Geocillin

Generic Name: Carbenicillin Indanyl Sodium
Class: Extended-spectrum Penicillins
Chemical Name: [2S - (2α,5α,6β)] - 6 - [[3 - [(2,3 - dihydro - 1H - inden - 5 - yl)oxy] - 1,3 - dioxo - 2 - phenylpropyl] - amino] - 3,3 - dimethyl - 7 - oxo - 4 - thia - 1 - azabicyclo[3.2.O]heptane - 2 - carboxylic acid monosodium salt
CAS Number: 26605-69-6

Introduction

Antibacterial; β-lactam antibiotic; α-carboxypenicillin classified as an extended-spectrum penicillin.1 3 6

Uses for Geocillin

Urinary Tract Infections (UTIs)

Treatment of acute or chronic infections of the upper and lower urinary tract or for asymptomatic bacteriuria caused by susceptible enterococci, Enterobacter, Escherichia coli, Morganella morganii, Proteus mirabilis, P. vulgaris, Providencia rettgeri, Pseudomonas, or enterococci.1 2 4 12 27 28 29 30 33

Slideshow: The Shocking Truth About Antibiotic Resistance

Not a drug of choice for these UTIs.2 4 33 Because only low carbenicillin concentrations are attained in urine and renal parenchyma in patients with severe renal impairment, the drug may be ineffective for treatment of UTIs in patients with Clcr <10 mL/minute.11

Prostatitis

Treatment of acute or chronic prostatitis caused by susceptible Enterobacter, E. coli, P. mirabilis, or enterococci.1 23 24

Perioperative Prophylaxis

Has been used for perioperative prophylaxis in patients undergoing transrectal biopsy of the prostate; 31 not a drug of choice for such prophylaxis.36 37

Geocillin Dosage and Administration

Administration

Oral Administration

Administer orally.1

Dosage

Available as carbenicillin indanyl sodium; dosage expressed in terms of carbenicillin.1

Adults

Urinary Tract Infections (UTIs)
UTIs Caused by Enterobacter, E. coli, or Proteus
Oral

382–764 mg 4 times daily.1 12 26 27 28 Usual duration is ≥10 days;12 29 prolonged therapy may be required for chronic UTIs.28

UTIs Caused by Pseudomonas or Enterococcus
Oral

764 mg 4 times daily.1 Usual duration is ≥10 days;12 29 prolonged therapy may be required for chronic UTIs.28

Prostatitis
Oral

764 mg 4 times daily.1 23 24 Usual duration is ≥2–4 weeks.23 24

Special Populations

Renal Impairment

Dosage may need to be decreased in patients with Clcr 10–20 mL/minute.1 Should not be used in those with Clcr <10 mL/minute.1

Geriatric Patients

No dosage adjustments except those related to renal impairment. (See Renal Impairment under Dosage and Administration.)

Cautions for Geocillin

Contraindications

  • Known hypersensitivity to any penicillin.1

Warnings/Precautions

Warnings

Superinfection

Possible emergence and overgrowth of nonsusceptible bacteria or fungi.1 Discontinue and institute appropriate therapy if superinfection occurs.1

Sensitivity Reactions

Hypersensitivity Reactions

Serious and occasionally fatal hypersensitivity reactions (including anaphylaxis) reported with penicillins.1 Anaphylaxis occurs most frequently with parenteral penicillins but has occurred with oral penicillins.1

Prior to initiation of therapy, make careful inquiry regarding previous hypersensitivity reactions to penicillins, cephalosporins, or other drugs.1 Partial cross-allergenicity occurs among penicillins and other β-lactam antibiotics including cephalosporins and cephamycins.1 19 20 21 22

If hypersensitivity reaction occurs, discontinue immediately and institute appropriate therapy as indicated (e.g., epinephrine, corticosteroids, maintenance of an adequate airway and oxygen).1

General Precautions

Laboratory Monitoring

Periodically assess organ system functions, including renal, hepatic, and hematopoietic, during prolonged therapy.1

Selection and Use of Anti-infectives

To reduce development of drug-resistant bacteria and maintain effectiveness of carbenicillin and other antibacterials, use only for treatment or prevention of infections proven or strongly suspected to be caused by susceptible bacteria.a

When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing.a In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.a

Coombs’ Test Results

Positive direct Coombs’ test results reported with carbenicillin.b This may interfere with certain hematologic studies or transfusion cross-matching procedures.b

Sodium Content

Each tablet of carbenicillin indanyl sodium containing 382 mg of carbenicillin contains 23 mg of sodium.1

