Transition to other antiarrhythmic agents following administration of diltiazem hydrochloride injection is generally safe. However, reference should be made to the respective agent manufacturer’s package insert for information relative to dosage and administration.

In controlled clinical trials, therapy with antiarrhythmic agents to maintain reduced heart rate in atrial fibrillation or atrial flutter or for prophylaxis of PSVT was generally started within 3 hours after bolus administration of diltiazem. These antiarrhythmic agents were intravenous or oral digoxin, Class 1 antiarrhythmics (e.g., quinidine, procainamide), calcium channel blockers, and oral beta-blockers.

Experience in the use of antiarrhythmic agents following maintenance infusion of diltiazem hydrochloride injection is limited. Patients should be dosed on an individual basis and reference should be made to the respective manufacturer's package insert for information relative to dosage and administration.

HOW SUPPLIED
Diltiazem Hydrochloride Injection is supplied in single-dose containers as follows:
10 Fliptop Vials/Carton - 10 mL
10 Fliptop Vials/Carton - 5 mL
---------------------
Fliptop Vials - 25 mL
---------------------
Powder:
NDC No. Container Size
0409–4350–03 [10 ADD-Vantage® Vials/Tray] 100 mg
---------------------

DISCARD UNUSED PORTION.

STORE PRODUCT UNDER REFRIGERATION 2 TO 8°C (36 TO 46°F). DO NOT FREEZE.

MAY BE STORED AT ROOM TEMPERATURE FOR UP TO 1 MONTH. DESTROY AFTER 1 MONTH AT ROOM TEMPERATURE.