AHFS Class:

28:08.08 Opioid Agonists

Generic Name

• FentaNYL Citrate

Fentanyl citrate is available in 2-, 5-, 10-, and 20-mL ampuls and vials, 1- and 2-mL prefilled syringes, 2-mL cartridges, and 50-mL vials.³⁶⁸⁶; ³⁶⁸⁷; ³⁶⁸⁸; ³⁶⁸⁹; ³⁶⁹⁰ Each mL contains fentanyl (as the citrate) 50 mcg (0.05 mg) with hydrochloric acid and/or sodium hydroxide for pH adjustment in water for injection.³⁶⁸⁶; ³⁶⁸⁷; ³⁶⁸⁸

pH

The pH of the injection ranges from 4 to 7.5.³⁶⁸⁶; ³⁶⁸⁷; ³⁶⁸⁸

Osmolality

The product osmolality was determined to be essentially 0 mOsm/kg.¹²³³

Trade Name(s)

Sublimaze

Fentanyl citrate is administered intramuscularly or intravenously.³⁶⁸⁶; ³⁶⁸⁷; ³⁶⁸⁸

Intact containers should be stored at controlled room temperature and protected from light.³⁶⁸⁶; ³⁶⁸⁷; ³⁶⁸⁸ Some manufacturers state that the drug should be kept in the carton until time of use.³⁶⁸⁷; ³⁶⁸⁸

pH Effects

Fentanyl citrate is most stable at pH 3.5 to 7.5.¹⁶³⁸

Syringes

In 2015, reports of decreased potency of certain drugs (e.g., fentanyl citrate) stored in Becton Dickinson syringes for extended periods (i.e., exceeding 24 hours) were confirmed by the manufacturer of these syringes; the cause of this change was later identified to be the inclusion of an alternate rubber stopper in the plunger of certain product lots of syringes.³⁰²⁹; ³⁰³⁶; ³⁰³⁷; ³⁰³⁹; ³⁰⁴¹; ³⁰⁴² Decreased potency was not observed when the syringes were filled and used promptly.³⁰³⁷ Use of the alternate stopper was later discontinued and use of the primary stopper in such syringes was resumed; however, Becton Dickinson states that its general-use syringes are cleared by FDA for immediate use in fluid aspiration and injection and that such syringes, regardless of the stopper material, have not been cleared by FDA for use as a closed-container system.³³⁹¹

Fentanyl citrate undiluted at a fentanyl concentration of 50 mcg/mL was tested for stability in polypropylene syringes. The fentanyl citrate injection was filled into polypropylene syringes that were then capped off. The samples were stored for 28 days under refrigeration at 5°C and at room temperature of 22°C exposed to light. No change in color or clarity occurred. No loss of fentanyl at either set of storage conditions occurred.²⁶⁴⁸

Fentanyl citrate (Hospira or Baxter, unspecified) undiluted at a fentanyl concentration of 50 mcg/mL and diluted to a fentanyl concentration of 10 mcg/mL in dextrose 5% or sodium chloride 0.9% was packaged as 5 mL in 10-mL polypropylene syringes (Becton Dickinson) and stored at ambient room temperature protected from light.³⁸⁸⁷ The solutions remained clear and colorless with 1.7% loss of drug in the undiluted solution and no loss in the 10-mcg/mL solutions in 100 days.³⁸⁸⁷

Fentanyl citrate (Elkins Sinn) prepared at a fentanyl concentration of 0.0167 mg/mL in sodium chloride 0.9% packaged in polypropylene syringes (Sherwood) was physically stable and exhibited little or no loss in 24 hours stored at 4 or 23°C in the dark.²¹⁹⁹

Fentanyl citrate (David Bull) prepared at a fentanyl concentration of 12.5 mcg/mL in sodium chloride 0.9% was packaged as 8 mL in 10-mL polypropylene syringes (Terumo) with attached needles. Fentanyl citrate (David Bull) prepared at a fentanyl concentration of 33.3 mcg/mL in sodium chloride 0.9% was packaged as 18 mL in 20-mL polypropylene syringes (Terumo) with attached needles. The syringes were stored at 5, 22, and 38°C for 7 days. The solutions were visually unchanged with no loss of drug at 5 and 22°C. At 38°C, the 12.5-mcg/mL solution had under 7% loss and the 33.3-mcg/mL solution had no loss.²²⁰²

Fentanyl citrate (Janssen) prepared at a fentanyl concentration of 35 mcg/mL in sodium chloride 0.9% was packaged in 2 types of polypropylene syringes. The Omnifix (B. Braun) syringes had polyisoprene piston tips while the Terumo syringes had no natural or synthetic rubber in the product. Stored at 4, 21, and 35°C for 30 days, the test solutions exhibited no visible or pH changes. Although the pH remained within the stability range for the drug, this does not demonstrate stability.²³⁸⁷

