VA Class:AM112
Dicloxacillin is a semisynthetic penicillinase-resistant penicillin antibiotic.1,2,6,7,18,29,30,37
Dicloxacillin shares the uses of other penicillinase-resistant penicillins and generally is used only in the treatment of infections caused by, or suspected of being caused by, susceptible penicillinase-resistant staphylococci.1,2,3,4,5,6,7,8 Oral dicloxacillin should not be used for the initial treatment of severe, life-threatening infections, including endocarditis, but may be used as follow-up after therapy with a parenteral penicillinase-resistant penicillin (e.g., nafcillin, oxacillin).1,2,5,6,8,9 For specific information on the uses of dicloxacillin, see Uses in the Penicillinase-Resistant Penicillins General Statement 8:12.16.12.
Reconstitution and Administration
Dicloxacillin sodium is administered orally at least 1 hour before or 2 hours after meals.1,2 Although the drug also has been given parenterally by slow IV injection or infusion or by IM injection,10 a parenteral dosage form is no longer commercially available in the US.
Oral dicloxacillin should not be used for the initial treatment of severe infections and should not be relied on in patients with nausea, vomiting, gastric dilatation, cardiospasm, or intestinal hypermotility.1,2,6,9
Dosage of dicloxacillin sodium is expressed in terms of dicloxacillin.1,2 Dosage of the drug should be adjusted according to the type and severity of infection.1,2,6
The usual adult oral dosage of dicloxacillin for the treatment of mild to moderate infections caused by susceptible penicillinase-producing staphylococci is 125 mg every 6 hours.1,2,6 For more severe infections, the usual adult oral dosage of dicloxacillin is 250 mg every 6 hours;1,2 higher dosage may be necessary depending on the severity of the infection.6
Children weighing 40 kg or more may receive the usual adult dosage of dicloxacillin.1,2,11
In children who weigh less than 40 kg, the usual oral dosage of dicloxacillin for the treatment of mild to moderate infections caused by susceptible penicillinase-producing staphylococci is 12.5 mg/kg daily given in divided doses every 6 hours.1,2,6,11 The usual oral dosage for the treatment of more severe infections is 25 mg/kg daily given in divided doses every 6 hours;1,2 higher dosage may be necessary depending on the severity of the infection.6,11 If dicloxacillin is used in neonates, they should be monitored closely for clinical and laboratory evidence of toxic or adverse effects, and serum concentrations of the drug should be determined frequently and appropriate reductions in dosage and frequency of administration made when indicated.1,2,6 (See Cautions: Pediatric Precautions.)
The American Academy of Pediatrics (AAP) suggests that children older than 1 month of age receive oral dicloxacillin in a dosage of 25-50 mg/kg daily in 4 divided doses for the treatment of mild to moderate infections; the AAP states that the oral drug is inappropriate for severe infections.9
Some clinicians suggest that, when dicloxacillin is used as follow-up therapy to parenteral penicillinase-resistant penicillin therapy in the treatment of acute or chronic osteomyelitis caused by susceptible staphylococci, children should receive an oral dosage of 50-100 mg/kg daily given in divided doses every 6 hours.12,13,14,16,54 If oral anti-infective therapy is used in the treatment of osteomyelitis, compliance must be assured and some clinicians suggest that serum bactericidal titers (SBTs) be used to monitor adequacy of therapy and to adjust dosage.13,14,15,16,17,53,54 (See Uses: Staphylococcal Infections, in the Penicillinase-Resistant Penicillins General Statement 8:12.16.12.)
The duration of dicloxacillin therapy depends on the type and severity of infection and should be determined by the clinical and bacteriologic response of the patient.1,2,5,6,8 Dicloxacillin therapy usually should be continued for at least 48 hours after cultures are negative and the patient becomes afebrile and asymptomatic.1,2 For severe staphylococcal infections, therapy should be continued for at least 14 days;1,2,5,6 more prolonged therapy is necessary for the treatment of osteomyelitis, endocarditis, or other metastatic infections.1,2,5,6,13,54 When oral dicloxacillin is used as follow-up therapy to parenteral penicillinase-resistant therapy in the treatment of acute osteomyelitis, the drug generally is given for 3-6 weeks or until the total duration of parenteral and oral therapy is at least 6 weeks;12,13,14,16,54 when used as follow-up therapy in the treatment of chronic osteomyelitis, the drug generally is given for at least 1-2 months and has been given for as long as 1-2 years.13,18,54
Adjustment of dicloxacillin dosage in patients with renal impairment generally is unnecessary.19,20,21
Adverse effects reported with dicloxacillin are similar to those reported with other penicillinase-resistant penicillins.1,2,6 For information on adverse effects reported with penicillinase-resistant penicillins, see Cautions in the Penicillinase-Resistant Penicillins General Statement 8:12.16.12.
