section name header

Introduction

VA Class:AM112

AHFS Class:

Generic Name(s):

Chemical Name:

Nafcillin is a semisynthetic penicillinase-resistant penicillin antibiotic.1,2,4,5,8,47,59,70

Uses

Nafcillin shares the uses of other parenteral penicillinase-resistant penicillins (e.g., oxacillin) and generally is used only in the treatment of infections caused by, or suspected of being caused by, susceptible penicillinase-producing staphylococci.1,6,10,46,48,59,66,70,71 For specific information on the uses of nafcillin, see Uses in the Penicillinase-Resistant Penicillins General Statement 8:12.16.12.

Dosage and Administration

[Section Outline]

Reconstitution and Administration !!navigator!!

Nafcillin sodium is administered by IM injection or by IV injection or infusion.1,63 Although nafcillin also has been administered orally, the drug is poorly absorbed from the GI tract70 and an oral preparation of the drug is no longer commercially available in the US.

Reconstituted, diluted, and thawed solutions of nafcillin sodium should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.1,63

To reduce the risk of thrombophlebitis and other adverse local reactions associated with IV administration of nafcillin sodium, particularly in geriatric patients, the drug should be administered slowly and care should be taken to avoid extravasation.41,62,63 In addition, the IV route should be used for relatively short periods of time (e.g., 24-48 hours).1,63 For additional information, see Cautions: Local Reactions, in the Penicillinase-Resistant Penicillins General Statement 8:12.16.12.

IM Injection

For IM injection, nafcillin sodium powder for injection is reconstituted by adding 3.4 or 6.8 mL of sterile water for injection, bacteriostatic water for injection (with benzyl alcohol or parabens), or 0.9% sodium chloride injection to a vial labeled as containing 1 or 2 g of nafcillin, respectively, to provide solutions containing 250 mg/mL.1

IM injections of nafcillin sodium should be made deeply into a large muscle (e.g., gluteus maximus)1 and care should be taken to avoid sciatic nerve injury.59

Intermittent IV Injection

For direct intermittent IV injection, nafcillin sodium powder for injection should be reconstituted as for IM administration and, when dissolved, the appropriate dose of the drug should be further diluted with 15-30 mL of sterile water for injection or sodium chloride injection.1

The appropriate dose of diluted nafcillin sodium should then be injected slowly over 5-10 minutes into the tubing of a free-flowing compatible IV solution.1

Intermittent IV Infusion

For intermittent IV infusion, vials labeled as containing 1 or 2 g of nafcillin should be reconstituted as for IM injection and, when dissolved, should be further diluted with a compatible IV solution according to the manufacturer's directions.1 Alternatively, ADD-Vantage vials containing 1 or 2 of the drug may be reconstituted according to the manufacturer's directions.

Pharmacy bulk packages containing 10 g of nafcillin should be reconstituted with 93 mL of sterile water for injection or 0.9% sodium chloride injection to provide a solution containing 100 mg/mL.1 Pharmacy bulk packages of the drug are not intended for direct IV infusion; doses of the drug from the reconstituted pharmacy bulk package must be further diluted in a compatible IV infusion solution prior to administration.

Thawed solutions of the commercially available frozen nafcillin sodium injection are administered by intermittent IV infusion.63 Commercially available frozen nafcillin sodium injections should not be thawed by warming them in a water bath or by exposure to microwave radiation.63 A precipitate may form while the commercially available frozen injection in dextrose is frozen; however, this usually will dissolve with little or no agitation upon reaching room temperature, and the potency of the injection is not affected.63 After thawing at room temperature or under refrigeration, the container should be checked for minute leaks by firmly squeezing the bag.63 The injection should be discarded if the container seal is not intact or leaks are found or if the solution is cloudy or contains a precipitate.63 Additives should not be introduced into the injection.63 The injection should not be used in series connections with other plastic containers, since such use could result in air embolism from residual air being drawn from the primary container before administration of fluid from the secondary container is complete.63

Intermittent IV infusions of nafcillin sodium generally are infused over at least 30-60 minutes.63 (See Chemistry and Stability: Stability.)

