VA Class:AM112
Oxacillin is a semisynthetic penicillinase-resistant penicillin antibiotic.1,4,5,9,46,70
Oxacillin shares the uses of other parenteral penicillinase-resistant penicillins (e.g., nafcillin) and generally is used only in the treatment of infections caused by, or suspected of being caused by, susceptible penicillinase-producing staphylococci.1,6,47,66,70,71 For specific information on the uses of oxacillin, see Uses in the Penicillinase-Resistant Penicillins General Statement 8:12.16.12.
Reconstitution and Administration
Oxacillin sodium is administered by IM injection or slow IV injection or infusion.1 Although oxacillin has been administered orally,3 an oral preparation of the drug is no longer commercially available in the US.
For IM injection, oxacillin sodium powder for injection is reconstituted by adding 5.7 or 11.4 mL of sterile water for injection to a vial containing 1 or 2 g of oxacillin, respectively, to provide solutions containing 167 mg of oxacillin per mL (250 mg/1.5 mL).1 The vials should be shaken well until a clear solution is obtained.1
IM injections of oxacillin sodium should be made deeply into a large muscle (e.g., gluteus maximus) and care should be taken to avoid sciatic nerve injury.58
For direct intermittent IV injection, a solution containing approximately 100 mg/mL may be prepared by adding 10 or 20 mL of sterile water for injection or 0.45 or 0.9% sodium chloride injection to vials containing 1 or 2 g of oxacillin, respectively.1
The appropriate dose should then be injected slowly over a period of about 10 minutes.1 Particular attention to the risk of thrombophlebitis should be given when oxacillin is administered IV to geriatric patients.58
Intermittent or Continuous IV Infusion
For intermittent IV infusion, vials containing 1 or 2 g of oxacillin should be reconstituted as for direct IV injection and then further diluted with a compatible IV solution1 to a concentration of 0.5-40 mg/mL. (See Chemistry and Stability: Stability.) Alternatively, ADD-Vantage® vials containing 1 or 2 g of the drug should be reconstituted according to the manufacturer's directions.63 Pharmacy bulk packages containing 10 g of oxacillin usually are reconstituted by adding 93 mL of sterile water for injection or 0.9% sodium chloride injection to provide a solution containing 100 mg/mL.2 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.2
Thawed solutions of the commercially available frozen oxacillin sodium in dextrose injection should be administered by continuous or intermittent IV infusion.64 These frozen oxacillin sodium injections should not be thawed by warming them in a water bath or by exposure to microwave radiation.64 A precipitate may form while the commercially available 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.64 After thawing at room temperature or under refrigeration, the containers should be checked for minute leaks by firmly squeezing the bag.64 The injection should be discarded if the container seal is not intact or leaks are found or if the solution is cloudy, discolored, or contains a precipitate.64 Additives should not be introduced into the injection.64 The injections 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.64
For IV infusion of oxacillin, the rate of infusion should be adjusted so that the total dose of oxacillin is administered before the drug is inactivated in the IV solution.1 (See Chemistry and Stability: Stability.)
Dosage of oxacillin sodium is expressed in terms of oxacillin.1 Dosage of the drug should be adjusted according to the type and severity of infection.1,58
For the treatment of infections caused by susceptible penicillinase-producing staphylococci, the usual adult IM or IV dosage of oxacillin is 250-500 mg every 4-6 hours for mild to moderate infections or 1 g every 4-6 hours for severe infections.1,58,64 When oxacillin is used for the treatment of acute or chronic osteomyelitis caused by susceptible penicillinase-producing staphylococci, some clinicians recommend that adults receive 1.5-2 g of the drug IV every 4 hours.49 If oxacillin is used for the treatment of staphylococcal infections related to intravascular catheters, some clinicians recommend that adults receive 2 g every 4 hours.73
For the treatment of native valve endocarditis caused by staphylococci susceptible to penicillinase-resistant penicillins, the American Heart Association (AHA) recommends that adults receive oxacillin in a dosage of 2 g IV every 4 hours for 4-6 weeks.50 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 oxacillin therapy.50
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 oxacillin 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 oxacillin therapy).50 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.50 (See Uses: Endocarditis in the Penicillinase-resistant Penicillins General Statement 8:12.16.12.)
