Tizanidine with Ciprofloxacin Interaction Details

Brand Names Associated with Tizanidine

Brand Names Associated with Ciprofloxacin

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

Interaction Effect

Increased tizanidine plasma concentrations resulting in increased hypotensive and sedative effects

Interaction Summary

Concomitant use of ciprofloxacin and tizanidine is contraindicated. Ciprofloxacin is a moderately potent inhibitor of CYP1A2-mediated metabolism of tizanidine. Tizanidine is a centrally acting skeletal muscle relaxant and an alpha-2 adrenergic agonist with blood pressure lowering effects. Concomitant use of ciprofloxacin with tizanidine potentiates tizanidine exposure and the risk of excessive sedation and hypotension .

Severity

Contraindicated

Onset

Rapid

Evidence

Established

How To Manage Interaction

Concomitant use of ciprofloxacin and tizanidine is contraindicated due to an increased risk of excessive hypotension and sedation. An alternative medication for the management of spasticity is recommended.

Mechanism Of Interaction

Inhibition by ciprofloxacin of CYP1A2-mediated tizanidine metabolism

Literature Reports

A) Concomitant use of ciprofloxacin and tizanidine resulted in significant inhibition of CYP1A2-mediated tizanidine metabolism in 10 healthy, male volunteers. Tizanidine plasma concentrations were raised to levels substantially increasing the risk of excessive sedation and potentially dangerous hypotension. In a double-blind, randomized, 2-phase crossover study volunteers received ciprofloxacin 500 mg twice daily for three days. On day three the volunteers received a single dose of tizanidine 4 mg one hour after the morning dose of ciprofloxacin. The mean area under the concentration-time curve (AUC) and maximum concentration (Cmax) of tizanidine were increased 980% and 660%, respectively. Ciprofloxacin had only a small impact on the half-life of tizanidine, increasing it from 1.5 hours to 1.8 hours. A significant increase in the pharmacodynamic effects of tizanidine were observed during the ciprofloxacin phase of the study compared to the placebo phase. Decrease in blood pressure was much more profound in the ciprofloxacin phase. Systolic pressure declined 35 mm Hg compared to a decline of 15 mm Hg, p=0.001, in the placebo phase. Diastolic pressure changes in the ciprofloxacin phase showed a decline of 24 mm Hg versus a decline of 11 mm Hg, P<.001, in the placebo phase. Performance of the Digital Symbol Substitution Test (DSST) was poorer and subjective drug effect and drowsiness were higher in the ciprofloxacin phase. There was no significant difference in heart rate between the two phases .

B) The concomitant use of ciprofloxacin and tizanidine resulted in significant decreases in heart rate (HR), blood pressure (BP), and body temperature (BT) in a case report, and a subsequent retrospective survey of 8 medical records. A 45-year-old female patient with a history of multiple sclerosis taking tizanidine 3 mg/day was admitted to the hospital complaining of left leg pain and walking difficulties. Immediately following administration of ciprofloxacin (400 mg/day for 7 days) for pyuria on day 2 of her hospitalization, the patient developed a reduction in HR from 86 to 58 beats/minute, and BP from 124/88 to 102/74 mmHg. On day 4, her BP dropped further to 92/54 mmHg, BT dropped from 36.5 to 35.4 degrees Celsius, and she complained of drowsiness. Following ciprofloxacin discontinuation, all symptoms resolved. In a medical record survey of 1,165 patients treated with tizanidine, 8 cases of ciprofloxacin/tizanidine drug interaction were identified. Patients received no other cytochrome P1A2 inhibitors. Adverse events included low HR (n=2), low BT (n=1), low BP (n=2), drowsiness (n=2), and confusion (n=1). Significant decreases (p less than 0.05) were noted in systolic BP (-21.3 +/- 16), diastolic BP (-15.4 +/- 17.5), HR (-14.9 +/17.5), and BT (-0.6 +/- 0.5 degrees Celsius) .

Tizanidine Overview

• Tizanidine is used to relieve the spasms and increased muscle tone caused by multiple sclerosis (MS, a disease in which the nerves do not function properly and patients may experience weakness, numbness, loss of muscle coordination and problems with vision, speech, and bladder control), stroke, or brain or spinal injury. Tizanidine is in a class of medications called skeletal muscle relaxants. It works by slowing action in the brain and nervous system to allow the muscles to relax.

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.

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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.