Dicloxacillin

470.33

470.33

221-488-3

COF19H7WBK

DTXSID1022924

C28986

J - Antiinfectives for systemic use

138.04000

3.02

Solid

1.6±0.1 g/cm3

218 °C (decomp)

692.4±55.0 °C at 760 mmHg

372.5±31.5 °C

1.691

H2O: 3.63 mg/L

Store in a tightly sealed container, protected form light, and at room temperature. Do not mix with other drugs.

3.37X10-16 mm Hg at 25 deg C (est)

pKa = 2.8|White to off-white, crystalline powder; soluble in alcohol; faint, characteristic odor; decomposes at 222-225 °C; pKa 2.67 /Dicloxacillin sodium/

197 Ų [M+H]+ [CCS Type: TW, Method: calibrated with Waters Major Mix]|205.9 Ų [M+Na]+ [CCS Type: TW, Method: calibrated with Waters Major Mix]|203.78 Ų [M-H]-

Reconstituted oral suspension is stable for 14 days refrigerated. Compounded formulations, especially aqueous formulations, may not be stable.

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.|Product: Offer surplus and non-recyclable solutions to a licensed disposal company. Contact a licensed professional waste disposal service to dispose of this material. Dissolve or mix the material with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber; Contaminated packaging: Dispose of as unused product. /Dicloxacillin sodium salt monohydrate/

Incompatible materials: Oxidizing agents. /Dicloxacillin sodium salt monohydrate/

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including , approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Dicloxacillin sodium/|The Generic Animal Drug and Patent Restoration act requires that each sponsor of an approved animal drug must submit to the FDA certain information regarding patents held for the animal drug or its method of use. The Act requires that this information, as well as a list of all animal drug products approved for safety and effectiveness, be made available to the public. Dicloxacillin sodium monohydrate is included on this list. /Dicloxacillin sodium monohydrate/|Oral dosage form new animal drugs. Dicloxacillin. ... Indications for use /in dogs/. For the treatment of pyoderma (pyogenic dermatitis) due to penicillinase-producing staphylococci sensitive to dicloxacillin. Limitations. Federal law restricts this drug to use by or on the order of a licensed veterinarian.

|Danger|H315: Causes skin irritation [Warning Skin corrosion/irritation]|P261, P264, P271, P280, P285, P302+P352, P304+P340, P304+P341, P305+P351+P338, P312, P321, P332+P313, P337+P313, P342+P311, P362, P403+P233, P405, and P501

Eye/face protection: Face shield and safety glasses. Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU). /Dicloxacillin sodium salt monohydrate/|Skin protection: Handle with gloves. /Dicloxacillin sodium salt monohydrate/|Body Protection: Complete suit protecting against chemicals. The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace. /Dicloxacillin sodium salt monohydrate/|Respiratory protection: For nuisance exposures use type P95 (US) or type P1 (EU EN 143) particle respirator. For higher level protection use type OV/AG/P99 (US) or type ABEK-P2 (EU EN 143) respirator cartridges. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU). /Dicloxacillin sodium salt monohydrate/

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide. /Dicloxacillin sodium salt monohydrate/|Advice for firefighters: Wear self-contained breathing apparatus for firefighting if necessary. /Dicloxacillin sodium salt monohydrate/

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Do not let product enter drains. Methods and materials for containment and cleaning up: Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal. /Dicloxacillin sodium salt monohydrate/

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Do not let product enter drains. /Dicloxacillin sodium salt monohydrate/|Precautions for safe handling: Avoid contact with skin and eyes. Avoid formation of dust and aerosols. Provide appropriate exhaust ventilation at places where dust is formed. Normal measures for preventive fire protection. /Dicloxacillin sodium salt monohydrate/|Appropriate engineering controls: Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and at the end of workday. /Dicloxacillin sodium salt monohydrate/|Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands. /Dicloxacillin sodium salt monohydrate/|SRP: Local exhaust ventilation should be applied wherever there is an incidence of point source emissions or dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants. Ensure that the local ventilation moves the contaminant away from the worker.

