Oxacillin is a semisynthetic antistaphylococcal penicillin. Like other antistaphylococcal penicillins, oxacillin is stable against penicillinase, making it active against penicillinase-producing S. aureus. As a result, its main use is for treating infections caused by this organism, including bacteremia, skin and soft-tissue infections, respiratory tract infections, bone and joint infections, and urinary tract infections. Some clinicians consider oxacillin the parenteral agent of choice, since methicillin has a higher incidence of interstitial nephritis and nafcillin has a higher incidence of phlebitis when administered IV. Oxacillin was approved by the FDA in 1962.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
NOTE: For severe infections, a 4-hour dosing interval is recommended to avoid subtherapeutic serum concentrations at the end of the dosing interval.
Route-Specific Administration
Injectable Administration
-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.
Intravenous Administration
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.
Intramuscular Administration
-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.
Hemorrhagic cystitis has occurred with methicillin use, usually following high-dose administration in patients with impaired renal function.
Hepatotoxicity resembling hepatitis and manifested by elevated hepatic enzymes and hepatomegaly has occurred with a higher frequency following administration of large doses of oxacillin than after other antistaphylococcal penicillins. In most cases, these effects resolved following discontinuation of the drug. It has been suggested than HIV-positive patients are more susceptible to oxacillin-induced hepatotoxicity than HIV-negative patients. Oxacillin should be used with caution in patients with preexisting hepatic dysfunction in HIV-positive patients.
Interstitial nephritis, a hypersensitivity reaction, with renal tubular necrosis (damage) has been reported infrequently with oxacillin use. Acute interstitial nephritis has been reported more frequently with methicillin than with the other penicillinase-producing penicillins. Characterized by rash, eosinophilia, hematuria, proteinuria, and renal insufficiency, the reaction usually regresses with discontinuation of the drug.
Dermatologic and hypersensitivity adverse effects can occur with penicillins, including oxacillin. Hypersensitivity reactions are among the most frequently reported adverse reactions to the penicillins. Penicillin allergy has been reported in up to 20% of patients; however, around 90% of reported allergies are incorrectly reported and patients lack penicillin-specific IgE antibodies. The actual prevalence of penicillin allergy is likely no greater than 5%. Severe reactions, such as anaphylactoid reactions and anaphylactic shock happen rarely (0.015-0.04%) and may include angioedema, laryngospasm, laryngeal edema, bronchospasm, hypotension, vascular collapse, and death. Other reactions include urticaria, pruritus, fever, serum sickness-like symptoms (fever, malaise, myalgia, arthralgia), and rash (unspecified). Rash may develop after the first week and may cover the entire body, including the soles, palms, and oral mucosa. The rash usually disappears in 3-7 days. Other skin reactions which occur infrequently, but can be serious, include Stevens-Johnson syndrome, exfoliative dermatitis, and toxic epidermal necrolysis.
A local injection site reaction, including pain and induration, can occur following IM injection of oxacillin. Phlebitis can occur during therapy with IV oxacillin and is possibly preventable , although some clinicians believe that the incidence of this adverse effect is less than with nafcillin.
Neurotoxic reactions, such as seizures, have been reported when large doses of penicillins were administered to patients with renal impairment. Appropriate dosage adjustments should be observed in these patients. Seizures are rarely reported with methicillin and oxacillin.
Gastrointestinal adverse events may occur in 2% to 5% of patients receiving penicillins. Reported side effects with oxacillin include nausea, vomiting, diarrhea, abdominal pain, stomatitis, black or hairy tongue (tongue discoloration), and other symptoms of gastrointestinal irritation.
Microbial overgrowth and superinfection can occur with antibiotic use. C. difficile-associated diarrhea (CDAD) or pseudomembranous colitis has been reported with oxacillin. If pseudomembranous colitis is suspected or confirmed, ongoing antibacterial therapy not directed against C. difficile may need to be discontinued. Institute appropriate fluid and electrolyte management, protein supplementation, C. difficile-directed antibacterial therapy, and surgical evaluation as clinically appropriate.
Agranulocytosis, neutropenia, and bone marrow depression have been associated with the use of oxacillin.
A false-positive reaction for glucose in the urine has been observed in patients receiving penicillins and using Benedict's solution, Fehling's solution and Clinitest(R) tablets. However, this has not been observed with Tes-tape (glucose Enzymatic Test Strip, USP, Lilly).
Antibiotic therapy can result in superinfection or suprainfection of non-susceptible organisms. Overgrowth of non susceptible organisms can occur with penicillin therapy. Patients should be monitored closely during therapy.
