From the FDA Drug Label
Tizanidine should be used with caution in patients with renal insufficiency (creatinine clearance < 25 mL/min), as clearance is reduced by more than 50%. In these patients, during titration, the individual doses should be reduced. If higher doses are required, individual doses rather than dosing frequency should be increased Tizanidine clearance is reduced by more than 50% in elderly patients with renal insufficiency (creatinine clearance < 25 mL/min) compared to healthy elderly subjects; this would be expected to lead to a longer duration of clinical effect.
Key Considerations:
- Dose Reduction: Tizanidine should be used with caution in patients with renal insufficiency, and the individual doses should be reduced during titration.
- Monitoring: These patients should be monitored closely for the onset or increase in severity of common adverse events as indicators of potential overdose.
- Dosing Frequency: If higher doses are required, individual doses rather than dosing frequency should be increased. 1 1
From the Research
Tizanidine should be used with caution in patients with renal impairment, with careful consideration of dose adjustments and monitoring of renal function, as its clearance is reduced in renal failure, leading to higher plasma concentrations and increased risk of adverse effects. When using tizanidine in patients with renal insufficiency, it is essential to start with lower doses, such as 2 mg, and gradually increase based on response and tolerability 2. The medication's clearance is reduced by approximately 50% in patients with renal failure, which can result in higher plasma concentrations and an increased risk of adverse effects, including hypotension, sedation, and dizziness 3. Patients with creatinine clearance less than 25 mL/min may experience three-fold higher plasma concentrations compared to those with normal renal function, emphasizing the need for careful dose titration and monitoring 4. Regular monitoring of renal function, blood pressure, and sedation levels is crucial during treatment with tizanidine, especially in patients with renal impairment 5. Tizanidine is primarily metabolized by the liver, but approximately 20% is excreted unchanged in urine, explaining why renal impairment affects its clearance 6. Consider alternative muscle relaxants if the patient has severe renal dysfunction or if they experience significant adverse effects despite dose adjustments.
Some key considerations when using tizanidine in patients with renal impairment include:
- Starting with lower doses and gradually increasing based on response and tolerability
- Monitoring renal function, blood pressure, and sedation levels regularly
- Being aware of the potential for increased plasma concentrations and adverse effects in patients with renal failure
- Considering alternative muscle relaxants if necessary
- Ensuring careful coordination of treatments and avoidance of medications that may worsen kidney disease or interact with tizanidine 2.
It is also important to note that patients with kidney disease are susceptible to further kidney injury and metabolic derangements from medications, which can worsen the disease, and that tizanidine-induced hepatic injury has been reported in the literature, although it is rare 5, 6.