oxacillin

Penicillinase-Resistant Penicillin Antibiotics

 
NOTE: For severe infections, a 4-hour dosing interval is recommended to avoid subtherapeutic serum concentrations at the end of the dosing interval.

Oxacillin may be administered intramuscularly (IM) or by intermittent IV injection or infusion.
Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

Direct IV Push:
Vials: To provide a solution containing 50 mg/mL reconstitute 250 mg with 5 mL of Sterile Water for Injection, 0.45% Sodium Chloride Injection, or 0.9% Sodium Chloride Injection. To provide a solution containing 100 mg/mL reconstitute 500 mg, 1 g, 2 g, 4 g with 5, 10, 20, or 40 mL, respectively, of Sterile Water for Injection, 0.45% Sodium Chloride Injection, or 0.9% Sodium Chloride Injection. Vigorously shake vials until solution is clear.
Inject appropriate dose slowly directly into a vein over 10 minutes. To minimize vein irritation, inject as slowly as possible.
Intermittent IV infusion:
Vials: The reconstituted powder (see Direct Intermittent above) may be further diluted to concentrations of 0.5 to 40 mg/mL with a compatible IV solution. For peripheral vein infusion, a concentration of <= 20 mg/mL is preferred to help lessen the possibility of phlebitis, unless fluid restrictions are necessary for the patient.
Pharmacy bulk packages: reconstitute 10 grams with 93 mL of Sterile Water for Injection to give a concentration of 100 mg/mL. Withdraw appropriate dose and further dilute as recommended in a compatible IV solution.
Frozen bags: Thaw at room temperature. Do not force thaw. No reconstitution necessary.
ADD-Vantage vials: for IV infusion only. Reconstitute only with 0.9% Sodium Chloride Injection or 5% Dextrose Injection in the appropriate flexible diluent container.
Infuse appropriate dose at a rate to ensure that the entire dose is given before 10% or more of the drug is inactivated by the IV solution. Because oxacillin may cause phlebitis, slow IV infusion is recommended; many infuse the drug over a 1 hour administration time. Care should particularly be taken with the elderly and with peripheral vein infusion.
Continuous IV infusion:
In one study, 10 g of oxacillin was mixed in 500 mL of 5% Dextrose Injection. The dose, 12 g/day continuous IV infusion, was administered at a rate of 500 mg/hour (25 mL/hour) via a peripheral or central venous catheter.

Vials: Reconstitute 250 mg, 500 mg, 1 g, 2 g, 4 g with 1.4, 2.8, 5.7, 11.4, or 21.8 mL, respectively, of Sterile Water for Injection, 0.45% Sodium Chloride Injection, or 0.9% Sodium Chloride Injection to give a concentration of 167 mg/mL (250 mg/1.5 mL). Vigorously shake vials until solution is clear.
Inject deeply into a large muscle (i.e., upper outer quadrant of the gluteus maximus or lateral part of the thigh). Care should be taken to avoid sciatic nerve injury.

serum sickness / Delayed / 0-5.0
interstitial nephritis / Delayed / 0-1.0
renal tubular necrosis / Delayed / 0-1.0
exfoliative dermatitis / Delayed / 0-1.0
Stevens-Johnson syndrome / Delayed / 0-1.0
toxic epidermal necrolysis / Delayed / 0-1.0
seizures / Delayed / 0-1.0
agranulocytosis / Delayed / 0-1.0
anaphylactic shock / Rapid / 0-0.1
laryngospasm / Rapid / 0-0.1
laryngeal edema / Rapid / 0-0.1
angioedema / Rapid / 0-0.1
bronchospasm / Rapid / 0-0.1
anaphylactoid reactions / Rapid / 0-0.1
C. difficile-associated diarrhea / Delayed / Incidence not known

elevated hepatic enzymes / Delayed / 1.0-10.0
hepatitis / Delayed / 1.0-10.0
stomatitis / Delayed / 2.0-5.0
neutropenia / Delayed / 0-1.0
hypotension / Rapid / 0-0.1
proteinuria / Delayed / Incidence not known
eosinophilia / Delayed / Incidence not known
hematuria / Delayed / Incidence not known
phlebitis / Rapid / Incidence not known
superinfection / Delayed / Incidence not known
pseudomembranous colitis / Delayed / Incidence not known

arthralgia / Delayed / 0-5.0
myalgia / Early / 0-5.0
fever / Early / 0-5.0
rash / Early / 0-5.0
malaise / Early / 0-5.0
pruritus / Rapid / 0-5.0
tongue discoloration / Delayed / 2.0-5.0
diarrhea / Early / 2.0-5.0
nausea / Early / 2.0-5.0
vomiting / Early / 2.0-5.0
abdominal pain / Early / 2.0-5.0
urticaria / Rapid / Incidence not known
injection site reaction / Rapid / Incidence not known

Rx

Semisynthetic antistaphylococcal penicillin. Stable against penicillinase. Main use is for treating infections caused penicillinase-producing S. aureus, including bacteremia, skin and soft-tissue infections, respiratory tract infections, bone and joint infections, and UTIs.

