Class: Penicillinase-resistant Penicillins
Chemical Name: [2S - (2α,5α,6β)] - 6 - [[[3 - (2,6 - Dichlorophenyl) - 5 - methyl - 4 - isoxazolyl]carbonyl]amino] - 3,3 - dimethyl - 7 - oxo - 4 - thia - 1 - azabicyclo[3.2.0]heptane - 2 - carboxylic acid monosodium salt monohydrate
CAS Number: 13412-64-1
Uses for Dicloxacillin Sodium
Should not be used for initial treatment of severe, life-threatening infections, including endocarditis, but may be used as follow-up after a parenteral penicillinase-resistant penicillin (nafcillin, oxacillin).1 2 5 6 8 9
If used empirically, consider whether staphylococci resistant to penicillinase-resistant penicillins (oxacillin-resistant [methicillin-resistant] staphylococci) are prevalent in the hospital or community.a (See Staphylococci Resistant to Penicillinase-resistant Penicillins under Cautions.)
Dicloxacillin Sodium Dosage and Administration
Duration of treatment depends on type and severity of infection and should be determined by the clinical and bacteriologic response of the patient.1 2 5 6 8 Usually continued for ≥48 hours after cultures are negative and patient becomes afebrile and asymptomatic.1 2 For severe staphylococcal infections, continue therapy for ≥14 days;1 2 5 6 more prolonged therapy is necessary for treatment of osteomyelitis, endocarditis, or other metastatic infections.1 2 5 6 13 54
Mild to Moderate InfectionsOral
Children ≥1 month of age: AAP recommends 25–50 mg/kg daily in 4 divided doses.9
More Severe InfectionsOral
Inappropriate for severe infections per AAP.9
Acute or Chronic OsteomyelitisOral
50–100 mg/kg daily given in divided doses every 6 hours as follow-up to initial parenteral therapy.12 13 14 16 54 If an oral regimen is used, compliance must be assured and some clinicians suggest that serum bactericidal titers (SBTs) be used to monitor adequacy of therapy and adjust dosage.13 14 15 16 17 53 54
When used as follow-up in treatment of acute osteomyelitis, oral regimen usually given for 3–6 weeks or until total duration of parenteral and oral therapy is ≥6 weeks;12 13 14 16 54 when used as follow-up in treatment of chronic osteomyelitis, oral regimen usually given for ≥1–2 months and has been given for as long as 1–2 years.13 18 54
Mild to Moderate InfectionsOral
More Severe InfectionsOral
Cautions for Dicloxacillin Sodium
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
Periodically assess organ system functions, including renal, hepatic, and hematopoietic, during prolonged therapy.1
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
Selection and Use of Anti-infectives
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
Staphylococci Resistant to Penicillinase-resistant Penicillins
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
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
Interactions for Dicloxacillin Sodium
In vitro evidence of synergistic antibacterial effects against penicillinase-producing and nonpenicillinase-producing S. aureusa
Anticoagulants, oral (warfarin)
Possible decreased hypothrombinemic effecta
Monitor PTs and adjust anticoagulant dosage if indicateda
Dicloxacillin Sodium Pharmacokinetics
Only minimal concentrations attained in CSF.2
Plasma Protein Binding
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
Children 2–16 years of age: average half-life is 1.9 hours.39
Actions and Spectrum
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
Advice to Patients
Advise patients that antibacterials (including dicloxacillin) should only be used to treat bacterial infections and not used to treat viral infections (e.g., the common cold).
Advise patients that skipping doses or not completing the full course of therapy may decrease effectiveness and increase the likelihood that bacteria will develop resistance and will not be treatable with dicloxacillin or other antibacterials in the future.
Importance of discontinuing dicloxacillin and notifying clinician if they develop shortness of breath, wheezing, rash, mouth irritation, black tongue, sore throat, nausea, vomiting, diarrhea, fever, swollen joints, or any unusual bleeding or bruising during dicloxacillin treatment.1 2
Importance of women informing clinician if they are or plan to become pregnant or to breast-feed.1
Importance of informing patients of other important precautionary information. (See Cautions.)
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
250 mg (of dicloxacillin)*
500 mg (of dicloxacillin)*
AHFS DI Essentials. © Copyright, 2004-2016, Selected Revisions May 1, 2004. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.
1. Apothecon. Dicloxacillin sodium capsules, USP prescribing information. Princeton, NJ; 1995 Apr.
2. Teva Pharmaceuticals. Dicloxacillin sodium capsules, USP prescribing information. Sellersville, PA; 1997 Jul.
3. Anon. The choice of antibacterial drugs. Med Lett Drugs Ther. 2001; 43:69-78. [PubMed 11518876]
4. Neu HC. Antistaphylococcal penicillins. Med Clin North Am. 1982; 66:51-60. [PubMed 7038340]
5. Kunin CM. Penicillinase-resistant penicillins. JAMA. 1977; 237:1605-6. [PubMed 576661]
6. US Food and Drug Administration. Penicillinase-resistant penicillin human prescription drugs class labeling guideline for professional labeling. [Notice of availability published in: Fed Regist. 1982; 47:41636.] Available from: Professional Labeling Branch, Division of Drug Advertising and Labeling, Food and Drug Administration, Rockville, MD.