Specific Populations

Pregnancy

Category B.1

Lactation

Distributed into milk.1 Use with caution.1

Pediatric Use

Safety and efficacy not established in pediatric patients.1

A high incidence of nausea, vomiting, and diarrhea reported when the drug was used in children.25

Hepatic Impairment

Serum concentrations of extended-spectrum penicillins may be increased and half-life prolonged in patients with hepatic impairment.b

Renal Impairment

Dosage adjustment may be necessary in patients with Clcr 10–20 mL/minute to prevent accumulation of the drug.1

Should not be used in patients with severe renal impairment (i.e., Clcr <10 mL/minute) since these patients will not achieve therapeutic concentrations in urine.1

Common Adverse Effects

GI effects,1 7 including dose-related13 nausea,1 2 12 13 15 vomiting,1 12 13 15 diarrhea,1 12 13 15 abdominal cramps,1 12 and flatulence.1 12 Unpleasant aftertaste and smell.2 12 15

Interactions for Geocillin

Specific Drugs and Laboratory Tests

Drug or Test

Interaction

Comments

Aminoglycosides

Some in vitro evidence of additive or synergistic antibacterial effects with extended-spectrum penicillins against some Enterobacteriaceae or Pseudomonas aeruginosa;b synergism is unpredictable and antagonism has been reported rarelyb

β-lactam anti-infectives

Some in vitro evidence of additive or partially synergistic antibacterial effects with other β-lactam antibiotics (e.g., cephalosporins, cephamycins);b synergism is unpredictable and indifference or antagonism has been reported more frequently than synergismb

Methotrexate

Possible decreased renal clearance of methotrexate and increased risk of methotrexate adverse effectsb

Patients receiving penicillins and methotrexate concomitantly should be monitored carefullyb

Probenecid

Decreased renal tubular secretion of carbenicillin and increased and prolonged carbenicillin plasma concentrations1 b

Tests for glucose

Possible false-positive reactions in urine glucose tests using Clinitest, Benedict’s solution, or Fehling’s solutionb

Use glucose tests based on enzymatic glucose oxidase reactions (e.g., Clinistix, Tes-Tape)b

Tests for uric acid

Possible falsely increased serum uric acid concentrations when the copper-chelate method is used;b phosphotungstate and uricase methods for serum uric acid appear to be unaffectedb

Geocillin Pharmacokinetics

Absorption

Bioavailability

Carbenicillin indanyl sodium is rapidly, but incompletely, absorbed following oral administration.1 2 4 5 13 Approximately 30–40% of an oral dose absorbed from GI tract.5 9 10 14

After absorption, carbenicillin indanyl sodium is rapidly and completely hydrolyzed to carbenicillin and indanol.2 5 8 13 Peak serum concentrations of carbenicillin generally attained within 0.5–2 hours.1 12 14 15

Distribution

Plasma Protein Binding

29–60%.b

Elimination

Metabolism

Following absorption from GI tract, carbenicillin indanyl sodium is rapidly hydrolyzed by plasma and tissue esterases to carbenicillin and indanol.2 8 13 18

Elimination Route

Indanol is rapidly excreted in urine as glucuronide and sulfate conjugates;2 13 carbenicillin and its metabolites are excreted principally in urine.1 2 16

Half-life

0.78–1 hour.b

Special Populations

Serum concentrations of extended-spectrum penicillins may be increased and half-life prolonged in patients with hepatic impairment.b In patients with both renal and hepatic impairment, serum half-life of carbenicillin may range up to 32 hours.b

Serum half-life ranges from 9.4–23.4 hours in patients with Clcr <10 mL/minute per 1.73 m2.b

Stability

Storage

Oral

Tablets

≤30°C in tight container;38 39 protect from moisture.39

Actions and Spectrum

  • Based on spectrum of activity, classified as an extended-spectrum penicillin.3 6 More active against gram-negative bacilli than natural penicillins, penicillinase-resistant penicillins, and aminopenicillins.b

  • Available as the sodium salt of the indanyl ester of carbenicillin.1 8 Carbenicillin indanyl sodium is rapidly hydrolyzed to carbenicillin in vivo;1 2 3 5 6 8 13 18 the antibacterial activity of the ester is not clinically important.2 6 18

  • Usually bactericidal.b

  • Like other β-lactam antibiotics, antibacterial activity results from inhibition of bacterial cell wall synthesis.1 b

  • Spectrum of activity includes some gram-positive aerobes and many gram-negative aerobes.1 b Inactive against mycobacteria, Mycoplasma, Rickettsia, fungi, and viruses.b

