Dicloxacillin Sodium

Antibacterial; β-lactam antibiotic; isoxazolyl penicillin classified as a penicillinase-resistant penicillin.1 2 6 7 18 29 30 37

Contraindications

• Known hypersensitivity to any penicillin.1 2 6

Warnings/Precautions

Sensitivity Reactions

Serious and occasionally fatal hypersensitivity reactions, including anaphylaxis, reported with penicillins.1 2 Anaphylaxis occurs most frequently with parenteral penicillins but has occurred with oral penicillins.1 2

Prior to initiation of therapy, make careful inquiry regarding previous hypersensitivity reactions to penicillins, cephalosporins, or other drugs.1 2 Partial cross-allergenicity occurs among penicillins and other β-lactam antibiotics including cephalosporins and cephamycins.1 2 22 23 24 25

If a severe hypersensitivity reaction occurs, discontinue immediately and institute appropriate therapy as indicated (e.g., epinephrine, corticosteroids, maintenance of an adequate airway and oxygen).1 2

General Precautions

Possible emergence and overgrowth of nonsusceptible bacteria or fungi.1 2 Discontinue and institute appropriate therapy if superinfection occurs.1 2

Periodically assess organ system functions, including renal, hepatic, and hematopoietic, during prolonged therapy.1

Peform urinalysis and determine serum creatinine and BUN concentrations prior to and periodically during therapy.1 2

To monitor for hepatotoxicity, determine AST and ALT concentrations prior to and periodically during therapy.1 2

Because adverse hematologic effects have occurred with penicillinase-resistant penicillins, total and differential WBC counts should be performed prior to and 1–3 times weekly during therapy.1 2 5 6 26 27

To reduce development of drug-resistant bacteria and maintain effectiveness of dicloxacillin and other antibacterials, use only for treatment or prevention of infections proven or strongly suspected to be caused by susceptible bacteria.

When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing.1 2 In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.1 2

Consider that staphylococci resistant to penicillinase-resistant penicillins (referred to as oxacillin-resistant [methicillin-resistant] staphylococci) are being reported with increasing frequency.a

If dicloxacillin used empirically for treatment of any infection suspected of being caused by staphylococci, the drug should be discontinued and appropriate anti-infective therapy substituted if the infection is found to be caused by any organism other than penicillinase-producing staphylococci susceptible to penicillinase-resistant penicillins.1 2 If staphylococci resistant to penicillinase-resistant penicillins (oxacillin-resistant staphylococci) are prevalent in the hospital or community, empiric therapy of suspected staphylococcal infections should include another appropriate anti-infective (e.g., vancomycin).a

Each 250-mg capsule contains approximately 0.6 mEq of sodium.52

Specific Populations

Category B.1 2 6

Distributed into milk.1 2 6 28 Use with caution.1 2 6

Elimination of penicillins is delayed in neonates because of immature mechanisms for renal excretion; abnormally high serum concentrations may occur in this age group.1 2 6

If used in neonates, monitor closely for clinical and laboratory evidence of toxic or adverse effects, determine serum concentrations frequently, and make appropriate reductions in dosage and frequency of administration when indicated.1 2 6

Common Adverse Effects

GI effects (nausea, vomiting, epigastric distress, loose stools, diarrhea, flatulence); hypersensitivity reactions.a

Absorption

Bioavailability

Rapidly, but incompletely, absorbed from GI tract.1 2 7 33

35–76% of an oral dose absorbed from GI tract;33 34 35 peak serum concentrations generally attained within 0.5–2 hours.1 2 35 36

Food

Food in the GI tract generally decreases the rate and extent of absorption.1 2 4 6 7 29 35

Distribution

Extent

Distributed into bone,4 39 bile,1 2 pleural fluid,1 2 4 7 ascitic fluid,4 and synovial fluid.4 40

Only minimal concentrations attained in CSF.2

Crosses the placenta42 and is distributed into milk.1 2 6 28

Plasma Protein Binding

95–99% bound to serum proteins.1 2 7 31 34 37 41

Elimination

Metabolism

Partially metabolized to active and inactive metabolites.4 43 46 47

Approximately 10% of absorbed drug is hydrolyzed to penicilloic acids which are microbiologically inactive;46 also hydroxylated to a small extent to a microbiologically active metabolite which appears to be slightly less active than dicloxacillin.47

Elimination Route

Dicloxacillin and its metabolites rapidly eliminated in urine mainly by tubular secretion and glomerular filtration.1 2 7 29 43 47 Also partly excreted in feces via biliary elimination.4

31–65% of a dose excreted in urine as unchanged drug and active metabolites within 6–8 hours;4 31 32 34 36 46 47 approximately 10–20% of this is the active metabolite.4 47

Only minimally removed by hemodialysis4 10 20 34 43 44 49 or peritoneal dialysis.4 44 49

Half-life

Adults with normal renal function: 0.6–0.8 hours.1 2 4 33 34 43 44 45

Children 2–16 years of age: average half-life is 1.9 hours.39

Neonates: half-life is longer than in older children.4 6

Special Populations

Patients with renal impairment: serum half-life is slightly prolonged and may range from 1–2.2 hours in those with severe renal impairment.4 33 34 45

Patients with cystic fibrosis eliminate dicloxacillin approximately 3 times faster than healthy individuals.7 48

Storage

Oral

15–30°C52 in tight containers.50

• Based on spectrum of activity, classified as a penicillinase-resistant penicillin.1 2 6 7 29 30 31 32

• Usually bactericidal.1 2

• Like other β-lactam antibiotics, antibacterial activity results from inhibition of bacterial cell wall synthesis.1 2

• Spectrum of activity includes many gram-positive aerobic cocci, some gram-positive bacilli, and a few gram-negative aerobic cocci; generally inactive against gram-negative bacilli and anaerobic bacteria.a Inactive against mycobacteria, Mycoplasma, Rickettsia, fungi, and viruses.a

• Gram-positive aerobes: active in vitro against penicillinase-producing and nonpenicillinase-producing Staphylococcus aureus and S. epidermidis, S. pyogenes (group A β-hemolytic streptococci), S. agalactiae (group B streptococci), groups C and G streptococci, S. pneumoniae, and some viridans streptococci.a Enterococci (including E. faecalis) usually are resistant.a

• Like other penicillinase-resistant penicillins, dicloxacillin is resistant to inactivation by staphylococcal penicillinases and is active against many penicillinase-producing strains of S. aureus and S. epidermidis resistant to natural penicillins, aminopenicillins, or extended-spectrum penicillins.1 2 4 6 7 30 31 32

• Staphylococci resistant to penicillinase-resistant penicillins (referred to as oxacillin-resistant [methicillin-resistant] staphylococci) are being reported with increasing frequency.a Complete cross-resistance occurs among the penicillinase-resistant penicillins (dicloxacillin, nafcillin, oxacillin).a