Professional Information — Dicloxacillin Sodium

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 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  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.

Dosage and Administration

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.

^{1 .} Patients weighing less than 40 kg (88 lbs)

Dicloxacillin is best absorbed when taken on an empty stomach, and should be administered at least 1 hour before or 2 hours after meals. Dicloxacillin should be taken with at least 4 fluid ounces (120 mL) of water and should not be taken in the supine position or immediately before going to bed (see PRECAUTIONS ).

Contraindications

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

Adverse Reactions

Hypersensitive Reactions

The reported incidence of allergic reactions to penicillin ranges from 0.7% to 10% (see WARNINGS ). Sensitization is usually the result of treatment, but some individuals have had immediate reactions to penicillin when first treated. In such cases, it is thought that the patients may have had prior exposure to the drug via trace amounts present in milk and vaccines.

Two types of allergic reactions to penicillin are noted clinically, immediate and delayed.

Immediate reactions usually occur within 20 minutes of administration and range in severity from urticaria and pruritus to angioneurotic edema, laryngospasm, bronchospasm, hypotension, vascular collapse and death. Such immediate anaphylactic reactions are very rare (see WARNINGS ) and usually occur after parenteral therapy, but have occurred in patients receiving oral therapy. Another type of immediate reaction, an accelerated reaction, may occur between 20 minutes and 48 hours after administration and may include urticaria, pruritus and fever. Although laryngeal edema, laryngospasm and hypotension occasionally occur, fatality is uncommon.

Delayed allergic reactions to penicillin therapy usually occur after 48 hours and sometimes as late as two to four weeks after initiation of therapy. Manifestations of this type of reaction include serum sickness-like symptoms (i.e., fever, malaise, urticaria, myalgia, arthralgia, abdominal pain) and various skin rashes.

Gastrointestinal Reactions

Nausea, vomiting, diarrhea, stomatitis, black or hairy tongue and other symptoms of gastrointestinal irritation may occur, especially during oral penicillin therapy.

Pseudomembranous colitis has been reported with the use of dicloxacillin. Therefore, it is important to consider its diagnosis in patients who develop diarrhea in association with dicloxacillin use.

Reports have been received during postmarketing surveillance of esophageal burning, esophagitis, and esophageal ulceration, particularly after ingestion of dicloxacillin capsules with an insufficient quantity of water and/or before going to bed (see PRECAUTIONS and DOSAGE AND ADMINISTRATION ).

Nervous System Reactions

Neurotoxic reactions similar to those observed with penicillin G (e.g., lethargy, confusion, twitching, multifocal myoclonus, localized or generalized epileptiform seizures) may occur with large intravenous doses of the penicillinase-resistant penicillins, especially with patients with renal insufficiency.

Renal Reactions

Renal tubular damage and interstitial nephritis have been associated with the administration of methicillin sodium and, infrequently, with the administration of nafcillin and oxacillin. Manifestations of this reaction may include rash, fever, eosinophilia, hematuria, proteinuria and renal insufficiency. Methicillin-induced nephropathy does not appear to be dose-related and is generally reversible upon prompt discontinuation of therapy.

Hematologic Reactions

Eosinophilia, hemolytic anemia, agranulocytosis, neutropenia, leukopenia, granulocytopenia, thrombocytopenia, and bone marrow depression have been associated with the use of penicillinase-resistant penicillins.

Hepatic Reactions

Hepatotoxicity, characterized by fever, nausea and vomiting associated with abnormal liver function tests, mainly elevated AST (SGOT) levels, has been associated with the use of oxacillin and cloxacillin. Chloestatic hepatitis has been reported rarely. Asymptomatic, transient increases in serum concentrations of alkaline phosphatase, AST (SGOT), and ALT (SGPT) have been reported.

Drug Interactions

Tetracycline, a bacteriostatic antibiotic, may antagonize the bactericidal effect of penicillin and concurrent use of these drugs should be avoided.

Probenecid administered concomitantly with penicillins increases and prolongs serum penicillin levels (see DOSAGE AND ADMINISTRATION ).

