Prescription Drug Information: Dicloxacillin Sodium

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.

DESCRIPTION

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:

Structural formula for dicloxacillin sodium
(click image for full-size original)

C19 H16 Cl2 N3 NaO5 S·H2 O MW 510.32

Inactive Ingredients

Capsules

Magnesium Stearate.

Capsule Shell and Print Constituents

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.

CLINICAL PHARMACOLOGY

Microbiology

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.

Susceptibility Plate Testing

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.

Table I STANDARDIZED DISC TEST METHOD OF BACTERIOLOGICAL SUSCEPTIBILITY TESTING USING A CLASS DISC CONTAINING 5 MICROGRAMS OF METHICILLIN SODIUM
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

Pharmacokinetics

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).

TABLE II PENICILLINASE-RESISTANT PENICILLINS PERCENT PROTEIN BINDING ± SD
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.

INDICATIONS AND USAGE

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 susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

Dicloxacillin is indicated in the treatment of infections caused by penicillinase-producing staphylococci which have demonstrated susceptibility to the drug. Cultures and susceptibility tests should be performed initially to determine the causative organisms and their sensitivity to the drug. (see CLINICAL PHARMACOLOGY – Susceptibility Plate Testing).

Dicloxacillin may be used to initiate therapy in suspected cases of resistant staphylococcal infections prior to the availability of laboratory test results. The penicillinase-resistant penicillins should not be used in infections caused by organisms susceptible to penicillin G. If the susceptibility tests indicate that the infection is due to an organism other than a resistant staphylococcus, therapy should not be continued with a penicillinase-resistant penicillin.

CONTRAINDICATIONS

A history of a hypersensitivity (anaphylactic) reaction to any penicillin is a contraindication.

WARNINGS

Serious and occasionally fatal hypersensitivity (anaphylactic shock with collapse) reactions have occurred in patients receiving penicillin. The incidence of anaphylactic shock in all penicillin-treated patients is between 0.015% and 0.04%. Anaphylactic shock resulting in death has occurred in approximately 0.002% of the patients treated. Although anaphylaxis is more frequent following a parenteral administration, it has occurred in patients receiving oral penicillins.

When penicillin therapy is indicated, it should be initiated only after a comprehensive patient drug and allergy history has been obtained. If an allergic reaction occurs, the drug should be discontinued and the patient should receive supportive treatment, e.g., artificial maintenance of ventilation, pressor amines, antihistamines and corticosteroids. Individuals with a history of penicillin hypersensitivity may also experience allergic reactions when treated with a cephalosporin.

PRECAUTIONS

General

Prescribing dicloxacillin sodium capsules USP in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

Dicloxacillin should generally not be administered to patients with a history of sensitivity to any penicillin.

Penicillin should be used with caution in individuals with histories of significant allergies and/or asthma. Whenever allergic reactions occur, penicillin should be withdrawn unless, in the opinion of the physician, the condition being treated is life-threatening and amenable only to penicillin therapy.

The oral route of administration should not be relied upon in patients with severe illness, or with nausea, vomiting, gastric dilatation, cardiospasm or intestinal hypermotility. Occasionally, patients will not absorb therapeutic amounts of orally administered penicillin.

The use of antibiotics may result in overgrowth of nonsusceptible organisms. If new infections due to bacteria or fungi occur, the drug should be discontinued and appropriate measures taken.

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