Carbenicillin

Pronunciation

(kar ben i SIL in)

U.S. Brand Names

Geocillin®

Synonyms

Carbenicillin Indanyl Sodium; Carindacillin

Generic Available

Use

Treatment of serious urinary tract infections and prostatitis caused by susceptible gram-negative aerobic bacilli

Pregnancy Risk Factor

Lactation

Enters breast milk/use caution

Contraindications

Hypersensitivity to carbenicillin, penicillins, or any component of the formulation

Warnings/Precautions

Do not use in patients with severe renal impairment (Clcr<10 mL/minute); dosage modification required in patients with impaired renal and/or hepatic function; oral carbenicillin should be limited to treatment of urinary tract infections. Use with caution in patients with history of hypersensitivity to cephalosporins.

Adverse Reactions

>10%: Gastrointestinal: Diarrhea

1% to 10%: Gastrointestinal: Nausea, bad taste, vomiting, flatulence, glossitis

<1%: Headache, skin rash, urticaria, anemia, thrombocytopenia, leukopenia, neutropenia, eosinophilia, hyperthermia, itchy eyes, vaginitis, hypokalemia, hematuria, thrombophlebitis

Overdosage/Toxicology

Symptoms of overdose include neuromuscular hypersensitivity and convulsions. Hemodialysis may be helpful to aid in removal of the drug from blood; otherwise, treatment is supportive or symptom-directed.

Drug Interactions

Aminoglycosides: May be synergistic against selected organisms

Methotrexate: Penicillins may increase the exposure to methotrexate during concurrent therapy; monitor.

Oral contraceptives: Anecdotal reports suggesting decreased contraceptive efficacy with penicillins have been refuted by more rigorous scientific and clinical data.

Probenecid, disulfiram: May increase levels of penicillins (carbenicillin)

Tetracyclines: May decrease effectiveness of penicillins (carbenicillin)

Warfarin: Effects of warfarin may be increased

Compatibility

Compatibility in Solution:

Compatible: Ampicillin, cimetidine, clindamycin, dopamine, hydrocortisone, lidocaine, potassium chloride, verapamil

Incompatible: Aminophylline, amphotericin B, epinephrine, erythromycin, gentamicin, levarterenol, tetracycline, vitamin B and C complex

Mechanism of Action

Inhibits bacterial cell wall synthesis by binding to one or more of the penicillin binding proteins (PBPs); which in turn inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis. Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested.

Pharmacodynamics/Kinetics

Absorption: 30% to 40%

Distribution: Crosses placenta; small amounts enter breast milk; distributes into bile; low concentrations attained in CSF

Protein binding: ~50%

Half-life elimination: Children: 0.8-1.8 hours; Adults: 1-1.5 hours, prolonged to 10-20 hours with renal insufficiency

Time to peak, serum: Normal renal function: 0.5-2 hours; concentrations are inadequate for treatment of systemic infections

Excretion: Urine (~80% to 99% as unchanged drug)

Dosage

Oral:

Children: 30-50 mg/kg/day divided every 6 hours; maximum dose: 2-3 g/day

Adults: 1-2 tablets every 6 hours for urinary tract infections or 2 tablets every 6 hours for prostatitis

Dosing interval in renal impairment: Adults:

Clcr 10-50 mL/minute: Administer 382-764 mg every 12-24 hours

Clcr<10 mL/minute: Administer 382-764 mg every 24-48 hours

Moderately dialyzable (20% to 50%)

Monitoring Parameters

Renal, hepatic, and hematologic function tests

Reference Range

Therapeutic: Not established; Toxic: >250 mcg/mL (SI: >660

mol/L)

Test Interactions

May interfere with urinary glucose tests using cupric sulfate (Benedict's solution, Clinitest®); may inactivate aminoglycosides in vitro ; false-positive urine or serum proteins

Dietary Considerations

Should be taken with water on empty stomach. Sodium content of 382 mg tablet: 23 mg (1 mEq).

Patient Education

Inform prescriber of all prescriptions, OTC medications, or herbal products you are taking, and any allergies you have. Do not take any new medication during therapy unless approved by prescriber. Take as prescribed, at equal intervals around-the-clock, with a full glass of water, and preferably on an empty stomach, 1 hour before or 2 hours after meals. Do not skip doses and take full course of treatment even if feeling better. If you have diabetes, drug may cause false test results with Clinitest® urine glucose monitoring; use of another form of glucose monitoring is preferable. May cause diarrhea (boiled milk, buttermilk, or yogurt may help - if diarrhea persists for more than 2 days, contact prescriber for approved antidiarrhea medication); or dry mouth and bitter aftertaste (frequent mouth care may help). Report respiratory difficulty; easy bruising or bleeding; rash, itching, hives; or signs of opportunistic infection (eg, sore throat, fever, chills, fatigue, thrush, vaginal discharge, diarrhea). Breast-feeding precaution: Consult prescriber if breast-feeding.

Dental Health: Effects on Dental Treatment

Key adverse event(s) related to dental treatment: Unpleasant taste and glossitis. Prolonged use of penicillins may lead to development of oral candidiasis.

Dental Health: Vasoconstrictor/Local Anesthetic Precautions

No information available to require special precautions

Mental Health: Effects on Mental Status

Penicillins have been reported to cause apprehension, illusions, agitation, insomnia, depersonalization, and encephalopathy

Mental Health: Effects on Psychiatric Treatment

Rare reports of leukopenia and neutropenia; use caution with clozapine and carbamazepine

Dosage Forms

Tablet [film coated]: 382 mg [contains sodium 23 mg/tablet]

References

Donowitz GR and Mandell GL, "Beta-Lactam Antibiotics," N Engl J Med , 1988, 318(7):419-26 and 318(8):490-500.

Wright AJ, "The Penicillins," Mayo Clin Proc , 1999, 74(3):290-307.

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