Dicloxacillin was not detected (detection limit 0.02 ug/L) in four sewage treatment plant effluents collected in Germany(1).

Oral LD50 in rat is 3579 mg/kg. Symptoms of overexposure include irritation, rash, labored breathing, hives, itching, wheezing, nausea, chills, and fever.|IDENTIFICATION AND USE: Dicloxacillin shares the uses of other penicillinase-resistant penicillins, and it is used in treatment of human patients, and animals. HUMAN STUDIES: Dicloxacillin is associated with a high incidence of infusion phlebitis. Acute kidney injury is a known complication of antibiotic use including dicloxacillin. Dicloxacillin exerts toxic effects on cultured endothelial cells. ANIMAL STUDIES: The high degree of protein binding exhibited by dicloxacillin could explain its relatively low chemotherapeutic activity in mice.

Dicloxacillin therapy has not been associated with serum enzyme elevations during treatment, but has been linked to rare instances of clinically apparent, cholestatic hepatitis. The typical time to onset is 1 to 6 weeks and the pattern of serum enzyme elevations is usually cholestatic, although cases with a mixed pattern have also been described (Case 1). The injury usually presents with jaundice and pruritus. Fever, rash and eosinophilia can occur, but are not prominent and autoantibodies are rarely detected. A similar pattern of injury occurs more frequently with flucloxacillin (also called floxacillin) and cloxacillin, two oral isoxazolyl penicillins similar in structure and activity to dicloxacillin, but never approved for use or available in the United States. Similar cholestatic hepatitis arising 1 to 6 weeks after starting therapy occurs with other penicillins.|Three forms of liver injury have been attributed to the penicillinase-resistant and other penicillins. The first is a transient and usually asymptomatic elevation in serum aminotransferase levels that occurs with high dose intravenous therapy with oxacillin (Case 1, Oxacillin) and rarely with standard penicillins (Case 1, Penicillin G). This reaction has not been described with nafcillin or dicloxacillin and patients can be safety switched to these or other forms of penicillin in the face of oxacillin injury. This form of penicillin-induced liver injury occurs only with high dose therapy that is likely due to direct hepatotoxicity.

Tetracycline, a bacteriostatic antibiotic, may antagonize the bactericidal effect of penicillin and concurrent use of these drugs should be avoided.|Intravenous administration of antibiotics is a known risk factor for infusion phlebitis. We have previously demonstrated differences in cell toxicity for 4 antibiotics. Clinical experience indicates that antibiotics differ in their tendency to cause phlebitis. The present study was done prospectively on 550 patients with 1386 peripheral venous catheters. The incidence of phlebitis was 18.5% with antibiotics and 8.8% without (odds ratio 2.34). Dicloxacillin (odds ratio 5.74) and erythromycin (odds ratio 5.33) had the greatest tendency to cause phlebitis in univariate, multivariate and Cox regression analyses. Benzylpenicillin, cefuroxime and cloxacillin were also associated with a greater risk of phlebitis, whereas ampicillin, imipenem/cilastatin, clindamycin, netilmicin and vancomycin were not. Other risk factors were the site of insertion and age 51-60 yr. Medication with warfarin was found to be protective, but not with aspirin. Treatment with low molecular weight heparin reduced the risk of phlebitis, but the difference was not significant. With regard to when antibiotics were given, the day-specific risk increased between Days 1 and 2, but no further on subsequent days. The hypothesis that antibiotics differ in their tendency to cause phlebitis was confirmed.|/The objective of the study was/ to report a case and retrospective review of seven patients who experienced a decrease in prothrombin time during concomitant administration of warfarin and dicloxacillin. A 41-year-old man receiving warfarin 22 mg/wk with a final baseline prothrombin time (PT) of 20.7 sec was prescribed dicloxacillin 500 mg qid for 10 days. Plasma collected for PT determinations was also used to measure trough warfarin R- and S- enantiomer concentrations. The PT and S- and R-warfarin concentrations decreased 17%, 25%, and 20%, respectively, on day 5 after initiation of dicloxacillin. For the retrospective review, the mean PT decreased 17.0% (range 10.5-25.9%) as soon as 4 days after the initiation of dicloxacillin. Our observations, which are consistent with those of two previously published reports, suggest a close temporal relationship between the administration of dicloxacillin and a decreased anticoagulant effect of warfarin. Limited data from our patient further suggest that this may result from declines in systemic warfarin concentrations. The time course of the fall of PTs appears to occur within 4-5 days; return of the PT to baseline after dicloxacillin administration is stopped appears to take up to 3 weeks. Until further controlled studies are conducted to confirm this interaction, clinicians should be aware that patients may be at risk for a decreased anticoagulant effect of warfarin when dicloxacillin is given concomitantly. Careful monitoring of international normalized ratios and titration of the warfarin dosage is recommended on initiation and for 3 weeks after discontinuation of dicloxacillin in patients receiving warfarin.

