Carbenicillin indanyl sodium is the sodium salt of the indanyl ester of carbenicillin, a semisynthetic a-carboxypenicillin that is an extended-spectrum penicillin antibiotic.
Uses
Carbenicillin indanyl sodium is used only for the treatment of acute or chronic infections of the upper and lower urinary tract, asymptomatic bacteriuria, or prostatitis caused by susceptible organisms.
Urinary Tract Infections
Oral carbenicillin indanyl sodium has been used with some success for short-term therapy or long-term suppressive therapy in the treatment of acute or chronic infections of the upper and lower urinary tract or for asymptomatic bacteriuria caused by susceptible strains of enterococci, Enterobacter, Escherichia coli, Morganella morganii, Proteus mirabilis, P. vulgaris, P. rettgeri, or Pseudomonas aeruginosa. However, most clinicians state that the drug is not a drug of choice for these infections. Some clinicians suggest that uncomplicated urinary tract infections should be treated with co-trimoxazole, fluoroquinolones, oral cephalosporins, nitrofurantoin, or fosfomycin; complicated urinary tract infections generally require parenteral therapy. Because only low urine and renal parenchyma concentrations of carbenicillin are attained with oral carbenicillin indanyl sodium in patients with severe renal impairment, the drug may be ineffective in the treatment of urinary tract infections in patients with creatinine clearances less than 10 mL/minute.
Prostatitis
Carbenicillin indanyl sodium has also been used with some success for the treatment of acute or chronic prostatitis caused by susceptible strains of Enterobacter, E. coli, P. mirabilis, or enterococci. In one controlled study, oral carbenicillin indanyl sodium appeared to be more effective than oral cephalexin for the treatment of acute or chronic prostatitis; however, men with recurrent urinary tract infections associated with prostatitis usually respond poorly to anti-infective therapy and optimum therapy for these infections has not been definitely established.
Prophylaxis
Carbenicillin indanyl sodium has been used for perioperative prophylaxis in patients undergoing transrectal biopsy of the prostate and, in one study, reduced the incidence of postoperative bacteriuria in these patients. However, extended-spectrum penicillins are not considered drugs of choice for such prophylaxis. If antimicrobial prophylaxis is used in patients undergoing urologic surgery who are considered at high risk for postoperative bacteriuria (e.g., those with prolonged postoperative catheterization, positive urine cultures, or in hospitals with infection rates greater than 20%), other anti-infectives (co-trimoxazole, lomefloxacin, cefazolin) generally are preferred. For patients undergoing transrectal prostatic biopsy or those with a preoperative urinary catheter or urine cultures that are positive or unavailable, some clinicians suggest preoperative use of ciprofloxacin.
Dosage and Administration
Administration
Carbenicillin indanyl sodium is administered orally.
Dosage
Dosage of carbenicillin indanyl sodium is expressed in terms of carbenicillin. The usual oral adult dosage of carbenicillin for the treatment of urinary tract infections or asymptomatic bacteriuria is 382-764 mg 4 times daily given for 10 days or longer. A dosage of 764 mg 4 times daily should be used for the treatment of infections caused by Pseudomonas or Enterobacter. Prolonged therapy may be required for the treatment of chronic urinary tract infections. The usual oral adult dosage of carbenicillin for the treatment of prostatitis is 764 mg 4 times daily for 2-4 weeks or longer.
Cautions
Adverse Effects
The most frequent adverse effects reported with carbenicillin indanyl sodium are GI effects including dose-related nausea, vomiting, diarrhea, abdominal cramps, and flatulence. Dry mouth, bad taste, glossitis, furry tongue, anorexia, rectal bleeding, and vaginitis have also been reported rarely. Carbenicillin indanyl sodium has a bitter taste and, although commercially available tablets of the drug are film-coated, patients receiving the drug generally complain of an unpleasant aftertaste and smell. As with other extended-spectrum penicillins, rash, urticaria, pruritus, eosinophilia, hemolytic anemia, neutropenia, thrombocytopenia, leukopenia, and increased serum concentrations of AST (SGOT) have been reported with carbenicillin indanyl sodium.
