Fentanyl Citrate (Page 7 of 7)

12.3 Pharmacokinetics

Fentanyl Citrate Injection is administered by the intravenous or intramuscular route. The pharmacokinetics of fentanyl can be described as a three-compartment model.

Distribution

Fentanyl plasma protein binding capacity increases with increasing ionization of the drug. Alterations in pH may affect its distribution between plasma and the central nervous system. It accumulates in skeletal muscle and fat and is released slowly into the blood. The volume of distribution for fentanyl is 4 L/kg. It has a distribution time of 1.7 minutes and redistribution time of 13 minutes.

Elimination

The terminal elimination half-life is 219 minutes.

Fentanyl, which is primarily transformed in the liver, demonstrates a high first pass clearance and releases approximately 75% of an intravenous dose in urine, mostly as metabolites with less than 10% representing the unchanged drug. Approximately 9% of the dose is recovered in the feces, primarily as metabolites.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

Long-term studies in animals to evaluate the carcinogenic potential of fentanyl citrate have not been conducted.

Mutagenesis

No formal studies to assess the mutagenic potential of fentanyl citrate have been conducted.

Impairment of Fertility

Decreased pregnancy rates occurred in a multigenerational study in which pregnant rats were treated subcutaneously during the first 21 days of pregnancy with 160 mcg/kg to 1250 mcg/kg fentanyl (0.26 times to 2.0 times a human dose of 100 mcg/kg based on body surface area).

Studies in animals to characterize the effect of fentanyl on male fertility have not been conducted.

16 HOW SUPPLIED/STORAGE AND HANDLING

Fentanyl Citrate Injection is supplied as a sterile, clear, and colorless solution.

Fentanyl Citrate Injection, equivalent to 50 mcg (0.05 mg) fentanyl base per mL, is a preservative-free solution, supplied as follows:

Product Code	Unit of Sale	Strength	Each
806711	NDC 63323-808-11Unit of 10 (Microvault®)	50 mcg/mL	NDC 63323-808-011 mL Single-Dose Prefilled Syringe
806722	NDC 63323-810-20Unit of 20	100 mcg/2 mL(50 mcg/mL)	NDC 63323-810-002 mL Single-Dose Prefilled Syringe

PROTECT FROM LIGHT. Store at 20° to 25°C (68° to 77°F), excursions permitted to 15° to 30°C (59° to 86°F) [See USP Controlled Room Temperature]. Contains no preservative. DISCARD ANY UNUSED CONTENTS.

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

To report SUSPECTED ADVERSE REACTIONS, contact Fresenius Kabi USA, LLC at 1-800-551-7176, or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

17 PATIENT COUNSELING INFORMATION

Serotonin Syndrome

Inform patients that Fentanyl Citrate Injection could cause a rare but potentially life-threatening condition resulting from concomitant administration of serotonergic drugs. Instruct patients to inform their healthcare provider if they are taking, or plan to take serotonergic medications [see Warnings and Precautions (5.7), Drug Interactions (7)].

Constipation

Advise patients of the potential for severe constipation, [see Clinical Pharmacology (12.2)].

INSTRUCTIONS FOR USE — Microvault^®

Figure 1: Outer Packaging (MicroVault^™ ) and Prefilled Syringe

NOTES:

–

Do not introduce any other fluid into the syringe at any time.

–

Do not dilute for IV push.

–

Do not re-sterilize the syringe.

–

Do not use this product on a sterile field.

–

This product is for single dose only.

1. Once removed from the bundle, inspect the outer packaging by verifying:

   –

   Integrity of the tube and the cap.

   –

   Tamper evident seal is intact (outer shrink wrap is not broken).Do not use if the outer packaging has been damaged.

2. Hold the outer packaging with both hands. To break the tamper evident seal, hold the tube and the cap close to the seal, and twist until broken. (See Figure 2)

   Figure 2

   

3. Remove the cap of the outer packaging by pulling it straight away from the tube to avoid dislodging the plunger rod of the syringe. (See Figure 3)

   Figure 3

   

4. Remove the syringe from the tube.
5. Visually inspect the syringe. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
6. Twist off the syringe tip cap. Do not remove the plastic wrap label around the luer lock collar. (See Figure 4)

   Figure 4

   

7. Expel air bubble(s). Adjust the dose (if applicable).
8. Administer the dose ensuring that pressure is maintained on the plunger rod during the entire administration.
9. Discard the used syringe into an appropriate receptacle.

For more information concerning this drug, please call Fresenius Kabi USA, LLC at 1-800-551-7176.

To report SUSPECTED ADVERSE REACTIONS, contact Fresenius Kabi USA, LLC at 1-800-551-7176 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

INSTRUCTIONS FOR USE – Blister Pack

Figure 1: Outer Packaging and Prefilled Syringe

NOTES:

–

Do not introduce any other fluid into the syringe at any time.

–

Do not dilute for IV push.