Dosage !!navigator!!

Dosage of nafcillin sodium is expressed in terms of nafcillin.1,63 Dosage of the drug should be adjusted according to the type and severity of infection.1,59

Adult Dosage

The usual adult IM dosage of nafcillin for the treatment of infections caused by susceptible penicillinase-producing staphylococci is 500 mg every 4-6 hours; severe infections may require 1 g IM every 4 hours.1

The usual adult IV dosage of nafcillin for the treatment of infections caused by susceptible penicillinase-producing staphylococci is 500 mg every 4 hours; severe infections may require 1 g every 4 hours.1 When nafcillin is used for the treatment of acute or chronic osteomyelitis caused by susceptible penicillinase-producing staphylococci, many clinicians recommend that adults receive 1-2 g of the drug IV every 4 hours.44,50,51,52,54 If nafcillin is used for the treatment of staphylococcal infections related to intravascular catheters, some clinicians recommend that adults receive 2 g every 4 hours.74 Some clinicians recommend that adults receive IV dosages of at least 100-200 mg/kg daily given in equally divided doses every 4-6 hours for the treatment of meningitis.21

Staphylococcal Endocarditis

For the treatment of native valve endocarditis caused by staphylococci susceptible to penicillinase-resistant penicillins, the American Heart Association (AHA) recommends that adults receive nafcillin in a dosage of 2 g IV every 4 hours for 4-6 weeks.54 Although the benefits of concomitant aminoglycoside therapy have not been clearly established in these infections, the AHA states that gentamicin (1 mg/kg IM or IV every 8 hours) may be given concomitantly during the first 3-5 days of nafcillin therapy.54

For the treatment of staphylococcal endocarditis in the presence of prosthetic valves or other prosthetic material in patients with infections caused by isolates susceptible to penicillinase-resistant penicillins, the AHA states that adults should receive nafcillin in a dosage of 2 g IV every 4 hours for 6 weeks or longer in conjunction with rifampin (300 mg orally every 8 hours for 6 weeks or longer) and gentamicin (1 mg/kg IM or IV every 8 hours during the first 2 weeks of nafcillin therapy).54 However, because coagulase-negative staphylococci causing prosthetic valve endocarditis usually are resistant to penicillinase-resistant penicillins (especially when endocarditis develops within 1 year after surgery), coagulase-negative staphylococci involved in prosthetic valve endocarditis should be assumed to be resistant to penicillinase-resistant penicillins unless results of in vitro testing indicate that the isolates are susceptible to the drugs.54 (See Uses: Endocarditis in the Penicillinase-resistant Penicillins General Statement 8:12.16.12.)

Pediatric Dosage

Children weighing 40 kg or more may receive the usual adult dosage of nafcillin.1

The manufacturer recommends that pediatric patients weighing less than 40 kg receive IM nafcillin in a dosage of 25 mg/kg twice daily and that neonates receive an IM dosage of 10 mg/kg twice daily.1

The American Academy of Pediatrics (AAP) recommends that children 1 month of age or older receive IM or IV nafcillin in a dosage of 50-100 mg/kg daily in 4 equally divided doses for the treatment of mild to moderate infections or 100-150 mg/kg daily in 4 equally divided doses for the treatment of severe infections.67 Other clinicians recommend that children receive nafcillin in a dosage of 100-200 mg/kg daily given in 4-6 equally divided doses for severe infections.71,72

The AAP and other clinicians recommend that neonates younger than 1 week of age receive IM or IV nafcillin in a dosage of 25 mg/kg every 12 hours if they weigh 2 kg or less or 25 mg/kg every 8 hours if they weigh more than 2 kg.67,72 Neonates 1-4 weeks should receive 25 mg/kg every 8 hours if they weigh 2 kg or less (25 mg/kg every 12 hours for those less than 1.2 kg) or 25-35 mg/kg every 6 hours if they weigh more than 2 kg.67,72 The higher dosages are recommended for meningitis.67