Children weighing 40 kg or more may receive the usual adult dosage of oxacillin.1,58,64
The usual IM or IV dosage of oxacillin for the treatment of mild to moderate infections caused by susceptible penicillinase-producing staphylococci in children weighing less than 40 kg is 50 mg/kg daily given in equally divided doses every 6 hours.1,58,64 For severe infections, the usual IM or IV dosage in children weighing less than 40 kg is 100-200 mg/kg daily given in equally divided doses every 4-6 hours.1,47,49,58,64,67,71 The American Academy of Pediatrics (AAP) recommends that children 1 month of age or older receive IM or IV oxacillin in a dosage of 100-150 mg/kg daily in 4 divided doses for the treatment of mild to moderate infections or 150-200 mg/kg daily in 4 divided doses for the treatment of severe infections.67
The manufacturer recommends that neonates receive IM or IV oxacillin in a dosage of 25 mg/kg daily.1 The AAP and other clinicians recommend that neonates younger than 1 week of age receive IM or IV oxacillin in a dosage of 25-50 mg/kg every 12 hours if they weigh 2 kg or less (25 mg/kg every 12 hours for those less than 1.2 kg) or 25-50 mg/kg every 8 hours if they weigh more than 2 kg.67,71,72 Neonates 1-4 weeks should receive 25-50 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 25-50 mg/kg every 6 hours if they weigh more than 2 kg.67,71,72 The higher dosages are recommended for meningitis.67
For the treatment of native valve endocarditis caused by staphylococci susceptible to penicillinase-resistant penicillins, the AHA recommends that pediatric patients receive oxacillin 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 oxacillin 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
The duration of oxacillin therapy depends on the type and severity of infection and should be determined by the clinical and bacteriologic response of the patient.1,58,64 In serious staphylococcal infections, therapy should be continued for at least 1-2 weeks; more prolonged therapy is necessary for the treatment of osteomyelitis or endocarditis.1,58,64,71
When oxacillin is used parenterally in the treatment of acute or chronic osteomyelitis caused by susceptible penicillinase-producing staphylococci, the drug generally is given for 3-8 weeks;48,49,52,57,71 follow-up therapy with an oral penicillinase-resistant penicillin (e.g., dicloxacillin) generally is recommended for the treatment of osteomyelitis.49,51,71 In the treatment of acute osteomyelitis, a shorter course of parenteral penicillinase-resistant therapy (5-28 days) followed by 3-6 weeks of oral penicillinase-resistant penicillin therapy also has been effective.49,51,52,57
Modification of dosage generally is unnecessary when oxacillin is used in patients with renal impairment;18,53,56 however, some clinicians suggest that the lower range of the usual dosage (1 g IM or IV every 4-6 hours) be used in adults with creatinine clearances less than 10 mL/minute.22,28,54,68
Adverse effects reported with oxacillin are similar to those reported with other penicillinase-resistant penicillins.1,58,64 However, adverse hepatic effects have been reported more frequently with IV oxacillin than with other commercially available penicillinase-resistant penicillins.35,36,37,38,39,58 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
Oxacillin is contraindicated in patients who are hypersensitive to any penicillin.1,58,64
Oxacillin shares the toxic potentials of the penicillins, including the risk of hypersensitivity reactions, and the usual precautions of penicillin therapy should be observed.1,58,64 Prior to initiation of therapy with oxacillin, careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins, or other drugs.1,58,64 There is clinical and laboratory evidence of partial cross-allergenicity among penicillins and other β-lactam antibiotics including cephalosporins and cephamycins.1,33,34,42,43
Renal, hepatic, and hematologic systems should be evaluated periodically during prolonged therapy with oxacillin.1,58 Because adverse hematologic effects have occurred during therapy with penicillinase-resistant penicillins, CBCs and differential should be performed prior to initiation of therapy and 1-3 times weekly during therapy.40,41,58,64 In addition, urinalysis should be performed and BUN and serum creatinine, AST (SGOT), and ALT (SGPT) concentrations should be determined prior to and periodically during therapy.1,58,64
For a more complete discussion of these and other precautions associated with the use of oxacillin, see Cautions: Precautions and Contraindications, in the Penicillinase-Resistant Penicillins General Statement 8:12.16.12.
