Ciprofloxacin with Clozapine Interaction Details

Brand Names Associated with Ciprofloxacin

Brand Names Associated with Clozapine

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

Interaction Effect

Increased clozapine exposure and risk of QT prolongation

Interaction Summary

If ciprofloxacin (strong CYP1A2 and moderate CYP3A4 inhibitor) and clozapine (CYP1A2 and CYP3A4 substrate) are used concomitantly, reduce the clozapine dose to one-third of the original dose. Increase the clozapine dose to its original strength based on clinical response once ciprofloxacin is discontinued. Additionally, clozapine may lead to QT prolongation, Torsade de pointes, and other life-threatening ventricular arrhythmias, cardiac arrest, or sudden cardiac death. Use caution when administering clozapine concomitantly with other medications that prolong the QT interval. Correct any electrolyte abnormalities. Discontinue clozapine if the QTc interval exceeds 500 msec. Cardiac evaluation and treatment discontinuation are warranted if the patient develops symptoms of torsade de pointes or other arrhythmias.

Severity

Major

Onset

Unspecified

Evidence

Probable

How To Manage Interaction

If ciprofloxacin (strong CYP1A2 and moderate CYP3A4 inhibitor) and clozapine (CYP1A2 and CYP3A4 substrate) are used concomitantly, reduce the clozapine dose to one-third of the original dose. Increase the clozapine dose to its original strength based on clinical response once ciprofloxacin is discontinued. Additionally, clozapine may lead to QT prolongation, Torsade de pointes, and other life-threatening ventricular arrhythmias, cardiac arrest, or sudden cardiac death. Use caution when administering clozapine concomitantly with other medications that prolong the QT interval. Correct any electrolyte abnormalities. Discontinue clozapine if the QTc interval exceeds 500 msec. Cardiac evaluation and treatment discontinuation are warranted if the patient develops symptoms of torsade de pointes or other arrhythmias.

Mechanism Of Interaction

Inhibition of CYP1A2 and CYP3A4-mediated clozapine metabolism and additive QT-interval prolongation

Literature Reports

A) Coadministration of ciprofloxacin and clozapine led to an elevated clozapine plasma level in a 46-year-old man presenting with urosepsis. History included smoking, caffeine use, and treatment at a psychiatric facility with citalopram, lorazepam, valproic acid, and clozapine. He was treated with a 5-day course of IV ciprofloxacin 400 mg twice daily and amoxicillin while on maintenance therapy of clozapine 900 mg daily for paranoid schizophrenia and was discharged after 4 days in good condition. He returned 3 days later with suspected rhabdomyolysis but did not report any pain. Lab results indicated CPK levels of 195,000 units/L, LDH of 6687 units/L, AST of 845 units/L, ALT of 93 units/L, and a urine test positive for myoglobin. Clozapine treatment was stopped and high-volume alkaline diuresis started. Three days after the end of ciprofloxacin treatment and 1 day after stopping clozapine, the patient’s clozapine plasma concentration was 890 nanograms (ng)/mL (2720 nanomols (nmol)/L), higher than the recommended therapeutic concentration of 350 to 600 ng/mL (1070 to 1800 nmol/L). Five days after stopping clozapine, the patient's clozapine plasma concentration was undetectable. LDH, AST, and ALT concentrations returned to normal by day 18, and CPK levels returned to normal by day 28. The patient did not show signs of worsening psychotic symptoms after the cessation of clozapine; however, clozapine was restarted 2 weeks after discharge. The Drug Interaction Probability Scale (DIPS) score was 5, indicating a probable reaction between the clozapine and the ciprofloxacin .

B) Coadministration of ciprofloxacin and clozapine led to an elevated clozapine plasma level in a 58-year-old man presenting with delirium and suspected urinary tract infection or pneumonia. History included smoking, caffeine use, and treatment at a psychiatric facility with valproic acid, hydrochlorothiazide, clonazepam, and clozapine 300 mg per day. Lab results before the addition of ciprofloxacin indicated normal AST (10 units/L) and ALT (13 units/L) levels, and his clozapine plasma concentration was 850 nanograms (ng)/mL (2600 nanomols (nmol)/L)). He was treated with IV ciprofloxacin 200 mg twice daily. AST and ALT levels slightly increased (46 units/L and 74 units/L, respectively), and ciprofloxacin was stopped after 2 days due to the suspected drug-drug interaction between ciprofloxacin and clozapine. Three days after the start of ciprofloxacin treatment, the patient’s clozapine plasma concentration was 1720 ng/mL (5260 nmol/L) although he did not show signs of rhabdomyolysis or other clozapine-induced adverse effects. He was discharged after 5 days. The Drug Interaction Probability Scale (DIPS) score was 6, indicating a probable reaction between the clozapine and the ciprofloxacin .

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.

Clozapine Overview

• Clozapine is used to treat the symptoms of schizophrenia (a mental illness that causes disturbed or unusual thinking, loss of interest in life, and strong or inappropriate emotions) in people who have not been helped by other medications or who have tried to kill themselves and are likely to try to kill or harm themselves again. Clozapine is in a class of medications called atypical antipsychotics. It works by changing the activity of certain natural substances 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.