7. Kucers A, Crowe S, Grayson ML et al, eds. The use of antibiotics. A clinical review of antibacterial, antifungal, and antiviral drugs. 5th ed. Jordan Hill, Oxford: Butterworth-Heinemann; 1997: 3-226.
8. Behrman RE, Kliegman RM, Jenson HB, eds. Nelson textbook of pediatrics. 16th ed. Philadelphia: WB Saunders Company; 2000.
9. Committee on Infectious Diseases, American Academy of Pediatrics. 2000 Red book: report of the Committee on Infectious Diseases. 25th ed. Elk Grove Village, IL: American Academy of Pediatrics; 1997:514-26,660.
10. Deresinski SC, Stevens DA. Clinical evaluation of parenteral dicloxacillin. Curr Ther Res Clin Exp. 1975; 18:151-63. [PubMed 809231]
11. Gunn VL, Nechyba C, eds. The Harriet Lane handbook: a manual for pediatric house officers. 16th ed. Philadelphia, PA: Mosby: 2002:660-1.
12. Bryson YJ, Connor JD, LeClerc M et al. High-dose dicloxacillin treatment of acute staphylococcal osteomyelitis in children. J Pediatr. 1979; 94:673-5. [PubMed 430319]
13. Dunkle LM, Brock N. Long-term follow-up of ambulatory management of osteomyelitis. Clin Pediatr. 1982; 21:650-5.
14. Kaplan SL, Mason EO, Feigin RD. Clindamycin versus nafcillin or methicillin in the treatment of Staphylococcus aureus osteomyelitis in children. South Med J. 1982; 75:138-42. [IDIS 145829] [PubMed 7036354]
15. Waldvogel FA, Vasey H. Osteomyelitis: the past decade. N Engl J Med. 1980; 303:360-70. [IDIS 119618] [PubMed 6993944]
16. Prober CG, Yeager AS. Use of the serum bactericidal titer to assess the adequacy of oral antibiotic therapy in the treatment of acute hematogenous osteomyelitis. J Pediatr. 1979; 95:131-5. [PubMed 113517]
17. McCracken GH, Eikenwald HF. Antimicrobial therapy in infants and children. Part II. Therapy of infectious conditions. J Pediatr. 1978; 93:357-77. [PubMed 357692]
18. Chambers HF. Penicillins. In: Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas, and Bennett’s principles and practice of infectious diseases. 5th ed. New York: Churchill Livingstone; 2000: 261-74.
19. Cheigh JS. Drug administration in renal failure. Am J Med. 1977; 62:555-63. [PubMed 851131]
20. Bennett WM, Aronoff GR, Morrison G et al. Drug prescribing in renal failure: dosing guidelines for adults. Am J Kidney Dis. 1983; 3:155-93. [PubMed 6356890]
21. Jackson EA, McLeod DC. Pharmacokinetics and dosing of antimicrobial agents in renal impairment, part ii. AM J Hosp Pharm. 1974; 31:137-48. [PubMed 4815846]
22. Idsoe O, Guthe T, Willcox RR et al. Nature and extent of penicillin side-reactions, with particular reference to fatalities from anaphylactic shock. Bull World Health Organ. 1968; 38:159-88. [PubMed 5302296]
23. Erffmeyer JE. Adverse reactions to penicillin. Ann Allergy. 1981; 47:288-300. [PubMed 6171185]
24. Isbister JP. Penicillin allergy: a review of the immunological and clinical aspects. Med J Aust. 1971; 1:1067-74. [PubMed 4398272]
25. Sullivan TJ, Wedner HJ, Shatz GS et al. Skin testing to detect penicillin allergy. J Allergy Clin Immunol. 1981; 68:171-80. [IDIS 140792] [PubMed 6267115]
26. Carpenter J. Neutropenia induced by semisynthetic penicillin. South Med J. 1980; 73:745-7. [IDIS 128169] [PubMed 7394597]
27. Homayouni H, Gross PA, Setia U et al. Leukopenia due to penicillin and cephalosporin homologues. Arch Intern Med. 1979; 139:827-8. [PubMed 454076]
28. Matsuda S. Transfer of antibiotics into maternal milk. Biol Res Pregnancy. 1984; 5:57-60.
29. Marcy SM, Klein JO. The isoxazolyl penicillins: oxacillin, cloxacillin, and dicloxacillin. Med Clin North Am. 1970; 52:1127-43.
30. Selwyn S. The mechanisms and range of activity of penicillins and cephalosporins. In: Selwyn S, ed. The beta-lactam antibiotics: penicillins and cephalosporins in perspective. London: Hodder and Stoughton; 1980:56-90.