Elimination of penicillins is delayed in neonates because of immature mechanisms for renal excretion, and abnormally high serum concentrations of the drugs may occur in this age group.58,63 If oxacillin is used in neonates, they should be monitored closely for clinical and laboratory evidence of toxic or adverse effects including renal impairment;1,58,63 organ systems1 and serum concentrations of the drug58 should be monitored frequently and appropriate reductions in dosage and frequency of administration made when indicated.58
Safe use of penicillinase-resistant penicillins during pregnancy has not been definitely established.1,58,63 Clinical experience with use of penicillins during pregnancy in humans has not revealed evidence of adverse effects on the fetus.58 However, there are no adequate and controlled studies using penicillinase-resistant penicillins in pregnant women, and oxacillin should be used during pregnancy only when clearly needed.58,63
Because oxacillin is distributed into milk, the drug should be used with caution in nursing women.58,63
Based on its spectrum of activity, oxacillin is classified as a penicillinase-resistant penicillin.4,5,9,46,58,70 For information on the classification of penicillins based on spectra of activity, see the Preface to the General Statements on Penicillins 8:12.16.
Like other penicillinase-resistant penicillins, oxacillin 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.9,11,58,70 For specific information on the spectrum of activity of oxacillin and resistance to the drug, see the sections on Spectrum and on Resistance in the Penicillinase-Resistant Penicillins General Statement 8:12.16.12.
In all studies described in the Pharmacokinetics section, oxacillin was administered as the sodium salt; dosages and concentrations of the drug are expressed in terms of oxacillin.
Oxacillin is resistant to inactivation in the presence of acidic gastric secretions and is rapidly but incompletely absorbed from the GI tract.32,70 In healthy, fasting adults, 30-35% of an orally administered dose of oxacillin is absorbed from the GI tract4,7,15,23 and peak serum concentrations of the drug are generally attained within 0.5-2 hours.5,12,25,29,30,31,32 Presence of food in the GI tract generally decreases the rate and extent of absorption of oxacillin.5,14,30,58,70
Following oral administration of a single 250- or 500-mg dose of oxacillin as capsules (no longer commercially available in the US) in healthy, fasting adults, peak serum concentrations of the drug average 1.65 or 2.6-3.9 mcg/mL, respectively.13,25 Following oral administration of oxacillin as an oral solution (no longer commercially available in the US), peak serum concentrations occur about 30 minutes after the dose and average 1.9 mcg/mL after a single 250-mg dose and 4.8 mcg/mL after a single 500-mg dose.3
Oxacillin is rapidly absorbed from IM injection sites.1,14,29,30,31 Following IM injection of a single 250- or 500-mg dose of oxacillin in healthy adults with normal renal function, peak serum concentrations of the drug are generally attained within 30 minutes1,14,31 and average 5.3 and 10.9 mcg/mL, respectively.1 Following IM administration of a single 500-mg dose of oxacillin in healthy adults, serum concentrations of the drug averaged 7.4, 7.4, 4.3, and 0.8 mcg/mL at 30 minutes, 1 hour, 2 hours, and 4 hours, respectively, after the dose.30
Following rapid IV injection of a single 500-mg dose of oxacillin in healthy adults, peak serum concentrations of the drug average 52-63 mcg/mL.29
In one study in children 1 week to 2 years of age with staphylococcal infections who received an IM oxacillin dosage of 100 mg/kg daily in divided doses every 6 hours, peak serum concentrations of the drug occurred 30 minutes after a dose and ranged from 45-86 mcg/mL; trough serum concentrations ranged from 2.5-7.5 mcg/mL.26 Following IM injection of a single 20-mg/kg dose of oxacillin in neonates, peak serum concentrations of the drug reportedly average 51.5 mcg/mL in those 8-15 days of age and 47 mcg/mL in those 20-21 days of age.70