Oxacillin, a penicillin, should not be used in patients with penicillin hypersensitivity. Oxacillin should be used cautiously in patients with carbapenem hypersensitivity, or cephalosporin hypersensitivity. These patients are more susceptible to hypersensitivity reactions during oxacillin therapy. Patients with allergies or allergic conditions including asthma, eczema, hives, or hay fever may have a greater risk for hypersensitivity reactions to penicillins.
Use oxacillin cautiously in patients with fluid and electrolyte imbalance and those who are particularly sensitive to sodium intake (e.g., patients with heart failure or hypertension). The amount of sodium and/or potassium can vary between oxacillin products. For example, oxacillin injection by Baxter Healthcare contains 92.4 mg (4.02 mEq) of sodium per gram. At the usual recommended doses, patients would receive between 92.4 and 554 mg/day (4.02 and 24.1 mEq) of sodium. The elderly may respond to sodium loading with a blunted natriuresis which may be clinically important in regard to such diseases as congestive heart failure. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
Oxacillin should be used cautiously in patients with renal impairment because it is known to be substantially excreted by the kidney. The risk of adverse reactions to this drug may be greater in patients with renal dysfunction. Seizures are possible if excessively large doses are administered to patients with renal failure.
Hepatotoxicity has been associated with oxacillin therapy. Oxacillin should be used cautiously in patients with preexisting hepatic disease.
Consider pseudomembranous colitis in patients presenting with diarrhea after antibacterial use. Careful medical history is necessary as pseudomembranous colitis has been reported to occur over 2 months after the administration of antibacterial agents. Almost all antibacterial agents, including oxacillin, have been associated with pseudomembranous colitis or C. difficile-associated diarrhea (CDAD) which may range in severity from mild to life-threatening. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.
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.
Oxacillin should be used with caution in neonates and infants. Transient hematuria, albuminuria, and azotemia have been reported in neonates and infants receiving large doses of oxacillin (150-175 mg/kg/day).
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.
Because geriatric patients are more likely to have decreased renal function, care should be taken in oxacillin dose selection, and it may be useful to monitor renal function. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents (e.g., geriatric adults) of long-term care facilities. According to OBRA, use of antibiotics should be limited to confirmed or suspected bacterial infections. Antibiotics are non-selective and may result in the eradication of beneficial microorganisms while promoting the emergence of undesired ones, causing secondary infections such as oral thrush, colitis, or vaginitis. Any antibiotic may cause diarrhea, nausea, vomiting, anorexia, and hypersensitivity reactions.
Per the manufacturer, this drug has been shown to be active against most strains of the following microorganisms either in vitro and/or in clinical infections: Staphylococcus aureus (MSSA), Staphylococcus sp.
NOTE: The safety and effectiveness in treating clinical infections due to organisms with in vitro data only have not been established in adequate and well-controlled clinical trials.
For the treatment of bacteremia due to methicillin-sensitive S. aureus:
Intravenous or Intramuscular dosage:
Adults: 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.
Children and Adolescents weighing 40 kg or more: 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.
Infants, Children, and Adolescents weighing less than 40 kg: 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.
Neonates older than 34 weeks gestation and older than 7 days: 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.
Neonates older than 34 weeks gestation and 0 to 7 days: 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.
Neonates 34 weeks gestation and younger and older than 7 days: 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.
Neonates 34 weeks gestation and younger and 0 to 7 days: 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.
For the treatment of infective endocarditis:
Intravenous dosage (Intermittent IV Infusion):
Adults: 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.
Children and Adolescents weighing 40 kg or more: 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.
Children and Adolescents weighing less than 40 kg: 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.
Infants: 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.
Neonates older than 34 weeks gestation and older than 7 days: 25 mg/kg/dose IV every 6 hours. The FDA-approved dosage is 25 mg/kg/day IV.
Neonates older than 34 weeks gestation and 0 to 7 days: 25 mg/kg/dose IV every 8 hours. The FDA-approved dosage is 25 mg/kg/day IV.
Neonates 34 weeks gestation and younger and older than 7 days: 25 mg/kg/dose IV every 8 hours. The FDA-approved dosage is 25 mg/kg/day IV.
Neonates 34 weeks gestation and younger and 0 to 7 days: 25 mg/kg/dose IV every 12 hours. The FDA-approved dosage is 25 mg/kg/day IV.
Intravenous dosage (Continuous IV Infusion)*:
Adults: 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).
For the treatment of bacterial meningitis:
Intravenous dosage:
Adults: 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.
Infants, Children, and Adolescents weighing 40 kg or more: 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.
Infants, Children, and Adolescents weighing less than 40 kg: 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.
Neonates older than 7 days weighing more than 2 kg: 50 mg/kg/dose IV every 6 hours. The FDA-approved dosage is 25 mg/kg/day IV.
