(kloks a SIL in)
Note: Not approved in the US
Bacterial infections: Treatment of bacterial infections including endocarditis, pneumonia, bone and joint infections, skin and soft-tissue infections, and sepsis that are 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 and is generally not used in clinical practice to treat streptococcal infections. Not effective against methicillin-resistant staphylococci.
Hypersensitivity to cloxacillin, other penicillins, cephalosporins, or any component of the formulation
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.
Susceptible infections (manufacturer 's labeling):
Oral: 250 to 500 mg every 6 hours (maximum adult dose: 6 g/day)
IM: 250 to 500 mg every 6 hours (maximum adult dose: 6 g/day). Note: Doses up to 2 g every 4 to 6 hours or 8 to 12 g/day in divided doses have been recommended by others (see indication-specific dosing).
IV: 250 to 500 mg every 6 hours (maximum adult dose 6 g/day). Note: Doses up to 2 g every 4 to 6 hours or 8 to 12 g/day in divided doses have been recommended by others (see indication-specific dosing).
Dosing recommendations of World Health Organization (WHO) unless otherwise noted:
Arthritis (septic) (off-label dosing) (WHO 2001): Empiric therapy: Adults: IM, IV: 2 g every 6 hours with concomitant ceftriaxone
Methicillin-sensitive Staphylococcus aureus (MSSA): IM, IV: 2 g every 6 hours for 2 to 3 weeks; Note: Cloxacillin oral therapy of 1 g every 6 hours may be used to complete therapy if parenteral therapy is discontinued prior to 2 to 3 week duration
Endocarditis (MSSA) (off-label dosing): IV:
Native valve: 2 g every 4 hours for 6 weeks; may give with gentamicin for initial 5 days (Choudri 2000)
Prosthetic valve: 2 g every 4 hours for 6 weeks; give with gentamicin for 2 weeks and rifampin for 6 weeks (Choudri 2000)
Uncomplicated endocarditis in IV drug users: 2 g every 4 hours for 4 weeks and gentamicin for initial 5 days or 2 g every 4 hours and gentamicin both given for 2 weeks total (Choudri 2000)
Osteomyelitis (MSSA) (off-label dosing) (WHO 2001): IM, IV: 2 g every 6 hours for 4 to 6 weeks (preferred) or for a minimum of 14 days, followed by 1 g every 6 hours orally to complete 4 to 6 weeks of therapy
Pneumonia (MSSA) (off-label dosing) (WHO 2001): IM, IV: 1 to 2 g every 6 hours for 10 to 14 days
Pneumonia (nosocomial) (off-label dosing) (WHO 2001): Empiric therapy: IV: 1 to 2 g every 6 hours with concomitant gentamicin for 7 days (add vancomycin for 10 to 14 days if in a hospital with a high prevalence of MRSA)
Septicemia (off-label dosing) (WHO 2001): Empiric therapy: IV: 2 g every 4 to 6 hours with concomitant gentamicin
Skin and soft tissue infections (off-label dosing) (WHO 2001): Empiric therapy:
Contaminated soft tissue injuries: IM, IV: 2 g every 6 hours for 5 to 10 days with concomitant gentamicin and metronidazole; with clinical improvement, may switch to oral cloxacillin 500 mg every 6 hours
Localized purulent skin lesions, impetigo: Oral: 250 to 500 mg every 6 hours for 5 to 7 days
Pyomyositis: IM, IV: 2 g every 6 hours for 5 to 10 days; with clinical improvement, may switch to oral cloxacillin 500 mg every 6 hours
Refer to adult dosing.
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.
Susceptible infections (manufacturer 's labeling):
Oral:
Children ≤20 kg: 25 to 50 mg/kg/day in divided doses every 6 hours
Children and Adolescents >20 kg: Refer to adult dosing.
IM, IV:
Children ≤20 kg: 25 to 50 mg/kg/day in divided doses every 6 hours. Note: Doses up to 50 mg/kg/dose every 4 to 6 hours or 200 mg/kg to 300 mg/kg/day in divided doses have been recommended by others (Nunn 2007; St. John 1981) (also see indication-specific dosing).
Children and Adolescents >20 kg: Refer to adult dosing.