Penicillinase-resistant penicillins, like other penicillins, are physically and/or chemically incompatible with aminoglycosides and can inactivate the drugs in vitro. In vitro mixing of penicillins and aminoglycosides should be avoided during concomitant therapy and the drugs should be administered separately. Penicillins can inactivate aminoglycosides in vitro in serum samples from patients receiving both drugs, which could produce falsely decreased results in serum aminoglycoside assays of the serum samples.

Dicloxacillin may reduce the anticoagulant response to dicumarol and warfarin. Careful monitoring of prothrombin times is suggested during concomitant therapy, and dosage of the anticoagulant should be adjusted as required. The mechanism of this possible interaction is unclear, but may be due to hepatic enzyme induction.

Description

Dicloxacillin sodium, USP is an antibacterial agent of the isoxazolyl penicillin series. It is a penicillinase resistant, acid resistant semisynthetic penicillin suitable for oral administration.

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, and has following structural formula:

C₁₉H₁₆Cl₂N₃NaO₅ S·H₂O MW 510.32

Each capsule for oral administration contains dicloxacillin sodium, USP equivalent to 250 mg or 500 mg of dicloxacillin. The inactive ingredient is Magnesium Stearate. The capsule shells and print constituents contains D&C Yellow #10 Aluminum Lake, FD&C Blue #1 Aluminum Lake, FD&C Blue #1, FD&C Blue #2 Aluminum Lake, FD&C Red #40 Aluminum Lake, D&C Yellow #10, Gelatin, Shellac, Sodium Lauryl Sulfate, Sorbitan Monolaurate, Black Iron Oxide, Titanium Dioxide, Propylene Glycol.

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

Dicloxacillin sodium is resistant to destruction by acid.

Absorption of dicloxacillin sodium 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 10 to 17 mcg/mL for dicloxacillin.

Oral absorption of dicloxacillin is delayed when the drugs are administered after meals.

Once absorbed, dicloxacillin sodium is 97.9 ± 0.6 percent bound to serum protein, mainly albumin. Dicloxacillin sodium 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. Dicloxacillin sodium is found in therapeutic concentrations in the pleural, bile and amniotic fluids.

Dicloxacillin sodiumis 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.

Dicloxacillin is not dialyzable. Only minimal amounts are removed by hemodialysis or peritoneal dialysis.

How Supplied / Storage and Handling

Product: 50090-0116

NDC: 50090-0116-1 40 CAPSULE in a BOTTLE

NDC: 50090-0116-0 28 CAPSULE in a BOTTLE

NDC: 50090-0116-4 20 CAPSULE in a BOTTLE

Product: 50090-0310

Patient Counseling Information

Patients should be counselled that antibacterial drugs including dicloxacillin sodium capsules should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When dicloxacillin sodium capsules are prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by dicloxacillin sodium capsules or other antibacterial drugs in the future.

Diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible.

Patients receiving penicillins should be given the following information and instructions by the physician:

1. Patients should be told that penicillin is an antibacterial agent which will work with the body’s natural defenses to control certain types of infections. They should be told that the drug should not be taken if they have had an allergic reaction to any form of penicillin previously, and to inform the physician of any allergies or previous allergic reactions to any drugs they may have had (see WARNINGS ).
2. Patients who have previously experienced an anaphylactic reaction to penicillin should be instructed to wear a medical identification tag or bracelet.
3. Because most antibacterial drugs taken by mouth are best absorbed on an empty stomach, patients should be directed, unless circumstances warrant otherwise, to take penicillin one hour before meals or two hours after eating (see CLINICAL PHARMACOLOGY - Pharmacokinetics ).
4. Patients should be told to take the entire course of therapy prescribed, even if fever and other symptoms have stopped (see PRECAUTIONS - General ).
5. If any of the following reactions occur, stop taking your prescription and notify the physician: shortness of breath, wheezing, skin rash, mouth irritation, black tongue, sore throat, nausea, vomiting, diarrhea, fever, swollen joints or any unusual bleeding or bruising (see ADVERSE REACTIONS ).
6. Do not take any additional medications without physician approval, including nonprescription drugs such as antacids, laxatives or vitamins.