Staphylococcal Endocarditis

For the treatment of native valve endocarditis caused by staphylococci susceptible to penicillinase-resistant penicillins, the AHA recommends that pediatric patients receive nafcillin in a dosage of 200 mg/kg daily given IV in divided doses every 4-6 hours for 6 weeks (maximum daily dosage 12 g).69 In addition, during the first 3-5 days of oxacillin therapy, gentamicin (3 mg/kg daily given IM or IV in divided doses every 8 hours; dosage adjusted to achieve peak serum gentamicin concentrations approximately 3 mcg/mL and trough concentrations less than 1 mcg/mL) may be given concomitantly if the causative organism is susceptible to the drug.69

For the treatment of staphylococcal endocarditis in the presence of prosthetic valves or other prosthetic material in patients with infections caused by isolates susceptible to penicillinase-resistant penicillins, the AHA recommends that pediatric patients receive nafcillin in a dosage of 200 mg/kg daily given IV in divided doses every 4-6 hours for 6 weeks or longer (maximum daily dosage 12 g) in conjunction with rifampin (20 mg/kg daily given orally in divided doses every 8 hours for 6 weeks or longer) and gentamicin (3 mg/kg daily given IM or IV in divided doses every 8 hours during the first 2 weeks of oxacillin therapy; dosage adjusted to achieve peak serum gentamicin concentrations approximately 3 mcg/mL and trough concentrations less than 1 mcg/mL).69

Duration of Therapy

The duration of nafcillin therapy depends on the type and severity of infection and should be determined by the clinical and bacteriologic response of the patient.46,49,59,71 In severe staphylococcal infections, therapy should be continued for at least 2 weeks;59 more prolonged therapy is necessary for the treatment of osteomyelitis, endocarditis, or other metastatic infections.46,52,53,55,56,59,71

When nafcillin is used in the treatment of acute or chronic osteomyelitis caused by susceptible penicillinase-producing staphylococci, the drug is generally given for 3-8 weeks;44,50,51,52,53,54,56,58,71 follow-up therapy with an oral penicillinase-resistant penicillin after nafcillin therapy generally is recommended for the treatment of chronic osteomyelitis.47,53,55,71

Dosage in Renal and Hepatic Impairment !!navigator!!

Modification of nafcillin dosage generally is unnecessary in patients with either renal impairment or hepatic impairment alone; however, modification of dosage may be necessary in patients with both severe renal impairment and hepatic impairment.18,27,33,57,60,63,70

Cautions

[Section Outline]

Adverse Effects !!navigator!!

Adverse effects reported with nafcillin are similar to those reported with other penicillinase-resistant penicillins. For information on adverse effects reported with penicillinase-resistant penicillins, see Cautions in the Penicillinase-Resistant Penicillins General Statement 8:12.16.12.

Precautions and Contraindications !!navigator!!

Nafcillin is contraindicated in patients who are hypersensitive to any penicillin.1,59

Nafcillin shares the toxic potentials of the penicillins, including the risk of hypersensitivity reactions, and the usual precautions of penicillin therapy should be observed. Prior to initiation of therapy with nafcillin, careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins, or other drugs. There is clinical and laboratory evidence of partial cross-allergenicity among penicillins and other β-lactam antibiotics including cephalosporins and cephamycins.1,34,35,43,45

Renal, hepatic, and hematologic systems should be evaluated periodically during prolonged therapy with nafcillin.46,59 Because adverse hematologic effects have occurred during therapy with penicillinase-resistant penicillins, white blood cell (CBC) count and differential should be performed prior to initiation of therapy and 1-3 times weekly during therapy.1,36,37,38,39,40,46,59 In addition, urinalysis should be performed and BUN, serum creatinine, AST (SGOT), and ALT (SGPT) concentrations should be determined prior to and periodically during therapy.1,46,59 If eosinophilia, suspected drug fever, rash, arthralgia, hematuria, or unexplained elevations of BUN or serum creatinine occur during penicillinase-resistant penicillin therapy, alternative anti-infective therapy should be considered.46

For a more complete discussion of these and other precautions associated with the use of nafcillin, see Cautions: Precautions and Contraindications, in the Penicillinase-Resistant Penicillins General Statement 8:12.16.12.

