Ciprofloxacin with Fosphenytoin Interaction Details

Brand Names Associated with Ciprofloxacin

Brand Names Associated with Fosphenytoin

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

Interaction Effect

Increased or decreased serum phenytoin levels

Interaction Summary

Increased and decreased serum phenytoin levels have been reported in patients receiving concomitant ciprofloxacin. Use caution when prescribing ciprofloxacin to patients who take phenytoin. Monitor for alterations in phenytoin serum concentrations during and shortly after concomitant ciprofloxacin therapy to avoid loss of seizure control associated with decreased phenytoin levels and to prevent phenytoin overdose-related effects when ciprofloxacin is discontinued. Discontinue ciprofloxacin if seizures occur.

Severity

Moderate

Onset

Unspecified

Evidence

Probable

How To Manage Interaction

Use caution when prescribing ciprofloxacin to patients who take phenytoin. Concomitant use of ciprofloxacin and phenytoin may cause elevated or decreased phenytoin serum concentrations. Monitor for alterations in phenytoin serum concentrations during and shortly after concomitant ciprofloxacin therapy to avoid loss of seizure control associated with decreased phenytoin levels and to prevent phenytoin overdose-related effects when ciprofloxacin is discontinued. Discontinue ciprofloxacin if seizures occur.

Mechanism Of Interaction

Unknown

Literature Reports

A) A 47-year-old woman was stabilized on phenytoin 400 mg daily with a steady-state trough concentration of 16.4 mg/L (65 mcmol/L). She was admitted to a hospital for a UTI and was started on ciprofloxacin 200 mg IV 3 times daily. Six days into the ciprofloxacin therapy, the patient experienced status epilepticus and was loaded with phenytoin 500 mg IV. Four hours later, her phenytoin concentration was 12.8 mg/L (50.7 mcmol/L). Using a pharmacokinetic program, the authors estimated that the patient's phenytoin level could have been less than 5 mg/L (20 mcmol/L) at the time the status epilepticus occurred. Oral phenytoin was increased to 450 mg daily for the remainder of the ciprofloxacin course, and the trough concentrations started to increase after the discontinuation of ciprofloxacin. The phenytoin dose was reduced to 400 mg daily, and 4 months later the patient's trough concentration was stabilized at 16.2 mg/L (64.2 mcmol/L) .

B) A 78-year-old woman hospitalized for radiation therapy was started on ciprofloxacin 500 mg orally twice daily for a suspected UTI. The next day she developed a left-sided twitch, which abated with diazepam but then returned. She was loaded with phenytoin 750 mg IV, followed by 100 mg every 8 hours IV. Due to swallowing difficulties, ciprofloxacin was switched to 400 mg twice daily IV at the time of the phenytoin loading dose. Her seizures became more generalized, and a phenytoin level 48 hours following the loading dose was 37 mcmol/L (normal, 40 to 80 mcmol/L). Ciprofloxacin was discontinued, a bolus dose of phenytoin 600 mg was given, and her seizures stopped 1 hour later. Subsequent phenytoin concentrations were therapeutic .

C) A 69-year-old man with a history of cerebral infarction was admitted to the hospital for nausea, vomiting, and dehydration. He developed numerous symptomatic generalized seizures after a few days in the hospital. He was treated successfully with phenytoin 400 mg IV daily after several dosage adjustments, and his phenytoin concentration stabilized at 9.1 mg/L (36.1 mcmol/L). The addition of ciprofloxacin 800 mg IV daily for pneumonia decreased the phenytoin concentration to 4.8 mg/L (19 mcmol/L) after 4 days, even though the phenytoin dose was increased to 600 mg daily. After the discontinuation of ciprofloxacin, the serum phenytoin concentration increased to between 11.5 and 14.5 mg/L (45.6 and 57.5 mcmol/L). The decrease in phenytoin concentration may have been caused by a change in volume of distribution or a change in enterohepatic circulation of phenytoin .

D) Phenytoin pharmacokinetics were studied in 4 healthy volunteers who received phenytoin 200 mg orally daily for 10 days followed by 5 days of combined therapy with phenytoin and ciprofloxacin 500 mg twice daily. No significant differences were found in phenytoin AUC, Cmax, or Tmax when phenytoin was given alone compared with levels during coadministration. One patient demonstrated a pronounced decline in phenytoin AUC and Cmax .

E) An 87-year-old woman with Alzheimer disease and hypertension developed seizures secondary to sepsis. She was treated with phenytoin for 2 days before ciprofloxacin 500 mg orally twice daily was initiated. Phenytoin levels reached 29.4 mcg/mL (116.5 mcmol/L) after 2 days of combined treatment, and the phenytoin was temporarily stopped. The phenytoin levels continued to rise, and after a total of 4 days of ciprofloxacin therapy, the antibiotic was discontinued. The phenytoin levels returned to normal 2 days later, and phenytoin was restarted .

F) A single case was reported in which IV ciprofloxacin (400 mg twice daily) was associated with a substantial decrease in serum phenytoin (300 mg daily) levels from 14.7 to 6.3 mg/L (58.3 to 25 mcmol/L) within 2 days of beginning ciprofloxacin. Breakthrough seizures occurred, necessitating an increase in phenytoin dose to 400 mg daily. The next day the phenytoin level was down to 4.8 mg/L (19 mcmol/L), and the phenytoin dose was increased to 500 mg daily. Seizure control was maintained over the following 10 days, and the ciprofloxacin was then discontinued. The following day the phenytoin serum level was 13.7 mg/L (54.3 mcmol/L) and the 500-mg daily dose was continued .

G) A preliminary study concluded that concurrent use of oral ciprofloxacin and phenytoin resulted in increased phenytoin serum levels. Seven epileptic patients who were maintained on phenytoin sufficient to give a steady-state level of 7 to 15 mg/L (28 to 59 mcmol/L) received ciprofloxacin 500 mg orally twice daily for 10 days. Mean phenytoin levels rose from 11.3 mg/L (44.8 mmol/L) on day 0 to 14.4 mg/L (57.1 mcmol/L) on day 5, and 14 mg/L (55 mcmol/L) on day 10. No clinical changes in phenytoin efficacy were reported .

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.

Fosphenytoin Overview

• Fosphenytoin injection is used to treat primary generalized tonic-clonic seizures (formerly known as a grand mal seizure; seizure that involves the entire body) and to treat and prevent seizures that may begin during or after surgery to the brain or nervous system. Fosphenytoin injection may also be used to control certain type of seizures in people who cannot take oral phenytoin. Fosphenytoin is in a class of medications called anticonvulsants. It works by decreasing abnormal electrical activity in the brain.

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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.