Oxacillin Sodium

Staphylococcal Infections

Treatment of infections caused by, or suspected of being caused by, susceptible penicillinase-producing staphylococci,1 6 47 66 70 71 including respiratory tract, skin and skin structure, bone and joint, and urinary tract infections and meningitis or bacteremia.a A drug of choice for these infections.a

Treatment of native valve or prosthetic valve endocarditis caused by susceptible staphylococci.50 69 A drug of choice;50 69 used with or without gentamicin for native valve endocarditis and used in conjunction with rifampin and gentamicin for prosthetic valve endocarditis.50 69

If used empirically, consider whether staphylococci resistant to penicillinase-resistant penicillins (oxacillin-resistant [methicillin-resistant] staphylococci) are prevalent in the hospital or community.a (See Staphylococci Resistant to Penicillinase-resistant Penicillins under Cautions.)

Perioperative Prophylaxis

Has been used for perioperative prophylaxis† in patients undergoing neurosurgery or cardiovascular or orthopedic surgery associated with high risk of staphylococcal infections.a Not considered a drug of choice.a

Administration

Administer by IV injection or infusion or by IM injection.1

To reduce risk of thrombophlebitis and other adverse local reactions associated with IV administration (particularly in geriatric patients), administer slowly and take care to avoid extravasation.1 a

IV Injection

Reconstitution

Reconstitute vials containing 1 or 2 g of oxacillin by adding 10 or 20 mL, respectively, of sterile water for injection or 0.45 or 0.9% sodium chloride injection to provide solutions containing approximately 100 mg/mL.1

Rate of Administration

Inject appropriate dose slowly over a period of about 10 minutes.1

IV Infusion

Reconstitution and Dilution

Reconstitute vials containing 1 or 2 g of oxacillin by adding 10 or 20 mL, respectively, of sterile water for injection or 0.45 or 0.9% sodium chloride injection to provide a solution containing approximately 100 mg/mL.1 Reconstituted solution should then be further diluted with a compatible IV solution (see Solution Compatibility under Stability) to a concentration of 0.5–40 mg/mL.1

Alternatively, ADD-Vantage vials containing 1 or 2 g of the drug should be reconstituted according to the manufacturer’s directions.63

Reconstitute 10-g pharmacy bulk package with 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; prior to administration, doses of the drug from the reconstituted pharmacy bulk package must be further diluted in a compatible IV infusion solution (see Solution Compatibility under Stability).2

Thaw the commercially available injection (frozen) at room temperature or in a refrigerator; do not force thaw by immersion in a water bath or by exposure to microwave radiation.64 A precipitate may have formed in the frozen injection, but should dissolve with little or no agitation after reaching room temperature.64 Discard thawed injection if an insoluble precipitate is present or if container seals or outlet ports are not intact.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

Rate of Administration

The rate of IV infusion should be adjusted so that the total dose is administered before the drug is inactivated in the IV solution.1

IM Administration

Inject IM deeply into a large muscle (e.g., gluteus maximus) avoiding sciatic nerve injury.58

Reconstitution

For IM injection, reconstitute vial containing 1 or 2 g of oxacillin by adding 5.7 or 11.4 mL, respectively, of sterile water for injection to provide solutions containing 167 mg/mL (250 mg/1.5 mL).1 Shake vial well until a clear solution is obtained.1

Dosage

Available as oxacillin sodium; dosage expressed in terms of oxacillin.1

Duration of treatment depends on type and severity of infection and should be determined by clinical and bacteriologic response of the patient.1 58 64 For serious staphylococcal infections, duration usually is ≥1–2 weeks; more prolonged therapy is necessary for treatment of osteomyelitis or endocarditis.1 58 64 71

Pediatric Patients

Staphylococcal Infections General Dosage in Neonates IV or IM

25 mg/kg daily recommended by manufacturer.1

Neonates <1 week of age: AAP recommends 25 mg/kg every 12 hours for those weighing <1.2 kg; 25–50 mg/kg every 12 hours for those weighing 1.2 to 2 kg; and 25–50 mg/kg every 8 hours for those weighing >2 kg.67 The higher dosages are recommended for meningitis.67