  • Gram-positive aerobes: active in vitro against enterococci (e.g., Enterococcus faecalis), Staphylococcus (non-penicillinase-producing strains), and Streptococcus.1 b

  • Gram-negative aerobes: active in vitro against Enterobacter, Escherichia coli, Proteus mirabilis, P. vulgaris, Morganella morganii, Providencia rettgeri, and Pseudomonas.1 b Klebsiella usually are resistant;1 b resistance has been reported in Pseudomonas.1 b

  • Complete cross-resistance generally occurs between carbenicillin and ticarcillin.b

Advice to Patients

  • Advise patients that antibacterials (including carbenicillin) should only be used to treat bacterial infections and not used to treat viral infections (e.g., the common cold).a

  • Importance of completing full course of therapy, even if feeling better after a few days.a

  • Advise patients that skipping doses or not completing the full course of therapy may decrease effectiveness and increase the likelihood that bacteria will develop resistance and will not be treatable with carbenicillin or other antibacterials in the future.a

  • Importance of discontinuing therapy and informing clinician if an allergic reaction occurs.a

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.1

  • Importance of women informing clinician if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Carbenicillin Indanyl Sodium

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

382 mg (of carbenicillin)

Geocillin

Pfizer

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions May 1, 2004. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Pfizer. Geocillin (carbenicillin indanyl sodium) tablets prescribing information. In: Physician’s desk reference. 57th ed. Montvale, NJ: Medical Economics Company Inc; 2003:2600-1.

2. Kucers A, Crowe S, Grayson ML et al, eds. The use of antibiotics. A clinical review of antibacterial, antifungal, and antiviral drugs. 5th ed. Jordan Hill, Oxford: Butterworth-Heinemann; 1997: 145-61.

3. Rolinson GN, Sutherland R. Semisynthetic penicillins. Adv Pharmacol Chemother. 1973; 11:152-220.

4. Barza M. Antimicrobial spectrum, pharmacology and therapeutic use of antibiotics. Part 2: penicillins. Am J Hosp Pharm. 1977; 34:57-67. [PubMed 318800]

5. Wolff ME, ed. Burger’s medicinal chemistry. 4th ed. New York: John Wiley & Sons; 1980:84-157.

6. Butler K, English AR, Ray VA et al. Carbenicillin: chemistry and mode of action. J Infect Dis. 1970; 122(Suppl):S1-8. [PubMed 4248289]

7. Neu HC. Carbenicillin and ticarcillin. Med Clin North Am. 1982; 66:61-77. [PubMed 7038341]

8. Butler AR, English B, Gralla E et al. Indanyl carbenicillin: chemistry and laboratory studies with a new semisynthetic penicillin. J Infect Dis. 1973; 127(Suppl):S97-104. [PubMed 4571995]

9. Barza M, Weinstein L. Pharmacokinetics of the penicillins in man. Clin Pharmacokinet. 1976; 1:297-308. [PubMed 797501]

10. Selwyn S. Applied pharmacology, adverse effects and drug interactions. In: Selwyn S, ed. The beta-lactam antibiotics: penicillins and cephalosporins in perspective. London: Hodder and Stoughton; 1980:91-126.

11. Cox CE. Pharmacology of carbenicillin indanyl sodium in renal insufficiency. J Infect Dis. 1973; 127(Suppl):S157-62. [PubMed 4695480]

12. Turck M. The treatment of urinary-tract infections with an oral carbenicillin. J Infect Dis. 1973; 127(Suppl):S133-4.

13. Knirsch AK, Hobbs DC, Korst JJ. Pharmacokinetics, toleration, and safety of indanyl carbenicillin in man. J Infect Dis. 1973; 127(Suppl):S105-8. [PubMed 4695476]

14. Fabre J, Burgy C, Rudhardt M et al. The behaviour in man of C.P. 15,464, a carbenicillin absorbed following oral administration. Chemotherapy. 1972; 17:334-43. [PubMed 4669556]

15. Bran JL, Karl DM, Kaye D. Human pharmacology and clinical evaluation of an oral carbenicillin preparation. Clin Pharmacol Ther. 1971; 12:525-30. [PubMed 5208911]

16. Libke RD, Clarke JT, Ralph ED et al. Ticarcillin vs carbenicillin: clinical pharmacokinetics. Clin Pharmacol Ther. 1975; 17:441-6. [PubMed 1122685]

17. Nakano H, Saski K, Mizoguchi M et al. Absorption and excretion of carbenicillin indanyl sodium in patients with reduced kidney function. Chemotherapy. 1977; 23:299-308. [PubMed 578496]

18. Martin AR. Antibiotics. In: Doerge RF, ed. Wilson and Gisvold’s textbook of organic medicinal and pharmaceutical chemistry. 8th ed. Philadelphia: JB Lippincott Company; 1982:228-47.

