Carbenicillin

1.13

logP = 1.13

1.8

451

WHITE TO OFF-WHITE, CRYSTALLINE POWDER; BITTER TASTE; HYGROSCOPIC; ODORLESS; PKA1: 2.76; PKA2: 3.5; SPECIFIC OPTICAL ROTATION: +175 TO +185 DEG; 1 G SOL IN 1.2 ML WATER, 25 ML ALCOHOL; SOL IN METHANOL, DIL ALKALI, DIL ACID; INSOL IN ACETONE, CHLOROFORM, ETHER /DISODIUM/

3.90e-01 g/L

UNSTABLE IN ACID /DISODIUM/

Extended-spectrum penicillins are generally stable for several yr in the dry state @ room temp; however, the drugs are stable only for short periods of time in soln unless frozen. Like other penicillins, stability of extended-spectrum penicillins is pH and temp dependent ... carbenicillin indanyl sodium is more resistant to acid-catalyzed hydrolysis than carbenicillin and is generally stable in the presence of acidic gastric secretions following oral admin.

Danger

H317 (100%): May cause an allergic skin reaction [Warning Sensitization, Skin]；H334 (100%): May cause allergy or asthma symptoms or breathing difficulties if inhaled [Danger Sensitization, respiratory]

P233, P260, P261, P271, P272, P280, P284, P302+P352, P304+P340, P321, P333+P317, P342+P316, P362+P364, P403, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 39 reports by companies from 1 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.；Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown. For more detailed information, please visit ECHA C&L website.

IMAP assessments - 4-Thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid, 6-[(carboxyphenylacetyl)amino]-3,3-dimethyl-7-oxo-, [2S-(2.alpha.,5.alpha.,6.beta.)]-: Environment tier I assessment；IMAP assessments - 4-Thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid, 6-[(carboxyphenylacetyl)amino]-3,3-dimethyl-7-oxo-, [2S-(2.alpha.,5.alpha.,6.beta.)]-: Human health tier I assessment

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).

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.

Extended-spectrum penicillins are physically and/or chemically incompatible with aminoglycosides and can inactivate the drugs in vitro. The extent of in vitro inactivation of aminoglycosides by penicillins depends on the specific drugs involved and appears to be directly proportional to the penicillin concn, length of exposure, and temp ... Most in vitro studies indicate that carbenicillin ... inactivates aminoglycosides at a faster rate than mazlocillin, piperacillin, or ticarcillin.

Extended-spectrum penicillins can also inactivate aminoglycosides in vivo. In patients with impaired renal function, concomitant admin of carbenicillin ... and gentamicin has resulted in decreased serum aminoglycoside concn and serum half-lives compared with admin of the aminoglycoside alone.

Some in vitro studies indicate that the antibacterial activity of extended-spectrum penicillins may be additive or partially synergistic with other beta-lactam antibiotics ... . /Extended-spectrum penicillins/

In vitro studies indicate that the combination of carbenicillin ... with clavulanic acid, a beta-lactamase inhibitor, results in a synergistic bactericidal effect against many strains of beta-lactamase-producing bacteria.

For more Interactions (Complete) data for CARBENICILLIN (7 total), please visit the HSDB record page.

MASSIVE IV DOSES IN MAN...MAY RESULT IN AN ENCEPHALOPATHY WITH MUSCULAR HYPERIRRITABILITY, MYOCLONUS, VISUAL & AUDITORY HALLUCINATIONS & GENERALIZED CONVULSIONS. ... ALLERGIC REACTIONS ARE FAR MORE COMMON THAN FRANK TOXICITY. ANAPHYLACTIC SHOCK IS RARE, BUT CAN FOLLOW ONE-MICROGRAM TEST DOSE. /PENICILLINS/

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 CARBENICILLIN (48 total), please visit the HSDB record page.

Drug-Induced Liver Injury Severity and Toxicity (DILIst)

carbenicillin

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 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 & GENERALIZED CONVULSIONS. ...ELICITED IN RATS & CATS WITH DOSES TO 3-4 MILLION UNITS/KG... /PENICILLINS/

IT HAD FEW SIDE EFFECTS WHEN GIVEN REPEATEDLY TO MICE, RATS, & CATS. IV LD50 VALUE FOR MICE WAS 47 MG/20 G. SC ADMIN OF 250 OR 1000 MG/KG TO RATS HAD NO SIDE EFFECTS. IN CATS, 300-500 MG/KG DECR ARTERIAL PRESSURE.