Neonates 1–4 weeks of age: AAP recommends 25 mg/kg every 12 hours for those weighing <1.2 kg; 25–50 mg/kg every 8 hours for those weighing 1.2 to 2 kg; and 25–50 mg/kg every 6 hours for those weighing >2 kg.67 The higher dosages are recommended for meningitis.67

Mild to Moderate Infections in Infants and Children IV or IM

Children weighing <40 kg: 50 mg/kg daily given in equally divided doses every 6 hours.1 58 64

Children weighing ≥40 kg: 250–500 mg every 4–6 hours.1 58 64

Children ≥1 month of age: AAP recommends 100–150 mg/kg daily in 4 divided doses.67

Severe Infections in Infants and Children IV or IM

Children weighing <40 kg: 100–200 mg/kg daily given in equally divided doses every 4–6 hours.1 47 49 58 64 67 71

Children weighing ≥40 kg: 1 g every 4–6 hours.1 58 64

Children ≥1 month of age: AAP recommends 150–200 mg/kg daily in 4–6 divided doses.67

Staphylococcal Native Valve Endocarditis IV

AHA recommends 200 mg/kg daily given in divided doses every 4–6 hours for 6 weeks (maximum 12 g daily).69

In addition, during the first 3–5 days of oxacillin therapy, IM or IV gentamicin (3 mg/kg daily given in divided doses every 8 hours; dosage adjusted to achieve peak serum gentamicin concentrations approximately 3 mcg/mL and trough concentrations <1 mcg/mL) may be given concomitantly if the causative organism is susceptible to the drug.69

Staphylococcal Prosthetic Valve Endocarditis IV

AHA recommends 200 mg/kg daily given in divided doses every 4–6 hours for 6 weeks or longer (maximum 12 g daily).

Used in conjunction with oral rifampin (20 mg/kg daily given in divided doses every 8 hours for 6 weeks or longer) and IM or IV gentamicin (3 mg/kg daily given 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 <1 mcg/mL).69

Adults

Staphylococcal Infections Mild to Moderate Infections IV or IM

250–500 mg every 4–6 hours.1 58 64

Severe Infections IV or IM

1 g every 4–6 hours.1 58 64

Acute or Chronic Staphylococcal Osteomyelitis IV

1.5–2 g every 4 hours.49

When used for treatment of acute or chronic osteomyelitis caused by susceptible penicillinase-producing staphylococci, parenteral therapy generally continued for 3–8 weeks;48 49 52 57 71 follow-up with an oral penicillinase-resistant penicillin (e.g., dicloxacillin) generally recommended.49 51 71 In 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

Staphylococcal Native Valve Endocarditis IV

AHA recommends 2 g every 4 hours for 4–6 weeks.50

Although benefits of concomitant aminoglycosides have not been clearly established, AHA states that IM or IV gentamicin (1 mg/kg every 8 hours) may be given concomitantly during the first 3–5 days of oxacillin therapy.50

Staphylococcal Prosthetic Valve Endocarditis IV

AHA recommends 2 g every 4 hours for ≥6 weeks in conjunction with oral rifampin (300 mg every 8 hours for 6 weeks or longer) and IM or IV gentamicin (1 mg/kg every 8 hours during the first 2 weeks of oxacillin therapy).50 (See Staphylococci Resistant to penicillinase-resistant Penicillins under Cautions.)

Staphylococcal Infections Related to Intravascular Catheters IV

2 g every 4 hours.73

Special Populations

Renal Impairment

Modification of dosage generally is unnecessary in patients with renal impairment;18 53 56 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 Clcr <10 mL/minute.22 28 54 68

