Ciprofloxacin with Theophylline Interaction Details

Brand Names Associated with Ciprofloxacin

Brand Names Associated with Theophylline

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

Interaction Effect

Elevated plasma theophylline concentrations, prolongation of theophylline elimination half-life, and theophylline toxicity (nausea, vomiting, palpitations, seizures)

Interaction Summary

Serious and fatal reactions have been reported in patients receiving concurrent administration of intravenous ciprofloxacin and theophylline. These reactions have included cardiac arrest, seizure, status epilepticus, and respiratory failure. Elevated serum levels of theophylline and prolongation of its elimination half-life may result with concurrent administration of ciprofloxacin and theophylline. This may result in an increased risk of theophylline-related adverse effects (nausea, vomiting, palpitations, seizures). Ciprofloxacin causes a clinically significant decrease in theophylline clearance and increase in serum theophylline concentrations .

Severity

Major

Onset

Delayed

Evidence

Established

How To Manage Interaction

If concomitant use cannot be avoided, serum levels of theophylline should be monitored and dosage adjustments made as appropriate.

Mechanism Of Interaction

Decreased clearance of theophylline

Literature Reports

A) Many studies have demonstrated that ciprofloxacin causes decreases in theophylline clearance by approximately 30% leading to significant increases in theophylline serum concentration . Many patients exhibit clinical symptoms of theophylline toxicity such as nausea, vomiting, tremor, restlessness, and insomnia . The probable mechanism of this interaction is ciprofloxacin interference of theophylline metabolism by the cytochrome P450 system .

B) Theophylline concentrations increased in patients when ciprofloxacin was coadministered. Within three days, there was a statistically significant increase in theophylline serum concentration over baseline (p less than 0.001). The mean maximum serum concentration increased from 9.2 mg/L to 11.3 mg/L (p less than 0.05). The mean minimum serum concentration was 6.3 mg/L with theophylline alone and 8.8 mg/L when ciprofloxacin was given cocnurrently (p less than 0.001). The elimination half-life of theophylline increased from 5.9 hours to 8.4 hours (p less than 0.01). Clearance decreased from 85.9 mL/min to 59.8 mL/min (p less than 0.05). Increases in theophylline serum concentrations were accompanied by clinical symptoms such as insomnia, nausea, and diarrhea, all of which may be associated with excessive theophylline serum concentrations .

C) The increase in theophylline serum concentrations is approximately 20% over baseline in most studies that examine this interaction , although three-fold increases in theophylline serum concentrations have also been reported . Theophylline serum concentrations begin to increase two or three days after ciprofloxacin therapy begins . After discontinuing ciprofloxacin, the theophylline serum concentration returns to baseline in one to seven days .

D) Of the available quinolone antibiotics, enoxacin appears to be the most potent inhibitor of the hepatic clearance of theophylline. Enoxacin consistently decreases theophylline clearance by greater than 50%, while pefloxacin and ciprofloxacin reduce theophylline clearance by 20% to 30%. Only minimal effects on theophylline clearance have been observed with norfloxacin, ofloxacin, and nalidixic acid .

E) Five nonsmoking volunteers completed a randomized, four-period crossover study to evaluate coadministration of clarithromycin, ciprofloxacin, and theophylline. Each treatment pahse lasted seven days, with a single dose of theophylline 400 mg being given on day 6. Treatment regimens were as follows: ciprofloxacin 500 mg twice daily for seven days, clarithromycin 1000 mg twice daily for seven days, ciprofloxacin 500 mg plus clarithromycin 1000 mg twice daily for seven days, or a single dose of theophylline on day 6. The AUC of theophylline was 144 mg/h/mL, and averaged 207 mg/h/mL during treatment with ciprofloxacin. This represented a mean increase of 45%, with the range from a 15% to 77% increase. The theophylline half-life was 9.8 hours when administered alone, and 15.2 hours when given with ciprofloxacin. Theophylline is metabolized by the cytochrome P450 1A2 enzyme system, and ciprofloxacin is known to inhibit this same enzymatic pathway .

F) A 79-year-old female with a long history of asthma was stabilized on oral sustained-release aminophylline 450 mg twice daily with plasma theophylline levels ranging from 8 mg/L to 12 mg/L over the preceding three years. Other medications included steroid and slabutamol inhalers and prednisolone 5 mg daily. Ciprofloxacin 500 mg twice daily was prescribed for a fever and productive cough seven days prior to hospital admission. She presented to the hospital with supraventricular tachycardia, hypokalemia, acidosis, hypotension, and difficulty breathing. Plasma theophylline at this time was 33.2 mg/L. Following two hours of hemodialysis, her plasma theophylline level had decreased to 14.7 mg/L and she made an uneventful recovery. Ciprofloxacin was believed to have competed with theophylline for metabolism resulting in toxic theophyllline levels .

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.

Theophylline Overview

• Theophylline is used to prevent and treat wheezing, shortness of breath, and chest tightness caused by asthma, chronic bronchitis, emphysema, and other lung diseases. It relaxes and opens air passages in the lungs, making it easier to breathe.

Return To Our Drug Interaction Homepage

Feedback, Question Or Comment About This Information?

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.