Pediatric Precautions !!navigator!!

If nafcillin is used in neonates, they should be monitored closely for clinical and laboratory evidence of toxic or adverse effects.1,59 In addition, serum concentrations of the drug should be determined frequently and appropriate reductions in dosage and frequency of administration made when indicated.1,59

Pregnancy, Fertility, and Lactation !!navigator!!

Pregnancy

Safe use of nafcillin during pregnancy has not been definitely established.1,59 Reproduction studies using nafcillin in rats and rabbits have not revealed evidence of impaired fertility or harm to the fetus. Clinical experience with use of penicillins during pregnancy in humans has not revealed evidence of adverse effects on the fetus.1,59 However, there are no adequate and controlled studies using penicillinase-resistant penicillins in pregnant women, and nafcillin should be used during pregnancy only when clearly needed.1,59

Lactation

Because penicillins are distributed into milk,1,19,20,59,70 nafcillin should be used with caution in nursing women.1,59

Other Information

[Section Outline]

Spectrum

Based on its spectrum of activity, nafcillin is classified as a penicillinase-resistant penicillin.4,5,8,59,70 For information on the classification of penicillins based on spectra of activity, see the Preface to the Penicillins General Statements 8:12.16.

Like other penicillinase-resistant penicillins, nafcillin is resistant to inactivation by most staphylococcal penicillinases and is active against many penicillinase-producing strains of Staphylococcus aureus and S. epidermidis that are resistant to other commercially available penicillins.8,10,59,70 For specific information on the spectrum of activity of nafcillin and resistance to the drug, see the sections on Spectrum and on Resistance in the Penicillinase-Resistant Penicillins General Statement 8:12.16.12.

Pharmacokinetics

In all studies described in the Pharmacokinetics section, nafcillin was administered as the sodium salt; dosages and concentrations of the drug are expressed in terms of nafcillin.

Absorption !!navigator!!

Nafcillin is poorly absorbed from the GI tract,70 and oral preparations of the drug are no longer commercially available in the US.

IM injection of a single 1-g dose of nafcillin results in peak serum concentrations of 7.6 mcg/mL at 30-60 minutes after the dose.1

Following IV injection over 5 minutes of a single 500-mg dose of nafcillin in healthy adults, serum concentrations of the drug average approximately 40, 10, 4.5, and 1.7 mcg/mL at 5 minutes, 30 minutes, 1 hour, and 2 hours, respectively, after the injection.22

In one study in children 1 month to 14 years of age who received nafcillin in a dosage of 150 mg/kg daily in divided doses every 6 hours, serum concentrations of the drug averaged 48.1, 23.6, 6.4, and 1.8 mcg/mL at 30 minutes, 1 hour, 2 hours, and 4 hours, respectively, after a dose.25

Distribution !!navigator!!

Nafcillin is distributed into synovial,10 pleural,10 pericardial,10 and ascitic fluids.10 The drug also is distributed into liver,30 bone,30 and bile.13,18,30,70 The volume of distribution of nafcillin reportedly ranges from 0.57-1.55 L/kg in adults,17,33 0.85-0.91 L/kg in children 1 month to 14 years of age,25 and 0.24-0.53 L/kg in neonates.24 In one study, the volume of distribution of nafcillin at steady state averaged 27.1 L in adults with normal renal and hepatic function, 19.9 L in adults with cirrhosis, and 15.9 L in adults with extrahepatic biliary obstruction.27

Concentrations of nafcillin in bile are generally equal to or greater than concurrent serum concentrations unless biliary obstruction is present.7,13,22,30

