Prosthetic joint infection (alternative agent): Oral continuation therapy for methicillin-susceptible S. aureus (following pathogen-specific IV therapy in patients undergoing 1-stage exchange or debridement with retention of prosthesis):
Oral: 500 mg 3 or 4 times daily (IDSA [Osmon 2013]). Note: Duration ranges from a minimum of 3 months to indefinitely, depending on patient-specific factors. For the first 3 to 6 months of therapy, combine with rifampin (Berbari 2021; IDSA [Osmon 2013]).
Skin and soft tissue infection:
Note: Not an appropriate agent if methicillin-resistant S. aureus is suspected or confirmed (Baddour 2021; IDSA [Stevens 2014]).
Cellulitis (nonpurulent)/erysipelas, mild: Oral: 500 mg 4 times daily for 5 days; duration may be extended up to 14 days if not resolved/slow response (IDSA [Stevens 2014]; Spelman 2021).
Impetigo or ecthyma: Note: For impetigo, reserve systemic therapy for patients with numerous lesions or in outbreak settings to decrease transmission (IDSA [Stevens 2014]).
Oral: 250 to 500 mg 4 times daily for 7 days (Baddour 2021; IDSA [Stevens 2014]).
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 specific dosage adjustments provided in the manufacturer's labeling; a reduction in total dosage should be considered in renal impairment.
Hemodialysis: Not dialyzable; supplemental dose is not necessary (Aronoff 2007).
Peritoneal dialysis effects: Supplemental dose is not necessary (Aronoff 2007).
There are no dosage adjustments provided in the manufacturer's labeling.
(For additional information see "Dicloxacillin: Pediatric drug information")
General dosing, susceptible infection (Bradley 2016; Red Book [AAP 2015]): Infants, Children, and Adolescents:
Mild to moderate infection: Oral: 12 to 25 mg/kg/day divided every 6 hours; maximum dose: 250 mg/dose
Severe infection (step-down therapy of bone and joint infection): Oral: 100 mg/kg/day divided every 6 hours; maximum dose: 500 mg/dose
Skin and soft tissue infection, methicillin-susceptible Staphylococcus aureus (MSSA): Infants, Children, and Adolescents: Oral: 25 to 50 mg/kg/day divided every 6 hours; maximum dose: 500 mg/dose (IDSA [Stevens 2014])
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Infants, Children, and Adolescents: There are no specific dosage adjustments provided in the manufacturer’s labeling; a reduction in total dosage should be considered.
Hemodialysis: Not dialyzable
Peritoneal dialysis: Not dialyzable
There are no dosage adjustments provided in the manufacturer’s labeling.
Refer to adult dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Generic: 250 mg, 500 mg
Yes
Oral: Administer 1 hour before or 2 hours after meals with at least 120 mL of water. Should not be administered in the supine position or immediately before going to bed.
Oral: Administer with water 1 hour before or 2 hours after meals with at least 4 ounces of water; should not be administered in the supine position or immediately before going to bed.
Staphylococcal infections: Treatment of infections caused by penicillinase-producing staphylococci.
KIDs List: Dicloxacillin, when used in neonates, is identified on the Key Potentially Inappropriate Drugs in Pediatrics (KIDs) list and should be used with caution due to risk of kernicterus (weak recommendation; very low quality of evidence) (PPA [Meyers 2020]).
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
Frequency not defined.
1% to 10%: Gastrointestinal: Abdominal pain diarrhea, nausea
<1%, postmarketing, and/or case reports: Agranulocytosis, anemia, eosinophilia, fever, hematuria, hemolytic anemia, hepatotoxicity, hypersensitivity reaction, increased blood urea nitrogen, increased liver enzymes (transient), increased serum creatinine, interstitial nephritis, leukopenia, neutropenia, prolonged prothrombin time, pseudomembranous colitis, seizure (with extremely high doses and/or renal failure), serum sickness-like reaction, skin rash (maculopapular rash to exfoliative dermatitis), thrombocytopenia, vaginitis, vomiting
Hypersensitivity to dicloxacillin, other penicillins, or any component of the formulation.
Documentation of allergenic cross-reactivity for beta-lactams (eg, penicillins, cephalosporins) is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.
