From the Guidelines
Tizanidine can cause significant hypotension, particularly when used concomitantly with CYP1A2 inhibitors, and its use should be avoided in patients with hepatic or renal dysfunction and in elderly patients due to its sedative and hypotensive effects. This is because tizanidine is an a2-adrenergic receptor agonist that reduces sympathetic outflow from the central nervous system, leading to decreased blood pressure 1. When prescribing tizanidine, it is essential to start with a low dose and gradually increase as needed, with close monitoring of blood pressure, especially during dose adjustments and when combining with other medications that lower blood pressure.
Some key considerations when using tizanidine include:
- Starting with a low dose of 2 mg and gradually increasing as needed, with a maximum of 36 mg daily divided into three doses
- Monitoring blood pressure closely, especially during dose adjustments and when combining with other medications that lower blood pressure
- Advising patients to change positions slowly to minimize orthostatic hypotension and avoid activities requiring alertness until their response to the medication is known
- Being cautious when using tizanidine in patients with significant cardiovascular disease or those already taking blood pressure medications
It is also important to note that tizanidine clearance is significantly reduced when given concomitantly with certain medications, such as ciprofloxacin and fluvoxamine, and its use is contraindicated in these cases 1. Additionally, the hypotensive effect of tizanidine tends to be dose-dependent and may diminish with continued use as tolerance develops.
In terms of managing hypotension, non-pharmacologic measures such as ensuring adequate salt intake, avoiding medications that aggravate hypotension, and using compressive garments over the legs and abdomen can be effective 1. However, the primary focus should be on careful patient selection, dose titration, and monitoring to minimize the risk of hypotension when using tizanidine.
From the FDA Drug Label
Tizanidine is an α2-adrenergic agonist (like clonidine) and can produce hypotension 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.
Hypotension is a potential side effect of tizanidine, with a dose-related effect. The chance of significant hypotension may be minimized by titration of the dose and monitoring for signs and symptoms of hypotension prior to dose advancement 2.
From the Research
Tizanidine-Associated Hypotension
- Tizanidine, a muscle relaxant, can lower blood pressure and is metabolized by the cytochrome P450 1A2 (CYP1A2) 3.
- The risk of hypotensive episodes associated with tizanidine use is increased when co-prescribed with strong CYP1A2 inhibitors 3.
- Severe hypotension occurred more often in patients prescribed tizanidine compared to those prescribed cyclobenzaprine, with an odds ratio of 1.60 (P = 0.029) 3.
Mechanism and Interactions
- Tizanidine is an α2 and imidazole receptor agonist that reduces central sympathetic outflow, causing hypotension, especially in patients receiving beta-blockers or angiotensin-converting enzyme inhibitors 4.
- Concomitant use of tizanidine with angiotensin-converting enzyme inhibitors, such as lisinopril, can lead to severe hypotension and bradycardia due to a synergistic effect on reducing the renin-angiotensin-aldosterone system 4, 5, 6.
Case Reports
- A 56-year-old hypertensive male experienced a significant drop in blood pressure from 140/90 to 80/40 mmHg after taking three doses of tizanidine 2mg, which was attributed to the interaction between tizanidine and his concurrent medications, including amlodipine, atenolol, and telmisartan 4.
- An 85-year-old man developed severe bradycardia and hypotension after taking three doses of tizanidine while being treated with lisinopril, highlighting the potential risk of concomitant therapy 5.
- A 48-year-old woman experienced significant hypotension after initiation of tizanidine while using lisinopril, which was classified as a possible drug interaction according to the Naranjo probability scale 6.