Version January 2024
Mastitis, lactational: Oral: 500 mg 4 times daily for 10 to 14 days; shorter courses (eg, 5 to 7 days) may be considered for patients with rapid clinical resolution (Ref).
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 (Ref). 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 (Ref).
Skin and soft tissue infection:
Note: Not an appropriate agent if methicillin-resistant S. aureus is suspected or confirmed (Ref).
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 (Ref).
Impetigo or ecthyma: Note: For impetigo, reserve systemic therapy for patients with numerous lesions or in outbreak settings to decrease transmission (Ref).
Oral: 250 to 500 mg 4 times daily for 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.
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 (Ref).
Peritoneal dialysis effects: Supplemental dose is not necessary (Ref).
There are no dosage adjustments provided in the manufacturer's labeling.
Refer to adult dosing.
(For additional information see "Dicloxacillin: Pediatric drug information")
General dosing: Infants, Children, and Adolescents: Oral: 3 to 6.25 mg/kg/dose every 6 hours; maximum dose: 250 mg/dose. Higher doses are recommended for some infections (eg, osteoarticular infections, skin and soft tissue infections) (Ref).
Osteoarticular infection; eg, septic (bacterial) arthritis, osteomyelitis: Step-down therapy following parenteral treatment:
Infants, Children, and Adolescents: Oral: 25 mg/kg/dose every 6 hours; maximum dose: 500 mg/dose (Ref). Minimum total duration is 2 to 3 weeks for septic arthritis and 3 to 4 weeks for osteomyelitis; however, duration is often longer and individualized based on several factors, including causative pathogen, response to therapy, and normalization of inflammatory markers (Ref).
Skin and soft tissue infection, methicillin-susceptible Staphylococcus aureus (MSSA): Infants, Children, and Adolescents: Oral: 6.25 to 12.5 mg/kg/dose every 6 hours; maximum dose: 500 mg/dose (Ref).
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.
The following adverse drug reactions and incidences 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 dicloxacillin.
Postmarketing:
Dermatologic: Skin photosensitivity (acute exanthematous pustulosis; Nielsen 2020), skin rash (Drivenes 2022)
Endocrine & metabolic: Hypokalemia (Johnson 2002)
Gastrointestinal: Cholestasis (Gosbell 2000), Clostridioides difficile colitis, diarrhea, esophageal ulcer, esophagitis, hairy tongue, heartburn, melanoglossia, nausea, stomatitis, vomiting
Hematologic & oncologic: Agranulocytosis, anemia, eosinophilia, granulocytopenia, hemolytic anemia, leukopenia, neutropenia, thrombocytopenia
Hepatic: Cholestatic hepatitis (Kleinman 1986), hepatotoxicity (Gosbell 2000), increased serum alanine aminotransferase, increased serum alkaline phosphatase, increased serum aspartate aminotransferase
Hypersensitivity: Hypersensitivity reaction (including anaphylaxis, angioedema, serum sickness-like reaction, type 1 hypersensitivity reaction and type IV hypersensitivity reaction)
Renal: Interstitial nephritis (Gosbell 2000), renal insufficiency (Gosbell 2000), renal tubular disease
Hypersensitivity to dicloxacillin, other penicillins, or any component of the formulation.
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.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Generic: 250 mg, 500 mg
Yes
Capsules (Dicloxacillin Sodium Oral)
250 mg (per each): $1.38 - $1.50
500 mg (per each): $2.51 - $2.73
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
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 120 mL (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]).
Substrate of OAT1/3; Induces CYP2C19 (moderate), CYP2C9 (weak), CYP3A4 (weak)
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 Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
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
Atogepant: CYP3A4 Inducers (Weak) may decrease the serum concentration of Atogepant. Management: For treatment of episodic migraine, the recommended dose of atogepant is 30 mg once daily or 60 mg once daily when combined with CYP3A4 inducers. When used for treatment of chronic migraine, use of atogepant with CYP3A4 inducers should be avoided. Risk D: Consider therapy modification
Bacillus clausii: Antibiotics may diminish the therapeutic effect 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 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
Fecal Microbiota (Live) (Oral): May diminish the therapeutic effect of Antibiotics. Risk X: Avoid combination
Fecal Microbiota (Live) (Rectal): Antibiotics may diminish the therapeutic effect of Fecal Microbiota (Live) (Rectal). Risk X: Avoid combination
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 (Anti-PD-1, -PD-L1, and -CTLA4 Therapies): Antibiotics may diminish the therapeutic effect of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor therapy
Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Risk C: Monitor therapy
Mavacamten: CYP2C19 Inducers (Moderate) may decrease the serum concentration of Mavacamten. Risk X: Avoid combination
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 Benzoate: Penicillins may diminish the therapeutic effect of Sodium Benzoate. 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).
Data related to the presence of dicloxacillin in breast milk has been located from 2 studies.
• A single oral dose of dicloxacillin 250 mg was administered 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). Using a breast milk concentration of 0.3 mcg/mL, the relative infant dose (RID) of dicloxacillin is 0.09% to 0.18% compared to an infant therapeutic dose of 25 to 50 mg/kg/day, providing an estimated daily infant dose via breast milk of 0.045 mg/kg/day.
• 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, breastfeeding is considered acceptable when the RID is <10% (Anderson 2016; Ito 2000).
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 (WHO 2002).
Although the manufacturer recommends that caution be exercised when administering dicloxacillin to patients who are breastfeeding, penicillins are considered compatible with breastfeeding when used in usual recommended doses (WHO 2002).
Dicloxacillin is a recommended antibiotic for the empiric treatment of bacterial mastitis in patients who are breastfeeding. Antibiotic use may be considered when symptoms are present for >24 hours and have not responded to conservative measures, or the patient has symptoms such as fever or tachycardia. Consider a milk culture if symptoms do not improve after 48 hours of antibiotic therapy. The diagnosis of mastitis does not require interruption of breastfeeding (ABM [Mitchell 2022]; WHO 2000).
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: CSF penetration is low.
Vd:
Infants and Children: 0.295 ± 0.092 L/kg (range: 0.08 to 0.512 L/kg) (Smith 1990).
Adults: 5.99 L; increased in patients with ESRD on IHD (Nauta 1976).
Protein binding: 95% to 99% (primarily albumin).
Bioavailability:
Infants and Children: 59.89% ± 24.44% (Smith 1990).
Adults: 49% to 76% (Nauta 1976).
Half-life elimination:
Infants and Children: 32 minutes (Smith 1990).
Adults: ~0.7 hours; prolonged with renal impairment (Nauta 1976).
Time to peak, serum:
Infants and Children: 1.68 ± 0.84 hours (range: 0.58 to 3.7 hours) (Smith 1990).
Adults: 1 to 1.5 hours.
Excretion: Feces; urine (as unchanged drug):
Neonates: Prolonged.
CF patients: More rapid excretion than healthy patients (Jusko 1975).
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