氯唑西林

Pharmaceuticals -> Antibiotics

Pharmaceuticals -> Antibiotics (Penicillins)

Pharmaceuticals -> Listed in ZINC15

LogP = 2.44

3

2.86

WHITE, CRYSTALLINE POWDER; SOL IN ALCOHOL; SLIGHTLY SOL IN ACETONE, CHLOROFORM; AQ SOLN IS ALKALINE; DECOMP BETWEEN 170 °C & 173 °C; ODORLESS; BITTER TASTE /MONOHYDRATE/

5.32e-02 g/L

Breast Feeding; Lactation; Milk, Human; Anti-Infective Agents; Antibacterial Agents; Penicillins

Access group antibiotics

CLOXACILLIN IS RELATIVELY STABLE IN GASTRIC ACID; STABLE IN LIGHT; SLIGHTLY HYGROSCOPIC. /MONOHYDRATE/

AQ SOLN FOR INJECTIONS ARE STABLE FOR AT LEAST 3 DAYS IF REFRIGERATED.

Penicillinase-resistant penicillins are generally stable in the dry state @ room temp for several yr; however, the drugs are stable only for short periods of time in soln unless frozen. Stability of the drugs is pH and temp dependent. Methicillin, nafcillin, and oxacillin are generally stable @ pH 5-8. /Penicillinase-resistant penicillins/

197.93 Ų [M+K]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

193.8 Ų [M+H]+ [CCS Type: TW; Method: calibrated with Waters Major Mix]

200.94 Ų [M-H]-

Danger

H315 (85.4%): Causes skin irritation [Warning Skin corrosion/irritation]

P233, P260, P261, P264, P264+P265, P271, P272, P280, P284, P302+P352, P304+P340, P305+P351+P338, P319, P321, P332+P317, P333+P317, P337+P317, P342+P316, P362+P364, P403, P403+P233, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 48 reports by companies from 5 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Danger

H317 (100%): May cause an allergic skin reaction [Warning Sensitization, Skin]

A tolerance is established for negligible residues of cloxacillin in the uncooked edible tissues of cattle and in milk.

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).

Skin Sens. 1 (100%)

Skin Irrit. 2 (85.4%)

Commercially available cloxacillin sodium capsules and powder for oral solution should be stored in tight containers at a temperature less than 40 °C, preferably between 15-30 °C. Following reconstitution, cloxacillin sodium oral solutions should be stored at 2-8 °C, and any unused soln should be discarded after 14 days. If stored at room temperature, the oral soln is stable for 3 days. /Cloxacillin sodium/

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

PENICILLINS SHOULD NOT BE ROUTINELY ADMIN WITH ERYTHROMYCIN. /PENICILLINS/

OTHER PENICILLIN ANALOGS SHOWN TO INTERACT WITH PROBENECID ARE...CLOXACILLIN...

TETRACYCLINE MAY ANTAGONIZE BACTERICIDAL EFFECT OF PENICILLIN... /PENICILLINS/

Concurrent use of other hepatotoxic medications with cloxacillin ... may increase the potential for hepatotoxicity.

For more Interactions (Complete) data for CLOXACILLIN (9 total), please visit the HSDB record page.

RASH & URTICARIA ARE PRINCIPAL ALLERGIC MANIFESTATIONS. NOT ALL PT ALLERGIC TO PENICILLIN G ARE SENSITIVE TO CLOXACILLIN, BUT CROSS-SENSITIZATION DOES OCCUR. CLOXACILLIN MAY ALSO CAUSE OCCASIONAL NAUSEA, VOMITING, ABDOMINAL DISCOMFORT, EPIGASTRIC FULLNESS, OR DIARRHEA. SUPERINFECTIONS OCCASIONALLY OCCUR. /MONOHYDRATE/

SKIN RASHES OF ALL TYPES HAVE BEEN OBSERVED WHEN PENICILLIN SENSITIZATION HAS OCCURRED. ...VESICULAR, & BULLOUS ERUPTIONS MAY DEVELOP. PURPURIC LESIONS ARE UNCOMMON & ARE USUALLY RESULT OF VASCULITIS; THROMBOPENIC PURPURA MAY OCCUR VERY RARELY. HENOCH-SCHOENLEIN PURPURA WITH RENAL INVOLVEMENT HAS BEEN RARE... /PENICILLINS/

CONTACT DERMATITIS IS OBSERVED...IN PHARMACISTS, NURSES, & PHYSICIANS WHO PREPARE PENICILLIN SOLN... MORE SEVERE REACTIONS INVOLVING SKIN ARE EXFOLIATIVE DERMATITIS & EXUDATIVE ERYTHEMA MULTIFORME OF EITHER ERYTHEMATOPAPULAR OR VESICULOBULLOUS TYPE...CONSTITUTE CHARACTERISTIC STEVENS-JOHNSON SYNDROME. /PENICILLINS/

VARIETY OF ORAL LESIONS HAVE RESULTED FROM SENSITIZATION TO PENICILLIN. AMONG THESE ARE ACUTE GLOSSITIS, SEVERE STOMATITIS WITH LOSS OF BUCCAL MUCOUS MEMBRANES, FURRED TONGUE, BLACK OR BROWN TONGUE, & CHEILOSIS. /PENICILLINS/

For more Human Toxicity Excerpts (Complete) data for CLOXACILLIN (42 total), please visit the HSDB record page.

