Cefaloridin

CRYSTALS

WHITE TO OFF-WHITE, CRYSTALLINE POWDER

SOL IN WATER

PRACTICALLY INSOL IN MOST ORG SOLVENTS

In water, >2.0X10+4 at 21 °C

EXPOSURE TO SUNLIGHT CAUSES DISCOLORATION

Aqueous solutions (20% w/v) are stable for four weeks at 4 °C in the dark.

Warning

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

P261, P272, P280, P302+P352, P321, P333+P317, P362+P364, 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.

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.

NON-IONIC, ANIONIC, & ZWITTERIONIC SURFACTANTS INDUCED RAPIDLY REVERSIBLE HYPER-ABSORPTIVE STATE IN THOMAS CANINE FUNDIC POUCH FOR CEPHALORIDINE...BLOOD LEVELS...MANY TIMES GREATER THAN VALUES IN CONTROLS.

CEPHALORIDINE SEEMS TO HAVE GREATEST POTENTIAL FOR NEPHROTOXICITY.../IT SHOULD NOT/ BE USED WITH GENTAMICIN /OR OTHER AMINOGLYCOSIDES, AMIKACIN, NEOMYCIN, PAROMOMYCIN & TOBRAMYCIN/ UNLESS LIFE-THREATENING CONDITION EXISTS /MAY INCR NEPHROTOXICITY/.

CEPHALORIDINE NEPHROTOXICITY IS ENHANCED BY CONCURRENT FUROSEMIDE ADMIN. SUCH THERAPY SHOULD BE AVOIDED IN PATIENTS WHO HAVE EVEN MILD PREEXISTING RENAL DISEASE.

...CEPHALOSPORINS...MAY BE AFFECTED BY CONCURRENT USE OF PROBENECID OR SULFINPYRAZONE. DIMINISHED TUBULAR SECRETION OF...WEAK ACIDS COULD RESULT IN HIGHER & MORE SUSTAINED SERUM LEVELS & HENCE, INTENSIFICATION OF DRUG ACTIVITY. /CEPHALOSPORINS/

Groups of ten male rats were treated with a high challenge dose of cephaloridine (3750 mg/kg), with methylprednisolone (100 mg/kg) or with cephaloridine and methylprednisolone by single sc injection. A control group received the injection vehicles only. Urine was collected from all animals daily over 18-hr collection periods, up to 96 hr after treatment. Blood was collected at 24, 48, 72 and 96 hr after treatment. At necropsy, kidneys were weighed, processed and examined histopathologically. Results show that methylprednisolone significantly ameliorated the nephrotoxicity of the challenge dose of cephaloridine. Cephaloridine-only treated rats had severe toxic nephrosis characterized by acute tubular necrosis, and elevated blood urea and creatinine. by contrast, the majority of cephaloridine plus methylprednisolone treated rats had only a slight or moderate toxic nephrosis, and had lower blood urea and creatinine levels compared with rats treated with cephaloridine only, indicating preservation of kidney function. Interestingly, rats treated with cephaloridine and methylprednisolone had higher urinary enzymes ... as well as protein and glucose, compared with rats treated with cephaloridine only. this is taken to indicate that rats treated with cephaloridine only had such marked kidney damage and necrosis that the population of cells able to produce these marker enzymes was significantly and rapidly depleted, but the protection afforded by methylprednisolone allowed cephaloridine plus methylprednisolone treated rats to sustain urinary enzyme output. Effects on urinary glucose and other parameters ... demonstrate interactions between glucocorticoid pharmacology and cephaloridine nephrotoxicity.

...CASE HAS BEEN REPORTED IN WHICH TREATMENT WITH THIS DRUG /CEPHALORIDINE/ IN EXTREMELY ILL 18-YR-OLD GIRL WITH STAPHYLOCOCCUS SEPTICEMIA WAS ASSOCIATED WITH ACUTE RENAL FAILURE & BLINDNESS, WITH MUCH PAPILLEDEMA & PIGMENTATION IN PERIPHERY OF FUNDI. RETINAL VESSELS WERE SAID TO BE NORMAL.

CEPHALORIDINE OCCASIONALLY CAUSES ALLERGY, MANIFESTED BY PRURITUS, URTICARIA, VARIOUS SKIN RASHES, FEVER, EOSINOPHILIA, OR ANAPHYLAXIS. ...MAY CAUSE NAUSEA & VOMITING. ... NEUROTOXICITY, SUCH AS TWITCHING, MYOCLONUS, & COMA, ALSO OCCURS WITH LARGE DOSES.

CEPHALORIDINE IS NEPHROTOXIC. RENAL INJURY DUE TO THIS DRUG OCCURS MOST OFTEN WITH ADMIN OF 6 G OR MORE/DAY. CLINICAL PICTURE THAT DEVELOPS HAS ALL FEATURES OF ACUTE TUBULAR NECROSIS. MECHANISM OF THIS REACTION IS UNKNOWN.

LARGE DOSES OF CEPHALORIDINE RESULT IN HIGH INCIDENCE OF GRANULAR CASTS IN URINE.

For more Human Toxicity Excerpts (Complete) data for CEPHALORIDINE (10 total), please visit the HSDB record page.

NEPHROTOXIC. MAY PRODUCE FALSE POSITIVE GLUCOSE & COOMB'S TESTS.

RENAL TUBULAR NECROSIS FOLLOWING IM INJECTIONS OF CEPHALOTHIN INTO RATS. LESIONS WERE CONSISTENTLY PRODUCED WITH 5.0 G/KG & WERE MAXIMAL IN SEVERITY @ 2ND & 3RD DAYS FOLLOWING INJECTION.

