dicloxacillin 500 MG Oral Capsule

INDICATIONS AND USAGE To reduce the development of drug-resistant bacteria and maintain the effectiveness of dicloxacillin sodium capsules and other antibacterial drugs, dicloxacillin sodium capsules 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 sodium capsules are 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 Testing ) . Dicloxacillin sodium capsules 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.

DOSAGE AND ADMINISTRATION Bacteriologic studies to determine the causative organisms and their sensitivity to the penicillinase-resistant penicillins should always be performed. Duration of therapy varies with the type and severity of infection as well as the overall condition of the patient, therefore it should be determined by the clinical and bacteriological response of the patient. In severe staphylococcal infections, therapy with penicillinase-resistant penicillins should be continued for at least 14 days. Therapy should be continued for at least 48 hours after the patient has become afebrile, asymptomatic and cultures are negative. The treatment of endocarditis and osteomyelitis may require a longer term of therapy. Concurrent administration of the penicillinase-resistant penicillins and probenecid increases and prolongs serum penicillin levels. Probenecid decreases the apparent volume of distribution and slows the rate of excretion by competitively inhibiting renal tubular secretion of penicillin. Penicillin-probenecid therapy is generally limited to those infections where very high serum levels of penicillin are necessary. Oral preparations of the penicillinase-resistant penicillins should not be used as initial therapy in serious, life-threatening infections (see PRECAUTIONS - General ). Oral therapy with the penicillinase-resistant penicillins may be used to follow up the previous use of a parenteral agent as soon as the clinical condition warrants. For intramuscular gluteal injections, care should be taken to avoid sciatic nerve injury. With intravenous administration, particularly in elderly patients, care should be taken because of the possibility of thrombophlebitis. NB: INFECTIONS CAUSED BY GROUP A BETA-HEMOLYTIC STREPTOCOCCI SHOULD BE TREATED FOR AT LEAST 10 DAYS TO HELP PREVENT THE OCCURRENCE OF ACUTE RHEUMATIC FEVER OR ACUTE GLOMERULONEPHRITIS.

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, dicloxacillin should be discontinued and appropriate therapy instituted. Individuals with a history of penicillin hypersensitivity may also experience allergic reactions when treated with a cephalosporin. Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including dicloxacillin sodium, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile . C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents. If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile , and surgical evaluation should be instituted as clinically indicated.

CONTRAINDICATIONS Dicloxacillin sodium capsules are contraindicated in persons who have shown hypersensitivity to any of the penicillins or any component of the formulations.

CLINICAL PHARMACOLOGY Microbiology Mechanism of Action Penicillinase-resistant penicillins exert a bactericidal action against penicillin-susceptible microorganisms during the state of active multiplication. All penicillins inhibit the biosynthesis of the bacterial cell wall. Antibacterial Activity Dicloxacillin sodium has been shown to be active against most isolates of the following microorganisms, both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section. Gram-positive Bacteria Staphylococcus spp. Susceptibility Testing For specific information regarding susceptibility test interpretive criteria and associated test methods and quality control standards recognized by FDA for this drug, please see: https://www.fda.gov/STIC. 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 to 1.5 hours. In one study, after ingestion of a single 500 mg oral dose, peak serum concentrations range from 5 to 7 micrograms/milliliter for oxacillin, from 7.5 to 14.4 mcg/mL for cloxacillin and from 10 to 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.