1 to 2 g IV or IM every 4 to 6 hours. The FDA-approved dose is 1 g IV or IM every 4 to 6 hours for severe infections.

100 to 200 mg/kg/day IV or IM divided every 4 to 6 hours (Max: 2 g/dose) for 7 to 14 days.  The FDA-approved dose is 1 g IV or IM every 4 to 6 hours for severe infections. Guidelines recommend oxacillin as a first-line therapy for methicillin-sensitive S. aureus bacteremia.

100 to 200 mg/kg/day IV or IM divided every 4 to 6 hours for 7 to 14 days.  The FDA-approved dose is 100 mg/kg/day IV or IM divided every 4 to 6 hours for severe infections. Guidelines recommend oxacillin as a first-line therapy for methicillin-sensitive S. aureus bacteremia.

25 mg/kg/dose IV or IM every 6 hours for 14 days.  The FDA-approved dose is 25 mg/kg/day IV or IM. Guidelines recommend oxacillin as a first-line therapy for methicillin-sensitive S. aureus bacteremia.

25 mg/kg/dose IV or IM every 8 hours for 14 days.  The FDA-approved dose is 25 mg/kg/day IV or IM. Guidelines recommend oxacillin as a first-line therapy for methicillin-sensitive S. aureus bacteremia.

25 mg/kg/dose IV or IM every 8 hours for 14 days.  The FDA-approved dose is 25 mg/kg/day IV or IM. Guidelines recommend oxacillin as a first-line therapy for methicillin-sensitive S. aureus bacteremia.

25 mg/kg/dose IV or IM every 12 hours for 14 days.  The FDA-approved dose is 25 mg/kg/day IV or IM. Guidelines recommend oxacillin as a first-line therapy for methicillin-sensitive S. aureus bacteremia.

12 g/day IV divided every 4 to 6 hours. The FDA-approved dosage for severe infections is 1 g IV every 4 to 6 hours. Guidelines recommend oxacillin for 6 weeks for uncomplicated left-sided native valve endocarditis (NVE) and for at least 6 weeks for complicated left-sided NVE due to methicillin-susceptible S. aureus. For MSSA prosthetic valve endocarditis (PVE), treat with oxacillin plus rifampin for at least 6 weeks; add gentamicin for the first 2 weeks.

200 mg/kg/day (Max: 12 g/day) IV divided every 4 to 6 hours. The FDA-approved dosage for severe infections is 1 g IV every 4 to 6 hours. Oxacillin is an alternative therapy for penicillin-susceptible staphylococcal native valve endocarditis (NVE). Oxacillin is a preferred therapy for penicillin-resistant, methicillin-sensitive S. aureus (MSSA) NVE; may consider adding gentamicin for the first 3 to 5 days. Treat NVE for at least 4 to 6 weeks. For MSSA prosthetic valve endocarditis (PVE), treat with nafcillin plus rifampin for 6 weeks; add gentamicin for the first 2 weeks.

200 mg/kg/day (Max: 12 g/day) IV divided every 4 to 6 hours. The FDA-approved dosage for severe infections is 100 mg/kg/day IV divided every 4 to 6 hours. Oxacillin is an alternative therapy for penicillin-susceptible staphylococcal native valve endocarditis (NVE). Oxacillin is a preferred therapy for penicillin-resistant, methicillin-sensitive S. aureus (MSSA) NVE; may consider adding gentamicin for the first 3 to 5 days. Treat NVE for at least 4 to 6 weeks. For MSSA prosthetic valve endocarditis (PVE), treat with nafcillin plus rifampin for 6 weeks; add gentamicin for the first 2 weeks.

100 to 200 mg/kg/day IV divided every 4 to 6 hours. The FDA-approved dosage is 100 mg/kg/day IV divided every 4 to 6 hours for severe infections.

25 mg/kg/dose IV every 6 hours. The FDA-approved dosage is 25 mg/kg/day IV.