Specific Drugs

Drug	Interaction	Comments
Aminoglycosides	In vitro evidence of synergistic antibacterial effects against penicillinase-producing and nonpenicillinase-producing S. aureusa
Anticoagulants, oral (warfarin)	Possible decreased hypothrombinemic effect reported with other penicillinase-resistant penicillins (dicloxacillin, nafcillin)a	Monitor PT and adjust anticoagulant dosage if indicateda
Cyclosporine	Decreased cyclosporine concentrations reported with some other penicillinase-resistant penicillins (e.g., nafcillin)a
Probenecid	Decreased renal tubular secretion of penicillinase-resistant penicillins and increased and prolonged plasma concentrationsa
Rifampin	In vitro evidence of indifference or synergism against S. aureus with low oxacillin concentrations and antagonism with high oxacillin concentrationsa Possible delay or prevention of emergence of rifampin-resistant S. aureusa
Tetracyclines	Possible antagonisma	Concomitant use not recommendeda

Absorption

Bioavailability

Rapidly absorbed from IM injection sites;1 14 29 30 31 peak serum concentrations generally attained within 30 minutes.1 14 31

Distribution

Extent

Distributed into synovial,5 24 pleural,1 5 pericardial,10 and ascitic fluids.10 Also distributed into bone,10 16 17 24 55 lungs,62 sputum,5 and bile.1 5 31

Only low concentrations attained in CSF.1 10 31

Crosses the placenta5 31 and is distributed into milk.1 5 31

Plasma Protein Binding

89–94% bound to serum proteins.4 15 19 20 70

Elimination

Metabolism

Partially metabolized to active and inactive metabolites.10 23 27

Approximately 49% of a dose is hydrolyzed to penicilloic acids which are microbiologically inactive;23 also hydroxylated to a small extent to a microbiologically active metabolite which appears to be slightly less active than oxacillin.27

Elimination Route

Oxacillin and its metabolites rapidly eliminated in urine principally by tubular secretion and glomerular filtration.1 5 10 27 70

Following IM administration, 40–70% of the dose is excreted in urine as unchanged drug and active metabolites within 6 hours.31

Half-life

Adults with normal renal function: 0.3–0.8 hours.1 7 10 15 21 22 45

Children 1 week to 2 years of age: 0.9–1.8 hours.26

Neonates: 1.6 hours in those 8–15 days of age and 1.2 hours in those 20–21 days of age.70

Special Populations

Patients with renal impairment: serum half-life slightly prolonged.7 15 18 28 45 Serum half-life may be 0.5–2 hours in patients with Clcr <10 mL/minute per 1.73 m2.7 15 18 45

Storage

Parenteral

Powder for Injection

15–30°C.68

Solutions reconstituted from ADD-Vantage vials using 0.9% sodium chloride injection or 5% dextrose injection are stable at room temperature for 4 days or 6 hours, respectively.63

IM solutions containing 167 mg/mL (250 mg/1.5 mL) prepared using sterile water for injection are stable for 3 days at room temperature or 7 days when refrigerated.1

Injection (Frozen)

≤ -20° C.64 Thawed solutions of the commercial frozen injection stable for 48 hours at room temperature (25°C) or 21 days at 5°C.64 65

Do not refreeze after thawing.64

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Compatibilityhid

Compatible
Amino acids 4.25%, dextrose 25%
Dextran 70 6% in dextrose 5%
Dextran 40 10% in dextrose 5%
Dextrose 5% in Ringer’s injection, lactated
Dextrose 10% in water
Hetastarch 6% in sodium chloride 0.9%
Ringer’s injection, lactated
Variable
Dextrose 5% in sodium chloride 0.9%
Dextrose 5% in water
Sodium chloride 0.9%

Drug Compatibility Admixture Compatibilityhid

Compatible
Chloramphenicol sodium succinate
Dopamine HCl
Potassium chloride
Incompatible
Cytarabine
Variable
Amikacin sulfate
Verapamil HCl

Y-Site Compatibilityhid

Compatible
Acyclovir sodium
Cyclophosphamide
Diltiazem HCl
Doxapram HCl
Famotidine
Fluconazole
Foscarnet sodium
Heparin sodium
Hydrocortisone sodium succinate
Hydromorphone HCl
Labetalol HCl
Levofloxacin
Magnesium sulfate
Meperidine HCl
Methotrexate sodium
Milrinone lactate
Morphine sulfate
Perphenazine
Potassium chloride
Tacrolimus
Vitamin B complex with C
Zidovudine
Incompatible
Sodium bicarbonate
Verapamil HCl