Geocillin, a semisynthetic penicillin, is the sodium salt of the indanyl ester of Geopen® (carbenicillin disodium). The chemical name is: 1-(5-Indanyl)-N-(2-carboxy-3,3- dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0] hept-6-yl)-2-phenylmalonamate monosodium salt.

The structural formula is:

The empirical formula is: C₂₆H₂₅N₂NaO₆S and mol. wt. is 516.55.

Geocillin tablets are yellow, capsule-shaped and film-coated, made of a white crystalline solid. Carbenicillin is freely soluble in water. Each Geocillin tablet contains 382 mg of carbenicillin, 118 mg of indanyl sodium ester. Each Geocillin tablet contains 23 mg of sodium.

Inert ingredients are: glycine; magnesium stearate and sodium lauryl sulfate. May also include the following: hydroxypropyl cellulose; hypromellose; opaspray (which may include Blue 2 Lake, Yellow 6 Lake, Yellow 10 Lake, and other inert ingredients); opadry light yellow (which may contain D&C Yellow 10 Lake, FD&C Yellow 6 Lake and other inert ingredients); opadry clear (which may contain other inert ingredients).

Last updated on RxList: 4/8/2008

Geocillin (carbenicillin indanyl sodium) is indicated in the treatment of acute and chronic infections of the upper and lower urinary tract and in asymptomatic bacteriuria due to susceptible strains of the following organisms:

Escherichia coli
Proteus mirabilis
Morganella morganii (formerly Proteus morganii)
Providencia rettgeri (formerly Proteus rettgeri)
Proteus vulgaris
Pseudomonas
Enterobacter
Enterococci

Geocillin is also indicated in the treatment of prostatitis due to susceptible strains of the following organisms:

Escherichia coli
   Enterococcus (S. faecalis)
Proteus mirabilis
Enterobacter sp.

WHEN HIGH AND RAPID BLOOD AND URINE LEVELS OF ANTIBIOTIC ARE INDICATED, THERAPY WITH GEOPEN (CARBENICILLIN DISODIUM) SHOULD BE INITIATED BY PARENTERAL ADMINISTRATION FOLLOWED, AT THE PHYSICIAN'S DISCRETION, BY ORAL THERAPY.

NOTE: Susceptibility testing should be performed prior to and during the course of therapy to detect the possible emergence of resistant organisms which may develop.

To reduce the development of drug-resistant bacteria and maintain effectiveness of Geocillin and other antibacterial drugs, Geocillin should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

Geocillin is available as a coated tablet to be administered orally.

Usual Adult Dose

URINARY TRACT INFECTIONS
Escherichia coli, Proteus species,   and Enterobacter	1-2 tablets 4 times daily
Pseudomonas and Enterococcus	2 tablets 4 times daily
PROSTATITIS
Escherichia coli, Proteus mirabilis, Enterobacter and Enterococcus	2 tablets 4 times daily

Geocillin is available as film-coated tablets in bottles of 100's (NDC 0049-1430-66). Each tablet contains carbenicillin indanyl sodium equivalent to 382 mg of carbenicillin.

Distributed by: Roerig, Division of Pfizer Inc., NY, NY 10017, May 2007. FDA revision date: 2/27/2008

Last updated on RxList: 4/8/2008

The following adverse reactions have been reported as possibly related to Geocillin administration in controlled studies which include 344 patients receiving Geocillin.

Gastrointestinal: The most frequent adverse reactions associated with Geocillin therapy are related to the gastrointestinal tract. Nausea, bad taste, diarrhea, vomiting, flatulence, and glossitis were reported. Abdominal cramps, dry mouth, furry tongue, rectal bleeding, anorexia, and unspecified epigastric distress were rarely reported.

Dermatologic: Hypersensitivity reactions such as skin rash, urticaria, and less frequently pruritus.

Hematologic: As with other penicillins, anemia, thrombocytopenia, leukopenia, neutropenia, and eosinophilia have infrequently been observed. The clinical significance of these abnormalities is not known.

Miscellaneous: Other reactions rarely reported were hyperthermia, headache, itchy eyes, vaginitis, and loose stools.