25 mg/kg/dose IV every 8 hours. The FDA-approved dosage is 25 mg/kg/day IV.

25 mg/kg/dose IV every 8 hours. The FDA-approved dosage is 25 mg/kg/day IV.

25 mg/kg/dose IV every 12 hours. The FDA-approved dosage is 25 mg/kg/day IV.

12 g/day continuous IV infusion. In a retrospective review of patients with MSSA infective endocarditis, oxacillin continuous IV infusion (CI) over 24 hours (n = 78) was compared to intermittent infusion (II) oxacillin (n = 28). The 30-day mortality (8% CI vs. 10% II, p = 0.7) and length of stay (20 days CI vs. 25 days II, p = 0.4) were similar between groups; however, data suggest an improved 30-day microbiological cure with CI (94% CI vs. 79% II, p = 0.03).[42284]

2 g IV every 4 hours for methicillin-sensitive S. aureus meningitis. The FDA-approved dosage for severe infections is 1 g IV every 4 to 6 hours.

200 mg/kg/day (Max: 12 g/day) IV divided every 6 hours for methicillin-sensitive S. aureus meningitis. The FDA-approved dosage for severe infections is 1 g IV every 4 to 6 hours.

200 mg/kg/day (Max: 12 g/day) IV divided every 6 hours for methicillin-sensitive S. aureus meningitis. The FDA-approved dosage for severe infections is 100 mg/kg/day IV divided every 4 to 6 hours.

50 mg/kg/dose IV every 6 hours. The FDA-approved dosage is 25 mg/kg/day IV.

50 mg/kg/dose IV every 8 hours. The FDA-approved dosage is 25 mg/kg/day IV.

50 mg/kg/dose IV every 8 hours. The FDA-approved dosage is 25 mg/kg/day IV.

50 mg/kg/dose IV every 12 hours. The FDA-approved dosage is 25 mg/kg/day IV.

250 to 500 mg IV or IM every 4 to 6 hours for mild to moderate infections and 1 g IV or IM every 4 to 6 hours for severe infections is the FDA-approved dose. Alternately, 6 g/day IV or IM divided every 4 hours for moderate infections and 9 to 12 g/day IV or IM divided every 4 hours for severe infections is suggested.

150 to 200 mg/kg/day IV or IM divided every 4 to 6 hours (Max: 2 g/dose). The FDA-approved dose is 250 to 500 mg IV or IM every 4 to 6 hours for mild to moderate infections and 1 g IV or IM every 4 to 6 hours for severe infections.

150 to 200 mg/kg/day IV or IM divided every 4 to 6 hours (Max: 2 g/dose).[63245] The FDA-approved dose is 50 mg/kg/day IV or IM divided every 6 hours for mild to moderate infection and 100 mg/kg/day IV or IM divided every 4 to 6 hours for severe infections.[46797]

25 mg/kg/dose IV or IM every 6 hours is recommended by the American Academy of Pediatrics (AAP). The FDA-approved dose is 25 mg/kg/day IV or IM.

25 mg/kg/dose IV or IM every 8 hours is recommended by the American Academy of Pediatrics (AAP). The FDA-approved dose is 25 mg/kg/day IV or IM.

25 mg/kg/dose IV or IM every 8 hours is recommended by the American Academy of Pediatrics (AAP). The FDA-approved dose for all neonates is 25 mg/kg/day IV or IM.

25 mg/kg/dose IV or IM every 12 hours is recommended by the American Academy of Pediatrics (AAP). The FDA-approved dose for all neonates is 25 mg/kg/day IV or IM.

150 to 200 mg/kg/day IV or IM divided every 4 to 8 hours (Max: 2 g/dose) for 10 days. Guidelines recommend a semisynthetic penicillin for hospitalized patients with infections due to methicillin-susceptible S. aureus.

1 to 2 g IV every 4 hours for 10 to 14 days.

100 to 200 mg/kg/day IV divided every 4 to 6 hours.

25 mg/kg/dose IV every 6 hours.

25 mg/kg/dose IV every 8 hours.

25 mg/kg/dose IV every 8 hours.

25 mg/kg/dose IV every 12 hours.

1 to 2 g IV or IM every 4 hours for 5 to 14 days. The FDA-approved dose is 250 to 500 mg IV or IM every 4 to 6 hours for mild to moderate infections and 1 g IV or IM every 4 to 6 hours for severe infections.

