DICLOXACILLIN SODIUM — dicloxacillin sodium capsule
H.J. Harkins Company, Inc.
To reduce the development of drug resistant bacteria and maintain the effectiveness of dicloxacillin sodium capsules USP and other antibacterial drugs, dicloxacillin sodium capsules USP should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.
Dicloxacillin sodium is a semisynthetic antibiotic substance which resists destruction by the enzyme penicillinase(beta — lactamase). It is monosodium (2S ,5R ,6R)-6-[3-(2,6-dichlorophenyl)- 5-methyl-4-isoxazolecarboxamido]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo [3.2.0]heptane-2-carboxylate monohydrate.
Dicloxacillin is administered orally via capsule form or powder for reconstitution. Structurally, dicloxacillin sodium may be represented as follows:
C19 H16 Cl2 N3 NaO5 S·H2 O MW 510.32
D&C Yellow #10 Aluminum Lake, FD&C Blue #1 Aluminum Lake, FD&C Blue #2 Aluminum Lake, FD&C Red #40 Aluminum Lake, Gelatin, Pharmaceutical Glaze, Silicon Dioxide, Sodium Lauryl Sulfate, Synthetic Black Iron Oxide, Titanium Dioxide and may contain Carboxymethylcellulose Sodium and/or Propylene Glycol.
Dicloxacillin exerts a bactericidal action against penicillin-susceptible microorganisms during the state of active multiplication. All penicillins inhibit the biosynthesis of the bacterial cell wall.
The drugs in this class are highly resistant to inactivation by staphylococcal penicillinase and are active against penicillinase-producing and nonpenicillinase-producing strains of Staphylococcus aureus. The penicillinase- resistant penicillins are active in vitro against a variety of other bacteria.
Quantitative methods of susceptibility testing that require measurements of zone diameters or minimal inhibitory concentrations (MICs) give the most precise estimates of antibiotic susceptibility. One such procedure has been recommended for use with discs to test susceptibility to this class of drugs. Interpretations correlate diameters on the disc test with MIC values.
A penicillinase-resistant class disc may be used to determine microbial susceptibility to dicloxacillin.
TABLE I shows the interpretation of test results for penicillinase-resistant penicillins using the FDA Standard Disc Test Method (formerly Bauer-Kirby-Sherris-Turck method) of disc bacteriological susceptibility testing for staphylococci with a disc containing 5 micrograms of methicillin sodium.
With this procedure, a report from a laboratory of “susceptible” indicates that the infecting organism is likely to respond to therapy. A report of “resistant” indicates that the infecting organism is not likely to respond to therapy. A report of “intermediate” susceptibility suggests that the organism might be susceptible if high doses of the antibiotic are used, or if the infection is confined to tissues and fluids (e.g., urine) in which high antibiotic levels are attained.
In general, all staphylococci should be tested against the penicillin G disc and against the methicillin disc. Routine methods of antibiotic susceptibility testing may fail to detect strains of organisms resistant to the penicillinase-resistant penicillins. For this reason, the use of large inocula and 48 hour incubation periods may be necessary to obtain accurate susceptibility studies with these antibiotics. Bacterial strains which are resistant to one of the penicillinase-resistant penicillins should be considered resistant to all of the drugs in the class.
|Diameter of Zone||Diameter of Zone||Diameter of Zone|
|Indicating “Susceptible”||Indicating||Indicating “Resistant”|
|at least||“Intermediate”||Less than|
|14 mm||10 – 13 mm||10 mm|
Methicillin sodium is readily destroyed by gastric acidity and must be administered by intramuscular or intravenous injection. The isoxazolyl penicillins (cloxacillin, dicloxacillin and oxacillin) and nafcillin are more acid-resistant and may be administered orally.
Absorption of the isoxazolyl penicillins after oral administration is rapid but incomplete; peak blood levels are achieved in 1-1.5 hours. In one study, after ingestion of a single 500 mg oral dose, peak serum concentrations range from 5-7 micrograms/milliliter for oxacillin, from 7.5-14.4 mcg/mL for cloxacillin and from 10-17 mcg/mL for dicloxacillin.
Oral absorption of cloxacillin, dicloxacillin, oxacillin and nafcillin is delayed when the drugs are administered after meals.
Once absorbed, the penicillinase-resistant penicillins bind to serum protein, mainly albumin. The degree of protein binding reported varies with the method of study and the investigator (see TABLE II).
|Methicillin||37.3 ± 7.9|
|Nafcillin||89.9 ± 1.5|
|Oxacillin||94.2 ± 2.1|
|Cloxacillin||95.2 ± 0.5|
|Dicloxacillin||97.9 ± 0.6|
The penicillinase-resistant penicillins vary in the extent to which they are distributed in the body fluids. With normal doses, insignificant concentrations are found in the cerebrospinal fluid and aqueous humor. All the drugs in this class are found in therapeutic concentrations in the pleural, bile and amniotic fluids.
The penicillinase-resistant penicillins are rapidly excreted, primarily as unchanged drug in the urine by glomerular filtration and active tubular secretion. The elimination half-life for dicloxacillin is about 0.7 hour. Nonrenal elimination includes hepatic inactivation and excretion in bile.
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