Like other penicillins, only low concentrations of nafcillin are attained in CSF; however, CSF concentrations of the drug are generally higher when meninges are inflamed than when meninges are uninflamed.10,13,21,23,28,42,70 In one study following IV administration of 1- or 2-g doses of nafcillin every 4 hours in adults with inflamed or uninflamed meninges, CSF concentrations of the drug ranged from 0.1-58 mcg/mL in specimens obtained approximately 1-2 hours after a dose.21 In one study in adults with uninflamed meninges who received a single 40-mg/kg dose of nafcillin IV over 30 minutes, CSF concentrations of the drug ranged from 0.02-0.09, 0.03-0.17, 0.06-0.12, and 0-0.07 mcg/mL in specimens obtained 1, 2, 3, and 4 hours, respectively, after the dose.29 In hydrocephalic children 3 weeks to 8.5 years of age with suspected ventriculoperitoneal shunt infections who received 50 mg/kg of nafcillin every 6 hours given by IV infusion over 30-40 minutes, peak concentrations of the drug in ventricular fluid were generally attained 2-2.5 hours after a dose and ranged from 0.2-10.3 mcg/mL.23

Only negligible concentrations of nafcillin are distributed into aqueous humor following parenteral administration.13,14 In patients with uninflamed eyes undergoing cataract surgery, IV administration of a single 2-g dose over 10 minutes resulted in serum and aqueous humor concentrations of the drug ranging from 70-120 mcg/mL and unmeasurable to 1.9 mcg/mL, respectively, 30-50 minutes after administration.14

Nafcillin is 70-90% bound to serum proteins.3,4,13,15,16

Nafcillin crosses the placenta.10,31,70 Nafcillin, like other penicillins, probably is distributed into milk.59

Elimination !!navigator!!

The serum half-life of nafcillin in adults with normal renal and hepatic function averages 0.5-1.5 hours.13,17,33 In one study in healthy adults, nafcillin had a distribution half-life (t½α) of 0.17 hours and an elimination half-life (t½β) of 1.02 hours.27

Approximately 60% of a dose of nafcillin is metabolized in the liver to inactive metabolites.10,27 Although small amounts of nafcillin are excreted in urine, the drug is eliminated mainly via bile10,13,26,27,33 and undergoes enterohepatic circulation.26 About 27-31% of a single IM or IV dose of nafcillin is excreted in urine as unchanged drug and active metabolites within 12 hours in adults with normal renal and hepatic function.12,33,70

Serum clearance of nafcillin is reportedly 410-583 mL/minute per 1.73 m2 in adults with normal renal and hepatic function.22,27

Serum concentrations of nafcillin may be higher and the serum half-life slightly prolonged in patients with impaired renal function.10,26,33 The serum half-life of the drug is reportedly 1.2-1.9 hours in patients with creatinine clearances of 3-59 mL/minute per 1.73 m210,13,22,26,33 and 1.8-2.8 hours in patients with creatinine clearances less than 3 mL/minute per 1.73 m2.33

In one study in patients with cirrhosis or extrahepatic biliary obstruction, the t½α of nafcillin averaged 0.26 or 0.29 hours, respectively, and the t½β averaged 1.2 and 1.7 hours, respectively.27 Serum clearance of the drug in these patients was lower than in patients with normal renal and hepatic function and averaged 291.5 mL/minute in those with cirrhosis and 163.4 mL/minute in those with extrahepatic obstruction.27

In children 1 month to 14 years of age, the serum half-life of nafcillin ranges from 0.75-1.9 hours.23,25 Serum concentrations of nafcillin are generally higher and the serum half-life is longer in neonates than in older children.1,24,31,32,59,73 In one study, the serum half-life of nafcillin ranged from 2.2-5.5 hours in neonates 3 weeks of age or younger and 1.2-2.3 hours in neonates 4-9 weeks of age.24

Nafcillin is only minimally removed by hemodialysis3,13,18,26,33,57,70 or peritoneal dialysis.3

Chemistry and Stability

Chemistry !!navigator!!