Abnormalities of Hepatic Function Tests: Mild SGOT elevations have been observed following Geocillin administration.

Geocillin (carbenicillin indanyl sodium) blood levels may be increased and prolonged by concurrent administration of probenecid.

Last updated on RxList: 4/8/2008

Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients on oral penicillin therapy. Although anaphylaxis is more frequent following parenteral therapy, it has occurred in patients on oral penicillins. These reactions are more apt to occur in individuals with a history of penicillin hypersensitivity and/or a history of sensitivity to multiple allergens.

There have been reports of individuals with a history of penicillin hypersensitivity who have experienced severe hypersensitivity reactions when treated with a cephalosporin, and vice versa. Before initiating therapy with a penicillin, careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins, or other allergens. If an allergic reaction occurs, the drug should be discontinued and the appropriate therapy instituted.

SERIOUS ANAPHYLACTOID REACTIONS REQUIRE IMMEDIATE EMERGENCY TREATMENT WITH EPINEPHRINE. OXYGEN, INTRAVENOUS STEROIDS AND AIRWAY MANAGEMENT, INCLUDING INTUBATION, SHOULD ALSO BE ADMINISTERED AS INDICATED.

Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including GEOCILLIN (carbenicillin indanyl sodium), and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.

C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.

If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.

General: As with any penicillin preparation, an allergic response, including anaphylaxis, may occur particularly in a hypersensitive individual.

Long term use of Geocillin may result in the overgrowth of nonsusceptible organisms. If superinfection occurs during therapy, appropriate measures should be taken.

Since carbenicillin is primarily excreted by the kidney, patients with severe renal impairment (creatinine clearance of less than 10 ml/min) will not achieve therapeutic urine levels of carbenicillin.

In patients with creatinine clearance of 10-20 ml/min it may be necessary to adjust dosage to prevent accumulation of drug.

Prescribing Geocillin in the absence of proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

Laboratory Tests: As with other penicillins, periodic assessment of organ system function including renal, hepatic, and hematopoietic systems is recommended during prolonged therapy.

Carcinogenesis, Mutagenesis, Impairment of Fertility: There are no long-term animal or human studies to evaluate carcinogenic potential. Rats fed 250-1000 mg/kg/day for 18 months developed mild liver pathology (e.g., bile duct hyperplasia) at all dose levels, but there was no evidence of drug-related neoplasia. Geocillin administered at daily doses ranging to 1000 mg/kg had no apparent effect on the fertility or reproductive performance of rats.

Pregnancy Category B: Reproduction studies have been performed at dose levels of 1000 or 500 mg/kg in rats, 200 mg/kg in mice, and at 500 mg/kg in monkeys with no harm to fetus due to Geocillin. There are, however, no adequate and well controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Labor and Delivery: It is not known whether the use of Geocillin in humans during labor or delivery has immediate or delayed adverse effects on the fetus, prolongs the duration of labor, or increases the likelihood that forceps delivery or other obstetrical intervention or resuscitation of the newborn will be necessary.

Nursing Mothers: Carbenicillin class antibiotics are excreted in milk although the amounts excreted are unknown; therefore, caution should be exercised if administered to a nursing woman.

Pediatric Use: Since only limited clinical data is available to date in children, the safety of Geocillin administration in this age group has not yet been established.

Last updated on RxList: 4/8/2008

Geocillin is generally nontoxic. Geocillin when taken in excessive amounts may produce mild gastrointestinal irritation. The drug is rapidly excreted in the urine and symptoms are transitory. The usual symptoms of anaphylaxis may occur in hypersensitive individuals.

Carbenicillin blood levels achievable with Geocillin are very low, and toxic reactions as a function of overdosage should not occur systematically. The oral LD₅₀ in mice is 3,600 mg/kg, in rats 2,000 mg/kg, and in dogs is in excess of 500 mg/kg. The lethal human dose is not known.

Although never reported, the possibility of accumulation of indanyl should be considered when large amounts of Geocillin are ingested. Free indole, which is a phenol derivative, may be potentially toxic. In general 8-15 grams of phenol, and presumably a similar amount of indole, are required orally before toxicity (peripheral vascular collapse) may occur. The metabolic by-products of indole are nontoxic. In patients with hepatic failure it may be possible for unmetabolized indole to accumulate.

