What precautions should be taken when taking tizanidine (Zanaflex)?

Tizanidine (Zanaflex) Precautions

Do not take tizanidine if you are using fluvoxamine or ciprofloxacin, as these combinations are absolutely contraindicated due to severe hypotension, excessive sedation, and psychomotor impairment. 1

Absolute Contraindications

• Fluvoxamine: Concomitant use is contraindicated due to significantly decreased blood pressure, increased drowsiness, and increased psychomotor impairment 1
• Ciprofloxacin: Concomitant use is contraindicated for the same reasons as fluvoxamine 1

Critical Drug Interactions Requiring Avoidance or Dose Adjustment

CYP1A2 Inhibitors (Avoid if Possible)

• Other fluoroquinolones (besides ciprofloxacin), zileuton, antiarrhythmics (amiodarone, mexiletine, propafenone, verapamil), cimetidine, famotidine, acyclovir, and ticlopidine should be avoided 1
• If clinically necessary, start with 2 mg dose and increase in 2-4 mg steps daily based on response 1
• Discontinue or reduce dose if hypotension, bradycardia, or excessive drowsiness occurs 1

Oral Contraceptives

• Concomitant use is not recommended 1
• If necessary, initiate with single 2 mg dose and titrate in 2-4 mg steps daily 1
• Monitor for hypotension, bradycardia, or excessive drowsiness 1

Alcohol

• Alcohol increases drug levels in the bloodstream and is associated with increased adverse reactions 1
• CNS depressant effects are additive 1

Other CNS Depressants

• Sedative effects with benzodiazepines, opioids, and tricyclic antidepressants are additive 1
• Monitor for symptoms of excess sedation 1

Other α2-Adrenergic Agonists

• Not recommended due to cumulative hypotensive effects 1

Dosing Precautions

• Never exceed 8 mg per single dose or 36 mg total daily dose due to increased risk of adverse events 1
• Take consistently either with or without food—do not switch 1
• Do not switch between tablets and capsules 1
• Do not suddenly discontinue as rebound hypertension and tachycardia may occur 1

Cardiovascular Monitoring

• Hypotension risk: Be careful when changing from lying or sitting to standing position 1
• Tizanidine may prolong the QT interval by blocking IKr, with potential for cardiac proarrhythmia 2
• Patients are at increased risk during impaired drug elimination, particularly with CYP1A2 inhibition 2

Central Nervous System Effects

• Sedation and somnolence are common adverse effects (reported in 60-82% of patients) 3
• Avoid activities requiring alertness such as driving or operating machinery 1
• Dry mouth is the other most common adverse effect 3

Special Populations

Elderly Patients (≥65 years)

• Start with 2 mg up to three times daily 4
• Titrate slowly based on response and tolerability 4

Renal Impairment

• For moderate renal impairment, use starting dose of 2 mg up to three times daily 4
• Monitor closely for adverse effects as drug clearance may be reduced

Appropriate vs. Inappropriate Use

• Appropriate: Tizanidine is for treating spasticity (increased muscle tone) from upper motor neuron syndromes such as stroke, multiple sclerosis, and spinal cord injury 4, 5
• Inappropriate: Tizanidine is NOT for hypotonia (reduced muscle tone)—it would worsen this condition 5
• Off-label use: May be used for acute low back pain for short-term relief (typically ≤2 weeks), though not FDA-approved for this indication 4

Functional Considerations

• If you depend on spasticity to sustain posture, balance, or locomotion, use caution as tizanidine decreases spasticity 1
• Muscle strength appears not to be adversely affected by objective measures, and subjective muscle weakness is reported less often than with baclofen or diazepam 3

Common Pitfalls to Avoid

• Facial pallor may occur (reported in 9.5% of pediatric patients in one study) and may warrant discontinuation 6
• Adverse effects are generally transient and occur in <6% of adult patients 7
• Maximum effects occur within 2 hours of administration 3
• Wide interpatient variability means optimal dosage must be titrated over 2-4 weeks 3