Oxacillin is distributed into synovial,5,24 pleural,1,5 pericardial,10 and ascitic fluids.10 The drug is also distributed into bone,10,16,17,24,55 lungs,62 sputum,5 and bile.1,5,31 The volume of distribution of oxacillin is reportedly 0.39-0.43 L/kg in healthy adults.74
Following IM or IV administration, oxacillin concentrations in bone may be 5-20% of concurrent serum concentrations.16,55 In one study in adults who received a single 2-g IV dose of oxacillin, concentrations of the drug in bone ranged from 1.1-18.5 mcg/g.17
Like other penicillins, only low concentrations of oxacillin are attained in CSF.1,10,31 Following IM administration, oxacillin does not appear to distribute into aqueous humor in measurable concentrations;44,59 in animals, the drug is not distributed into aqueous humor even in the presence of inflammation.44 In rabbits, subconjunctival injection of a 100-mg dose of oxacillin produced aqueous humor concentrations of 145 mcg/mL 1 hour after the injection and 70 mcg/mL 2 hours after the injection.60
Oxacillin is 89-94% bound to serum proteins.4,15,19,20,70
Oxacillin is distributed into cord serum and amniotic fluid31 and crosses the placenta5,31 Oral administration of a single 500-mg dose of oxacillin to pregnant women in labor has resulted in fetal serum concentrations of the drug of 1.4 mcg/mL and amniotic fluid concentrations of 3.2 mcg/mL.31 Oxacillin is distributed into milk.1,5,31 Following IM administration of a single 500-mg dose of oxacillin in lactating women, milk concentrations of the drug were 0.2-0.7 mcg/mL 1 and 2 hours after the dose and 0.2-0.4 mcg/mL 4 hours after the dose.61
The serum half-life of oxacillin in adults with normal renal function is 0.3-0.8 hours.1,7,10,15,21,22,45
Oxacillin is partially metabolized to active and inactive metabolites.10,23,27 In one study following a single 500-mg oral dose of oxacillin (no longer commercially available in the US), 49% of the absorbed dose was hydrolyzed to penicilloic acids which are microbiologically inactive.23 Oxacillin is also hydroxylated to a small extent to a microbiologically active metabolite which appears to be slightly less active than oxacillin.27
Oxacillin and its metabolites are rapidly excreted in urine mainly by tubular secretion and glomerular filtration.1,5,10,27,70 Following oral administration of a single 500-mg dose of oxacillin in adults with normal renal function, 17-24% of the dose is excreted in urine as unchanged drug and active metabolites within 6 hours;13,23,31 approximately 21% of the antibacterial activity in urine is represented by the active metabolite.27 Following IM administration of a single 500-mg or 1-g dose of oxacillin in adults with normal renal function, 40-70% of the dose is excreted in urine as unchanged drug and active metabolites within 6 hours.31
In one study, serum clearance of oxacillin averaged 380 mL/minute per 1.73 m2 in adults with normal renal function.45
Serum concentrations of oxacillin may be higher and the serum half-life slightly prolonged in patients with impaired renal function.7,15,18,28,45 The serum half-life of the drug is reportedly 0.5-2 hours in patients with creatinine clearances less than 10 mL/minute per 1.73 m2.7,15,18,45
In one study in children 1 week to 2 years of age, the elimination half-life of oxacillin ranged from 0.9-1.8 hours.26 Serum concentrations of oxacillin are generally higher and the serum half-life is longer in neonates than in older children.10 The serum half-life of oxacillin reportedly is 1.6 hours in neonates 8-15 days of age and 1.2 hours in neonates 20-21 days of age.70
Oxacillin is only minimally removed by hemodialysis10,15,22,28,56 or peritoneal dialysis.10,18,22,56
Oxacillin is a semisynthetic penicillinase-resistant penicillin.4,5,9,10,46,58,70,64 Oxacillin, like cloxacillin (no longer commercially available in the US) and dicloxacillin, is an isoxazolyl penicillin.4,5,14,46,70
Oxacillin is commercially available as the monohydrate sodium salt.1,68 Potency of oxacillin sodium is expressed in terms of oxacillin.1,64,68 Each mg of oxacillin sodium contains 815-950 mcg of oxacillin.68 Oxacillin sodium occurs as a fine, white, crystalline powder which is odorless or may have a slight odor.68 The drug is freely soluble in water.68 Oxacillin sodium has a pKa of approximately 2.8.75