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/

◉ Summary of Use during Lactation；Carbenicillin indanyl disodium is no longer marketed. Limited information indicates that carbenicillin produces low levels in milk that are not expected to cause adverse effects in breastfed infants. Occasionally disruption of the infant's gastrointestinal flora, resulting in diarrhea or thrush have been reported with penicillins, but these effects have not been adequately evaluated. Carbenicillin indanyl disodium is acceptable in nursing mothers.；◉ Effects in Breastfed Infants；Relevant published information was not found as of the revision date.；◉ Effects on Lactation and Breastmilk；Relevant published information was not found as of the revision date.

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；J01 - Antibacterials for systemic use；J01C - Beta-lactam antibacterials, penicillins；J01CA - Penicillins with extended spectrum；J01CA03 - Carbenicillin

QJ - Antiinfectives for systemic use；QJ01 - Antibacterials for systemic use；QJ01C - Beta-lactam antibacterials, penicillins；QJ01CA - Penicillins with extended spectrum；QJ01CA03 - Carbenicillin

Carbenicillin is a semisynthetic penicillin. Though carbenicillin provides substantial <i>in vitro</i> activity against a variety of both gram-positive and gram-negative microorganisms, the most important aspect of its profile is in its antipseudomonal and antiproteal activity. Because of the high urine levels obtained following administration, carbenicillin has demonstrated clinical efficacy in urinary infections due to susceptible strains of: <i>Escherichia coli</i>, <i>Proteus mirabilis</i>, <i>Proteus vulgaris</i>, <i>Morganella morganii</i>, <i>Pseudomonas</i> species, <i>Providencia rettgeri</i>, <i>Enterobacter</i> species, and <i>Enterococci</i> (<i>S. faecalis</i>).

Free carbenicillin is the predominant pharmacologically active fraction of the salt. Carbenicillin exerts its antibacterial activity by interference with final cell wall synthesis of susceptible bacteria. Penicillins acylate the penicillin-sensitive transpeptidase C-terminal domain by opening the lactam ring. This inactivation of the enzyme prevents the formation of a cross-link of two linear peptidoglycan strands, inhibiting 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 carbenicillin interferes with an autolysin inhibitor.

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/

1 hour

...T 1/2...IN INDIVIDUALS WITH NORMAL RENAL FUNCTION IS ABOUT 1 HR...PROLONGED TO ABOUT 2 HR IN PRESENCE OF HEPATIC DYSFUNCTION.

G42ZU72N5G

CARBENICILLIN

Established Pharmacologic Class [EPC] - Penicillin-class Antibacterial

Chemical Structure [CS] - Penicillins

Carbenicillin is a Penicillin-class Antibacterial.

Rapidly absorbed from the small intestine following oral administration. Oral bioavailability is 30 to 40%.

CARBENICILLIN IS NOT ABSORBED FROM GI TRACT &, THEREFORE MUST BE GIVEN PARENTERALLY. ... IM INJECTION OF 1 G PRODUCES PEAK PLASMA CONCN OF 15-20 UG/ML IN 1/2-2 HR... MAX PLASMA CONCN ARE ABOUT 4 TIMES HIGHER AFTER IV THAN AFTER IM ADMIN... IV INFUSION...1 G/HR RESULTS IN AVG PLASMA CONCN OF APPROX 150 UG/ML.

ABOUT 50% OF ANTIBIOTIC IN PLASMA IS PROTEIN BOUND. ...CARBENICILLIN IS EXCRETED PRIMARILY BY RENAL TUBULES. ABOUT 75-80%...IS RECOVERABLE IN ACTIVE FORM IN URINE IN 9 HR.

Carbenicillin is not stable in acids nor does it resist penicillinases; thus it is administered parenterally because of poor absorption following oral administration. A parenteral dose of 50-200 mg/kg is divided for administration every 4-6 hr.

Although carbenicillin is eliminated from the bovine mammary gland within 72 hr posttreatment, mastitis produced by P. aeruginosa is not effectively treated; resistant organisms are recovered 24-48 hr postinfusion.

For more Absorption, Distribution and Excretion (Complete) data for CARBENICILLIN (11 total), please visit the HSDB record page.

(1976) 1.4X10+5 G-PRINCPL CUSTMS DIST-DISODIUM

(1979) 4.7X10+6 G-PRINCPL CUSTMS DIST-DISODIUM

(1977) PROBABLY MORE THAN 9.07X10+5 G-DISODIUM

(1979) PROBABLY MORE THAN 9.07X10+5 G-DISODIUM

THIS DRUG IS PENICILLINASE-SUSCEPTIBLE DERIVATIVE OF 6-AMINOPENICILLANIC ACID.

PREPN OF DISODIUM SALT: BELG PATENT 646,991, CORRRESPONDING TO BRAIN, NAYLER, US PATENT 3,282,926 (1964 & 1966 TO BEECHAM).