19. Idsoe O, Guthe T, Willcox RR et al. Nature and extent of penicillin side-reactions, with particular reference to fatalities from anaphylactic shock. Bull World Health Organ. 1968; 38:159-88. [PubMed 5302296]

20. Erffmeyer JE. Adverse reactions to penicillin. Ann Allergy. 1981; 47:288-300. [PubMed 6171185]

21. Isbister JP. Penicillin allergy: a review of the immunological and clinical aspects. Med J Aust. 1971; 1:1067-74. [PubMed 4398272]

22. Sullivan TJ, Wedner HJ, Shatz GS et al. Skin testing to detect penicillin allergy. J Allergy Clin Immunol. 1981; 68:171-80. [IDIS 140792] [PubMed 6267115]

23. Mobley DF. Bacterial prostatitis: treatment with carbenicillin indanyl sodium. Invest Urol. 1981; 19:31-3. [IDIS 134873] [PubMed 7019153]

24. Oliveri RA, Sachs RM, Caste PG. Clinical experience with geocillin in the treatment of bacterial prostatitis. Curr Ther Res Clin Exp. 1979; 25:415-21.

25. Eichenwald HF, McCracken GH. Antimicrobial therapy in infants and children. Part I. Review of antimicrobial agents. J Pediatr. 1978; 93:336-56.

26. Ries KM, Cobbs GC, Gillenwater JY et al. Comparison of carbenicillin idanyl sodium, ampicillin, and cephaloglycin in treatment of urinary-tract infection. J Infect Dis. 1973; 127(Suppl):S148-53. [PubMed 4695479]

27. Baker DA, Andriole VT. The treatment of difficult urinary-tract infections with carbenicillin indanyl sodium. J Infect Dis. 1973; 127(Suppl):S136-42. [PubMed 4714084]

28. Holloway WJ, Taylor WA. Long-term oral carbenicillin therapy in complicated urinary-tract infections. J Infect Dis. 1973; 127(Suppl):S143-7. [PubMed 4576799]

29. Westenfelder M, Madsen PO. Ambulatory treatment of chronic urinary-tract infections in elderly males: a comparative study of three oral antibiotics. J Infect Dis. 1973; 127(Suppl):S154-6. [PubMed 4714085]

30. Jabbar A, Nahid M, Nasir A et al. Use of oral carbenicillin in urinary tract infection. Curr Ther Res Clin Exp. 1978; 23:22-6.

31. Crawford ED, Haynes AL, Story MW et al. Prevention of urinary tract infection and sepsis following transrectal prostatic biopsy. J Urol. 1982; 127:449-51. [IDIS 148340] [PubMed 6895918]

32. Fang LS, Tolkoff-Rubin NE, Rubin RH. Clinical management of urinary tract infection. Pharmacotherapy. 1982; 2:91-9. [IDIS 150331] [PubMed 6765394]

33. Anon. The choice of antibacterial drugs. Med Lett Drugs Ther. 2001; 43:69-78. [PubMed 11518876]

34. National Committee for Clinical Laboratory Standards. MIC testing supplemental tables; M100-S13 (M7). Wayne, PA:NCCLS; 2003 Jan.

35. National Committee for Clinical Laboratory Standards. Disk diffusion supplemental tables; M100-S13 (M2). Wayne, PA:NCCLS; 2003 Jan.

36. American Society Health-System Pharmacists. ASHP therapeutic guidelines on antimicrobial prophylaxis in surgery. Am J Health-Syst Pharm. 1999; 56:1839-88. [PubMed 10511234]

37. Anon. Antimicrobial prophylaxis in surgery. Med Lett Drugs Ther. 2001; 43:92-7. [PubMed 11689761]

38. The United States pharmacopoeia, 26th rev, and The national formulary, 21st ed. Rockville, MD: The United States Pharmacopeial Convention, Inc; 2003:326-7,2552.

39. Roerig. Product information summary on Geocillin (carbenicillin indanyl sodium). New York; 1972 Nov.

a. Pfizer. Geocillin (carbenicillin indanyl sodium) tablets prescribing information. New York, NY; 2003 Sept.

b. AHFS Drug Information 2004. McEvoy GK, ed. Extended-spectrum Penicillins General Statement. American Society of Health-System Pharmacists; 2004:341-9.

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