100 to 150 mg/kg/day IV or IM divided every 6 hours (Max: 2 g/dose) for 5 to 14 days. The FDA-approved dose is 250 to 500 mg IV or IM every 4 to 6 hours for mild to moderate infections and 1 g IV or IM every 4 to 6 hours for severe infections.

100 to 150 mg/kg/day IV or IM divided every 6 hours for 5 to 14 days. The FDA-approved dose is 50 mg/kg/day IV or IM divided every 6 hours for mild to moderate infections and 100 mg/kg/day IV or IM divided every 4 to 6 hours for severe infections.

25 mg/kg/dose IV or IM every 6 hours for 5 to 14 days.   The FDA-approved dose is 25 mg/kg/day IV or IM.

25 mg/kg/dose IV or IM every 8 hours for 5 to 14 days.   The FDA-approved dose is 25 mg/kg/day IV or IM.

25 mg/kg/dose IV or IM every 8 hours for 5 to 14 days.   The FDA-approved dose is 25 mg/kg/day IV or IM.

25 mg/kg/dose IV or IM every 12 hours for 5 to 14 days.   The FDA-approved dose is 25 mg/kg/day IV or IM.

500 mg/hour (12 g/day) continuous IV infusion for 5 to 14 days.

2 g IV every 6 hours for incisional surgical site infections of the trunk or extremity away from the axilla or perineum.

1 to 2 g IV or IM every 4 hours for 14 to 21 days.  The FDA-approved dose is 1 g IV or IM every 4 to 6 hours for severe infections.

100 to 150 mg/kg/day IV or IM divided every 6 hours (Max: 2 g/dose) for 14 to 21 days. The FDA-approved dose is 1 g IV or IM every 4 to 6 hours for severe infections.

100 to 150 mg/kg/day IV or IM divided every 6 hours for 14 to 21 days. The FDA-approved dose is 100 mg/kg/day IV or IM divided every 4 to 6 hours for severe infections.

25 mg/kg/dose IV or IM every 6 hours for 14 to 21 days.  The FDA-approved dose is 25 mg/kg/day IV or IM.

25 mg/kg/dose IV or IM every 8 hours for 14 to 21 days. The FDA-approved dose is 25 mg/kg/day IV or IM.

25 mg/kg/dose IV or IM every 8 hours for 14 to 21 days. The FDA-approved dose is 25 mg/kg/day IV or IM.

25 mg/kg/dose IV or IM every 12 hours for 14 to 21 days.  The FDA-approved dose is 25 mg/kg/day IV or IM.

1 to 2 g IV or IM every 4 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours. The FDA-approved dose is 1 g IV or IM every 4 to 6 hours for severe infections.

50 mg/kg/dose (Max: 2 g/dose) IV or IM every 6 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours. The FDA-approved dose is 1 g IV or IM every 4 to 6 hours for severe infections.

50 mg/kg/dose IV or IM every 6 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours. The FDA-approved dose is 100 mg/kg/day IV or IM divided every 4 to 6 hours for severe infections.

25 mg/kg/dose IV or IM every 6 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours.  The FDA-approved dose is 25 mg/kg/day IV or IM.

25 mg/kg/dose IV or IM every 8 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours. The FDA-approved dose is 25 mg/kg/day IV or IM.

25 mg/kg/dose IV or IM every 8 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours. The FDA-approved dose is 25 mg/kg/day IV or IM.

25 mg/kg/dose IV or IM every 12 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours. The FDA-approved dose is 25 mg/kg/day IV or IM.

1 to 2 g IV or IM every 4 hours for 5 to 10 days plus incision and drainage. The FDA-approved dose is 250 to 500 mg IV or IM every 4 to 6 hours for mild to moderate infections and 1 g IV or IM every 4 to 6 hours for severe infections.

100 to 150 mg/kg/day IV or IM divided every 6 hours (Max: 2 g/dose) for 5 to 10 days plus incision and drainage. The FDA-approved dose is 250 to 500 mg IV or IM every 4 to 6 hours for mild to moderate infections and 1 g IV or IM every 4 to 6 hours for severe infections.

100 to 150 mg/kg/day IV or IM divided every 6 hours for 5 to 10 days plus incision and drainage. The FDA-approved dose is 50 mg/kg/day IV or IM divided every 6 hours for mild to moderate infections and 100 mg/kg/day IV or IM divided every 4 to 6 hours for severe infections.

25 mg/kg/dose IV or IM every 6 hours for 5 to 10 days plus incision and drainage. The FDA-approved dose is 25 mg/kg/day IV or IM.