The metabolic by-products of Geocillin, indanyl sulfate and glucuronide, as well as free carbenicillin, are dialyzable.

Geocillin is ordinarily contraindicated in patients who have a known penicillin allergy.

Last updated on RxList: 4/8/2008

Free carbenicillin is the predominant pharmacologically active fraction of Geocillin. Carbenicillin exerts its antibacterial activity by interference with final cell wall synthesis of susceptible bacteria.

Geocillin is acid stable, and rapidly absorbed from the small intestine following oral administration. It provides relatively low plasma concentrations of antibiotic and is primarily excreted in the urine. After absorption, Geocillin is rapidly converted to carbenicillin by hydrolysis of the ester linkage. Following ingestion of a single 500 mg tablet of Geocillin, a peak carbenicillin plasma concentration of approximately 6.5 mcg/ml is reached in 1 hour. About 30% of this dose is excreted in the urine unchanged within 12 hours, with another 6% excreted over the next 12 hours.

In a multiple dose study utilizing volunteers with normal renal function, the following mean urine and serum levels of carbenicillin were achieved:

		Mean Urine Concentration of Carbenicillin mcg/ml Hours After Initial Dose
DRUG	DOSE	0-3				3-6		6-24
Geocillin	1 tablet q.6 hr	1130				352		292
Geocillin	2 tablets q.6 hr	1428				789		809
Mean serum concentrations of carbenicillin in this study for these dosages are:
		Mean Serum Concentration mcg/ml Hours After Initial Dose
DRUG	DOSE	½	1	2	4	6	24	25	26	28
Geocillin	1 tablet q.6 hr	5.1	6.5	3.2	1.9	0.0	0.4	8.8	5.4	0.4
Geocillin	2 tablets q.6 hr	6.1	9.6	7.9	2.6	0.4	0.8	13.2	12.8	3.8

Microbiology

The antibacterial activity of Geocillin is due to its rapid conversion to carbenicillin by hydrolysis after absorption. Though Geocillin provides substantial in vitro 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, Geocillin has demonstrated clinical efficacy in urinary infections due to susceptible strains of:

Escherichia coli
Proteus mirabilis
Proteus vulgaris
Morganella morganii (formerly Proteus morganii)
Pseudomonas species
   Providencia rettgeri (formerly Proteus rettgeri)
Enterobacter species
Enterococci (S. faecalis)

In addition, in vitro data, not substantiated by clinical studies, indicate the following pathogens to be usually susceptible to Geocillin:

Staphylococcus species (nonpenicillinase producing)
Streptococcus species

Resistance

Most Klebsiella species are usually resistant to the action of Geocillin. Some strains of Pseudomonas species have developed resistance to carbenicillin.

Susceptibility Testing

Geopen (carbenicillin disodium) Susceptibility Powder or 100 g Geopen Susceptibility Discs may be used to determine microbial susceptibility to Geocillin using one of the following standard methods recommended by the National Committee for Clinical Laboratory Standards:

M2-A3, “Performance Standards for Antimicrobial Disk Susceptibility Tests"

M7-A, “Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically"

M11-A, “Reference Agar Dilution Procedure for Antimicrobial Susceptibility Testing of Anaerobic Bacteria"

M17-P, “Alternative Methods for Antimicrobial Susceptibility Testing of Anaerobic Bacteria"

Tests should be interpreted by the following criteria:

	Disk Diffusion Zone diameter (mm)
Organisms	Suscept.	Intermed.	Resist.
Enterobacter	≥ 23	18-22	≤ 17
Pseudomonas sp.	≥ 17	14-16	≤ 13

	Dilution MIC ( g/ml) Moderately
Organisms	Suscept.	Suscept.	Resist.
Enterobacter	≤ 16	32	≥ 64
Pseudomonas sp.	≤ 128	-	≥ 156

Interpretations of susceptible, intermediate, and resistant correlate zone size diameters with MIC values. A laboratory report of “susceptible" indicates that the suspected causative microorganism most likely will respond to therapy with carbenicillin. A laboratory report of “resistant" indicates that the infecting microorganism most likely will not respond to therapy. A laboratory report of “moderately susceptible" indicates that the microorganism is most likely susceptible if a high dosage of carbenicillin is used, or if the infection is such that high levels of carbenicillin may be attained as in urine. A report of “intermediate" using the disk diffusion method may be considered an equivocal result, and dilution tests may be indicated.