31. Gravenkemper CF, Bennett JV, Brodie JL et al. Dicloxacillin: in vitro and pharmacologic comparisons with oxacillin and cloxacillin. Arch Intern Med. 1965; 116:340-5. [PubMed 14325906]
32. Hammerstrom CF, Cox F, McHenry MC et al. Clinical, laboratory, and pharmacological studies of dicloxacillin. Antimicrob Agents Chemother. 1966:69-74.
33. Nauta EH, Mattie H. Dicloxacillin and cloxacillin: pharmacokinetics in healthy and hemodialysis subjects. Clin Pharmacol Ther. 1976; 20:98-108. [PubMed 1277730]
34. Barza M, Weinstein L. Pharmacokinetics of the penicillins in man. Clin Pharmacokinet. 1976; 1:297-308. [PubMed 797501]
35. Doluisio JT, LaPiana JC, Wilkinson GR et al. Pharmacokinetic interpretation of dicloxacillin levels in serum after extravascular administration. Antimicrob Agents Chemother. 1969:49-55.
36. DeFelice EA. Serum levels, urinary recovery, and safety of dicloxacillin, a new semisynthetic penicillin, in normal volunteers. J Clin Pharmacol. 1967; (Sep-Oct):275-7.
37. Hou JP, Poole JW. β-Lactam antibiotics: their physiochemical properties and biological activities in relation to structure. J Pharm Sci. 1971; 60:503-27. [PubMed 4336386]
38. Bass JW, Bruhn FW, Merritt WT et al. Comparison of oral penicillinase-resistant penicillins: contrasts between agents and assays. South Med J. 1982; 75:408-10. [IDIS 150080] [PubMed 7041278]
39. Tetzlaff TR, Howard JB, McCracken GH et al. Antibiotic concentrations in pus and bone in children with osteomyelitis. J Pediatr. 1978; 92:135-40. [IDIS 172809] [PubMed 619056]
40. Nelson JD, Howard JB, Shelton S. Oral antibiotic therapy for skeletal infections of children. J Pediatr. 1978; 92:131-4. [IDIS 172808] [PubMed 619055]
41. Kunin CM. Clinical significance of protein binding of the penicillins. Ann NY Acad Sci. 1967; 145:282-90. [PubMed 4998178]
42. Depp R, Kind AC, Kirby WM et al. Transplacental passage of methicillin and dicloxacillin into the fetus and amniotic fluid. Am J Obstet Gynecol. 1970; 107:1054-7. [PubMed 5429971]
43. Bergan T. Penicillins. In: Schonfeld H, ed. Antibiotics and chemotherapy. Vol 25. Basel: S. Karger; 1978:1-122.
44. Giusti DL. A review of the clinical use of antimicrobial agents in patients with renal and hepatic insufficiency: the penicillins. Drug Intell Clin Pharm. 1973; 7:62-74.
45. Rosenblatt JE, Kind AC, Brodie JL et al. Mechanisms responsible for the blood level differences of isoxazolyl penicillins: oxacillin, cloxacillin, and dicloxacillin. Arch Intern Med. 1968; 121:345-8. [PubMed 5645708]
46. Cole M, Kening MD, Hewitt VA. Metabolism of penicillins to penicilloic acids and 6-aminopenicillanic acid in man and its significance in assessing penicillin absorption. Antimicrob Agents Chemother. 1973; 3:463-8. [PubMed 4364176]
47. Thijssen HH, Mattie H. Active metabolites of isoxazolylpenicillins in humans. Antimicrob Agents Chemother. 1976; 10:441-6. [PubMed 825029]
48. Jusko WJ, Mosovich LL, Gerbracht LM et al. Enhanced renal excretion of dicloxacillin in patients with cystic fibrosis. Pediatrics. 1975; 56:1038-44. [PubMed 1196754]
49. Neu HC. Penicillins: microbiology, pharmacology, and clinical use. In: Kagan BM, ed. Antimicrobial therapy. 3rd ed. Philadelphia: WB Saunders Company; 1980:20-34.
50. The United States pharmacopeia, 26th rev, and The national formulary, 21st ed. Rockville, MD: The United States Pharmacopeial Convention, Inc; 2003:597-8,1261-3,1355-7,2571-2.
51. Newton DW, Kluza RB. pKa Values of medicinal compounds in pharmacy practice. Drug Intell Clin Pharm. 1978; 12:546-54.
52. Porter EG (Bristol Laboratories, Syracuse, NY): Personal communication; 1984 Dec 28.
53. Hedstrom SA. Treatment of chronic staphylococcal osteomyelitis with cloxacillin and dicloxacillin—a comparative study in 12 patients. Scand J Infect Dis. 1975; 7:55-7. [PubMed 1145134]
54. Armstrong EP, Rush DR. Treatment of osteomyelitis. Clin Pharm. 1983; 2:213-24. [IDIS 170639] [PubMed 6349907]
a. AHFS Drug Information 2004. McEvoy GK, ed. Penicillinase-resistant Penicillins General Statement. American Society of Health-System Pharmacists; 2004:328-34.