Precautions and Contraindications
Dicloxacillin is contraindicated in patients who are hypersensitive to any penicillin.1,2,6
Dicloxacillin shares the toxic potentials of the penicillins, including the risk of hypersensitivity reactions, and the usual precautions of penicillin therapy should be observed.1,2,6 Prior to initiation of therapy with dicloxacillin, careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins, or other drugs.2,6 There is clinical and laboratory evidence of partial cross-allergenicity among penicillins and other β-lactam antibiotics including cephalosporins and cephamycins.1,2,22,23,24,25
Renal, hepatic, and hematologic systems should be evaluated periodically during prolonged therapy with dicloxacillin.1,2,6 Because adverse hematologic effects have occurred during therapy with penicillinase-resistant penicillins, white blood cell (WBC) count and differential should be performed prior to initiation of therapy and 1-3 times weekly during therapy.1,2,5,6,26,27 In addition, urinalysis should be performed and BUN, serum creatinine, AST (SGOT), and ALT (SGPT) concentrations should be determined prior to and periodically during therapy.1,2,5,6
Patients should be advised to discontinue dicloxacillin and notify their clinicians 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 therapy with the drug.1,2
For a more complete discussion of these and other precautions associated with the use of dicloxacillin, see Cautions: Precautions and Contraindications, in the Penicillinase-Resistant Penicillins General Statement 8:12.16.12.
Elimination of penicillins is delayed in neonates because of immature mechanisms for renal excretion, and abnormally high serum concentrations of the drugs may occur in this age group.1,2,6 If dicloxacillin is used in neonates, they should be monitored closely for clinical and laboratory evidence of toxic or adverse effects, and serum concentrations of the drug should be determined frequently and appropriate reductions in dosage and frequency of administration made when indicated.1,2,6
Safe use of penicillinase-resistant penicillins during pregnancy has not been definitely established.1,2,6 Clinical experience with use of penicillins during pregnancy in humans has not revealed evidence of adverse effects on the fetus.1,2,6 However, there are no adequate and controlled studies using penicillinase-resistant penicillins in pregnant women, and dicloxacillin should be used during pregnancy only when clearly needed.1,2,6
Because dicloxacillin is distributed into milk,1,2,6,28 the drug should be used with caution in nursing women.1,2,6
Based on its spectrum of activity, dicloxacillin is classified as a penicillinase-resistant penicillin.1,2,6,7,29,30,31,32 For information on the classification of penicillins based on spectra of activity, see the Preface to the General Statements on Penicillins 8:12.16.
Like other penicillinase-resistant penicillins, dicloxacillin is resistant to inactivation by staphylococcal penicillinases and is active against many penicillinase-producing strains of Staphylococcus aureus and S . epidermidis that are resistant to other commercially available penicillins.1,2,4,6,7,30,31,32 For specific information on the spectrum of activity of dicloxacillin and resistance to the drug, see the sections on Spectrum and on Resistance in the Penicillinase-Resistant Penicillins General Statement 8:12.16.12.
In all studies described in the Pharmacokinetics section, dicloxacillin was administered as the sodium salt; dosages and concentrations of the drug are expressed in terms of dicloxacillin.
Dicloxacillin is resistant to inactivation in the presence of acidic gastric secretions and is rapidly but incompletely absorbed from the GI tract.1,2,7,33 In healthy, fasting adults, 35-76% of an orally administered dose of dicloxacillin is absorbed from the GI tract33,34,35 and peak serum concentrations of the drug are generally attained within 0.5-2 hours.1,2,35,36
Presence of food in the GI tract generally decreases the rate and extent of absorption of dicloxacillin.1,2,4,6,7,29,35
Following oral administration of a single 500-mg dose of dicloxacillin in fasting adults, peak serum concentrations of the drug average 10-18 µg/mL;1,2,4,32,34,36,37,38 serum concentrations of the drug decline rapidly and are generally low 6 hours after the drug is administered.31,32,35,38 In fasting adults who receive a single 250-mg oral dose of dicloxacillin as a capsule, serum concentrations of the drug average 2.9-3, 4.6-5.5, 3-5.6, and 1.5-1.7 µg/mL at 30 minutes, 1 hour, 2 hours, and 4 hours, respectively, after the dose.32,35,36
In one study in children with acute osteomyelitis who received oral dicloxacillin in a dosage of 100 mg/kg daily given in divided doses every 6 hours, serum concentrations of the drug ranged from 12-40 µg/mL 1 hour after dosing and 6.5-20 µg/mL 3 hours after dosing.12
Dicloxacillin is distributed into bone,4,39 bile,1,2 pleural fluid,1,2,4,7 ascitic fluid,4 and synovial fluid.4,40 In one study in children 2-16 years of age with acute osteomyelitis who received dicloxacillin IM in a dosage of 50 mg/kg daily, dicloxacillin concentrations in bone ranged from 1.8-21.6 µg/g and concurrent serum concentrations of the drug ranged from 7-9 µg/mL in samples taken 1-3 hours after a dose.39 In children 7 months to 14 years of age with suppurative arthritis who received a single oral dicloxacillin dose of 25 mg/kg, dicloxacillin concentrations in synovial fluid obtained 2 hours after the dose were 70% of concurrent serum concentrations; synovial fluid concentrations averaged 9.5 µg/mL and serum concentrations averaged 13.6 µg/mL.40 Like other penicillins, only minimal concentrations of dicloxacillin are attained in CSF.2
