Fentanyl Citrate (Page 7 of 8)

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 characterized 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 No.	NDC No.	Strength	Each
806101	63323-806-0125 vials percarton	50 mcg in 1 mL(50 mcg per mL)(0.05 mg per mL)	63323-806-111 mL fill in a 2 mLsingle-dose vial
806102	63323-806-0225 vials percarton	100 mcg in 2 mL(50 mcg per mL)(0.05 mg per mL)	63323-806-122 mL single-dosevial
806105	63323-806-0525 vials percarton	250 mcg in 5 mL(50 mcg per mL)(0.05 mg per mL)	63323-806-135 mL single-dosevial

For Intravenous Use by Hospital Personnel Specifically Trained in the Use of Narcotic Analgesics:

Product No.	NDC No.	Strength	Each
806120	63323-806-2025 vials percarton	1,000 mcg in20 mL(50 mcg per mL)(0.05 mg per mL)	63323-806-1420 mL single-dose vial
806150	63323-806-501 vial perindividual carton	2,500 mcg in50 mL(50 mcg per mL)(0.05 mg per mL)	63323-806-5050 mL single-dose vial

PROTECT FROM LIGHT. Keep covered in carton until time of use. 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.

This container closure is not made from natural rubber latex.

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)].

Lake Zurich, IL 60047

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

451610C

PACKAGE LABEL – PRINCIPAL DISPLAY PANEL – Fentanyl Citrate 50 mcg per 1 mL Vial Label

NDC 63323-806-11

Fentanyl

Citrate Injection, USP CII

50 mcg per 1 mL

(50 mcg per mL) (0.05 mg per mL)

FOR INTRAVENOUS OR INTRAMUSCULAR USE

Preservative-free

1 mL Single-Dose Vial Rx only

PACKAGE LABEL – PRINCIPAL DISPLAY PANEL – Fentanyl Citrate 50 mcg per 1 mL Carton

NDC 63323-806-01

Fentanyl

Citrate Injection, USP CII

50 mcg per 1 mL

(50 mcg per mL) (0.05 mg per mL)*

FOR INTRAVENOUS OR INTRAMUSCULAR USE

Preservative-free

25 x 1 mL

Single-Dose Vials Rx only