Tizanidine with Fluvoxamine Interaction Details
Brand Names Associated with Tizanidine
- Tizanidine
- Zanaflex®
Brand Names Associated with Fluvoxamine
- Fluvoxamine
- Luvox®
- Luvox® CR
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 14, 2023
Interaction Effect
Increased tiZANidine exposure
Interaction Summary
Concomitant use of fluvoxaMINE and tiZANidine is contraindicated. Use of these drugs together has resulted in increased plasma concentrations and half-life of tiZANidine which may lead to decreased blood pressure, increased psychomotor impairment, and excessive drowsiness. Concurrent administration of fluvoxaMINE, a potent CYP1A2 inhibitor, and tiZANidine, a CYP1A2 substrate, induced a profound increase in tiZANidine bioavailability. The inhibition of CYP1A2-mediated tiZANidine metabolism provokes clinically significant hypotension and alteration of consciousness . In a retrospective case series, tiZANidine-associated adverse events occurred significantly more often in patients treated concomitantly with fluvoxaMINE and tiZANidine compared with tiZANidine monotherapy .
Severity
Contraindicated
Onset
Rapid
Evidence
Established
How To Manage Interaction
The concomitant use of fluvoxaMINE and tiZANidine is contraindicated. Use of tiZANidine with fluvoxaMINE can increase the plasma concentrations of tiZANidine which may lead to decreased blood pressure, increased psychomotor impairment, and excessive drowsiness.
Mechanism Of Interaction
Inhibition of CYP1A2-mediated tiZANidine metabolism by fluvoxaMINE
Literature Reports
A) In a study of 10 healthy volunteers treated with fluvoxaMINE (100 mg daily for 4 days) and a single 4 mg dos e of tiZANidine, the half-life, Cmax, and AUC of tiZANidine increased by 3-fold, 12-fold, and 33-fold, respectively . The mean decrease in the systolic blood pressure was 35 mm Hg and a mean decrease in the diastolic blood pressure was 20 mm Hg .
B) Coadministration of fluvoxaMINE with tiZANidine resulted in profound increases in tiZANidine bioavailability due to P450 CYP1A2-mediated inhibition of tiZANidine metabolism and was associated with multiple adverse clinical effects. In a randomized, double-blind, crossover study (4-week wash out period), healthy subjects (n=10) received a 4-day regimen of fluvoxaMINE 100 milligrams (mg) or placebo once daily. On day 4, each subject received a single oral dose of tiZANidine 4 mg. Serial blood pharmacokinetic analysis was performed over the next 24 hours, in conjunction with measurement of pharmacodynamic response. When compared with placebo, the presence of fluvoxaMINE dramatically increased tiZANidine mean maximum serum concentration (by 1210% (from 2.2 to 26.6 nanograms/milliliter), p=0.000001), mean area under the concentration-time curve (AUC 0-infinity; by 3260%, p=0.000002), and mean elimination half-life from 1.5 hours to 4.3 hours (by 290%, p=0.00004). Pharmacodynamic responses to fluvoxaMINE-enhanced tiZANidine exposure were also dramatic: mean systolic blood pressure declined by 35 millimeters mercury (mmHg; from 115 to 79 mmHg), mean diastolic blood pressure decreased by 20 mmHg (from 66 to 46 mmHg), heart rate decreased by 4 beats per minute, and subjectively perceived drowsiness (0-100 visual analogue scale) increased by a mean of 42 points compared with the placebo-tiZANidine phase (p=0.000009, p=0.00002, p=0.007, and p=0.0002, respectively). During the fluvoxaMINE-tiZANidine phase, all subjects experienced somnolence and dizziness for between 3 and 6 hours after the dose of tiZANidine. There was no compensatory tachycardic response to the treatment-associated hypotension .
C) In a retrospective case series review of patients treated with tiZANidine (n=913), tiZANidine-related adverse events occurred with significantly greater frequency in patients treated concurrently with fluvoxaMINE and tiZANidine (n=23) when compared with tiZANidine monotherapy (26.1% (6/23) versus 5.3%, respectively; p less than 0.0001). Bradycardia occurred in the 6 affected patients, with dizziness, hypothermia, drowsiness, hypotension, and impaired speech occurring in order of descending frequency .
Tizanidine Overview
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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.
Fluvoxamine Overview
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Fluvoxamine is used to treat obsessive-compulsive disorder (bothersome thoughts that won't go away and the need to perform certain actions over and over) and social anxiety disorder (extreme fear of interacting with others or performing in front of others that interferes with normal life). Fluvoxamine is in a class of medications called selective serotonin reuptake inhibitors (SSRIs). It works by increasing the amount of serotonin, a natural substance in the brain that helps maintain mental balance.
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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:
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.