25 mg/kg/dose IV or IM every 8 hours for 5 to 10 days plus incision and drainage.  The FDA-approved dose is 25 mg/kg/day IV or IM.

25 mg/kg/dose IV or IM every 8 hours for 5 to 10 days plus incision and drainage.  The FDA-approved dose is 25 mg/kg/day IV or IM.

25 mg/kg/dose IV or IM every 12 hours for 5 to 10 days plus incision and drainage.  The FDA-approved dose is 25 mg/kg/day IV or IM.

2 g IV every 4 to 6 hours for 4 to 6 weeks. The FDA-approved dosage is 1 g IV every 4 to 6 hours for severe infections.

100 to 200 mg/kg/day (Max: 12 g/day) IV divided every 4 to 6 hours. Treat for 2 to 4 days or until clinically improved, followed by oral step-down therapy for a total duration of 3 to 4 weeks for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for severe or complicated infections. The FDA-approved dosage is 1 g IV every 4 to 6 hours for severe infections.

100 to 200 mg/kg/day IV divided every 4 to 6 hours. Treat for 2 to 4 days or until clinically improved, followed by oral step-down therapy for a total duration of 3 to 4 weeks for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for severe or complicated infections.

100 to 200 mg/kg/day IV divided every 4 to 6 hours. Treat for 2 to 4 days or until clinically improved, followed by oral step-down therapy for a total duration of 3 to 4 weeks for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for severe or complicated infections.[

100 to 200 mg/kg/day IV divided every 4 to 6 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.

25 mg/kg/dose IV every 6 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections. The FDA-approved dosage is 25 mg/kg/day IV.

25 mg/kg/dose IV every 8 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections. The FDA-approved dosage is 25 mg/kg/day IV.

25 mg/kg/dose IV every 8 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections. The FDA-approved dosage is 25 mg/kg/day IV.

25 mg/kg/dose IV every 12 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections. The FDA-approved dosage is 25 mg/kg/day IV.

2 g IV every 4 to 6 hours.  Treat for 1 to 2 weeks or until clinically improved, followed by oral step-down therapy for 2 to 4 weeks. The FDA-approved dosage is 1 g IV every 4 to 6 hours for severe infections.

100 to 200 mg/kg/day (Max: 12 g/day) IV divided every 4 to 6 hours. Treat for 2 to 4 days or until clinically improved, followed by oral step-down therapy for a total duration of 2 to 3 weeks for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for septic hip arthritis or severe or complicated infections. The FDA-approved dosage is 1 g IV every 4 to 6 hours for severe infections.

100 to 200 mg/kg/day IV divided every 4 to 6 hours. Treat for 2 to 4 days or until clinically improved, followed by oral step-down therapy for a total duration of 2 to 3 weeks for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for septic hip arthritis or severe or complicated infections.

100 to 200 mg/kg/day IV divided every 4 to 6 hours. Treat for 2 to 4 days or until clinically improved, followed by oral step-down therapy for a total duration of 2 to 3 weeks for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for septic hip arthritis or severe or complicated infections.

100 to 200 mg/kg/day IV divided every 4 to 6 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.

25 mg/kg/dose IV every 6 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections. The FDA-approved dosage is 25 mg/kg/day IV.

25 mg/kg/dose IV every 8 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections. The FDA-approved dosage is 25 mg/kg/day IV.

25 mg/kg/dose IV every 8 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections. The FDA-approved dosage is 25 mg/kg/day IV.

25 mg/kg/dose IV every 12 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections. The FDA-approved dosage is 25 mg/kg/day IV.

2 g IV every 4 to 6 hours in combination with rifampin for 2 to 6 weeks, followed by oral step-down therapy, which may be followed by chronic oral suppressive therapy.

2 g IV every 4 to 6 hours for 6 weeks. The FDA-approved dosage is 1 g IV every 4 to 6 hours for severe infections.

1 g IV every 4 hours for 2 to 3 weeks. Generally, 2 weeks is appropriate for most patients; immunocompromised patients may require a longer duration.

100 to 200 mg/kg/day (Max: 12 g/day) IV divided every 4 to 6 hours for 2 to 3 weeks. Generally, 2 weeks is appropriate for most patients; immunocompromised patients may require a longer duration. The FDA-approved dosage is 1 g IV every 4 to 6 hours for severe infections.

100 to 200 mg/kg/day IV divided every 4 to 6 hours for 2 to 3 weeks. Generally, 2 weeks is appropriate for most patients; immunocompromised patients may require a longer duration.