Concerns related to adverse effects:
• Hypersensitivity reactions: Serious and occasionally fatal hypersensitivity (anaphylactic shock with collapse) reactions have been reported in patients on penicillin therapy. Initiate therapy only after a comprehensive drug and allergy history; use with caution in patients with a history of significant allergies and/or asthma. Discontinue use and institute appropriate therapy if a hypersensitivity reaction occurs.
• 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.
Special populations:
• Neonates: Use with caution in neonates; elimination of drug is slow.
Induces CYP2C19 (moderate), CYP2C9 (weak), CYP3A4 (weak)
Abrocitinib: CYP2C19 Inducers (Moderate) may decrease the serum concentration of Abrocitinib. Risk C: Monitor therapy
Acemetacin: May increase the serum concentration of Penicillins. Risk C: Monitor therapy
Aminoglycosides: Penicillins may decrease the serum concentration of Aminoglycosides. Primarily associated with extended spectrum penicillins, and patients with renal dysfunction. Risk C: Monitor therapy
BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Risk C: Monitor therapy
Brivaracetam: CYP2C19 Inducers (Moderate) may decrease the serum concentration of Brivaracetam. Risk C: Monitor therapy
CarBAMazepine: CYP3A4 Inducers (Weak) may decrease the serum concentration of CarBAMazepine. Risk C: Monitor therapy
Carisoprodol: CYP2C19 Inducers (Moderate) may increase serum concentrations of the active metabolite(s) of Carisoprodol. CYP2C19 Inducers (Moderate) may decrease the serum concentration of Carisoprodol. Risk C: Monitor therapy
Cholera Vaccine: Antibiotics may diminish the therapeutic effect 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 combination
CloZAPine: CYP3A4 Inducers (Weak) may decrease the serum concentration of CloZAPine. Risk C: Monitor therapy
DiazePAM: CYP2C19 Inducers (Moderate) may decrease the serum concentration of DiazePAM. Risk C: Monitor therapy
Dichlorphenamide: Penicillins may enhance the hypokalemic effect of Dichlorphenamide. Risk C: Monitor therapy
Etravirine: CYP2C19 Inducers (Moderate) may decrease the serum concentration of Etravirine. Risk C: Monitor therapy
Fosphenytoin-Phenytoin: CYP2C19 Inducers (Moderate) may decrease the serum concentration of Fosphenytoin-Phenytoin. Risk C: Monitor therapy
Hormonal Contraceptives: CYP3A4 Inducers (Weak) may decrease the serum concentration of Hormonal Contraceptives. Management: Advise patients to use an alternative method of contraception or a back-up method during coadministration, and to continue back-up contraception for 28 days after discontinuing a weak CYP3A4 inducer to ensure contraceptive reliability. Risk D: Consider therapy modification
Immune Checkpoint Inhibitors: Antibiotics may diminish the therapeutic effect of Immune Checkpoint Inhibitors. Risk C: Monitor therapy
Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Risk C: Monitor therapy
Methotrexate: Penicillins may increase the serum concentration of Methotrexate. Risk C: 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. Risk C: Monitor therapy
Nelfinavir: CYP2C19 Inducers (Moderate) may decrease the serum concentration of Nelfinavir. Risk C: Monitor therapy
NiMODipine: CYP3A4 Inducers (Weak) may decrease the serum concentration of NiMODipine. Risk C: Monitor therapy
Omeprazole: CYP2C19 Inducers (Moderate) may decrease the serum concentration of Omeprazole. Risk C: Monitor therapy
Ospemifene: Dicloxacillin may decrease the serum concentration of Ospemifene. Risk C: Monitor therapy
Probenecid: May increase the serum concentration of Penicillins. Risk C: Monitor therapy
Selpercatinib: CYP3A4 Inducers (Weak) may decrease the serum concentration of Selpercatinib. Risk C: Monitor therapy
Sirolimus (Conventional): CYP3A4 Inducers (Weak) may decrease the serum concentration of Sirolimus (Conventional). Risk C: Monitor therapy
Sirolimus (Protein Bound): CYP3A4 Inducers (Weak) may decrease the serum concentration of Sirolimus (Protein Bound). Risk C: Monitor therapy
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. Risk D: Consider therapy modification
Tacrolimus (Systemic): CYP3A4 Inducers (Weak) may decrease the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy
Tetracyclines: May diminish the therapeutic effect of Penicillins. Risk C: Monitor therapy
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect 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
Ubrogepant: CYP3A4 Inducers (Weak) may decrease the serum concentration of Ubrogepant. Management: Use an initial ubrogepant dose of 100 mg and second dose (if needed) of 100 mg when used with a weak CYP3A4 inducer. Risk D: Consider therapy modification
Vitamin K Antagonists (eg, warfarin): Dicloxacillin may diminish the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy
Voriconazole: CYP2C19 Inducers (Moderate) may decrease the serum concentration of Voriconazole. Risk C: Monitor therapy
Food decreases drug absorption rate and serum concentration. Management: Administer on an empty stomach with a large glass of water 1 hour before or 2 hours after meals.