... Effects on the ERG of rabbit retina in vitro were found, and in tests in rabbits it was shown that, while intravitreal injections of 0.25 mg or less caused no damage, 5 mg produced small retinal hemorrhages, and 10 mg caused clumping of the outer segments of the photoreceptors, destruction of retinal pigment epithelium, and extinction of the electroretinogram. Intravitreal injection of 25 mg caused complete destruction of the outer segments of photoreceptors and phagocytosis by cells from the retinal pigment epithelium; these changes proved irreversible.

... No retinotoxic effect was detected when this substance was injected intravenously, subconjunctivally or into the anterior chamber in rabbits in very large doses.

For more Non-Human Toxicity Excerpts (Complete) data for CEPHALORIDINE (8 total), please visit the HSDB record page.

ADMIN OF PROBENECID CAN AMELIORATE NEPHROTOXICITY OF CEPHALORIDINE.

PERITONEAL DIALYSIS OR HEMODIALYSIS SIGNIFICANTLY REDUCES PLASMA CONCN OF /CEPHALORIDINE/...

LD50 MOUSE ORAL GREATER THAN 15 G/KG

LD50 MONKEY INTRAMUSCULAR GREATER THAN 0.2 G/KG

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

CEPHALOTHIN & ITS CONGENERS INHIBIT BACTERIAL CELL-WALL SYNTHESIS IN MANNER SIMILAR TO THAT OF PENICILLIN. /CEPHALOSPORINS/

Cephaloglycin and cephaloridine are acutely toxic to the proximal renal tubule, in part because of their cellular uptake by a contraluminal anionic secretory carrier and in part through their intracellular attack on the mitochondrial transport and oxidation of tricarboxylic acid (TCA) cycle anionic substrates. Preliminary studies with cephaloglycin have provided evidence of a role of fatty acid (FA) metabolism in its nephrotoxicity, and work with cephaloridine has shown it to be a potent inhibitor of renal tubular cell and mitochondrial carnitine (Carn) transport.

.../CEPHALORIDINE/ PEAK PLASMA CONCN ARE REACHED ABOUT 30 MIN AFTER DRUG IS INJECTED... WHILE ITS T/2 (60 TO 90 MIN)...ONLY SMALL AMT ARE DETECTABLE AFTER 8 HR.

/IN RATS/ RATIOS OF BONE TO SERUM CONCN AVG...1:7 FOR CEPHALORIDINE...DURING 0.25-4 HR AFTER /ORAL OR SC/ DOSING. DESPITE DIFFERENCES IN CONCN, T/2 IN BONE & SERUM WERE SIMILAR.

Renal.

.../CEPHALORIDINE/ POORLY ABSORBED FROM GI TRACT. PEAK PLASMA CONCN ARE REACHED ABOUT 30 MIN AFTER DRUG IS INJECTED; 10 TO 20% OF PLASMA CEPHALORIDINE IS BOUND TO PROTEIN.

IM INJECTIONS OF 0.5 & 1 G YIELD PEAK PLASMA CONCN OF 15 & 30 UG/ML, RESPECTIVELY. APPROX 75% OF GIVEN DOSE IS EXCRETED IN URINE, MAINLY BY GLOMERULAR FILTRATION. CEPHALORIDINE ACCUM IN BLOOD OF PATIENTS WITH DECR RENAL FUNCTION, & IN AZOTEMIC PATIENTS PLASMA CONCN ARE VERY HIGH...

PLACENTAL DRUG TRANSFER- CEPHALORIDINE: TIME TO APPEAR IN FETUS 30 MIN; TIME TO FETAL/MATERNAL CONCN EQUIL 5 HR. /FROM TABLE/

.../CEPHALORIDINE/ READILY PENETRATE NORMAL EYE FOLLOWING SYSTEMIC OR SUBCONJUNCTIVAL ADMIN...

...CEPHALORIDINE...SHOWN...TO PENETRATE INTO BONE TO VERY LIMITED EXTENT AFTER SC OR ORAL DOSES TO RATS. RATIOS OF BONE TO SERUM CONCN AVG...1:7 FOR CEPHALORIDINE...DURING 0.25-4 HR AFTER DOSING.

MEDICATION

MEDICATION (VET)

(1977) PROBABLY GREATER THAN 4.54X10+5 GRAMS

(1979) PROBABLY GREATER THAN 4.54X10+5 GRAMS

REACTION OF 7-AMINOCEPHALOSPORANIC ACID WITH THIOPHENE ACETYL CHLORIDE IN ACETONE TO FORM CEPHALOTHIN, THEN HEATING WITH A THIOCYANATE, PYRIDINE, AND PHOSPHORIC ACID, FOLLOWED BY PH ADJUSTMENT WITH A MINERAL ACID

AQ MIXT OF CEPHALOTHIN, THIOCYANATE, PYRIDINE, & PHOSPHORIC ACID IS HEATED FOR SEVERAL HR. ON COOLING, DILUTING WITH WATER, & ADJUSTING PH WITH MINERAL ACID, CEPHALORIDINE THIOCYANATE SALT PRECIPITATES WHICH IS PURIFIED & CONVERTED TO CEPHALORIDINE BY PH ADJUSTMENT OR BY INTERACTION WITH ION-EXCHANGE RESIN.

Cefalotin + pyridine (deacetylation)

CEPHALOSPORINS ARE INCOMPATIBLE WITH ERYTHROMYCIN & TETRACYCLINES IN PARENTERAL MIXTURES. /CEPHALOSPORINS, FROM TABLE/

Because of its renal toxicity and the development of newer and more active synthetic cephalosporins, cephaloridine's use is declining.

This agent in no longer available in the US.