Version July 2025
Note: Dose and duration of therapy can vary depending on infecting organism, severity of infection, and clinical response of patient. Treat severe staphylococcal infections for at least 14 days; endocarditis and osteomyelitis require an extended duration of therapy for 4 to 6 weeks. The intravenous route should be used for severe infections.
Usual dosage range:
Oral: 250 to 500 mg every 6 hours; may increase dose for serious infections (maximum dose: 6 g/day).
IM, IV: 1 to 2 g every 4 to 6 hours (Ref).
Bloodstream infection due to methicillin-susceptible Staphylococcus aureus: IV: 2 g every 4 to 6 hours (Ref); treat uncomplicated S. aureus bacteremia for ≥14 days starting from day of first negative blood culture, with longer courses warranted for endocarditis or metastatic sites of infection (Ref).
Osteomyelitis due to methicillin-susceptible Staphylococcus aureus: IV: 2 g every 4 hours for ≥6 weeks (Ref).
Skin and soft tissue infection:
Localized purulent skin lesions, impetigo: Oral: 250 to 500 mg every 6 hours for 5 to 7 days (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Kidney impairment prior to treatment initiation:
Altered kidney function:
Oral: No dosage adjustment necessary.
IV:
CrCl ≥10 mL/minute: No dosage adjustment necessary.
CrCl <10 mL/minute: No specific dosage adjustment recommended; however, monitor patients closely as studies conducted in critically ill patients with severe kidney impairment have found supratherapeutic cloxacillin concentrations (eg, >100 mg/L) in this population as well as neurotoxicity and nephrotoxicity (Ref). When treating less severe infections, consider limiting dose to 8 g/day (Ref).
Hemodialysis, intermittent (thrice weekly): Not significantly dialyzed (Ref):
Oral, IV: Dose as per CrCl <10 mL/minute (Ref).
Peritoneal dialysis: Unlikely to be significantly dialyzed (highly protein bound) (Ref):
Oral, IV: Dose as per CrCl <10 mL/minute (Ref).
CRRT:
Note: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Recommendations are based on high-flux dialyzers and effluent flow rates of 20 to 25 mL/kg/hour (or ~1,500 to 3,000 mL/hour) and minimal residual kidney function unless otherwise noted. Appropriate dosing requires consideration of adequate drug concentrations (eg, site of infection). Close monitoring of response and adverse reactions (eg, neurotoxicity) due to drug accumulation is important.
Oral, IV: No dosage adjustment necessary (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration):
Note: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Appropriate dosing requires consideration of adequate drug concentrations (eg, site of infection). Close monitoring of response and adverse reactions (eg, neurotoxicity) due to drug accumulation is important.
Oral, IV: No dosage adjustment necessary (Ref).
Nephrotoxicity during treatment: Nephrotoxicity has been reported with cloxacillin use, particularly in patients receiving high-dose IV therapy (eg, ≥8 g per day). Risk factors include older age (eg, >75 years of age) and concomitant use of other nephrotoxins. If acute kidney injury occurs, discontinue cloxacillin and administer an alternate antibiotic (Ref).
There are no dosage adjustments provided in the manufacturer’s labeling.
Refer to adult dosing.
(For additional information see "Cloxacillin (United States: Not available): Pediatric drug information")
Dosage guidance:
Dosage form information: Not available in the United States.
General dosing:
Note: Doses are presented in mg/kg or fixed mg doses depending on weight; use caution. Duration depends on patient-specific factors including site of infection and clinical response.
Oral: Children and Adolescents (Ref):
5 to <40 kg: Oral: 50 mg/kg/day in divided doses every 6 hours.
≥40 kg: Oral: 250 to 500 mg every 6 hours. For very severe infections, higher doses may be required; maximum daily dose: 6,000 mg/day.
Parenteral: Infants, Children, and Adolescents: IV, IM: 100 to 200 mg/kg/day in divided doses every 6 hours (Ref); maximum dose: 2,000 mg/dose (Ref).
Endocarditis (methicillin-susceptible Staphylococcus aureus): Children and Adolescents: IV: 200 to 300 mg/kg/day divided every 4 to 6 hours (Ref); maximum dose: 2,000 mg/dose (Ref). Recommended treatment duration is 4 to 6 weeks for native valve endocarditis and ≥6 weeks (as part of an appropriate combination regimen) for prosthetic valve endocarditis (Ref).
Osteoarticular infection, acute (eg, bacterial arthritis, osteomyelitis):
IV: Children and Adolescents: IV: 100 to 200 mg/kg/day in divided doses every 4 to 6 hours (Ref); maximum dose: 2,000 mg/dose (Ref); maximum daily dose: 12,000 mg/day (Ref). May transition to oral therapy as appropriate (eg, following initial response to parenteral therapy, tolerating oral intake) (Ref).
Oral step-down therapy: Children and Adolescents: Oral: 100 mg/kg/day in divided doses every 6 hours; maximum dose: 1,000 mg/dose (Ref).