LD50 Mouse iv 0.9 g/kg /Dicloxacillin sodium salt monohydrate/|LD50 Rat ip 0.63 g/kg /Dicloxacillin sodium salt monohydrate/

Patients with cystic fibrosis eliminate dicloxacillin approximately 3 times faster than healthy individuals. In one study following oral administration of a single 6.25-mg/kg dose of the drug, peak serum concentrations and areas under the serum concentration-time curves (AUCs) were, on average, 2.5 times lower in patients with cystic fibrosis than in healthy individuals. Patients with cystic fibrosis had renal clearances of the drug averaging 282 mL/minute per 1.73 sq m while healthy individuals had renal clearances averaging 95 mL/minute per 1.73 sq m.|The serum half-life of dicloxacillin is slightly prolonged in patients with impaired renal function and has been reported to range from 1-2.2 hours in patients with severe renal impairment.|Elimination of penicillins is delayed in neonates because of immature mechanisms for renal excretion, and abnormally high serum concentrations of the drugs may occur in this age group. If dicloxacillin is used in neonates, they should be monitored closely for clinical and laboratory evidence of toxic or adverse effects, and serum concentrations of the drug should be determined frequently and appropriate reductions in dosage and frequency of administration made when indicated.|Pediatric Use: 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.|Single oral doses of 6.25 mg/kg of dicloxacillin suspension were given to ten cystic fibrosis (CF) patients and eight normal subjects. Peak serum concentrations and areas under the concentration versus time curves for dicloxacillin were variable and, on average, were 2 1/2 times lower in the CF patients. The time of occurrence of the peak serum concentration was similar in both groups and the total urinary recovery of dicloxacillin was normal or increased in the CF patients, suggesting that the intestinal absorption of the drug was unaffected by the disease. The low serum concentrations in the CF patients were caused by unusually high renal clearances of dicloxacillin which average 282 +/- 135 compared to 95 +/- 28 mL/min/1.73 sq m in the normal subjects. Creatinine clearances were also elevated in the CF patients by 55% on average, while urea clearances were normal. The serum protein binding of dicloxacillin was similar in both groups of subjects. Because the rapid excretion results in low and variable serum concentrations of the antibiotic, treatment of CF patients with dicloxacillin may warrant use of increased or more frequent doses and monitoring of serum antibiotic levels.

Binds to serum protein, mainly albumin.

Dicloxacillin's production and administration as a human and veterinary antibiotic(1) may result in its release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 1060(SRC), determined from a structure estimation method(2), indicates that dicloxacillin is expected to have low mobility in soil(SRC). The pKa of dicloxacillin is 2.8(3), indicating that this compound will exist almost entirely in the anion form in the environment and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization of the anion from moist soil is not expected because anions do not volatilize(SRC). Dicloxacillin is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 3.4X10-16 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). Dicloxacillin may biodegrade in soil based on its removal in a sewage treatment plant where 27% of the 32% removed was attributed to biodegradation(3).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 1060(SRC), determined from a structure estimation method(2), indicates that dicloxacillin is expected to adsorb to suspended solids and sediment(SRC). A pKa of 2.8(3) indicates dicloxacillin will exist almost entirely in the anion form at pH values of 5 to 9 and, therefore, volatilization from water surfaces is not expected to be an important fate process(SRC). Dicloxacillin is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(4). According to a classification scheme(5), an estimated BCF of 3(SRC), from its log Kow of 2.91(6) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low. Dicloxacillin may biodegrade in water based on its removal in a sewage treatment plant where 27% of the 32% removed was attributed to biodegradation(3).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), dicloxacillin, which has an estimated vapor pressure of 3.4X10-16 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase dicloxacillin may be removed from the air by wet and dry deposition(SRC). Dicloxacillin contains chromophores that absorb at wavelengths >290 nm(3) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