Dosing recommendations of World Health Organization (WHO) unless otherwise noted:
Arthritis (septic) (off-label dosing) (WHO 2001): Empiric therapy: Infants ≥2 months, Children, and Adolescents: IM, IV: 25 to 50 mg/kg/dose (maximum: 2 g/dose) every 6 hours with concomitant ceftriaxone
Methicillin-sensitive Staphylococcus aureus (MSSA):
Infants ≥2 months and Children ≤5 years: IM, IV: 25 to 50 mg/kg/dose (maximum: 2 g/dose) every 4 to 6 hours with concomitant ceftriaxone for 4 to 6 days or until clinical improvement, followed by oral cloxacillin 12.5 mg/kg/dose (maximum: 500 mg/dose) every 6 hours; total duration of therapy 2 to 3 weeks
Children >5 years and Adolescents: IM, IV: 25 to 50 mg/kg/dose (maximum: 2 g/dose) every 4 to 6 hours (maximum daily dose: 12 g/day) for 4 to 6 days or until clinical improvement, followed by oral cloxacillin 25 mg/kg/dose (maximum: 500 mg/dose) every 6 hours; total duration of therapy 2 to 3 weeks
Endocarditis (MSSA) (off-label dosing) (WHO 2001): Children and Adolescents: IV: 50 mg/kg/dose (maximum: 2 g/dose) every 4 hours for 6 weeks; with concomitant gentamicin for initial 7 days
Osteomyelitis (off-label dosing) (WHO 2001):
Haemophilus influenza or unknown pathogen: Infants ≥2 months and Children ≤5 years: IM, IV: 25 to 50 mg/kg/dose (maximum: 2 g/dose) every 4 to 6 hours with concomitant ceftriaxone for 4 to 6 days or until clinical improvement, followed by oral therapy with amoxicillin/clavulanate; total duration of therapy 3 to 4 weeks
MSSA:
Infants ≥2 months and Children ≤5 years: IM, IV: 25 to 50 mg/kg/dose (maximum: 2 g/dose) every 4 to 6 hours with concomitant ceftriaxone for 4 to 6 days until clinical improvement, followed by oral cloxacillin 12.5 mg/kg/dose (maximum: 500 mg/dose) every 6 hours; total duration of therapy 3 to 4 weeks
Children >5 years and Adolescents: IM, IV: 25 to 50 mg/kg/dose (maximum: 2 g/dose) every 4 to 6 hours (maximum daily dose: 12 g/day) for 4 to 6 days until clinical improvement, followed by oral cloxacillin 25 mg/kg/dose (maximum: 500 mg/dose) every 6 hours; total duration of therapy 3 to 4 weeks
Salmonella spp: Infants ≥2 months and Children ≤5 years: IM, IV: 25 to 50 mg/kg/dose (maximum: 2 g/dose) every 4 to 6 hours with concomitant ceftriaxone for 4 to 6 days or until clinical improvement, followed by oral therapy with sulfamethoxazole/trimethoprim or amoxicillin or ciprofloxacin; total duration of therapy 6 weeks.
Pneumonia (MSSA) (off-label dosing) (WHO 2001):
Infants ≥2 months and Children ≤5 years: Oral: 25 to 50 mg/kg/dose (maximum: 2 g/dose) every 6 hours for at least 3 weeks with concomitant gentamicin
Children >5 years and Adolescents: IM, IV: 50 mg/kg/dose (maximum: 2 g/dose) every 6 hours for 10 to 14 days
Pneumonia (nosocomial) (off-label dosing) (WHO 2001): Empiric therapy: Children and Adolescents: IV: 50 mg/kg/dose (maximum: 2 g/dose) every 6 hours with concomitant gentamicin for 7 days (add vancomycin for 10 to 14 days if in a hospital with a high prevalence of MRSA)
Septicemia (off-label dosing) (WHO 2001): Empiric therapy:
Infants ≥2 months to 5 years: IV: 50 mg/kg/dose (maximum: 2 g/dose) every 4 to 6 hours with concomitant ceftriaxone
Children >5 years and Adolescents: IV: 2 g every 4 to 6 hours with concomitant gentamicin
Skin and soft tissue infections (off-label dosing) (WHO 2001): Empiric therapy:
Contaminated soft tissue injuries: Children and Adolescents: IM, IV: 25 to 50 mg/kg/dose (maximum: 2 g/dose) every 6 hours for 5 to 10 days with concomitant gentamicin and metronidazole; with clinical improvement, may switch to oral cloxacillin 12.5 to 25 mg/kg/dose (maximum: 500 mg) every 6 hours
Localized purulent skin lesions, impetigo: Children and Adolescents: Oral: 12.5 to 25 mg/kg/dose (maximum: 500 mg/dose) every 6 hours for 5 to 7 days
Pyomyositis: Children and Adolescents: IM, IV: 25 to 50 mg/kg/dose (maximum: 2 g/dose) every 6 hours for 5 to 10 days; with clinical improvement, may switch to oral cloxacillin 12.5 to 25 mg/kg/dose (maximum: 500 mg/dose) every 6 hours
No dosage adjustment necessary.
There are no dosage adjustments provided in the manufacturer 's labeling.
IM injection: Reconstitute vial with appropriate volume of SWFI to make a final concentration of 125 mg/mL or 250 mg/mL
IV injection: Reconstitute vial with appropriate volume of SWFI to make a final concentration of 50 mg/mL or 100 mg/mL
IV infusion: Reconstitute vial with appropriate volume of SWFI to make a concentration of 250 mg/mL, followed by further dilution in a compatible solution.
