From the Guidelines
Tizanidine should be prescribed with caution due to its potential for sedation, hypotension, and significant drug interactions, particularly with CYP1A2 inhibitors, as noted in a 2021 consensus statement published in the Mayo Clinic Proceedings 1. When considering tizanidine for patients, healthcare providers must weigh the benefits of improved postoperative pain control and decreased opioid consumption against the risks of adverse effects.
- Key considerations include:
- Dose-dependent sedation, drowsiness, dizziness, ataxia, or lethargy
- Significant hypotension and bradycardia, especially when combined with other CYP1A2 inhibitors
- Contraindications with ciprofloxacin and fluvoxamine due to reduced tizanidine clearance
- Caution in patients with hepatic or renal dysfunction, as well as elderly patients, due to increased risk of sedative and hypotensive effects
- Potential for rebound tachycardia, hypertension, and hypertonia if discontinued abruptly after prolonged use, as reported in the 2021 study 1. Tizanidine's mechanism as a centrally acting alpha-2 adrenergic agonist contributes to its efficacy but also to its side effect profile, which includes dry mouth and fatigue, in addition to the more serious interactions and effects mentioned, highlighting the need for careful patient selection and monitoring, as emphasized in the recent literature 1.
From the FDA Drug Label
ADVERSE REACTIONS In multiple dose, placebo-controlled clinical studies, 264 patients were treated with tizanidine and 261 with placebo. Adverse events, including severe adverse events, were more frequently reported with tizanidine than with placebo Common Adverse Events Leading to Discontinuation Forty-five of 264 (17%) patients receiving tizanidine and 13 of 261 (5%) patients receiving placebo in three multiple dose, placebo-controlled clinical studies discontinued treatment for adverse events. The adverse events most frequently leading to withdrawal of tizanidine treated patients in the controlled clinical studies were asthenia (weakness, fatigue and/or tiredness) (3%), somnolence (3%), dry mouth (3%), increased spasm or tone (2%) and dizziness (2%) Most Frequent Adverse Clinical Events Seen in Association with the Use of Tizanidine In multiple dose, placebo-controlled clinical studies involving 264 patients with spasticity, the most frequent adverse events were dry mouth, somnolence/sedation, asthenia (weakness, fatigue and/or tiredness) and dizziness
The potential side effects of Tizanidine include:
- Dry mouth
- Somnolence (drowsiness)
- Asthenia (weakness, fatigue, and/or tiredness)
- Dizziness
- Increased spasm or tone Other side effects that have been reported include:
- UTI
- Infection
- Constipation
- Liver function tests abnormal
- Vomiting
- Speech disorder
- Amblyopia (blurred vision)
- Urinary frequency
- Flu symptom
- SGPT/ALT increased
- Dyskinesia
- Nervousness
- Pharyngitis
- Rhinitis 2
From the Research
Considerations for Prescribing Tizanidine
- Tizanidine is a central alpha 2 adrenoceptor agonist used to treat spasticity in patients with cerebral or spinal injury 3
- The optimal dosage of tizanidine must be titrated over 2 to 4 weeks for each patient, with dosages ranging from 2 to 36 mg/day 3
- Maximum effects of tizanidine occur within 2 hours of administration 3
Potential Side Effects of Tizanidine
- The most common adverse effects associated with tizanidine are dry mouth and somnolence/drowsiness 3, 4
- Tizanidine may also cause bradycardia and/or hypotension, as reported in case studies 5
- Muscle strength does not appear to be adversely affected by tizanidine, and subjective muscle weakness is reported less often compared to baclofen or diazepam 3
- Global tolerability of tizanidine is generally good to excellent, with 44 to 100% of patients reporting good tolerability 3
Special Considerations for Older Adults
- Tizanidine may be associated with a higher risk of falls in older adults, with a reported incidence of 29.2% 5
- Older adults may be more susceptible to the adverse effects of tizanidine, such as dry mouth, somnolence, and bradycardia 5, 6
- Alternative agents or lower doses of tizanidine may be considered for older adults to minimize the risk of adverse effects 5, 6
Comparison to Other Muscle Relaxants
- Tizanidine has similar efficacy to baclofen for treating spasticity, but may have a more favorable tolerability profile 3, 4
- Tizanidine may be associated with more dry mouth compared to baclofen, while baclofen may cause more weakness 4
- Cyclobenzaprine, carisoprodol, and orphenadrine may also be effective for treating musculoskeletal conditions, but have varying adverse effect profiles 4