†Indicates off-label use

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Specific guidelines for dosage adjustments in renal impairment are not available. However, oxacillin is significantly eliminated by the kidneys and dosage adjustments may be necessary in patients with renal impairment.

Acetaminophen; Aspirin, ASA; Caffeine: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Acetaminophen; Aspirin: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Acetaminophen; Aspirin; Diphenhydramine: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Aspirin, ASA: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Aspirin, ASA; Butalbital; Caffeine: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Aspirin, ASA; Caffeine: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Aspirin, ASA; Caffeine; Orphenadrine: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Aspirin, ASA; Carisoprodol: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Aspirin, ASA; Carisoprodol; Codeine: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Aspirin, ASA; Dipyridamole: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Aspirin, ASA; Omeprazole: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Aspirin, ASA; Oxycodone: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Butalbital; Aspirin; Caffeine; Codeine: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Caffeine; Sodium Benzoate: (Moderate) Antibiotics that undergo tubular secretion such as penicillins may compete with phenylacetlyglutamine and hippuric acid for active tubular secretion. The overall usefulness of sodium benzoate; sodium phenylacetate is due to the excretion of its metabolites. An increase in metabolite concentrations could contribute to failed treatment and worsening of the patient's clinical status. This combination should be used with caution.
Choline Salicylate; Magnesium Salicylate: (Minor) Due to high protein binding, salicylates could be displaced from binding sites, or could displace other highly protein-bound drugs such as penicillins, and sulfonamides. An enhanced effect of the displaced drug may occur.
Dichlorphenamide: (Moderate) Use dichlorphenamide and oxacillin together with caution. Dichlorphenamide increases potassium excretion and can cause hypokalemia and should be used cautiously with other drugs that may cause hypokalemia including oxacillin. Measure potassium concentrations at baseline and periodically during dichlorphenamide treatment. If hypokalemia occurs or persists, consider reducing the dose or discontinuing dichlorphenamide therapy.
Digoxin: (Minor) Displacement of penicillins from plasma protein binding sites by highly protein bound drugs like digoxin will elevate the level of free penicillin in the serum. The clinical significance of this interaction is unclear. It is recommended to monitor these patients for increased adverse effects.
Ethacrynic Acid: (Minor) Ethacrynic acid may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. This combination should be used with caution and patients monitored for increased side effects.
Furosemide: (Minor) Furosemide may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. This combination should be used with caution and patients monitored for increased side effects.
Indomethacin: (Minor) Indomethacin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. This combination should be used with caution and patients monitored for increased side effects.
Mafenide: (Minor) Sulfonamides may compete with oxacillin for renal tubular secretion, increasing oxacillin serum concentrations. Use this combination with caution, and monitor patients for increased side effects.
Magnesium Salicylate: (Minor) Due to high protein binding, salicylates could be displaced from binding sites, or could displace other highly protein-bound drugs such as penicillins, and sulfonamides. An enhanced effect of the displaced drug may occur.
Methotrexate: (Major) Avoid concomitant use of methotrexate with penicillins due to the risk of severe methotrexate-related adverse reactions. If concomitant use is unavoidable, closely monitor for adverse reactions.
Oral Contraceptives: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Probenecid: (Minor) Probenecid competitively inhibits renal tubular secretion and causes higher, prolonged serum levels of penicillins. In general, this pharmacokinetic interaction is not harmful and can be used therapeutically if needed.
Probenecid; Colchicine: (Minor) Probenecid competitively inhibits renal tubular secretion and causes higher, prolonged serum levels of penicillins. In general, this pharmacokinetic interaction is not harmful and can be used therapeutically if needed.
Salsalate: (Minor) Due to high protein binding, salicylates could be displaced from binding sites or could displace other highly protein-bound drugs such as penicillins. An enhanced effect of the displaced drug may occur.
Sodium Benzoate; Sodium Phenylacetate: (Moderate) Antibiotics that undergo tubular secretion such as penicillins may compete with phenylacetlyglutamine and hippuric acid for active tubular secretion. The overall usefulness of sodium benzoate; sodium phenylacetate is due to the excretion of its metabolites. An increase in metabolite concentrations could contribute to failed treatment and worsening of the patient's clinical status. This combination should be used with caution.
Sodium picosulfate; Magnesium oxide; Anhydrous citric acid: (Major) Prior or concomitant use of antibiotics with sodium picosulfate; magnesium oxide; anhydrous citric acid may reduce efficacy of the bowel preparation as conversion of sodium picosulfate to its active metabolite bis-(p-hydroxy-phenyl)-pyridyl-2-methane (BHPM) is mediated by colonic bacteria. If possible, avoid coadministration. Certain antibiotics (i.e., tetracyclines and quinolones) may chelate with the magnesium in sodium picosulfate; magnesium oxide; anhydrous citric acid solution. Therefore, these antibiotics should be taken at least 2 hours before and not less than 6 hours after the administration of sodium picosulfate; magnesium oxide; anhydrous citric acid solution.
Sulfadiazine: (Minor) Sulfonamides may compete with oxacillin for renal tubular secretion, increasing oxacillin serum concentrations. Use this combination with caution, and monitor patients for increased side effects.
Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Minor) Sulfonamides may compete with oxacillin for renal tubular secretion, increasing oxacillin serum concentrations. Use this combination with caution, and monitor patients for increased side effects.
Sulfasalazine: (Minor) Sulfonamides may compete with oxacillin for renal tubular secretion, increasing oxacillin serum concentrations. Use this combination with caution, and monitor patients for increased side effects.
Sulfonamides: (Minor) Sulfonamides may compete with oxacillin for renal tubular secretion, increasing oxacillin serum concentrations. Use this combination with caution, and monitor patients for increased side effects.
Tetracyclines: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
Typhoid Vaccine: (Major) Antibiotics which possess bacterial activity against salmonella typhi organisms may interfere with the immunological response to the live typhoid vaccine. Allow 24 hours or more to elapse between the administration of the last dose of the antibiotic and the live typhoid vaccine.
Warfarin: (Moderate) The concomitant use of warfarin with many classes of antibiotics, including penicillins, may result in an increased INR thereby potentiating the risk for bleeding. Inhibition of vitamin K synthesis due to alterations in the intestinal flora may be a mechanism; however, concurrent infection is also a potential risk factor for elevated INR. Monitor patients for signs and symptoms of bleeding. Additionally, increased monitoring of the INR, especially during initiation and upon discontinuation of the antibiotic, may be necessary.