Precautions and Contraindications
Carbenicillin indanyl sodium is contraindicated in patients who are hypersensitive to any penicillin. Carbenicillin 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 carbenicillin indanyl sodium, 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 b-lactam antibiotics including cephalosporins, cephamycins, and 1-oxa-b-lactams. Renal, hepatic, and hematologic systems should be evaluated periodically during prolonged therapy with carbenicillin indanyl sodium. Because of the risk of therapeutic failure from subtherapeutic drug concentrations, carbenicillin indanyl sodium should not be used when rapid high blood and/or urine concentrations are necessary or in patients with severe renal impairment (i.e., creatinine clearances less than 10 mL/minute). For a more complete discussion of these and other precautions associated with the use of carbenicillin indanyl sodium.
Pediatric Precautions
The manufacturer states that because only limited data are available to date on use of carbenicillin indanyl sodium in children, safe use of the drug in these patients has not been definitely established. Use of carbenicillin indanyl sodium in children has generally been associated with a high incidence of nausea, vomiting, and diarrhea.
Pregnancy
Safe use of carbenicillin indanyl sodium during pregnancy has not been definitely established.
The drug should be used during pregnancy only when clearly needed. Spectrum Carbenicillin indanyl sodium has some antibacterial activity in vitro and is reportedly more active than carbenicillin against susceptible gram-positive organisms. However, carbenicillin indanyl sodium is rapidly hydrolyzed to carbenicillin in vivo and the antibacterial activity of the ester is not clinically important. Based on its spectrum of activity, carbenicillin is classified as an extended-spectrum penicillin.
In Vitro Susceptibility Testing
Because carbenicillin indanyl sodium is rapidly hydrolyzed to carbenicillin in vivo, carbenicillin is used to determine in vitro susceptibility to carbenicillin indanyl sodium.
Disk Susceptibility Tests
When the disk-diffusion procedure is used to test susceptibility to carbenicillin indanyl sodium, a disk containing 100 mcg of carbenicillin is used. When the disk-diffusion procedure is performed as recommended by the National Committee for Clinical Laboratory Standards (NCCLS), urinary tract isolates of Enterobacteriaceae with growth inhibition zones of 23 mm or greater are susceptible to carbenicillin, those with zones of 20-22 mm have intermediate susceptibility, and those with zones of 19 mm or less are resistant to the drug. Urinary tract isolates of Ps. aeruginosa with growth inhibition zones of 17 mm or greater are susceptible to carbenicillin, those with zones of 14-16 mm have intermediate susceptibility, and those with zones of 13 mm or less are resistant to the drug. Urinary tract isolates of Acinetobacter with growth inhibition zones of 23 mm or greater are susceptible to carbenicillin, those with zones of 20-22 mm have intermediate susceptibility, and those with zones of 19 mm or less are resistant to the drug.
Dilution Susceptibility Tests
When dilution susceptibility testing (agar or broth dilution) is performed according to NCCLS standardized procedures, urinary isolates of Enterobacteriaceae with MICs of 16 mcg/mL or less are susceptible to carbenicillin, those with MICs of 32 mcg/mL have intermediate susceptibility, and those with MICs of 64 mcg/mL or greater are resistant to the drug. NCCLS states that urinary tract isolates of Ps. aeruginosa with MICs of 128 mcg/mL or less are susceptible to carbenicillin, those with MICs of 256 mcg/mL have intermediate susceptibility, and those with MICs of 512 mcg/mL or greater are resistant to the drug. Urinary tract isolates of other non-Enterobacteriaceae gram-negative bacilli (e.g., other Pseudomonas spp., Acinetobacter, Stenotrophomonas maltophilia) with MICs of 16 mcg/mL or less are susceptible to carbenicillin, those with MICs of 32 mcg/mL have intermediate susceptibility, and those with MICs of 64 mcg/mL or greater are resistant to the drug.