Dicloxacillin is 95-99% bound to serum proteins.1,2,7,31,34,37,41
Dicloxacillin reportedly distributes into amniotic fluid in therapeutic concentrations following usual dosages.1,2 The drug also crosses the placenta42 and is distributed into milk.1,2,6,28 Following oral administration of a single 250-mg dose of dicloxacillin in lactating women, milk concentrations of the drug were 0.1-0.3 µg/mL 2 and 4 hours after the dose and undetectable 6 hours after the dose.28
The serum half-life of dicloxacillin in adults with normal renal function is 0.6-0.8 hours.1,2,4,33,34,43,44,45 In one study in children 2-16 years of age, the serum half-life of the drug averaged 1.9 hours.39
Dicloxacillin is partially metabolized to active and inactive metabolites.4,43,46,47 In one study following administration of a single 500-mg oral dose of dicloxacillin, 10% of the absorbed drug was hydrolyzed to penicilloic acids which are microbiologically inactive.46 Dicloxacillin is also hydroxylated to a small extent to a microbiologically active metabolite which appears to be slightly less active than dicloxacillin.47
Dicloxacillin and its metabolites are rapidly excreted in urine mainly by tubular secretion and glomerular filtration.1,2,7,29,43,47 The drug is also partly excreted in feces via biliary elimination.4 Following oral administration of a single 250-mg, 500-mg, or 1-g dose of dicloxacillin in adults with normal renal function, 31-65% of the dose is 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
The serum half-life of dicloxacillin is slightly prolonged in patients with impaired renal function and has been reported to range from 1-2.2 hours in patients with severe renal impairment.4,33,34,45
Serum concentrations of dicloxacillin are higher and the serum half-life longer in neonates than in older children.4,6
Patients with cystic fibrosis eliminate dicloxacillin approximately 3 times faster than healthy individuals.7,48 In one study following oral administration of a single 6.25-mg/kg dose of the drug, peak serum concentrations and areas under the serum concentration-time curves (AUCs) were, on average, 2.5 times lower in patients with cystic fibrosis than in healthy individuals.48 Patients with cystic fibrosis had renal clearances of the drug averaging 282 mL/minute per 1.73 m2 while healthy individuals had renal clearances averaging 95 mL/minute per 1.73 m2.48
Dicloxacillin is only minimally removed by hemodialysis4,10,20,34,43,44,49 or peritoneal dialysis.4,44,49
Dicloxacillin is a semisynthetic penicillinase-resistant penicillin.1,2,6,7,18,29,30,37 Dicloxacillin, like cloxacillin (no longer commercially available in the US) and oxacillin, is an isoxazolyl penicillin.1,2,7,18,29,31,32
Dicloxacillin is commercially available as the monohydrate sodium salt.1,2,50 Potency of dicloxacillin sodium is expressed in terms of dicloxacillin.2,50 Each mg of dicloxacillin sodium contains not less than 850 µg of dicloxacillin.50 Dicloxacillin sodium occurs as a white to off-white, crystalline powder.50 The drug is freely soluble in water.50 Dicloxacillin sodium has a pKa of 2.7-2.8.43,51
Each 250-mg capsule of dicloxacillin contains approximately 0.6 mEq of sodium.52
Commercially available dicloxacillin sodium capsules should be stored in tight containers50 at a temperature less than 40°C, preferably between 15-30°C.52
Additional Information
For further information on chemistry and stability, mechanism of action, spectrum, resistance, pharmacokinetics, uses, cautions, drug interactions, laboratory test interferences, and dosage and administration of dicloxacillin sodium, see the Penicillinase-Resistant Penicillins General Statement 8:12.16.12.
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.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
---|---|---|---|---|
Oral | Capsules | 250 mg (of dicloxacillin)* | Dicloxacillin Sodium | |
500 mg (of dicloxacillin)* | Dicloxacillin Sodium |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
AHFS® Drug Information. © Copyright, 1959-2024, Selected Revisions January 1, 2009. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 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. [PubMed 7036354]
15. Waldvogel FA, Vasey H. Osteomyelitis: the past decade. N Engl J Med . 1980; 303:360-70. [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. [PubMedCentral][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. [PubMed 6267115]
26. Carpenter J. Neutropenia induced by semisynthetic penicillin. South Med J . 1980; 73:745-7. [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. [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. [PubMed 619056]
40. Nelson JD, Howard JB, Shelton S. Oral antibiotic therapy for skeletal infections of children. J Pediatr . 1978; 92:131-4. [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. [PubMedCentral][PubMed 4364176]
47. Thijssen HH, Mattie H. Active metabolites of isoxazolylpenicillins in humans. Antimicrob Agents Chemother . 1976; 10:441-6. [PubMedCentral][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 dicloxacillina 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. [PubMed 6349907]