Drug-Induced Liver Injury Severity and Toxicity (DILIst)

cloxacillin

DILI Positive

Oral

DOI:10.1016/j.drudis.2019.09.022

DEATH FROM RESP FAILURE WITH OR WITHOUT CONVULSIONS OCCURRED 6-18 HR AFTER SINGLE ORAL DOSES /TO MICE, RATS, RABBITS/. ACUTE GASTROENTERITIS & CARDIOVASCULAR SHOCK... /PENICILLINS/

IN HAMSTERS THE DRUG IS SOMEWHAT MORE TOXIC BY ORAL THAN BY SC ROUTE WHEN OBSERVED FOR 14 DAYS AFTER SINGLE DOSES. ... PERHAPS SENSITIVITY OF GUINEA PIGS IS RELATED TO EFFECTS ON INTESTINAL MICROFLORA. /PENICILLINS/

...ENCEPHALOPATHY WITH MUSCULAR HYPERIRRITABILITY, MYOCLONUS, VISUAL & AUDITORY HALLUCINATIONS & GENERAL CONVULSIONS. ...ELICITED IN RATS & CATS WITH DOSES TO 3-4 MILLION UNITS/KG, & SYNDROME CAN BE REVERSED BY PENICILLINASE. /PENICILLINS/

DEATH FROM RESP FAILURE WITH OR WITHOUT CONVULSIONS OCCURRED 6-18 HR AFTER SINGLE ORAL DOSES /TO CATS & DOGS/. ACUTE GASTROENTERITIS & CARDIOVASCULAR SHOCK...ALSO TRUE FOR GUINEA PIGS EXCEPT THAT A LATE...GRADUALLY DEVELOPING TOXEMIA KILLED ALL SURVIVORS OF ACUTE RESPONSE. /PENICILLINS/

1. ESTABLISHMENT OF RESP & CREATION OF ARTIFICIAL AIRWAY... CHECK ADEQUACY OF TIDAL VOL... 2. ACUTE TOXICITY: HYPERSENSITIVITY REACTION. DRUG SHOULD BE IMMEDIATELY DISCONTINUED & PT OBSERVED FOR POSSIBILITY OF ANAPHYLACTIC SHOCK. ... 3. CHRONIC TOXICITY: DISCONTINUE USE OF DRUG. /PENICILLINS/

4. PREVENTION OF ABSORPTION: A. EMESIS SHOULD BE INITIATED UNLESS PT IS COMATOSE, CONVULSING OR HAS LOST GAG REFLEX. B. ...ENDOTRACHEAL INTUBATION SHOULD PRECEDE GASTRIC LAVAGE WITH LARGE BORE TUBE. C. ACTIVATED CHARCOAL... D. SODIUM OR MAGNESIUM SULFATE...AS CATHARTIC... /PENICILLINS/

A tolerance is established for negligible residues of cloxacillin in the uncooked edible tissues of cattle and in milk.

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).

J - Antiinfectives for systemic use

QJ - Antiinfectives for systemic use

QS - Sensory organs

QJ - Antiinfectives for systemic use

J01CF02

By binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, cloxacillin 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 cloxacillin interferes with an autolysin inhibitor.

...ITS ANTIBACTERIAL SPECTRUM AGAINST GRAM-POSITIVE BACTERIA IS LIKE THAT OF PENICILLIN EXCEPT IT IS BROADER BY MARGIN OF THOSE STRAINS OR SPECIES THAT PRODUCE PENICILLINASE. ...IT IS LESS ACTIVE THAN PENICILLIN G AGAINST NON-PENICILLINASE-PRODUCING BACTERIA, ESPECIALLY STREPTOCOCCI. /CLOXACILLIN MONOHYDRATE/

SINCE PENICILLIN HAS NO EFFECT ON EXISTING CELL WALLS, BACTERIA MUST BE MULTIPLYING FOR BACTERIAL ACTION OF PENICILLIN TO BE MANIFEST. /PENICILLINS/

The penicillins and their metabolites are potent immunogens because of their ability to combine with proteins and act as haptens for acute antibody-mediated reactions. The most frequent (about 95 percent) or "major" determinant of penicillin allergy is the penicilloyl determinant produced by opening the beta-lactam ring of the penicillin. This allows linkage of the penicillin to protein at the amide group. "Minor" determinants (less frequent) are the other metabolites formed, including native penicillin and penicilloic acids. /Penicillins/

Bactericidal; inhibit bacterial cell wall synthesis. Action is dependent on the ability of penicillins to reach and bind penicillin-binding proteins (PBPs) located on the inner membrane of the bacterial cell wall. Penicillin-binding proteins (which include transpeptidases, carboxypeptidases, and endopeptidases) are enzymes that are involved in the terminal stages of assembling the bacterial cell wall and in reshaping the cell wall during growth and division. Penicillins bind to, and inactivate, penicillin-binding proteins, resulting in the weakening of the bacterial cell wall and lysis. /Penicillins/

TOLERANCE DEVELOPED TO MULTIPLE DOSING. /PENICILLINS/

HALF-LIVES...BETWEEN 30 AND 60 MINUTES.