Dicloxacillin is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(1). Dicloxacillin contains chromophores that absorb at wavelengths >290 nm(1) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

An estimated BCF of 3 was calculated in fish for dicloxacillin(SRC), using a log Kow of 2.91(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of dicloxacillin can be estimated to be 1060(SRC). According to a classification scheme(2), this estimated Koc value suggests that dicloxacillin is expected to have low mobility in soil. The pKa of dicloxacillin is 2.8(3), indicating that this compound will exist almost entirely in anion form in the environment and anions generally do not adsorb to soils containing organic carbon and clay than their neutral counterparts(4).

A pKa of 2.8(1) indicates dicloxacillin will exist almost entirely in the anion form at pH values of 5 to 9 and, therefore, volatilization from water and moist soil surfaces is not expected to be an important fate process(SRC). Dicloxacillin is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 3.4X10-16 mm Hg(SRC), determined from a fragment constant method(2).

GROUND WATER: Dicloxacillin was not detected (detection limit 0.02 ug/L) in 37 ground water samples collected in Germany(1).|SURFACE WATER: Dicloxacillin was not detected (detection limit 0.02 ug/L) in 14 surface water samples collected in Germany(1).

Occupational exposure to dicloxacillin may occur through dermal contact with this compound at workplaces where dicloxacillin is produced or used. Direct human exposure occurs through ingestion of the drug when dispensed as an antibiotic. (SRC)

Used to treat infections caused by penicillinase-producing staphylococci which have demonstrated susceptibility to the drug.

Dicloxacillin is an oral, second generation penicillin antibiotic that is used to treat bacterial infections caused by penicillinase-resistant staphylococci. Dicloxacillin has been linked to rare instances of clinically apparent, idiosyncratic liver injury.

Penicillin (Penicillinase-Resistant)

Anti-Bacterial Agents|Penicillins|/CLINICAL TRIALS/ ClinicalTrials.gov is a registry and results database of publicly and privately supported clinical studies of human participants conducted around the world. The Web site is maintained by the National Library of Medicine (NLM) and the National Institutes of Health (NIH). Each ClinicalTrials.gov record presents summary information about a study protocol and includes the following: Disease or condition; Intervention (for example, the medical product, behavior, or procedure being studied); Title, description, and design of the study; Requirements for participation (eligibility criteria); Locations where the study is being conducted; Contact information for the study locations; and Links to relevant information on other health Web sites, such as NLM's MedlinePlus for patient health information and PubMed for citations and abstracts for scholarly articles in the field of medicine. Dicloxacillin is included in the database.|Dicloxacillin shares the uses of other penicillinase-resistant penicillins and generally is used only in the treatment of infections caused by, or suspected of being caused by, susceptible penicillinase-resistant staphylococci. Oral dicloxacillin should not be used for the initial treatment of severe, life-threatening infections, including endocarditis, but may be used as follow-up after therapy with a parenteral penicillinase-resistant penicillin (e.g., nafcillin, oxacillin).|For more Therapeutic Uses (Complete) data for Dicloxacillin (14 total), please visit the HSDB record page.

