Tizanidine Causes Hypotension
Yes, tizanidine definitively causes hypotension as a well-established adverse effect, and this risk is explicitly documented in FDA labeling and multiple clinical guidelines. 1
Mechanism and Incidence
Tizanidine is an α2-adrenergic receptor agonist (structurally similar to clonidine) that produces hypotension through central mechanisms. 2, 1
In controlled studies, two-thirds of patients treated with 8 mg of tizanidine experienced a 20% reduction in either diastolic or systolic blood pressure. 1 The hypotensive effect is:
- Dose-related, occurring with single doses as low as 2 mg 1
- Time-dependent, typically seen within 1 hour after dosing, peaking at 2-3 hours 1
- Often accompanied by bradycardia, orthostatic hypotension, lightheadedness/dizziness, and rarely syncope 1
Clinical Evidence of Severity
The hypotensive effects can be clinically significant:
- In overdose cases, the lowest dose associated with hypotension was 28 mg in a 63-year-old female (BP 88/52, HR 54) 3
- Severe hypotension (systolic BP ≤70 mmHg) occurred in 2.03% of patients when tizanidine was co-prescribed with strong CYP1A2 inhibitors 4
- Case reports document dramatic blood pressure drops requiring discontinuation of all antihypertensive medications 5
- Pediatric overdose cases have resulted in cardiovascular failure requiring intensive care 6
High-Risk Situations
The risk of hypotension is substantially increased in several clinical scenarios:
Drug Interactions
- Concomitant use with CYP1A2 inhibitors (ciprofloxacin, fluvoxamine) significantly increases hypotension risk due to reduced tizanidine clearance 2, 4, 7
- Combination with opioids (such as oxycodone) carries significant risk due to additive hypotensive effects 2, 8
- Use with other antihypertensive agents (ACE inhibitors, other α2-agonists) is specifically cautioned against in FDA labeling 1, 5
Patient Factors
- Hepatic or renal dysfunction increases risk due to reduced drug clearance 2, 8, 1
- Elderly patients are at higher risk for hypotensive effects 2, 8
- Patients moving from supine to upright positions face increased risk of orthostatic hypotension 1
Clinical Management Recommendations
To minimize hypotension risk:
- Start with 2 mg up to three times daily, particularly in older adults or those with renal impairment 8
- Titrate the dose gradually and monitor for signs and symptoms of hypotension prior to dose advancement 1
- Consider taking initial doses at bedtime to allow sedation and hypotension to occur during sleep 2
- Review all concurrent medications for potential interactions before initiating therapy 2
- Monitor blood pressure closely, especially during dose titration and when combining with other medications that lower blood pressure 2, 1
Critical Safety Warnings
The FDA label explicitly warns that tizanidine should not be used with other α2-adrenergic agonists and caution is advised when used with concurrent antihypertensive therapy. 1
Never abruptly discontinue tizanidine in long-term users, as withdrawal can cause rebound tachycardia and hypertension; taper slowly over several weeks. 2, 9