Ciprofloxacin with Probenecid Interaction Details

Brand Names Associated with Ciprofloxacin

Brand Names Associated with Probenecid

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 19, 2023

Interaction Effect

An increase in the serum level of ciprofloxacin

Interaction Summary

Probenecid interferes with the renal tubular secretion of ciprofloxacin, causing an increase in the serum level of ciprofloxacin. In a randomized, two-way crossover study, coadministration of probenecid with ciprofloxacin decreased total body clearance of ciprofloxacin by 42%, primarily by competitive inhibition of the renal tubular secretion of ciprofloxacin and M1 by probenecid . For patients receiving both ciprofloxacin and probenecid concurrently, this resultant increase in ciprofloxacin serum levels should be considered , and patients should be monitored for an increased incidence of ciprofloxacin adverse effects, including nervousness, agitation, nausea, and diarrhea.

Severity

Moderate

Onset

Delayed

Evidence

Established

How To Manage Interaction

Probenecid interferes with the renal tubular secretion of ciprofloxacin producing increases in ciprofloxacin serum levels. This should be considered in patients receiving both drugs concurrently. If probenecid is used concurrently with ciprofloxacin, monitor the patient for an increased incidence of ciprofloxacin adverse effects, including nervousness, agitation, nausea, and diarrhea.

Mechanism Of Interaction

Inhibition of renal tubular secretion

Literature Reports

A) A randomized, two-way crossover study revealed coadministration of probenecid with ciprofloxacin resulted in a 42% decrease in total body clearance of ciprofloxacin (p=less than 0.001). Twelve subjects received IV ciprofloxacin 200 mg alone or with oral probenecid 3 g in 5 divided doses with at least a 7 day wash-out period between treatment periods. Plasma and urine samples were collected at specified times throughout the study. Administration of probenecid with ciprofloxacin reduced the median renal clearance of ciprofloxacin and its metabolite 2-aminoethylamino-metabolite (M1) by 65% and 66%, respectively (p=less than 0.001), and reduced nonrenal clearance of ciprofloxacin by 8%. Coadministration of probenecid resulted in Cmax values that were significantly higher for M1 and only slightly higher for ciprofloxacin. The mean residence time was significantly prolonged for both ciprofloxacin (3.54 to 5.49 hours) and M1 (6.3 to 9.18 hours), whereas the plasma half-life was prolonged for ciprofloxacin (4.95 to 5.8 hours), but not for M1. Pharmacokinetic modelling suggests that competitive inhibition of the renal tubular secretion of ciprofloxacin and M1 by probenecid is primarily responsible for this interaction as probenecid does not significantly affect the formation of M1, nonrenal clearance, and Vd of ciprofloxacin and M1 .

Ciprofloxacin Overview

• Ciprofloxacin is used to treat or prevent certain infections caused by bacteria such as pneumonia; gonorrhea (a sexually transmitted disease); typhoid fever (a serious infection that is common in developing countries); infectious diarrhea (infections that cause severe diarrhea); and infections of the skin, bone, joint, abdomen (stomach area), and prostate (male reproductive gland), Ciprofloxacin is also used to treat or prevent plague (a serious infection that may be spread on purpose as part of a bioterror attack) and inhalation anthrax (a serious infection that may be spread by anthrax germs in the air on purpose as part of a bioterror attack). Ciprofloxacin may also be used to treat bronchitis, sinus infections, or urinary tract infections but should not be used for bronchitis and sinus infections, or certain types of urinary tract infections if there are other treatment options. Ciprofloxacin extended-release (long-acting) tablets are used to treat kidney and urinary tract infections; however, some types of urinary tract infections should only be treated with ciprofloxacin extended release tablets if no other treatment options are available. Ciprofloxacin is in a class of antibiotics called fluoroquinolones. It works by killing bacteria that cause infections.

• Antibiotics such as ciprofloxacin will not work for colds, flu, or other viral infections. Using antibiotics when they are not needed increases your risk of getting an infection later that resists antibiotic treatment.

Probenecid Overview

• Probenecid is used to treat chronic gout and gouty arthritis. It is used to prevent attacks related to gout, not treat them once they occur. It acts on the kidneys to help the body eliminate uric acid. Probenecid is also used to make certain antibiotics more effective by preventing the body from passing them in the urine.

• This medication is sometimes prescribed for other uses; ask your doctor or pharmacist for more information.

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Definitions

Severity Categories

Contraindicated

These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.

Major

This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.

Moderate

This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.

Minor

While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.

Onset

Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.

Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.

Evidence

Level of documentation of the interaction.

Established: The interaction is documented and substantiated in peer-reviewed medical literature.

Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.

How To Manage The Interaction

Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.

It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.

Mechanism Of Interaction

The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.

Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.

Where Does Our Information Come From?

Information for our drug interactions is compiled from several drug compendia, including:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

The prescribing information for each drug, as published on DailyMED, is also used. 

Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.

The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.