Dicloxacillin is contraindicated in patients who are hypersensitive to any penicillin. Dicloxacillin shares the toxic potentials of the penicillins, including the risk of hypersensitivity reactions, and the usual precautions of penicillin therapy should be observed. Prior to initiation of therapy with dicloxacillin, careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins, or other drugs. There is clinical and laboratory evidence of partial cross-allergenicity among penicillins and other beta-lactam antibiotics including cephalosporins and cephamycins.|Renal, hepatic, and hematologic systems should be evaluated periodically during prolonged therapy with dicloxacillin. Because adverse hematologic effects have occurred during therapy with penicillinase-resistant penicillins, white blood cell (WBC) count and differential should be performed prior to initiation of therapy and 1-3 times weekly during therapy. In addition, urinalysis should be performed and BUN, serum creatinine, AST (SGOT), and ALT (SGPT) concentrations should be determined prior to and periodically during therapy.|Patients should be advised to discontinue dicloxacillin and notify their clinicians if they develop shortness of breath, wheezing, rash, mouth irritation, black tongue, sore throat, nausea, vomiting, diarrhea, fever, swollen joints, or any unusual bleeding or bruising during therapy with the drug.|Elimination of penicillins is delayed in neonates because of immature mechanisms for renal excretion, and abnormally high serum concentrations of the drugs may occur in this age group. If dicloxacillin is used in neonates, they should be monitored closely for clinical and laboratory evidence of toxic or adverse effects, and serum concentrations of the drug should be determined frequently and appropriate reductions in dosage and frequency of administration made when indicated.|For more Drug Warnings (Complete) data for Dicloxacillin (18 total), please visit the HSDB record page.

Dicloxacillin is a beta-lactamase resistant penicillin similar to oxacillin. Dicloxacillin has in vitro activity against gram-positive and gram-negative aerobic and anaerobic bacteria. The bactericidal activity of dicloxacillin results from the inhibition of cell wall synthesis and is mediated through dicloxacillin binding to penicillin binding proteins (PBPs). Dicloxacillin is stable against hydrolysis by a variety of beta-lactamases, including penicillinases, and cephalosporinases and extended spectrum beta-lactamases.

Substances that inhibit the growth or reproduction of BACTERIA. (See all compounds classified as Anti-Bacterial Agents.)