–

Do not re-sterilize the syringe.

–

Do not use this product on a sterile field.

–

This product is for single dose only.

1. Inspect the outer packaging (blister pack) to confirm the integrity of the packaging. Do not use if the blister pack or the prefilled syringe has been damaged.
2. Remove the syringe from the outer packaging. (See Figure 2)

   Figure 2

   

3. Visually inspect the syringe. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
4. Twist off the syringe tip cap. Do not remove the label around the luer lock collar. (See Figure 3)

   Figure 3

   

5. Expel air bubble(s). Adjust the dose (if applicable).
6. Administer the dose ensuring that pressure is maintained on the plunger rod during the entire administration.
7. Discard the used syringe into an appropriate receptacle.

For more information concerning this drug, please call Fresenius Kabi USA, LLC at 1-800-551-7176.

To report SUSPECTED ADVERSE REACTIONS, contact Fresenius Kabi USA, LLC at 1-800-551-7176 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

US Patents 9,731,082 and 10,064,998

The brand names mentioned in this document are the trademarks of their respective owners.

Lake Zurich, IL 60047

For Product Inquiry:
1-800-551-7176 or
www.fresenius-kabi.com/us

451657A

PACKAGE LABEL — PRINCIPAL DISPLAY – Fentanyl 1 mL Syringe Label

1 mL Single-Dose. For IV or IM use.

Rx only

Fresenius Kabi
Fentanyl CII

Citrate Injection, USP 50 mcg/ mL

PACKAGE LABEL — PRINCIPAL DISPLAY – Fentanyl 1 mL Tip Cap Label

Fentanyl CII

Citrate Inj., USP 50 mcg/mL

For intravenous or intramuscular use.

PACKAGE LABEL — PRINCIPAL DISPLAY – Fentanyl 1 mL Carton Panel

Rx only NDC 63323-808-11
Fentanyl CII

Citrate Injection, USP
50 mcg/mL
For Intravenous or Intramuscular Use. Preservative-free

Do NOT place syringe on a Sterile Field.

10 x 1 mL Single-Dose Prefilled Syringes

Discard unused portion.

PACKAGE LABEL – PRINCIPAL DISPLAY – Fentanyl 2 mL Syringe Label

2 mL Single-Dose. For IV or IM use. Rx only

Fresenius Kabi

Fentanyl Citrate Inj., USP CII

100 mcg/2 mL (50 mcg/mL)

PACKAGE LABEL – PRINCIPAL DISPLAY – Fentanyl 2 mL Blister Label

Rx only NDC 63323-810-00

Fentanyl Citrate Injection, USP CII

100 mcg/2 mL (50 mcg/mL)

For Intravenous or Intramuscular Use.

PACKAGE LABEL – PRINCIPAL DISPLAY – Fentanyl 2 mL Carton Panel

Rx Only NDC 63323-810-20

Fentanyl CII

Citrate Injection, USP

100 mcg/2 mL (50 mcg/mL)

For Intravenous or Intramuscular Use.

Preservative-free

Do NOT place syringe on a Sterile Field.

20 x 2 mL Single-Dose Prefilled Syringes

Discard unused portion.

FENTANYL CITRATE fentanyl citrate injection, solution

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:63323-808 Route of Administration INTRAVENOUS, INTRAMUSCULAR DEA Schedule CII

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Fentanyl Citrate (Fentanyl) Fentanyl 50 ug in 1 mL

Inactive Ingredients Ingredient Name Strength Hydrochloric Acid Sodium Hydroxide Water

Packaging # Item Code Package Description Multilevel Packaging 1 NDC:63323-808-11 10 SYRINGE in 1 CARTON contains a SYRINGE (63323-808-01) 1 NDC:63323-808-01 1 mL in 1 SYRINGE This package is contained within the CARTON (63323-808-11)

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA212086 09/30/2020

FENTANYL CITRATE fentanyl citrate injection, solution

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:63323-810 Route of Administration INTRAVENOUS, INTRAMUSCULAR DEA Schedule CII

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Fentanyl Citrate (Fentanyl) Fentanyl 100 ug in 2 mL

Inactive Ingredients Ingredient Name Strength Hydrochloric Acid Sodium Hydroxide Water

Packaging # Item Code Package Description Multilevel Packaging 1 NDC:63323-810-20 20 SYRINGE in 1 CARTON contains a SYRINGE (63323-810-00) 1 NDC:63323-810-00 2 mL in 1 SYRINGE This package is contained within the CARTON (63323-810-20)

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA212086 01/15/2021

Labeler — Fresenius Kabi USA, LLC (608775388)

Establishment
Name	Address	ID/FEI	Operations
Fresenius Kabi USA, LLC		964475045	MANUFACTURE (63323-808), ANALYSIS (63323-808), MANUFACTURE (63323-810), ANALYSIS (63323-810)

Revised: 02/2023 Fresenius Kabi USA, LLC