Neonates older than 7 days weighing 2 kg or less: 50 mg/kg/dose IV every 8 hours. The FDA-approved dosage is 25 mg/kg/day IV.
Neonates 0 to 7 days weighing more than 2 kg: 50 mg/kg/dose IV every 8 hours. The FDA-approved dosage is 25 mg/kg/day IV.
Neonates 0 to 7 days weighing 2 kg or less: 50 mg/kg/dose IV every 12 hours. The FDA-approved dosage is 25 mg/kg/day IV.
For the treatment of lower respiratory tract infections (LRTIs), including community-acquired pneumonia (CAP):
-for the treatment of nonspecific lower respiratory tract infections (LRTIs):
Intravenous or Intramuscular dosage:
Adults: 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.
Children and Adolescents weighing 40 kg or more: 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.
Infants, Children, and Adolescents weighing less than 40 kg: 150 to 200 mg/kg/day IV or IM divided every 4 to 6 hours (Max: 2 g/dose). 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.
Neonates older than 34 weeks gestation and older than 7 days: 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.
Neonates older than 34 weeks gestation and 0 to 7 days: 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.
Neonates 34 weeks gestation and younger and older than 7 days: 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.
Neonates 34 weeks gestation and younger and 0 to 7 days: 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.
-for the treatment of community-acquired pneumonia (CAP):
Intravenous or Intramuscular dosage:
Infants 4 to 11 months, Children, and Adolescents: 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.
For the treatment of mastitis:
Intravenous dosage:
Adults: 1 to 2 g IV every 4 hours for 10 to 14 days.
For the treatment of neonatal mastitis:
Intravenous dosage:
Infants 1 to 2 months: 100 to 200 mg/kg/day IV divided every 4 to 6 hours.
Neonates older than 34 weeks gestation and older than 7 days: 25 mg/kg/dose IV every 6 hours.
Neonates older than 34 weeks gestation and 0 to 7 days: 25 mg/kg/dose IV every 8 hours.
Neonates 34 weeks gestation and younger and older than 7 days: 25 mg/kg/dose IV every 8 hours.
Neonates 34 weeks gestation and younger and 0 to 7 days: 25 mg/kg/dose IV every 12 hours.
For the treatment of bone and joint infections, including osteomyelitis, infectious arthritis, infectious bursitis, and orthopedic device-related infection*:
-for the treatment of unspecified osteomyelitis due to methicillin-sensitive S. aureus:
Intravenous dosage:
Adults: 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.
Children and Adolescents weighing 40 kg or more: 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.
Children and Adolescents weighing less than 40 kg: 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.
Infants 3 to 11 months: 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.[
Infants 1 to 2 months: 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.
Neonates older than 34 weeks gestation and older than 7 days: 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.
Neonates older than 34 weeks gestation and 0 to 7 days: 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.
Neonates 34 weeks gestation and younger and older than 7 days: 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.
Neonates 34 weeks gestation and younger and 0 to 7 days: 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.
-for the treatment of native vertebral osteomyelitis due to methicillin-sensitive S. aureus:
Intravenous dosage:
Adults: 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.
-for the treatment of infectious arthritis due to methicillin-sensitive S. aureus:
Intravenous dosage:
Adults: 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.
Children and Adolescents weighing 40 kg or more: 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.
Children and Adolescents weighing less than 40 kg: 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.
Infants 3 to 11 months: 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.
Infants 1 to 2 months: 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.
Neonates older than 34 weeks gestation and older than 7 days: 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.
Neonates older than 34 weeks gestation and 0 to 7 days: 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.
Neonates 34 weeks gestation and younger and older than 7 days: 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.
Neonates 34 weeks gestation and younger and 0 to 7 days: 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.
-for the treatment of infectious bursitis due to methicillin-sensitive S. aureus:
Intravenous dosage:
Adults: 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.
Children and Adolescents weighing 40 kg or more: 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.
Children and Adolescents weighing less than 40 kg: 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.
-for the treatment of prosthetic joint infections due to methicillin-sensitive S. aureus:
Intravenous dosage:
Adults: 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.
For the treatment of skin and skin structure infections, including cellulitis, erysipelas, skin abscesses, furunculosis, carbuncle, necrotizing infections, pyomyositis, and surgical incision site infections:
-for the treatment of nonpurulent skin infections, including cellulitis and erysipelas, due to methicillin-sensitive S. aureus:
Intravenous or Intramuscular dosage:
Adults: 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.
Children and Adolescents weighing 40 kg or more: 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.
Infants, Children, and Adolescents weighing less than 40 kg: 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.
Neonates older than 34 weeks gestation and older than 7 days: 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.
Neonates older than 34 weeks gestation and 0 to 7 days: 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.