Absorption of the isoxazolyl penicillins after oral administration is rapid but incomplete: peak blood levels are achieved in 1-1.5 hours. Oral absorption of cloxacillin, dicloxacillin, oxacillin and nafcillin is delayed when the drugs are administered after meals.|Dicloxacillin sodium is rapidly excreted as unchanged drug in the urine by glomerular filtration and active tubular secretion.|Differences in the elimination, distribution, and absorption of dicloxacillin and cloxacillin were studied in a group of healthy individuals with the use of a 2-compartment model. In patients on chronic intermittent hemodialysis, only dicloxacillin was investigated and the results were compared with data obtained in earlier studies on cloxacillin and flucloxacillin. In healthy volunteers the bioavailability after oral administration of 2 g dicloxacillin or 2 g cloxacillin amounted to 48.8% and 36.9% of the dose, respectively, when calculated from the area under the serum concentration-time curve, and to 74.1% and 48.5%, respectively, when calculated from the urinary excretion. Individual variation in bioavailability after oral administration was slightly lower for docloxacillin than for cloxacillin. The higher serum concentrations of dicloxacillin, as compared with cloxacillin, are also attributable to slower (renal) elimination (T 1/2: 42 and 33 min, respectively). Analysis of serum concentrations after intravenous administration of 1 and 2 g dicloxacillin to healthy subjects revealed concentration-dependent kinetics with respect ot renal elimination. In hemodialysis patients the elimination rate of dicloxacillin (T 1/2: 129 min) corresponds with the extrarenal elimination rate in healthy subjects. The bioavailability after oral administration of 1 g in patients is good (75.9% of the dose).|Dicloxacillin, a semisynthetic isoxazolyl penicillin antibiotic, has antimicrobial activity against a wide variety of gram-positive bacteria including Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumonia, Streptococcus epidermidis, Streptococcus viridans, Streptococcus agalactiae, and Neisseria meningitidis. The objective of this study was to evaluate the safety and pharmacokinetic profile of dicloxacillin after single and multiple oral dose in healthy Chinese volunteers. A single-center, open-label, randomized, two-phase study was conducted in 16 subjects. In the single-dose phase, subjects were randomly assigned to receive single doses of 0.25, 0.5, 1.0, and 2.0 g of dicloxacillin sodium capsule in a 4-way crossover design with a 5-day washout period between administrations. In the multiple-dose phase, subjects were assigned to receive 0.25 or 0.5 g every 6 hours for 3 days in a 2-way crossover design. Plasma and urine pharmacokinetic samples were assayed by a validated high-performance liquid chromatography-tandem mass spectrometry method. Pharmacokinetic parameters were calculated and analyzed statistically. Safety assessments were conducted throughout the study. Following a single oral dose of 0.25-2.0 g dicloxacillin sodium, the maximum plasma drug concentration (Cmax) and the corresponding values for the area under the concentration- time curve from 0 to 10 hours (AUC0-10 hr) increased in a dose-proportional manner. The mean elimination half-life (t1/2) was in the range of 1.38-1.71 hours. Dicloxacillin was excreted in its unchanged form via the kidney, with no tendency of accumulation, and varied from 38.65% to 50.10%. No appreciable accumulation of drug occurred with multiple oral doses of dicloxacillin. No serious adverse events were reported. Adverse events were generally mild. Dicloxacillin was safe and well tolerated in the volunteers and displayed linear increases in the Cmax and AUC0-10 hr values.|The purpose of antibiotic treatment in pregnant women is to treat the mother and/or the fetus since it is known that antibiotics administered to the mother cross the placenta and reach the fetus. A comparison of the drug concentration in maternal and fetal plasma gives an indication of the exposure of the fetus to the maternally administered antibiotics. The aim of this study was to review the literature pertaining to the placental transfer of antibiotics in man and to classify the antibiotics according to the type of transfer involved ... 3 types of placental transfers were identified. A few antibiotics cross the placenta rapidly and equilibrate in the maternal and cord plasma; this type of transfer is termed "complete" and include the antibiotics ampicillin, methicillin, cefmenoxime and cefotiam. Antibiotics which show incomplete transfer to the placenta where concentrations are lower in the cord than maternal plasma are said to have "incomplete" transfer and these include azlocillin, dicloxacillin, piperacillin, sulbenicillin, cefoxitin, amikacin, gentamicin, kanamycin, streptomycin, fosfomycin, thiamphenicol, griseofulvin, vancomycin and colistimethate. ... All examined antibiotics cross the human placenta including those with a molecular weight greater than 1000 kDa such as vancomycin and colistimethate but there are 3 distinct types of placental transfer: complete, incomplete and exceeding and most antibiotics exhibit incomplete transfer.|/The objective of the study was/ to determine whether upregulation of P-glycoprotein is responsible for the enhanced renal clearance of dicloxacillin in patients with cystic fibrosis ... Eleven patients with cystic fibrosis and 11 age-matched healthy volunteers /were used/. All subjects received a single oral dose of dicloxacillin 500 mg alone, dicloxacillin 500 mg plus probenecid (an organic anion transport inhibitor) 1 g, and dicloxacillin 500 mg plus cyclosporine (a P-glycoprotein inhibitor) 5 mg/kg; each treatment was separated by a washout period of 48 hours. A bolus dose of iothalamate meglumine 456 mg was administered on each study day as a marker of glomerular filtration. Blood and urine samples were taken serially up to 6 hours after each dose. Pharmacokinetics of dicloxacillin and iothalamate were determined by using compartmental and noncompartmental methods. Quantitative polymerase chain reaction was performed on peripheral blood mononuclear cells to measure expression of multidrug resistance 1 (MDR1) messenger RNA (mRNA). Genotyping for ABCB1 was performed to determine the presence of single nucleotide polymorphisms (exons 21 and 26). In both healthy subjects and patients with cystic fibrosis, compared with dicloxacillin alone, coadministration with probenecid produced a significantly lower renal clearance of dicloxacillin, whereas coadministration with cyclosporine resulted in no significant change; renal clearance was not significantly different between the two study groups. No correlation was found between MDR1 mRNA expression and renal clearance of dicloxacillin. The renal excretion of dicloxacillin was significantly greater in subjects with the ABCB1 exon 26 TT polymorphism when compared with subjects with the CT genotype. We found no significant difference in the pharmacokinetics of dicloxacillin between patients with cystic fibrosis and healthy volunteers. Renal clearance of dicloxacillin was significantly reduced in the presence of probenecid but not with cyclosporine, suggesting that the rate-limiting step in tubular secretion of dicloxacillin is uptake mediated by the organic anion transporter, and not P-glycoprotein inhibition.|For more Absorption, Distribution and Excretion (Complete) data for Dicloxacillin (22 total), please visit the HSDB record page.

