Can I take Xanax (alprazolam) and Zanaflex (tizanidine) together?

Concurrent Use of Xanax and Zanaflex

Taking Xanax (alprazolam) and Zanaflex (tizanidine) together is not recommended due to the significant risk of additive central nervous system depression that can lead to excessive sedation, respiratory depression, and potentially life-threatening outcomes.

Mechanism of Interaction

The interaction between these medications occurs through multiple mechanisms:

• CNS Depression: Both medications cause central nervous system depression 1

  • Xanax (alprazolam) is a benzodiazepine that enhances GABA effects
  • Zanaflex (tizanidine) is a centrally acting muscle relaxant with sedative properties

• Additive Sedation: The FDA label for tizanidine specifically warns that "sedation may be additive when tizanidine is taken in conjunction with drugs (baclofen, benzodiazepines) or substances (e.g., alcohol) that act as CNS depressants" 2

• Cardiovascular Effects: Tizanidine can cause hypotension, bradycardia, and potentially QT interval prolongation 3, which may be exacerbated when combined with other CNS depressants

Specific Risks

1. Respiratory Depression: The combination increases the risk of respiratory suppression, particularly concerning in patients with underlying respiratory conditions

2. Excessive Sedation: Profound sedation may occur, impairing ability to perform daily activities 2

3. Fall Risk: Increased risk of falls and traumatic injuries, with research showing a rate ratio of 1.42 for injury when alprazolam is combined with tizanidine 4

4. Cardiovascular Effects: Potential for additive hypotensive effects and cardiac rhythm disturbances 3

Alternative Approaches

If you require both muscle relaxation and anxiety management, consider these safer alternatives:

• Sequential Rather Than Concurrent Use: If both medications are absolutely necessary, they should be separated by several hours and used at the lowest effective doses

• Alternative Muscle Relaxants: Consider muscle relaxants with less sedating properties if you need to continue Xanax

• Non-Pharmacological Approaches: Physical therapy, cognitive behavioral therapy for anxiety, and other non-medication approaches may reduce the need for either medication

Monitoring If Concurrent Use Is Unavoidable

In rare situations where concurrent use cannot be avoided:

1. Reduced Dosing: Both medications should be used at the lowest effective doses

2. Close Monitoring: Regular assessment for excessive sedation, respiratory depression, and hypotension

3. Limited Duration: The combination should be used for the shortest possible time

4. Avoid Other CNS Depressants: No alcohol or other sedating medications should be used concurrently

Important Precautions

• Driving/Operating Machinery: Absolutely avoid driving or operating dangerous machinery when taking this combination 2

• Gradual Discontinuation: Neither medication should be stopped abruptly due to risk of withdrawal effects 1, 2

• Medical Alert: Ensure all healthcare providers are aware of all medications you are taking

The combination of Xanax and Zanaflex represents a potentially dangerous drug interaction that should be avoided whenever possible to prevent serious adverse outcomes related to excessive CNS depression.