Dicloxacillin crosses the placenta (Depp 1970; MacAulay 1968; Seiga 1974).
Penicillin class antibiotics cross the placenta in varying degrees. Dicloxacillin 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).
Dicloxacillin is present in breast milk (Matsuda 1984; Muysson 2020).
The relative infant dose (RID) of dicloxacillin is 0.09% to 0.18% when calculated using the highest breast milk concentration located and compared to an infant therapeutic dose of 25 to 50 mg/kg/day.
In general, breastfeeding is considered acceptable when the RID is <10% (Anderson 2016; Ito 2000).
The RID of dicloxacillin was calculated using a milk concentration of 0.3 mcg/mL, providing an estimated daily infant dose via breast milk of 0.045 mg/kg/day. This milk concentration was obtained following maternal administration of a single oral dose of dicloxacillin 250 mg to 2 or 3 women 5 to 7 days postpartum. Breast milk concentrations were ≤0.3 mcg/mL over a 6-hour period, with the highest concentrations observed 4 hours after the maternal dose. In contrast, the highest maternal serum concentration (5.2 mcg/mL) was found 1 hour after the dose, decreasing to ≤0.4 mcg/mL 6 hours after the dose (Matsuda 1984). The RID of dicloxacillin was calculated by the authors of a second study following multiple doses for the treatment of mastitis. Included were 3 women, 1 to 6 months postpartum, receiving dicloxacillin 500 mg every 6 hours; breast milk was sampled at intervals from 0 to 6 hours after the maternal dose on or after the fourth day of therapy. The highest breast milk concentration was 0.0676 mcg/mL, which occurred 4 hours after the maternal dose. Authors of the study calculated the RID of dicloxacillin to be 0.03% of the weight-adjusted maternal dose, providing an estimated daily dose of 0.008 mg/kg/day via breast milk (Muysson 2020).
In general, antibiotics that are present in breast milk may cause non-dose-related modification of bowel flora. Monitor infants for GI disturbances (WHO 2002).
Although the manufacturer recommends that caution be exercised when administering dicloxacillin to breastfeeding women, penicillins are considered compatible with breastfeeding when used in usual recommended doses (WHO 2002).
Dicloxacillin may be used to treat mastitis in lactating women. The treatment of mastitis with antibiotics is generally not considered unless symptoms do not improve with conservative management or the woman is acutely ill (ABM [Amir 2014]; WHO 2000). Penicillinase-resistant antibiotics are preferred when antibiotics are clinically indicated for treatment. Dicloxacillin is one of the suggested therapies (ABM [Amir 2014]).
Baseline and periodic CBC with differential; periodic BUN, serum creatinine, AST and ALT (especially with prolonged therapy); prothrombin time if patient concurrently on warfarin; signs of anaphylaxis during first dose
Inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins (PBPs) which in turn inhibits 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: Rapid and incomplete; reduced by food
Distribution: Vd: 5.99 L; increased in patients with ESRD on IHD (Nauta 1976); CSF penetration is low
Protein binding: 95% to 99% (primarily albumin)
Bioavailability: 49% to 76% (Nauta 1976)
Half-life elimination: ~0.7 hours; prolonged with renal impairment (Nauta 1976)
Time to peak, serum: 1 to 1.5 hours
Excretion: Feces; urine (as unchanged drug);
Neonates: Prolonged
CF patients: More rapid excretion than healthy patients (Jusko 1975)
Capsules (Dicloxacillin Sodium Oral)
250 mg (per each): $0.66 - $1.38
500 mg (per each): $1.20 - $2.51
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