Dicloxacillin is partially metabolized to active and inactive metabolites. In one study following administration of a single 500-mg oral dose of dicloxacillin, 10% of the absorbed drug was hydrolyzed to penicilloic acids which are microbiologically inactive. Dicloxacillin is also hydroxylated to a small extent to a microbiologically active metabolite which appears to be slightly less active than dicloxacillin.

The elimination half-life for dicloxacillin is about 0.7 hour.|... In hemodialysis patients the elimination rate of dicloxacillin (T 1/2: 129 min) corresponds with the extrarenal elimination rate in healthy subjects ...|... Following a single oral dose of 0.25-2.0 g dicloxacillin sodium, the maximum plasma drug concentration (Cmax) and the corresponding values for the area under the concentration- time curve from 0 to 10 hours (AUC0-10 hr) increased in a dose-proportional manner. The mean elimination half-life (t1/2) was in the range of 1.38-1.71 hours ...|The serum half-life of dicloxacillin in adults with normal renal function is 0.6-0.8 hours. In one study in children 2-16 years of age, the serum half-life of the drug averaged 1.9 hours.|The serum half-life of dicloxacillin is slightly prolonged in patients with impaired renal function and has been reported to range from 1-2.2 hours in patients with severe renal impairment.

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. By binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, dicloxacillin inhibits the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins; it is possible that dicloxacillin interferes with an autolysin inhibitor.

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W TKO /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/|Emergency and supportive measures: 1. Maintain an open airway and assist ventilation if necessary. 2. Treat coma, seizures, hypotension, anaphylaxis, and hemolysis if they occur. 3. Replace fluid losses resulting form gastroenteritis with IV crystalloids. ... /Antibacterial Agents/.|For more Antidote and Emergency Treatment (Complete) data for Dicloxacillin (6 total), please visit the HSDB record page.