Nafcillin is a semisynthetic penicillinase-resistant penicillin.2,4,5,8,47,59,70

Nafcillin is commercially available as the monohydrate sodium salt.68 Potency of nafcillin sodium is expressed in terms of nafcillin.1,68 Each mg of nafcillin sodium contains not less than 820 mcg of nafcillin.68 Nafcillin sodium occurs as a white to yellowish white powder which may have a slight characteristic odor.68 The drug is freely soluble in water and soluble in alcohol.68 Nafcillin sodium has a pKa of approximately 2.7.2,7,11

Commercially available frozen nafcillin sodium in dextrose injections are sterile, nonpyrogenic, iso-osmotic solutions of the drug; about 1.8 or 1 g of dextrose has been added to the 1- or 2-g injections of nafcillin sodium, respectively, to adjust osmolality to about 300 mOsm/kg.63,65 Nafcillin sodium in dextrose frozen injections also contain sodium citrate as a buffer and hydrochloric acid and/or sodium hydroxide to adjust pH to 6-8.5.61,63,65

Stability !!navigator!!

Following reconstitution with sterile water for injection, bacteriostatic water for injection, or 0.9% sodium chloride injection, nafcillin sodium solutions containing 250 mg of nafcillin per mL are stable for 3 days at room temperature, 7 days when refrigerated, or 90 days when frozen.1 The manufacturer states that solutions containing 10-200 mg/mL are stable for 24 hours at room temperature, 7 days when refrigerated, or 90 days when frozen.1

The manufacturer states that the stability of the commercially available frozen nafcillin sodium injection may vary.65 These injections are stable for at least 90 days from the date of shipment when stored at -20°C.61,63,65 The frozen injection should be thawed at room temperature (25°C) or under refrigeration (5°C) and, once thawed, should not be refrozen.63 Thawed solutions of the commercially available frozen injection are stable for 72 hours at room temperature (25°C) or 21 days when refrigerated at 5°C.65 The commercially available frozen injection of the drug in dextrose is provided in a plastic container fabricated from specially formulated multilayered plastic PL 2040 (Galaxy®).63 Solutions in contact with the plastic can leach out some of its chemical components in very small amounts within the expiration period of the injection; however, safety of the plastic has been confirmed in animals according to USP biological tests for plastic containers as well as by tissue culture toxicity studies.63

Nafcillin sodium is potentially physically and/or chemically incompatible with some drugs, including aminoglycosides and admixtures resulting in a pH greater than 8 or less than 5, but the compatibility depends on several factors (e.g., concentrations of the drugs, specific diluents used, resulting pH, temperature).9,64 For information on the in vitro and in vivo incompatibility of penicillins and aminoglycosides, see Drug Interactions: Aminoglycosides, in the Penicillinase-Resistant Penicillins General Statement 8:12.16.12. Specialized references should be consulted for specific compatibility information.64 Because of the potential for incompatibility, nafcillin sodium and other drugs should not be admixed.63

Additional Information

For further information on chemistry and stability, mechanism of action, spectrum, resistance, pharmacokinetics, uses, cautions, drug interactions, laboratory test interferences, and dosage and administration of nafcillin sodium, see the Penicillinase-Resistant Penicillins General Statement 8:12.16.12.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Nafcillin Sodium in Dextrose

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection

1 g (of nafcillin)*

Nafcillin Sodium for Injection

2 g (of nafcillin)*

Nafcillin Sodium for Injection

10 g (of nafcillin) pharmacy bulk package*

Nafcillin Sodium for Injection

For injection, for IV infusion

1 g (of nafcillin)*

Nafcillin Sodium for Injection ADD-Vantage®

Sandoz

2 g (of nafcillin)*

Nafcillin Sodium for Injection ADD-Vantage®

Sandoz

Injection (frozen), for IV infusion

20 mg (of nafcillin) per mL (1 g) in 3.6% Dextrose*

Nafcillin Sodium in Iso-osmotic Dextrose Injection Galaxy®

Baxter

20 mg (of nafcillin) per mL (2 g) in 3.6% Dextrose*

Nafcillin Sodium in Iso-osmotic Dextrose Injection Galaxy®

Baxter

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Copyright

AHFS® Drug Information. © Copyright, 1959-2024, Selected Revisions January 1, 2009. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.

References

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