Fluoroquinolones are broad-spectrum antibiotics used to treat a wide variety of bacterial infections. However, they have a long list of medication interactions that require careful consideration when prescribing and counseling. In this blog post, I will highlight my top 5 fluoroquinolone drug interactions that will likely appear in your practice or on your board exams.

QTc Prolonging Medications

One rare, but serious, fluoroquinolone drug interaction is QTc prolongation. QTc intervals lasting over 500 ms may lead to the development of Torsades de Pointes, a potentially life-threatening cardiac arrhythmia. Most fluoroquinolones only lead to a modest increase in QTc interval; however, risk of prolonged QTc interval increases when QT-prolonging medications are used in combination with each other. Some of these QT-prolonging medications include antipsychotics (quetiapine, haloperidol, risperidone), antiarrhythmics (amiodarone, quinidine), 5-HT3 receptor antagonists (ondansetron), and many other commonly prescribed medications. When prescribing fluoroquinolones, it is important to review concomitant medications, consider pre-existing conditions, and monitor EKG results, especially in patients at high risk for complications.

Multivalent Cations

Multivalent cations are extremely common in over-the-counter medications. Some examples include iron, calcium, magnesium, and aluminum. Patients often feel comfortable taking over-the-counter medications without medical advice. However, it is important to recognize that can cause important fluoroquinolone drug interactions. It is recommended to separate fluoroquinolones from products containing multivalent cations by at least 2 hours, as concomitant ingestion can decrease the effectiveness of these antibiotics due to chelation. This could be potentially harmful to the patient, as it may lead to the failure of oral fluoroquinolone therapy. Therefore, patient counseling is extremely important in ensuring the efficacy of fluoroquinolone therapy.

Sulfonylureas

The FDA released a label change for fluoroquinolones in 2018, identifying its risk of causing hypoglycemia and coma. Fluoroquinolones are able to alter the release of insulin from beta cells. Therefore, they may alter blood glucose levels, leading to hypoglycemia. This risk is substantially increased when combined with sulfonylureas, which are classified as high hypoglycemic risk agents. Therefore, according to the 2025 ADA Guidelines, prescribers should temporarily decrease or hold sulfonylureas during treatment with fluoroquinolones.

Warfarin

The exact mechanisms of the warfarin flouroquinolone interaction aren’t totally understood but there is at least one theory that seems reasonable to me. Fluoroquinolones may reduce the amount of bacteria in the gut that produce vitamin K, ultimately leading to an elevated INR and increased anticoagulation effects. This can be dangerous, as it increases the risk of hemorrhage. Therefore, it is recommended to either avoid the use of fluoroquinolones in patients on warfarin therapy or increase the frequency of INR checks to ensure the patient’s INR stays within their goal range.

CYP1A2 Inhibition

One of the fluoroquinolones, ciprofloxacin, acts as an inhibitor of the cytochrome P450 enzyme, CYP1A2. This may lead to adverse effects if administered with CYP1A2 substrates. Tizanidine, clozapine, and theophylline are three medications that may have their concentrations increased when used in combination with ciprofloxacin. Some references even indicate tizanidine as a contraindicated drug interaction. With clozapine and theophylline (rarely used), we can typically monitor drug levels and clinically monitor the patient for toxicity risk. 

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This article was written by Christiana Carpenter, PharmD Candidate in collaboration with Eric Christianson, PharmD, BCPS, BCGP

Sources

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