Duration of therapy: Minimum total duration is 10 to 14 days for bacterial arthritis and 21 to 28 days for osteomyelitis; however, duration may be longer and should be individualized based on several factors, including causative pathogen, response to therapy, and normalization of inflammatory markers (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling.
There are no dosage adjustments provided in the manufacturer’s labeling.
The following adverse drug reactions are derived from product labeling unless otherwise specified. Reactions listed are based on reports for other agents in this same pharmacologic class and may not be specifically reported for cloxacillin.
Postmarketing:
Cardiovascular: Thrombophlebitis (IV)
Dermatologic: Acute generalized exanthematous pustulosis (Choon 2018), erythematous maculopapular rash (Moreno-Ancillo 2003)
Endocrine & metabolic: Hypokalemia (Nagasayi 2017)
Gastrointestinal: Clostridioides difficile colitis, diarrhea, epigastric discomfort, esophagitis (Zezos 2016), flatulence, hairy tongue, loose stools, nausea, stomatitis, vomiting (St John 1981)
Genitourinary: Hematuria (St John 1981)
Hematologic & oncologic: Agranulocytosis (Mani 2017), anemia, eosinophilia (Jayaweera 2018), granulocytopenia, hemolytic anemia, immune thrombocytopenia, leukopenia (St John 1981), neutropenia (Jayaweera 2018), thrombocytopenia
Hepatic: Cholestatic hepatitis (Goland 1998), cholestatic jaundice (Enat 1980), hepatic disease (vanishing bile duct syndrome) (Faragalia 2022), hepatotoxicity, increased serum alkaline phosphatase, increased serum transaminases (including increased serum alanine aminotransferase and increased serum aspartate aminotransferase) (St. John 1981)
Hypersensitivity: Anaphylaxis, angioedema, hypersensitivity angiitis (Garcia-Porrua 1999), hypersensitivity reaction (Rodriguez-Jimenez 2009), type IV hypersensitivity reaction (Moreno-Ancillo 2003)
Renal: Interstitial nephritis (Grimm 1989) renal tubular disease
Miscellaneous: Fever
Hypersensitivity to cloxacillin, other penicillins, cephalosporins, or any component of the formulation
Concerns related to adverse effects:
• Anaphylactoid/hypersensitivity reactions: Serious and occasionally severe or fatal hypersensitivity (anaphylactoid) reactions have been reported in patients on penicillin therapy, especially with a history of beta-lactam hypersensitivity, history of sensitivity to multiple allergens, or previous IgE-mediated reactions (eg, anaphylaxis, angioedema, urticaria). Use with caution in asthmatic patients.
• CNS effects: Although not reported with cloxacillin, the transport of penicillins across the blood-brain barrier may be enhanced by inflamed meninges or during cardiopulmonary bypass. An increased risk of myoclonia, seizures, or reduced consciousness may be observed in these patients (particularly those with renal failure).
• Hematologic effects: Penicillin use has been associated with hematologic disorders (eg, agranulocytosis, neutropenia, thrombocytopenia) believed to be a hypersensitivity phenomena. Reactions are most often reversible upon discontinuing therapy.
• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
Disease-related concerns:
• Renal impairment: Use with caution in patients with renal impairment; rate of elimination is reduced.
• Seizure disorders: Use with caution in patients with a history of seizure disorder; high serum levels, particularly in the presence of renal impairment, may increase risk for seizures.
Special populations:
• Neonates: May have decreased renal clearance of cloxacillin; frequent evaluation of serum levels and of clinical status for adverse effects as well as frequent dosage adjustments may be necessary in this patient population.
Not available in the US
Yes
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Generic: 250 mg, 500 mg
Solution Reconstituted, Injection:
Generic: 500 mg (1 ea); 1 g (1 ea); 2 g (1 ea); 10 g (1 ea)
Suspension Reconstituted, Oral:
Generic: 125 mg/5 mL (60 mL, 100 mL, 200 mL)
Oral: Administer with water 1 hour before or 2 hours after meals.
IV:
IV push: Administer slowly over 2 to 4 minutes.
IV infusion: Administer over 30 to 40 minutes.
Oral: Administer 1 to 2 hours before meals.
Oral solution: Shake well. Administer liquid with an accurate measuring device; do not use a household teaspoon (under- or overdosage may occur).
Parenteral:
IM: Administer in appropriate anatomical site for age.
IV push: Administer slowly over 2 to 4 minutes.
IV infusion: Administer over 30 to 60 minutes (Ref).
Note: Not approved in the United States.
Bacterial infections: Treatment of bacterial infections (eg, bloodstream infection, endocarditis, pneumonia, bone and joint infections, skin and soft-tissue infections) caused by susceptible strains of penicillinase-producing staphylococci.
Limitations of use: Exhibits good activity against Staphylococcus aureus; has activity against many streptococci, but is less active than penicillin. Not effective against methicillin-resistant staphylococci.