IN CHILDREN BEING TREATED FOR STAPHYLOCOCCAL INFECTIONS, MEAN ELIMINATION HALF-LIFE WAS 71 MIN.

The serum half-life of cloxacillin in adults with normal renal function is 0.4-0.8 hr.

The serum half-life of cloxacillin is slightly prolonged in patients with impaired renal function and has been reported to range from 0.8-2.3 hr in patients with severe renal impairment.

In one study in children 1 week to 2 years of age, the serum elimination half-life of cloxacillin was 0.8-1.5 hr. Serum concentrations of cloxacillin are generally higher and the serum half-life more prolonged in neonates than in older children.

Cloxacillin, like other penicillins, appears to be metabolized via breakage of the beta-lactam ring to form an inactive penicilloic acid metabolite.

PENICILLIN CAN UNDERGO SLOW CONVERSION IN VIVO TO INTERMEDIATES, SUCH AS PENICILLENIC ACID, WHICH CAN REACT WITH APPROPRIATE CONSTITUENTS OF TISSUES. /PENICILLINS/

Cloxacillin is partially metabolized to active and inactive metabolites. In one study following administration of a single 500-mg oral cloxacillin dose, 22% of the absorbed dose was hydrolyzed to penicilloic acids which are microbiologically inactive. Cloxacillin is also hydroxylated to a small extent to a microbiologically active metabolite which appears to be as active as cloxacillin.

Well absorbed from the gastrointestinal tract.

.../ANTIMICROBIAL AGENTS/ ARE RAPIDLY BUT INCOMPLETELY (30-80%) ABSORBED FROM GI TRACT. ABSORPTION OF DRUGS IS MORE EFFICIENT WHEN THEY ARE TAKEN ON AN EMPTY STOMACH. PEAK PLASMA CONCN ARE ATTAINED BY 1 HR & APPROX 5-10 UG/ML AFTER INGESTION OF 1 G OF OXACILLIN, & SIMILAR VALUES ARE OBTAINED WITH CLOXACILLIN.

SINCE ABSORPTION IS LESS THAN COMPLETE, HIGHER PLASMA CONCN ARE ACHIEVED FOLLOWING IM INJECTION, & LARGER QUANTITIES OF DRUGS ARE RECOVERABLE IN URINE. ...BOUND TO PLASMA ALBUMIN TO GREAT EXTENT (APPROX 90-95%); NONE IS REMOVED FROM CIRCULATION TO SIGNIFICANT DEGREE BY HEMODIALYSIS.

NORMALLY, ABOUT ONE HALF OF.../DRUG/ IS EXCRETED IN URINE IN FIRST 6 HR AFTER CONVENTIONAL ORAL DOSE. THERE IS ALSO SIGNIFICANT HEPATIC ELIMINATION...IN BILE.

ISOXAZOLYL PENICILLINS ARE RAPIDLY EXCRETED BY KIDNEY, & CONCURRENT ADMIN OF PROBENECID RESULTS IN HIGHER & MORE PERSISTENT PLASMA CONCN. /PENICILLINS/

For more Absorption, Distribution and Excretion (Complete) data for CLOXACILLIN (16 total), please visit the HSDB record page.

NOT RECOMMENDED IN US FOR USE IN FOOD PRODUCING ANIMALS.

MORE RECENTLY INTRODUCED SEMISYNTHETIC DERIVATIVES OF PENICILLIN... CLOXACILLIN...SIMILAR IN ACTION TO PARENT COMPD BUT SOME ARE ALSO EFFECTIVE AGAINST...PENICILLINASE PRODUCING STAPHYLOCOCCI. /PENICILLINS/

...SAFE TO ASSUME THAT AFTER...RECOMMENDED OR NON-RECOMMENDED USAGE FDA INSISTS TO ZERO TOLERANCE FOR DRUG IN EDIBLE TISSUES OF ANIMALS & POULTRY INCLUDING THEIR BY-PRODUCTS, MILK, OR EGGS DESTINED FOR HUMAN USE...CURRENTLY PERMITTING 0.05 PPM FOR ITS NEGLIGIBLE RESIDUE IN UNCOOKED EDIBLE TISSUES OF CATTLE. /PENICILLINS/

PROPERTIES & PHARMACOLOGY: NAYLOR ET AL, NATURE 195, 1264 (1962).