From the FDA Drug Label
In a single dose study where blood pressure was monitored closely after dosing, two-thirds of patients treated with 8 mg of tizanidine had a 20% reduction in either the diastolic or systolic BP. The reduction was seen within 1 hour after dosing, peaked 2 to 3 hours after dosing and was associated, at times, with bradycardia, orthostatic hypotension, lightheadedness/dizziness and rarely syncope The hypotensive effect is dose related and has been measured following single doses of ≥ 2 mg. Infrequent adverse events are those occurring in 1/100 to 1/1000 patients... Cardiovascular System: Infrequent: ... syncope
The use of tizanidine may increase the risk of syncope due to its side effects of dizziness and hypotension. The reduction in blood pressure is dose-related and can be associated with bradycardia, orthostatic hypotension, lightheadedness/dizziness, and rarely syncope.
- Dizziness and hypotension are common side effects of tizanidine, occurring in a significant proportion of patients.
- Syncope is a less common but potential side effect of tizanidine, particularly in patients who experience significant hypotension.
- Patients should be cautioned about the risk of clinically significant orthostatic hypotension and advised to be careful when changing positions or performing activities that require alertness 1.
From the Research
Tizanidine increases the risk of syncope due to its side effects of dizziness and hypotension, particularly when used in combination with CYP1A2 inhibitors or in patients with pre-existing cardiovascular conditions, as evidenced by a recent study published in 2022 2.
Mechanism of Action
Tizanidine, a central-acting alpha-2 adrenergic agonist, reduces sympathetic nervous system activity, leading to decreased blood pressure. When blood pressure drops too low (hypotension), there is reduced blood flow to the brain, which can cause dizziness. The combination of these effects can be particularly problematic when changing positions, such as standing up quickly, as this can trigger orthostatic hypotension where blood pressure drops suddenly.
Risk Factors
The risk of syncope associated with tizanidine is higher in:
- Elderly patients
- Those on other blood pressure medications
- Those with pre-existing cardiovascular conditions
- Patients taking CYP1A2 inhibitors, such as ciprofloxacin or fluvoxamine, as reported in a study published in 2022 2
Prevention and Management
To minimize the risk of syncope, patients taking tizanidine should:
- Be cautious about sudden position changes
- Stay well-hydrated
- Monitor for warning signs like lightheadedness
- Start with a low dose and gradually increase as needed, as recommended by a study published in 2019 3
- Avoid concurrent use of CYP1A2 inhibitors, if possible, as suggested by a study published in 2022 2
Recent Evidence
A recent case report published in 2024 4 highlights the importance of close monitoring of patients receiving tizanidine, especially when co-medicated with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, due to the risk of hypotension and bradycardia.