/HUMAN EXPOSURE STUDIES/ Intravenous administration of antibiotics is a known risk factor for infusion phlebitis. We have previously demonstrated differences in cell toxicity for 4 antibiotics. Clinical experience indicates that antibiotics differ in their tendency to cause phlebitis. The present study was done prospectively on 550 patients with 1386 peripheral venous catheters. The incidence of phlebitis was 18.5% with antibiotics and 8.8% without (odds ratio 2.34). Dicloxacillin (odds ratio 5.74) and erythromycin (odds ratio 5.33) had the greatest tendency to cause phlebitis in univariate, multivariate and Cox regression analyses. Benzylpenicillin, cefuroxime and cloxacillin were also associated with a greater risk of phlebitis, whereas ampicillin, imipenem/cilastatin, clindamycin, netilmicin and vancomycin were not. Other risk factors were the site of insertion and age 51-60 yr. Medication with warfarin was found to be protective, but not with aspirin. Treatment with low molecular weight heparin reduced the risk of phlebitis, but the difference was not significant. With regard to when antibiotics were given, the day-specific risk increased between Days 1 and 2, but no further on subsequent days. The hypothesis that antibiotics differ in their tendency to cause phlebitis was confirmed.|/HUMAN EXPOSURE STUDIES/ Ever since dicloxacillin and cloxacillin were introduced in the 1960s, it has been known that they are associated with a high incidence of infusion phlebitis. Some in vitro studies and clinical experience have indicated that dicloxacillin is the more vessel-irritating of the 2 drugs. In this prospective observational study on 39 patients with 111 peripheral venous catheters (PVCs), the incidence of infusion phlebitis was compared between these 2 drugs. The incidence of phlebitis was 38% with dicloxacillin and 21% with cloxacillin; which, compared by logistic regression with other risk factors as covariates, was significant [odds ratio 5.06, 95% confidence interval (95% CI) 1.45-17.60]. Since the duration of catheterization is also an important risk factor, Cox regression was performed, and the difference between the 2 drugs was still significant (proportional hazard rate 3.48, 95%, CI 1.64-7.38). The only other significant risk factor found in the study was the insertion site; the risk was higher in PVCs inserted in the forearm/antecubital fossa than in the hand/wrist. The infusion time and dilution of the infusate were not significant risk factors.|/HUMAN EXPOSURE STUDIES/ Of 163 patients with intertrochanteric hip fractures 87 received 2 g dicloxacillin and 240 mg of gentamicin preoperatively, and 76 patients had no antibiotic prophylaxis. Preoperative antibiotic prophylaxis was not shown to have any significant effect on wound infections. However, 16 reversible and 1 irreversible cases of kidney toxicity were found among patients receiving antibiotic prophylaxis, whereas there were only four cases of reversible kidney damage among the patients not receiving antibiotics.|/HUMAN EXPOSURE STUDIES/ In a prospective pilot study 70 patients (age greater than 65 years) who underwent hip arthroplasty were treated with dicloxacillin, a total of 6 g given pre-, per- and postoperatively as antibiotic prophylaxis. Creatinine in serum and beta 2-microglobulin in serum and urine were determined as estimates of renal function. Values were obtained preoperatively and on days 2, 4 and 10 after operation. A slight but significant increase of serum creatinine was seen on day 2 with a gradual decrease almost down to the preoperative baseline value on day 10. Serum beta 2-microglobulin increased more gradually; the increase was significant on day 10. Raised levels of beta 2-microglobulin in urine were most pronounced: a 20-fold increase on day 2, then a slow decrease, still significant increase on day 10. This may indicate a reversible damage of proximal tubules with blocked tubular reabsorption of beta 2-microglobulin. The slightly increased levels of serum creatinine and beta 2-microglobulin would also indicate a minor reversible decrease in glomerular filtration rate. Whether these effects are caused by the operation trauma per se or by the dicloxacillin prophylaxis cannot be determined from this pilot study. It seems quite clear that hip arthroplasty with short term prophylaxis with dicloxacillin does not result in clinically important changes in renal function.|For more Human Toxicity Excerpts (Complete) data for Dicloxacillin (10 total), please visit the HSDB record page.

Cilpen

Table: Dicloxacillin Preparations [Table#4500]|Dicloxacillin sodium, USP (dynapen, pathocil, veracillin), is avail only for oral use, in capsules (125 and 250 mg) and as suspension (62.5 mg/5 mL). /Sodium/

UV and NMR spectra of oxacillin, cloxacillin and dicloxacillin are reported.

A simple high-performance liquid chromatographic method for the determination of dicloxacillin in plasma has been developed. The method only requires 0.5 mL of plasma, phosphate buffer solution (pH = 4.7), acidification with 0.5N hydrochloride acid and liquid extraction with dichloromethane. Posterior evaporation of organic under nitrogen steam and redissolution in mobile phase is carried out. The analysis was performed on a Spherisorb C18 (5 um) column, using methanol -0.05 M phosphate buffer, pH = 4.7 (75:25; v/v) as mobile phase, with ultraviolet detection at 220 nm. Results showed that the assay is sensitive: 0.5 ug/mL. The response is linear in the range of 0.5 -10 ug/mL. Maximum inter-day coefficient of variation was 12.4%. Mean extraction recovery obtained was 96.95%. Stability studies showed that the loss was not higher than 10%, samples are stable at room temperature for 6 hr, at -20 Celsius for 2 months, processed samples were stable at least for 24 hr and also after two freeze-thaw cycles. The method has been used to perform pharmacokinetic and bioequivalence studies in humans.

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