Last updated on RxList: 4/8/2008

Patients should be counseled that antibacterial drugs including Geocillin should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Geocillin is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by Geocillin or other antibacterial drugs in the future.

Diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible.

Last updated on RxList: 4/8/2008

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

CARBENICILLIN - ORAL

(kar-BEN-ih-SILL-in)

COMMON BRAND NAME(S): Geocillin

USES: Carbenicillin is used to treat urinary tract infections and prostate infections caused by bacteria. This medication belongs to the class of antibiotics called penicillins. It works by stopping the growth of bacteria.

This antibiotic treats only bacterial infections. It will not work for viral infections (e.g., common cold, flu). Unnecessary use or misuse of any antibiotic can lead to its decreased effectiveness.

HOW TO USE: Take this medication by mouth with or without food, usually 4 times a day or as directed by your doctor. The dosage is based on your medical condition and response to therapy.

Antibiotics work best when the amount of medicine in your body is kept at a constant level. Therefore, take this drug at evenly spaced intervals.

Continue to take this medication until the full prescribed amount is finished, even if symptoms disappear after a few days. Stopping the medication too early may result in a return of the infection.

Inform your doctor if your condition persists or worsens.

SIDE EFFECTS: Nausea, bad taste in the mouth, diarrhea, vomiting, gas, or mouth/tongue sores may occur. If any of these effects persist or worsen, notify your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these rare but very serious side effects occur: unusual tiredness, easy or unusual bruising/bleeding, signs of infection (e.g., fever, persistent sore throat), change in the amount of urine, persistent nausea/vomiting, severe stomach/abdominal pain, yellowing eyes/skin, dark urine.

This medication may rarely cause a severe intestinal condition (pseudomembranous colitis) due to a type of resistant bacteria. This condition may occur during treatment or weeks after treatment has stopped. Do not use anti-diarrhea products or narcotic pain medications if you have any of the following symptoms because these products may make them worse. Tell your doctor immediately if you develop: persistent diarrhea, abdominal or stomach pain/cramping, blood/mucus in your stool.

Use of this medication for prolonged or repeated periods may result in oral thrush or a new vaginal yeast infection. Contact your doctor if you notice white patches in your mouth, a change in vaginal discharge, or other new symptoms.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any of the following symptoms of a serious allergic reaction: rash, itching, swelling, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before taking carbenicillin, tell your doctor or pharmacist if you are allergic to it; or to other penicillins (e.g., amoxicillin, penicillin); or to cephalosporin antibiotics (e.g., cefuroxime, cephalexin); or if you have any other allergies.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: kidney disease.

During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.

Based on information from related drugs, this medication may pass into breast milk. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with them first.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: guar gum, khat, live bacterial vaccines, methotrexate, tetracyclines.

Before taking carbenicillin, tell your doctor or pharmacist if you are also taking probenecid. Probenecid slows down the removal of carbenicillin from your body, resulting in higher levels of this antibiotic in your blood. Consult your doctor or pharmacist for more details.

This medication may decrease the effectiveness of combination-type birth control pills. This can result in pregnancy. You may need to use an additional form of reliable birth control while using this medication. Consult your doctor or pharmacist for details.

Carbenicillin may cause false-positive results with certain diabetic urine testing products (cupric sulfate-type). This drug may also affect the results of certain lab tests. Make sure laboratory personnel and all your doctors know you use this drug.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include: severe nausea, vomiting.

NOTES: Do not share this medication with others.

This medication has been prescribed for your current condition only. Do not use it later for another infection unless told to do so by your doctor. A different medication may be necessary in that case.

With prolonged treatment, laboratory and/or medical tests (e.g., kidney and liver function, urine tests, complete blood counts) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store at room temperature below 86 degrees F (30 degrees C) away from light and moisture. Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.