Neonates 34 weeks gestation and younger and older than 7 days: 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.
Neonates 34 weeks gestation and younger and 0 to 7 days: 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.
Continuous Intravenous Infusion dosage*:
Adults: 500 mg/hour (12 g/day) continuous IV infusion for 5 to 14 days.
-for the treatment of purulent skin infections, including carbuncle, furunculosis, and skin abscesses, due to methicillin-sensitive S. aureus:
Intravenous or Intramuscular dosage:
Adults: 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.
Children and Adolescents weighing 40 kg or more: 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.
Infants, Children, and Adolescents weighing less than 40 kg: 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.
Neonates older than 34 weeks gestation and older than 7 days: 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.
Neonates older than 34 weeks gestation and 0 to 7 days: 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.
Neonates 34 weeks gestation and younger and older than 7 days: 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.
Neonates 34 weeks gestation and younger and 0 to 7 days: 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.
-for the treatment of necrotizing infections of the skin, fascia, and muscle due to methicillin-sensitive S. aureus:
Intravenous or Intramuscular dosage:
Adults: 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.
Children and Adolescents weighing 40 kg or more: 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.
Infants, Children, and Adolescents weighing less than 40 kg: 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.
Neonates older than 34 weeks gestation and older than 7 days: 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.
Neonates older than 34 weeks gestation and 0 to 7 days: 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.
Neonates 34 weeks gestation and younger and older than 7 days: 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.
Neonates 34 weeks gestation and younger and 0 to 7 days: 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.
-for the treatment of pyomyositis due to methicillin-sensitive S. aureus:
Intravenous or Intramuscular dosage:
Adults: 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.
Children and Adolescents weighing 40 kg or more: 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.
Infants, Children, and Adolescents weighing less than 40 kg: 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.
Neonates older than 34 weeks gestation and older than 7 days: 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.
Neonates older than 34 weeks gestation and 0 to 7 days: 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.
Neonates 34 weeks gestation and younger and older than 7 days: 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.
Neonates 34 weeks gestation and younger and 0 to 7 days: 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.
-for the treatment of surgical incision site infections:
Intravenous dosage:
Adults: 2 g IV every 6 hours for incisional surgical site infections of the trunk or extremity away from the axilla or perineum.
Maximum Dosage Limits:
-Adults
6 g/day IV/IM is the FDA-approved dosage; however, 12 g/day IV/IM has been used off-label.
-Geriatric
6 g/day IV/IM is the FDA-approved dosage; however, 12 g/day IV/IM has been used off-label.
-Adolescents
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.
-Children
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.
-Infants
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.
-Neonates
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.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
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.
*non-FDA-approved indication
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, 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; 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.
Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (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.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (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.
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.
Demeclocycline: (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.
Desogestrel; Ethinyl Estradiol: (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.
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.
Dienogest; Estradiol valerate: (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.
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.
Doxycycline: (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.
Drospirenone: (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.
Drospirenone; Estetrol: (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.
Drospirenone; Estradiol: (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.
Drospirenone; Ethinyl Estradiol: (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.
Drospirenone; Ethinyl Estradiol; Levomefolate: (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.
Elagolix; Estradiol; Norethindrone acetate: (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.
Estradiol; Levonorgestrel: (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.
Estradiol; Norethindrone: (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.
Estradiol; Norgestimate: (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.
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.
Ethinyl Estradiol; Norelgestromin: (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.
Ethinyl Estradiol; Norethindrone Acetate: (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.
Ethinyl Estradiol; Norgestrel: (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.
Ethynodiol Diacetate; Ethinyl Estradiol: (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.
Etonogestrel; Ethinyl Estradiol: (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.
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.
Leuprolide; Norethindrone: (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.
Levonorgestrel: (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.
Levonorgestrel; Ethinyl Estradiol: (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.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (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.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (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.
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.
Minocycline: (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.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (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.
Norethindrone: (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.
Norethindrone; Ethinyl Estradiol: (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.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (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.
Norgestimate; Ethinyl Estradiol: (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.
Norgestrel: (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.
Omadacycline: (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.
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.
Relugolix; Estradiol; Norethindrone acetate: (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.
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.
Sarecycline: (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.
Segesterone Acetate; Ethinyl Estradiol: (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.
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.
Tetracycline: (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.
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, 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.
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.
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). 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. 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.
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.
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.
-Route-Specific Pharmacokinetics
Oral Route
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.
Intramuscular Route
Peak serum levels of oxacillin occur within 30 minutes following an IM dose.
-Special Populations
Renal Impairment
Oxacillin is significantly eliminated by the kidneys. Although dosage recommendations are not provided in the product labeling, the manufacturer states that dosage adjustments may be necessary in patients with renal impairment.