The following Structured Product Label (SPL) was submitted to the FDA by Stat Rx Usa Llc for the product Dicloxacillin Sodium (NDC 16590-076). This document serves as the official prescribing information, containing essential scientific data and clinical materials required for healthcare providers and patients.
This specific version of the label includes detailed information regarding other, description, clinical pharmacology, indications and usage, contraindications, warnings, precautions, information for the patient, and other regulatory disclosures. Use the navigation below to review specific sections of the FDA submission.
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:
C19H16Cl2N3NaO5 S·H2O MW 510.32
Magnesium Stearate.
Capsule Shell and Print ConstituentsD and C Yellow #10 Aluminum Lake, FD and C Blue #1 Aluminum Lake, FD and C Blue #2 Aluminum Lake, FD and 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.
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.
A history of a hypersensitivity (anaphylactic) reaction to any penicillin is a contraindication.
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.
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.
Patients should be counselled that antibacterial drugs including dicloxacillin sodium capsules USP should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When dicloxacillin sodium capsules USP 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 USP or other antibacterial drugs in the future.
Patients receiving penicillins should be given the following information and instructions by the physician:
Bacteriologic studies to determine the causative organisms and their susceptibility to the penicillinase-resistant penicillins should be performed (see CLINICAL PHARMACOLOGY - Microbiology). In the treatment of suspected staphylococcal infections, therapy should be changed to another active agent if culture tests fail to demonstrate the presence of staphylococci.
Periodic assessment of organ system function, including renal, hepatic and hematopoietic, should be made during prolonged therapy with the penicillinase-resistant penicillins.
Blood cultures, white blood cell and differential cell counts should be obtained prior to initiation of therapy and at least weekly during therapy with penicillinase-resistant penicillins.
Periodic urinalysis, blood urea nitrogen and creatinine determinations should be performed during therapy with the penicillinase-resistant penicillins and dosage alterations should be considered if these values become elevated. If any impairment of renal function is suspected or known to exist, a reduction in the total dosage should be considered and blood levels monitored to avoid possible neurotoxic reactions (see DOSAGE AND ADMINISTRATION).
SGOT and SGPT values should be obtained periodically during therapy to monitor for possible liver function abnormalities.
Tetracycline, a bacteriostatic antibiotic, may antagonize the bactericidal effect of penicillin and concurrent use of these drugs should be avoided.
No long-term animal studies have been conducted with these drugs.
Studies on reproduction (nafcillin) in rats and rabbits reveal no fetal or maternal abnormalities before conception and continuously through weaning (one generation).
Reproduction studies performed in the mouse, rat and rabbit have revealed no evidence of impaired fertility or harm to the fetus due to the penicillinase-resistant penicillins. Human experience with the penicillins during pregnancy has not shown any positive evidence of adverse effects on the fetus. There are, however, no adequate or well-controlled studies in pregnant women showing conclusively that harmful effects of these drugs on the fetus can be excluded. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
Penicillins are excreted in breast milk. Caution should be exercised when penicillins are administered to a nursing woman.
Because of incompletely developed renal function in newborns, penicillinase-resistant penicillins (especially methicillin) may not be completely excreted, with abnormally high blood levels resulting. Frequent monitoring of blood levels is advisable in this group, with dosage adjustments when necessary. All newborns treated with penicillins should be monitored closely for clinical and laboratory evidence of toxic or adverse effects (see DOSAGE AND ADMINISTRATION).
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. Nausea, vomiting, diarrhea, stomatitis, black or hairy tongue and other symptoms of gastrointestinal irritation may occur, especially during oral penicillin therapy.
Neurotoxic reactions similar to those observed with penicillin G may occur with large intravenous doses of the penicillinase-resistant penicillins, especially with patients with renal insufficiency.
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.
Agranulocytosis, neutropenia and bone marrow depression have been associated with the use of methicillin sodium and nafcillin. Hepatotoxicity, characterized by fever, nausea and vomiting associated with abnormal liver function tests, mainly elevated SGOT levels, has been associated with the use of oxacillin.
| DRUG | ADULTS | CHILDREN | ||
| Dicloxacillin | Mild to Moderate | Severe | Mild to Moderate | Severe |
| 125 mg every | 250 mg every | 12.5 mg/kg/day* | 25 mg/kg/day* | |
| 6 hours | 6 hours | in equally | in equally | |
| divided doses | divided doses | |||
| every 6 hours | every 6 hours |
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.
Dicloxacillin sodium capsules USP are available as follows:
250 mg: Each capsule contains dicloxacillin sodium monohydrate equivalent to 250 mg dicloxacillin, with green colored cap and light green colored body, imprinted "TEVA" on the cap and “3123” on the body, available in bottles of 100.
500 mg: Each capsule contains dicloxacillin sodium monohydrate equivalent to 500 mg dicloxacillin, with green colored cap and light green colored body, imprinted "TEVA" on the cap and “3125” on the body, available in bottles of 100.
Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].
Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure (as required).
References Available Upon Request.
Manufactured In Canada By:
TEVA CANADA LIMITED
Toronto, Canada M1B 2K9
Manufactured For:
TEVA PHARMACEUTICALS USA
Sellersville, PA 18960
Rev. E 10/2010
PACKAGE LABEL - DICLOXACILLIN SODIUM 500MG
* Please review the disclaimer below.
