Summary

Tizanidine and fluvoxamine have a clinically significant drug interaction that is contraindicated due to fluvoxamine's potent inhibition of CYP1A2, the primary enzyme responsible for tizanidine metabolism. This interaction can lead to dramatically increased tizanidine levels, resulting in severe hypotension, excessive sedation, and potentially life-threatening cardiovascular effects.

Introduction

Tizanidine is a centrally-acting alpha-2 adrenergic agonist muscle relaxant primarily used to treat muscle spasticity associated with conditions like multiple sclerosis and spinal cord injuries. Fluvoxamine is a selective serotonin reuptake inhibitor (SSRI) antidepressant commonly prescribed for depression, obsessive-compulsive disorder, and anxiety disorders. Both medications are metabolized through the cytochrome P450 enzyme system, which creates the potential for significant pharmacokinetic interactions when used together.

Mechanism of Interaction

The interaction between tizanidine and fluvoxamine occurs through cytochrome P450 enzyme inhibition. Tizanidine is primarily metabolized by the CYP1A2 enzyme, while fluvoxamine is a potent inhibitor of CYP1A2. When fluvoxamine inhibits CYP1A2, it dramatically reduces tizanidine's metabolism and clearance from the body. Studies have shown that fluvoxamine can increase tizanidine plasma concentrations by up to 33-fold and extend its half-life significantly, leading to prolonged and intensified pharmacological effects.

Risks and Symptoms

The primary risks of this interaction include severe hypotension, which can lead to dizziness, fainting, and cardiovascular collapse. Patients may experience excessive sedation, drowsiness, and impaired cognitive function that can persist for extended periods. Additional risks include bradycardia, respiratory depression, and potential coma in severe cases. The interaction can also cause prolonged muscle weakness and coordination problems, increasing the risk of falls and injuries. Due to the unpredictable and potentially life-threatening nature of these effects, this combination is considered contraindicated in clinical practice.

Management and Precautions

The concurrent use of tizanidine and fluvoxamine should be avoided entirely due to the contraindicated nature of this interaction. If a patient requires both muscle relaxation therapy and SSRI treatment, alternative medications should be considered. For muscle relaxation, alternatives may include baclofen, cyclobenzaprine, or other muscle relaxants that are not primarily metabolized by CYP1A2. For antidepressant therapy, SSRIs with less CYP1A2 inhibition such as sertraline, escitalopram, or citalopram may be safer options. If switching medications, appropriate washout periods should be observed, and patients should be closely monitored during transitions. Healthcare providers should always verify current medications and review potential interactions before prescribing either drug.

Tizanidine interactions with food and lifestyle

Tizanidine should not be taken with alcohol as it can significantly increase sedation and drowsiness, potentially leading to dangerous levels of central nervous system depression. Food can affect tizanidine absorption - taking tizanidine with food increases absorption and peak concentrations, while taking it on an empty stomach results in lower but more consistent absorption. Patients should be consistent in how they take tizanidine (always with food or always without food) to maintain stable drug levels. Smoking may reduce tizanidine effectiveness due to enzyme induction.

Fluvoxamine interactions with food and lifestyle

Fluvoxamine should not be taken with alcohol as it may increase drowsiness and impair cognitive function. Caffeine intake should be limited or avoided as fluvoxamine significantly inhibits caffeine metabolism, potentially leading to caffeine toxicity with symptoms including jitteriness, rapid heartbeat, and insomnia. Smoking cessation may be necessary as tobacco use can reduce fluvoxamine effectiveness by increasing its metabolism. Patients should maintain consistent timing of doses with regard to meals, as food can affect absorption, though fluvoxamine can be taken with or without food.