Powder for oral solution:
60 mL bottle: Reconstitute by adding 42 mL of sterile water to make a final concentration of 125 mg/5 mL.
100 mL bottle: Reconstitute by adding 70 mL of sterile water to make a final concentration of 125 mg/5 mL.
200 mL bottle: Reconstitute by adding 140 mL of sterile water to make a final concentration of 125 mg/5 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
Capsule: Store at room temperature not exceeding 25 ‹ šC (77 ‹ šF).
Powder for injection: Store at controlled room temperature 15 ‚ °C to 30 ‚ °C (59 ‚ °F to 86 ‚ °F). Upon reconstitution the resulting solution is stable for up to 24 hours at controlled room temperature not exceeding 25 ‹ šC (77 ‹ šF) or up to 48 hours under refrigeration 2 ‚ °C to 8 ‚ °C (36 ‚ °F to 46 ‚ °F).
IV infusion: Note: After reconstitution of powder with appropriate volume of sterile water for injection, the manufacturer suggests further dilution to concentrations of 1 to 2 mg/mL in a compatible solution (eg, D5W, NS); solutions are stable for up to 12 hours at controlled room temperature.
Powder for oral solution: Prior to mixing, store powder at room temperature not exceeding 25 ‹ šC (77 ‹ šF). Refrigerate oral solution after reconstitution; discard after 14 days.
Solutions: Stable in NS, D5W, LR
Y-site administration: Incompatible with pantoprazole, vancomycin.
Compatibility in syringe: Incompatible with erythromycin, gentamicin, pantoprazole, polymyxin B.
BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Avoid combination
BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Monitor therapy
Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Avoid combination
Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Monitor therapy
Methotrexate: Penicillins may increase the serum concentration of Methotrexate. Monitor therapy
Mycophenolate: Penicillins may decrease serum concentrations of the active metabolite(s) of Mycophenolate. This effect appears to be the result of impaired enterohepatic recirculation. Monitor therapy
Probenecid: May increase the serum concentration of Penicillins. Management: Avoid the routine use of penicillins and probenecid, but this combination may be used advantageously in select cases with careful monitoring. Monitor for toxic effects of penicillins if probenecid is initiated or the dose is increased. Consider therapy modification
Sodium Picosulfate: Antibiotics may diminish the therapeutic effect 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. Consider therapy modification
Tetracycline Derivatives: May diminish the therapeutic effect of Penicillins. Consider therapy modification
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Vaccination with live attenuated typhoid vaccine (Ty21a) should be avoided in patients being treated with systemic antibacterial agents. Use of this vaccine should be postponed until at least 3 days after cessation of antibacterial agents. Consider therapy modification
Vitamin K Antagonists (eg, warfarin): Cloxacillin may diminish the anticoagulant effect of Vitamin K Antagonists. Cloxacillin may enhance the anticoagulant effect of Vitamin K Antagonists. Monitor therapy
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
May interfere with urinary glucose tests using cupric sulfate (Benedicts solution, Clinitest); may inactivate aminoglycosides in vitro; false-positive urine and serum proteins; false-positive in uric acid, urinary steroids
Frequency not defined. Adverse effects may be reported as class effects rather than specific to cloxacillin.
Cardiovascular: Hypotension, thrombophlebitis
Central nervous system: Confusion, lethargy, myoclonus, seizure (high doses and/or renal failure), twitching
Dermatologic: Pruritus, skin rash, urticaria
Gastrointestinal: Abdominal pain, diarrhea, epigastric distress, flatulence, hairy tongue, loose stools, melanoglossia, nausea, oral candidiasis, pseudomembranous colitis, stomatitis, vomiting
Genitourinary: Hematuria, proteinuria
Hematologic & oncologic: Agranulocytosis, anemia, bone marrow depression, eosinophilia, granulocytopenia, hemolytic anemia, immune thrombocytopenia, leukopenia, neutropenia, thrombocytopenia
Hepatic: Increased serum alkaline phosphatase, increased serum ALT, increased serum AST, hepatotoxicity
Hypersensitivity: Anaphylaxis, angioedema, hypersensitivity reaction (immediate and delayed)
Immunologic: Serum sickness-like reaction
Neuromuscular & skeletal: Laryngospasm
Renal: Interstitial nephritis, renal insufficiency, renal tubular disease
Respiratory: Bronchospasm, laryngeal edema, sneezing, wheezing
Miscellaneous: Fever
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.
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
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.
Cloxacillin crosses the placenta and distributes into fetal tissue
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.
Oral: ~50%; reduced by food
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
Hepatic to active and inactive metabolites
Urine and feces
Oral: Serum: ~1 hour
0.5 to 1.5 hours; prolonged with renal impairment and in neonates
~94% (primarily albumin)
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience abdominal pain or gas. Have patient report immediately to prescriber sneezing, severe nausea, severe vomiting, severe diarrhea, bruising, bleeding, seizures, or vaginitis (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.