What is the interaction between acyclovir and Zanaflex (tizanidine)?

Interaction Between Acyclovir and Tizanidine (Zanaflex)

There is a potentially significant interaction between acyclovir and tizanidine (Zanaflex) that can lead to increased tizanidine levels, resulting in enhanced sedation, hypotension, and other adverse effects. 1

Mechanism of Interaction

The interaction occurs because:

• Acyclovir is known to inhibit CYP1A2, an enzyme responsible for tizanidine metabolism 1
• Tizanidine is primarily metabolized by CYP1A2 enzymes in the liver 1
• When these medications are co-administered, acyclovir can inhibit the metabolism of tizanidine, leading to increased blood levels of tizanidine

Clinical Implications

When acyclovir and tizanidine are used together, patients may experience:

• Enhanced sedation and drowsiness
• Significant hypotension (low blood pressure)
• Dizziness and potential for falls
• Bradycardia (slow heart rate)
• Increased risk of other tizanidine-related adverse effects

Management Recommendations

1. Avoid concurrent use if possible

   • Consider alternative muscle relaxants that don't have this interaction when acyclovir therapy is needed

2. If co-administration is necessary:

   • Reduce tizanidine dosage (start with lower doses and titrate slowly)
   • Monitor blood pressure and heart rate closely
   • Assess for excessive sedation
   • Educate patient about potential symptoms of toxicity (severe drowsiness, dizziness, weakness)
   • Consider more frequent follow-up during co-administration

3. Patient monitoring:

   • Blood pressure measurements
   • Heart rate monitoring
   • Assessment of sedation level
   • Evaluation for other adverse effects

Important Considerations

• The Mayo Clinic Proceedings guidelines specifically list acyclovir as a CYP1A2 inhibitor that can significantly affect tizanidine levels 1
• This interaction is particularly concerning in elderly patients or those with hepatic or renal dysfunction
• Tizanidine should be avoided in patients with hepatic dysfunction and used cautiously in elderly patients due to its significant sedative and hypotensive effects 1
• The interaction may be more pronounced when higher doses of either medication are used

Clinical Pearls

• Tizanidine has a short half-life (2-4 hours), so effects of the interaction may be most pronounced shortly after dosing
• If a patient develops signs of tizanidine toxicity (severe hypotension, bradycardia, excessive sedation), temporarily withhold the medication and seek medical attention
• The interaction may be less significant with topical acyclovir formulations compared to oral or intravenous administration
• Patients should avoid activities requiring mental alertness until the effects of this combination are known in the individual

Remember that while tizanidine has potential benefits for perioperative pain control and reduced opioid consumption, these benefits must be weighed against the risks of this drug interaction when acyclovir therapy is needed.