Each gram of commercially available oxacillin sodium powder for injection contains approximately 2.5 mEq of sodium and is buffered with 20 mg of dibasic sodium phosphate.1
Commercially available frozen oxacillin sodium in dextrose injection are sterile, nonpyrogenic, iso-osmotic solutions of the drug; about 1.5 or 0.3 g of dextrose has been added to the 1- or 2-g injection of oxacillin sodium, respectively, to adjust osmolality to about 300 mOsm/kg.64 Frozen oxacillin sodium in dextrose injection also contains sodium citrate as a buffer and hydrochloric acid and/or sodium hydroxide to adjust pH to 6-8.5.64
Commercially available oxacillin sodium powder for IM or IV injection should be stored at controlled room temperature;68 the pharmacy bulk package containing 10 g of the drug should be stored at 15-30°C.2
When oxacillin sodium powder for injection is reconstituted with sterile water for injection, solutions for IM injection containing 167 mg of oxacillin per mL (250 mg/1.5 mL) are stable for 3 days at room temperature or 7 days when refrigerated.1 When reconstituted as directed in 0.9% sodium chloride injection or 5% dextrose injection, solutions prepared from ADD-Vantage® vials of the drug are stable for 4 days or 6 hours, respectively, at room temperature.63
At concentrations of 0.5-4 mg/mL, oxacillin loses less than 10% of its activity within 6 hours at room temperature in the following IV solutions: 5% dextrose and 0.9% sodium chloride; 10% fructose or 10% fructose and 0.9% sodium chloride; 10% invert sugar and 0.9% sodium chloride or 0.3% potassium chloride; or 10% invert sugar with electrolytes (Travert® 10% with Electrolytes No. 1, 2, or 3).1
The commercially available preparations of frozen oxacillin sodium in dextrose injection should be stored at -20°C or lower64 and are stable for at least 90 days from the date of shipment when stored at -20°C.65 The frozen injection should be thawed at room temperature (25°C) or under refrigeration (5°C) and, once thawed, should not be refrozen.64 Thawed solutions of the commercially available frozen injection are stable for 48 hours at room temperature (25°C) or 21 days when refrigerated at 5°C.64,65 The commercially available frozen injections of the drug are provided in a plastic container fabricated from specially formulated multilayered plastic PL 2040 (Galaxy®).64 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 tests in animals according to USP biological tests for plastic containers as well as by tissue culture toxicity studies.64
Oxacillin sodium is potentially physically and/or chemically incompatible with some drugs, including aminoglycosides and tetracyclines, but the compatibility depends on several factors (e.g., concentrations of the drugs, specific diluents used, resulting pH, temperature).8 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.8
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 oxacillin sodium, see the Penicillinase-Resistant Penicillins General Statement 8:12.16.12.
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.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
---|---|---|---|---|
Parenteral | For injection | 1 g (of oxacillin)* | Oxacillin Sodium for Injection | |
2 g (of oxacillin)* | Oxacillin Sodium for Injection | |||
10 g (of oxacillin) pharmacy bulk package* | Oxacillin Sodium for Injection | |||
For injection, for IV infusion | 1 g (of oxacillin)* | Oxacillin Sodium ADD-Vantage® | ||
2 g (of oxacillin)* | Oxacillin Sodium ADD-Vantage® | Sandoz |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
---|---|---|---|---|
Parenteral | Injection (frozen), for IV infusion | 20 mg (of oxacillin) per mL (1 g) in 3% Dextrose* | Oxacillin Sodium® in Iso-osmotic Dextrose Injection | |
40 mg (of oxacillin) per mL (2 g) in 0.6% Dextrose* | Oxacillin Sodium® in Iso-osmotic Dextrose Injection | Baxter |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
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.
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3. Apothecon. Oxacillin sodium for oral solution, USP prescribing information. Princeton, NJ; 1998 Mar.
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