Oxacillin/Oxacillin Sodium Intramuscular Inj Pwd F/Sol: 1g, 2g, 10g
Oxacillin/Oxacillin Sodium Intravenous Inj Pwd F/Sol: 1g, 2g, 10g
Oxacillin/Oxacillin Sodium Intravenous Inj Sol: 1g, 2g, 50mL

6 g/day IV/IM is the FDA-approved dosage; however, 12 g/day IV/IM has been used off-label.

6 g/day IV/IM is the FDA-approved dosage; however, 12 g/day IV/IM has been used off-label.

weight 40 kg or more: 6 g/day IV/IM is the FDA-approved dosage; however, up to 200 mg/kg/day IV/IM (Max: 12 g/day) has been used off-label.
weight less than 40 kg: 100 mg/kg/day IV/IM is the FDA-approved dosage; however, up to 200 mg/kg/day IV/IM has been used off-label.

weight 40 kg or more: 6 g/day IV/IM is the FDA-approved dosage; however, up to 200 mg/kg/day IV/IM (Max: 12 g/day) has been used off-label.
weight less than 40 kg: 100 mg/kg/day IV/IM is the FDA-approved dosage; however, up to 200 mg/kg/day IV/IM has been used off-label.

100 mg/kg/day IV/IM is the FDA-approved dosage; however, up to 200 mg/kg/day IV/IM has been used off-label.

25 mg/kg/day IV/IM is FDA-approved for all neonates; however, the following doses have been used off-label:
older than 7 days weighing more than 2 kg: up to 200 mg/kg/day IV/IM.
older than 7 days weighing 2 kg or less: up to 150 mg/kg/day IV/IM.
0 to 7 days weighing more than 2 kg: up to 150 mg/kg/day IV/IM.
0 to 7 days weighing 2 kg or less: up to 100 mg/kg/day IV/IM.