Fentanyl citrate (Hospira) was prepared at a fentanyl concentration of 5 mcg/mL in sodium chloride 0.9% and packaged as 1.1 mL in 12-mL polypropylene syringes (Terumo).²⁷⁹¹ The syringes were stored for 90 days at a controlled temperature of 23 to 27°C and relative humidity of 55 to 65% while being protected from light.²⁷⁹¹ Neither changes in color or clarity nor appreciable changes in pH from baseline values occurred.²⁷⁹¹ Samples exhibited a loss of less than 1% at 90 days.²⁷⁹¹

Fentanyl citrate (Janssen) was prepared at a fentanyl concentration of 9.6 mcg/mL in dextrose 5% and packaged as 50 mL in 50-mL syringes.³⁶⁰⁷; ³⁶⁰⁸ The syringes were stored for 7 days at a temperature of 25 to 28°C and relative humidity of 70 to 80%.³⁶⁰⁷ While visual observations revealed physical compatibility throughout the study period, substantial pH changes were noted after 72 hours.³⁶⁰⁷ Fentanyl concentrations were not measured using a stability indicating assay.³⁶⁰⁷; ³⁶⁰⁸

Ambulatory Pumps

Fentanyl citrate (Merck) prepared at fentanyl concentrations of 50 and 30 mcg/mL in sodium chloride 0.9% was evaluated in CADD-1 and CADD-PRIZM medication cassettes. About 4% drug loss occurred in 14 days at room and refrigeration temperatures.²⁷¹⁷

Sorption

Fentanyl citrate prepared at a fentanyl concentration of 2 mcg/mL in various buffer solutions ranging from pH 5.5 to pH 6.7 packaged in polyvinyl chloride (PVC) containers (Baxter) was shown to undergo slow sorption to the PVC in amounts dependent on the pH of the solution. The lower pH solutions exhibited less loss with increasing loss as the pH increased. At the highest pH tested of 6.7, 17% fentanyl loss occurred in 1 day. Refrigeration decreased the extent of loss but did not eliminate it. See Table 1. Little or no fentanyl loss was found in identical fentanyl citrate 2-mcg/mL solutions packaged in glass containers.²³⁰⁵

Fentanyl citrate undiluted at a fentanyl concentration of 50 mcg/mL was tested for stability in PVC bags. The fentanyl citrate injection was filled into PVC bags that were stored for 28 days under refrigeration at 5°C and at room temperature of 22°C exposed to light. No change in color or clarity occurred. No loss of fentanyl citrate at either set of storage conditions occurred.²⁶⁴⁸

Table 1. Percentage of Fentanyl 2 mcg/mL Remaining After Storage for 30 Days at 23°C in PVC Containers²³⁰⁵

Filtration

Fentanyl citrate (Janssen) prepared at a fentanyl concentration of 2.5 mcg/mL in dextrose 5% or sodium chloride 0.9% was delivered over 4 hours through 3 kinds of 0.2-µm membrane filters varying in size and composition. No fentanyl loss occurred due to sorption to the filter.¹³⁹⁹

Central Venous Catheter

Fentanyl citrate (Abbott) prepared at a fentanyl concentration of 10 mcg/mL in dextrose 5% was found to be compatible with the ARROWg+ard Blue Plus (Arrow International) chlorhexidine-bearing triple-lumen central catheter. Essentially complete delivery of the drug was found with little or no drug loss occurring. Furthermore, chlorhexidine delivered from the catheter remained at trace amounts with no substantial increase due to the delivery of the drug through the catheter.²³³⁵

Standardize 4 Safety

One or more standardized concentrations for this drug have been established through Standardize 4 Safety (S4S), a national patient safety initiative to reduce medication errors, especially during transitions of care. (See Standardize 4 Safety in Users Guide.) Recommendations developed to date through this initiative are available at www.ashp.org/pharmacy-practice/standardize-4-safety-initiative.

Table 2: Standardize 4 Safety Continuous IV Infusion Standard Concentrations for Fentanyl³⁶³⁵; ³⁶³⁶

^a These concentrations are for continuous infusions not delivered by a PCA device.^b Babies weighing under 500 grams may require a lower concentration.

Table 3: Standardize 4 Safety PCA Standard Concentrations for Fentanyl³⁹⁹⁰

Table 4: Standardize 4 Safety Epidural Standard Concentrations for Fentanyl as a Single Drug³⁹⁹⁰

Table 5: Standardize 4 Safety ADULT Epidural Combination Drug Standard Concentrations for Fentanyl³⁹⁹⁰

Table 6: Standardize 4 Safety PEDIATRIC (50 kg) Epidural Combination Drug Standard Concentrations for Fentanyl³⁹⁹⁰

Solution Compatibility

Additive Compatibility

Drugs in Syringe Compatibility

Y-Site Injection Compatibility (1:1 Mixture)

For a list of references cited in the text of this monograph, search the monograph titled References.

ASHP^® Injectable Drug Information^TM. Selected Revisions September 12, 2024. © Copyright, 2024. American Society of Health-System Pharmacists^®, 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.