AHFS Class:

8:12.16.12 Penicillinase-resistant Penicillins

Generic Name

• Nafcillin Sodium

Nafcillin sodium is available as a powder in vials containing the equivalent of 1 or 2 g of nafcillin and a 10-g pharmacy bulk package.²⁸⁰¹; ²⁸⁰⁸ The formulation contains sodium citrate 40 mg per gram of nafcillin as buffer.²⁸⁰¹ Reconstitute the 1-g vial with 3.4 mL and the 2-g vial with 6.6 mL of sterile water for injection, sodium chloride 0.9%, or bacteriostatic water for injection containing parabens or benzyl alcohol to yield a solution containing nafcillin 250 mg/mL.²⁸⁰¹ The final volumes of the 1- and 2-g vials are 4 and 8 mL, respectively.²⁸⁰¹

The 10-g pharmacy bulk package should be reconstituted with 93 mL of sterile water for injection or sodium chloride 0.9% to yield a 100-mg/mL solution.²⁸⁰⁸

Nafcillin sodium is also available as a frozen premixed infusion solution in single-dose Galaxy plastic containers containing the equivalent of 1 or 2 g of nafcillin in 50- or 100-mL, respectively, with dextrose to adjust osmolality and hydrochloric acid and/or sodium hydroxide to adjust the pH.²⁸⁰⁹ The premixed solution also contains sodium citrate approximately 90 mg for each gram of nafcillin as buffer.²⁸⁰⁹

pH

The pH of the reconstituted solution and frozen premixed solution is 6 to 8.5.²⁸⁰¹; ²⁸⁰⁹

Osmolality

The osmolality of nafcillin sodium 250 mg/mL in sterile water for injection was 709 mOsm/kg by freezing-point depression and 665 mOsm/kg by vapor pressure.¹⁰⁷¹

The frozen premixed solution is iso-osmotic.²⁸⁰⁹

The osmolality of nafcillin sodium (Wyeth) 40 mg/mL was determined to be 403 mOsm/kg in dextrose 5% and 402 mOsm/kg in sodium chloride 0.9%.¹³⁷⁵

The osmolality of nafcillin sodium was calculated for the following dilutions¹⁰⁵⁴:

The following maximum nafcillin sodium concentrations were recommended to achieve osmolalities suitable for peripheral infusion in fluid-restricted patients¹¹⁸⁰:

Sodium Content

Each gram of nafcillin sodium with sodium citrate buffer contains 66 mg (2.9 mEq) of sodium.²⁷; ²⁸⁰¹

The frozen premixed solution contains 76.6 mg (3.33 mEq) of sodium per gram of nafcillin.^2809(2809)

Nafcillin sodium is administered by intramuscular (deep intragluteal) injection, direct intravenous injection, or intermittent intravenous infusion.²⁸⁰¹ For direct intravenous injection, the reconstituted solution should be diluted with 15 to 30 mL of sterile water for injection or sodium chloride injection and administered over 5 to 10 minutes.²⁸⁰¹ For intermittent intravenous infusion, the dose should be diluted in a compatible infusion solution and administered over 30 to 60 minutes.²⁸⁰¹

Premixed infusion solutions and diluted solutions prepared from pharmacy bulk packages are intended for intravenous infusion only.²⁸⁰⁸; ²⁸⁰⁹ The intravenous infusion should be administered over 30 to 60 minutes.²⁸⁰⁸; ²⁸⁰⁹

Nafcillin sodium is a white to yellowish-white powder.²⁸⁰¹; ²⁸⁰⁸ Intact vials and pharmacy bulk packages should be stored at controlled room temperature.²⁸⁰¹; ²⁸⁰⁸

Solutions reconstituted with sterile water for injection or sodium chloride 0.9% are stated to be stable for 24 hours at room temperature (25°C) or 7 days under refrigeration (5°C) at concentrations of 10 to 200 mg/mL, or 90 days frozen at -15°C at a concentration of 250 mg/mL.²⁸⁰¹ Reconstituted solutions prepared from pharmacy bulk packages should be further diluted for infusion within 4 hours after initial entry into the vial.²⁸⁰⁸ Unused portions of pharmacy bulk packages should be discarded after 4 hours of initial entry.²⁸⁰⁸

Solutions further diluted for infusion are stated to be stable for 24 hours at room temperature or 7 days under refrigeration for the following diluents and concentrations: Sterile water for injection or sodium chloride 0.9% at 10 to 200 mg/mL; dextrose 5% or dextrose 5% in sodium chloride 0.45% at 2 to 30 mg/mL; sodium lactate M at 30 mg/mL; and Ringer's injection, lactated at 10 to 30 mg/mL.²⁸⁰¹; ²⁸⁰⁸