Pharmacokinetics
In all studies described in the Pharmacokinetics section, carbenicillin was administered as carbenicillin indanyl sodium; dosages and concentrations of the drug are expressed in terms of carbenicillin. For information on distribution of carbenicillin and further information on elimination of the drug
Absorption
Carbenicillin indanyl sodium is generally stable in the presence of acidic gastric secretions and is rapidly, but incompletely, absorbed following oral administration. Approximately 30-40% of an oral dose of carbenicillin indanyl sodium is absorbed from the GI tract.
Peak serum concentrations of carbenicillin indanyl sodium generally are attained within 30 minutes after oral administration; however, the drug is rapidly and completely hydrolyzed to carbenicillin and indanol after absorption and only carbenicillin is detectable in serum 90 minutes after administration. Peak serum concentrations of carbenicillin generally are attained within 0.5-2 hours after oral administration of carbenicillin indanyl sodium; serum carbenicillin concentrations usually are low or may be undetectable 6 hours after the dose.
Following oral administration of a single 382-mg dose of carbenicillin as carbenicillin indanyl sodium in healthy adults with normal renal function, serum concentrations of carbenicillin 1, 2, and 4 hours after the dose average 6.5, 3.2, and 1.9 mcg/mL, respectively. Following oral administration of a single 764-mg dose of carbenicillin as carbenicillin indanyl sodium to healthy fasting adults, peak serum concentrations of carbenicillin average 6.8-17 mcg/mL. In one study, serum concentrations of carbenicillin 1, 2, 4, and 6 hours after a single 764-mg dose of the drug averaged 9.6, 7.9, 2.6, and 0.4 mcg/mL, respectively. Serum concentrations of carbenicillin attained after oral administration of carbenicillin indanyl sodium are inadequate for the treatment of systemic infections; however, unless renal function is impaired, high concentrations of the drug may be attained in urine.
Elimination
Following absorption from the GI tract, carbenicillin indanyl sodium is rapidly hydrolyzed by plasma and tissue esterases to carbenicillin and indanol. Indanol is rapidly excreted in urine as glucuronide and sulfate conjugates; carbenicillin and its metabolites are excreted principally in urine. Following oral administration of a single 382- or 764-mg dose of carbenicillin as carbenicillin indanyl sodium in adults with normal renal function, urinary concentrations of carbenicillin in specimens collected during the first 3 hours after administration range from 0.576-1.13 and 1-1.4 mg/mL, respectively.
Urinary concentrations of carbenicillin attained in patients with mild to moderate renal impairment (creatinine clearances of 30 mL/minute or greater) following administration of usual dosages of carbenicillin indanyl sodium are generally similar to those attained in patients with normal renal function; however, concentrations of the drug in urine and renal parenchyma are markedly reduced in patients with severe renal impairment and generally are inadequate for the treatment of urinary tract infections in these patients.
Chemistry and Stability
Chemistry
Carbenicillin indanyl sodium is the sodium salt of the indanyl ester of carbenicillin. Carbenicillin is a semisynthetic a-carboxypenicillin. Carbenicillin is commercially available for oral administration as carbenicillin indanyl sodium. Potency of carbenicillin indanyl sodium is expressed in terms of carbenicillin. Each tablet of carbenicillin indanyl sodium containing 382 mg of carbenicillin provides 1 mEq of sodium. Carbenicillin indanyl sodium occurs as a white to off-white powder and has a bitter taste. The drug is soluble in water and in alcohol.
Stability
Carbenicillin indanyl sodium tablets should be protected from moisture and stored in tight containers at a temperature not exceeding 30°C. Esterification of the a-carboxy group of carbenicillin helps prevent decarboxylation of the drug; therefore, 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 administration. For further information on chemistry and stability, mechanism of action, spectrum, resistance, pharmacokinetics, uses, cautions, drug interactions, laboratory test interferences, and dosage and administration of carbenicillin.
Preparations
Carbenicillin Indanyl Sodium Oral Tablets, film- 382 mg (of carbenicillin) Geocillin®, coated Pfizer