Oxacillin, a beta-lactam antibiotic, is mainly bactericidal. It inhibits the third and final stage of bacterial cell wall synthesis by preferentially binding to specific penicillin-binding proteins (PBPs) that are located inside the bacterial cell wall. PBPs are responsible for several steps in cell wall synthesis and are found in quantities of several hundred to several thousand molecules per bacterial cell. PBPs vary among different bacterial species. Thus, the intrinsic activity of oxacillin and other beta-lactams against a particular organism depends on their ability to gain access to and bind with the necessary PBP. Like all beta-lactam antibiotics, oxacillin's ability to interfere with PBP-mediated cell wall synthesis ultimately leads to cell lysis. Lysis is mediated by bacterial cell wall autolytic enzymes (i.e., autolysins). The relationship between PBPs and autolysins is unclear, but it is possible that the beta-lactam antibiotic interferes with an autolysin inhibitor. Prevention of the autolysin response to beta-lactam antibiotic exposure through loss of autolytic activity (mutation) or inactivation of autolysin (low-medium pH) by the microorganism can lead to tolerance to the beta-lactam antibiotic resulting in bacteriostatic activity.[51465]
 
Oxacillin, because of its side chain, resists destruction by beta-lactamases. This makes it useful for treating bacteria that resist penicillin due to the presence of penicillinase. Oxacillin is ineffective, however, against methicillin-resistant S. aureus (MRSA). These organisms appear to resist oxacillin and related antistaphylococcal penicillins due to the presence of a relatively insensitive PBP, although this mechanism is not fully understood.[53205]
 
Beta-lactams, including oxacillin, exhibit concentration-independent or time-dependent killing. In vitro and in vivo animal studies have demonstrated that the major pharmacodynamic parameter that determines efficacy for beta-lactams is the amount of time free (non-protein bound) drug concentrations exceed the minimum inhibitory concentration (MIC) of the organism (free T above MIC).[34143] [34145] [35436] [35437] [35438] [35439] This microbiological killing pattern is due to the mechanism of action, which is acylation of PBPs. There is a maximum proportion of PBPs that can be acylated; therefore, once maximum acylation has occurred, killing rates cannot increase.[35439] Free beta-lactam concentrations do not have to remain above the MIC for the entire dosing interval. The percentage of time required for both bacteriostatic and maximal bactericidal activity is different for the various classes of beta-lactams. Penicillins require free drug concentrations to exceed the MIC for 30% of the dosing interval to achieve bacteriostatic activity and 50% of the dosing interval to achieve bactericidal activity.[35436] [35437] [35438]
 
The susceptibility interpretive criteria for oxacillin are delineated by pathogen. The MICs are defined for S. aureus and S. lugdunensis as susceptible at 2 mcg/mL or less and resistant at 4 mcg/mL or more. The MICs are defined for other Staphylococcus sp. as susceptible at 0.5 mcg/mL or less and resistant at 1 mcg/mL or more. [63320] [63321]

Oxacillin is administered orally, intravenously, and intramuscularly. Protein binding ranges from 89—94%. Oxacillin is distributed into lungs; bone; bile; sputum; and pleural, pericardial, peritoneal, and synovial fluids. Low levels are attained within the CSF; however, higher concentrations are obtained when the meninges are inflamed. Oxacillin does cross the placenta. Between 45—50% of a dose is metabolized by the liver to active and inactive metabolites. Oxacillin and its metabolites are excreted primarily in the urine via tubular secretion and glomerular filtration. A small percentage may be excreted in breast milk. The elimination half-life of oxacillin is approximately 30 minutes.

Approximately 30% of an oral oxacillin dose is absorbed. Peak serum levels of oxacillin occur within 30—120 minutes following an oral dose. Food in the stomach inhibits the rate and extent of absorption, and oxacillin therefore should be taken on an empty stomach, preferably 1 hour prior to or 2 hours following a meal.

Peak serum levels of oxacillin occur within 30 minutes following an IM dose.

Use of penicillins in human pregnancy has not shown any evidence of harmful effects on the fetus. Animal data have also not demonstrated any evidence of impaired fertility or harmful fetal effects. However, there are no adequate and well-controlled studies in pregnant women showing conclusively that harmful effects of penicillins on the fetus can be excluded. Because animal reproduction studies are not always predictive of human response, oxacillin should be used in pregnant women only if clearly needed.

Penicillins are excreted in breast milk. Use caution when oxacillin is administered to a breast-feeding woman. After oral doses of oxacillin, concentrations in breast milk ranged from 0.04 to 0.68 mg/L. After IV or IM doses of oxacillin, concentrations in breast milk ranged from 0.18 to 0.68 mg/L. In a study in which 10 women received 3 g/day of oxacillin orally for 5 to 6 days, oxacillin was detectable in the urine in 5 of the 6 breast-fed infants with concentrations ranging from 0.2 to 3.7 mg/L. Penicillins may cause diarrhea (due to disruption of GI flora), candidiasis, and skin rash in breast-feeding infants. Unless the infant is allergic to penicillins, breast-feeding is generally safe during maternal penicillin therapy; the infant should be observed for potential effects.