Substrate of OAT1/3;
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Acemetacin: May increase serum concentration of Penicillins. Risk C: Monitor
Aminoglycosides: Penicillins may decrease serum concentration of Aminoglycosides. Primarily associated with extended spectrum penicillins, and patients with renal dysfunction. Risk C: Monitor
Bacillus clausii: Antibiotics may decrease therapeutic effects of Bacillus clausii. Management: Bacillus clausii should be taken in between antibiotic doses during concomitant therapy. Risk D: Consider Therapy Modification
BCG (Intravesical): Antibiotics may decrease therapeutic effects of BCG (Intravesical). Risk X: Avoid
BCG Vaccine (Immunization): Antibiotics may decrease therapeutic effects of BCG Vaccine (Immunization). Risk C: Monitor
Cholera Vaccine: Antibiotics may decrease therapeutic effects of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Risk X: Avoid
Dichlorphenamide: Penicillins may increase hypokalemic effects of Dichlorphenamide. Risk C: Monitor
Fecal Microbiota (Live) (Oral): May decrease therapeutic effects of Antibiotics. Risk X: Avoid
Fecal Microbiota (Live) (Rectal): Antibiotics may decrease therapeutic effects of Fecal Microbiota (Live) (Rectal). Risk X: Avoid
Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies): Antibiotics may decrease therapeutic effects of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor
Lactobacillus and Estriol: Antibiotics may decrease therapeutic effects of Lactobacillus and Estriol. Risk C: Monitor
Methotrexate: Penicillins may increase serum concentration of Methotrexate. Risk C: Monitor
Mycophenolate: Antibiotics may decrease active metabolite exposure of Mycophenolate. Specifically, concentrations of mycophenolic acid (MPA) may be reduced. Risk C: Monitor
Probenecid: May increase serum concentration of Penicillins. Risk C: Monitor
Sodium Benzoate: Penicillins may decrease therapeutic effects of Sodium Benzoate. Risk C: Monitor
Sodium Picosulfate: Antibiotics may decrease therapeutic effects of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Risk D: Consider Therapy Modification
Tetracyclines: May decrease therapeutic effects of Penicillins. Risk C: Monitor
Typhoid Vaccine: Antibiotics may decrease therapeutic effects of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Avoid use of live attenuated typhoid vaccine (Ty21a) in patients being treated with systemic antibacterial agents. Postpone vaccination until 3 days after cessation of antibiotics and avoid starting antibiotics within 3 days of last vaccine dose. Risk D: Consider Therapy Modification
Vancomycin: Cloxacillin may increase nephrotoxic effects of Vancomycin. Risk C: Monitor
Vitamin K Antagonists: Cloxacillin may decrease anticoagulant effects of Vitamin K Antagonists. Cloxacillin may increase anticoagulant effects of Vitamin K Antagonists. Risk C: Monitor
Food decreases cloxacillin absorption; serum levels are reduced by ~50%. Management: Administer with water on an empty stomach 1 hour before or 2 hours after meals.
Penicillin class antibiotics cross the placenta in varying degrees. Cloxacillin is highly protein bound which may influence fetal exposure (Nau 1987).
As a class, penicillin antibiotics are widely used in pregnant women. Based on available data, penicillin antibiotics are generally considered compatible for use during pregnancy (Ailes 2016; Bookstaver 2015; Crider 2009; Damkier 2019; Lamont 2014; Muanda 2017a; Muanda 2017b).
Cloxacillin is present in breast milk.
Concentrations of penicillin class antibiotics in breast milk are limited (Nau 1987). Following a single dose of cloxacillin 500 mg IM to 2 or 3 women 5 to 7 days postpartum, breast milk concentrations were ≤0.4 mcg/mL over a 6-hour period, with the highest concentrations observed 4 to 6 hours after the maternal dose. In contrast, the highest maternal serum concentration (3.7 mcg/mL) was found 1 hour after the dose, decreasing to ≤0.3 mcg/mL 6 hours after the dose (Matsuda 1984).
A prospective cohort study evaluated the outcomes of breastfed infants whose mothers were taking various medications. Among 10 mother-infant pairs with reported cloxacillin exposure (dose, duration, relationship to breastfeeding not provided), diarrhea was reported in 2 infants (Ito 1993).
In general, antibiotics that are present in breast milk may cause non-dose-related modification of bowel flora. Monitor infants for GI disturbances, such as thrush or diarrhea. Cloxacillin is considered compatible with breastfeeding when used in usual recommended doses (WHO 2002).
Observe for signs and symptoms of anaphylaxis during first dose; CBC with differential (prior to initiating therapy and weekly thereafter), periodic urinalysis, BUN, creatinine, hepatic function
Inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins (PBPs) which in turn inhibit the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis. Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested.
Absorption: Oral: ~50%; reduced by food
Distribution: Widely to most body fluids and bone; penetration into cells, into eye, and across normal meninges is poor; inflammation increases amount that crosses blood-brain barrier
Protein binding: ~94% (primarily albumin)
Metabolism: Hepatic to active and inactive metabolites
Half-life elimination: 0.5 to 1.5 hours; prolonged with renal impairment and in neonates
Time to peak, serum: Oral: ~1 hour
Excretion: Urine and feces