Commercially-available frozen premixed solutions in single-dose Galaxy containers should be stored at -20°C and thawed at room temperature (25°C) or under refrigeration (5°C).²⁸⁰⁹ Do not force thaw by immersion in water baths or microwaving.²⁸⁰⁹ Thawed solutions are stable for 72 hours at room temperature or 21 days under refrigeration.²⁸⁰⁹ Thawed solutions should not be refrozen.²⁸⁰⁹ The manufacturer states that precipitation may occur in the frozen solution which will dissolve with little or no agitation upon reaching room temperature.²⁸⁰⁹ The container should be agitated upon reaching room temperature.²⁸⁰⁹ Discard the solution if it is cloudy or precipitate is present.²⁸⁰⁹

pH Effects

The stability of nafcillin sodium is pH dependent, with a maximum stability at pH 6 and a preferred range of pH 5 to 8. Drug decomposition is increased as pH values vary from this range. Additives that may result in a final pH of above 8 or below 5 should not be mixed with nafcillin sodium.²⁷

Freezing Solutions

Reconstituted solutions at a concentration of 250 mg/mL in sterile water for injection or sodium chloride 0.9% are stated to be stable for 90 days frozen at -15°C.²⁸⁰¹; ²⁸⁰⁸ Solutions at concentrations of 10 to 250 mg/mL in dextrose 5%; dextrose 5% in sodium chloride 0.45%; sodium lactate M; and Ringer's injection, lactated are stated to be stable for 90 days frozen at -15°C.²⁸⁰¹; ²⁸⁰⁸

In one study, however, when nafcillin sodium (Wyeth) 1 g/4 mL was frozen at -20°C in glass syringes (Hy-Pod), the drug was stable for nine months.⁵³²

In another study, nafcillin sodium (Wyeth) 1 g/50 mL of dextrose 5% in PVC bags frozen at -20°C for 30 days and then thawed by exposure to ambient temperature or microwave radiation showed no evidence of precipitation or color change but had a 2 to 3% loss. Subsequent storage of the admixture at room temperature for 24 hours also yielded physically compatible solutions with no additional loss of activity.⁵⁵⁵

Syringes

Nafcillin sodium (Apothecon) 10 mg/mL in sodium chloride 0.9% was packaged in 10-mL polypropylene syringes (Becton Dickinson) and stored at 5 and 25°C. The solutions remained clear under refrigeration for 44 days and at room temperature for seven days. A yellow color developed after 14 days at room temperature. About 2% loss of nafcillin sodium occurred after seven days and 18% loss in 14 days at 25°C. Under refrigeration, 1% loss occurred after 44 days. Stability in glass containers was comparable.²³²⁵

Ambulatory Pumps

Nafcillin sodium (Marsam) 20 mg/mL in sterile water for injection in PVC portable pump reservoirs (Pharmacia Deltec) exhibited no loss in three days stored at 25°C and in 14 days at 5°C. However, at a concentration of 120 mg/mL, 6% loss was found in three days at 25°C, and 2% loss occurred in 14 days at 5°C.²⁰⁸⁰

Nafcillin sodium 40 and 50 mg/mL in sodium chloride 0.9% precipitated in as little as one day at the simulated ambulatory use temperature of 35°C. At 20 mg/mL, precipitation appeared in three days. When stored at room temperature, no precipitation appeared at any concentration in three days.²⁶⁶⁴

Solution Compatibility

Additive Compatibility

Drugs in Syringe Compatibility

Y-Site Injection Compatibility (1:1 Mixture)

Additional Compatibility Information

Peritoneal Dialysis Solutions

The activity of nafcillin 100 mg/L was evaluated in peritoneal dialysis fluids containing dextrose 1.5 or 4.25% (Dianeal 137, Travenol). Storage at 25°C resulted in no loss of antimicrobial activity in 24 hours.⁵¹⁵

The stability of nafcillin sodium (Wyeth) 100 mg/L in peritoneal dialysis solutions (Dianeal 137 and PD2) with heparin sodium 500 units/L was evaluated. About 98% activity remained after 24 hours at 25°C.¹²²⁸

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

ASHP^® Injectable Drug Information^TM. Selected Revisions December 5, 2024. © Copyright, 2024. American Society of Health-System Pharmacists^®, 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.