Is it safe to start tizanidine (Zanaflex) 4mg every 8 hours in a patient with moderate impaired renal function (GFR of 48)?

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.

The patient's GFR is 48, which indicates moderate impaired renal function. According to the drug label, tizanidine should be used with caution in patients with renal insufficiency. Since the patient's GFR is above 25 mL/min, it is not considered severe renal insufficiency. However, dose reduction may still be necessary.

• The recommended dose is 4mg every 8 hours, but individual doses should be reduced during titration.
• It is essential to monitor the patient closely for the onset or increase in severity of common adverse events, such as dry mouth, somnolence, asthenia, and dizziness, as indicators of potential overdose 1.
• The patient's renal function should be closely monitored, and the dose adjusted accordingly. 1

From the Research

Starting tizanidine (Zanaflex) 4mg every 8 hours in a patient with moderate renal impairment (GFR of 48) requires caution but may be appropriate with careful monitoring, as indicated by the most recent study on tizanidine-induced hypotension 2.

Key Considerations

• The dose should be initiated at a lower level, such as 2mg every 8 hours, and gradually titrated based on response and tolerability.
• Tizanidine is primarily metabolized by the liver, but approximately one-third is eliminated unchanged through the kidneys, which means renal impairment can lead to increased drug exposure.
• Patients with moderate renal impairment may experience more pronounced side effects including hypotension, dizziness, and sedation.
• Blood pressure and heart rate should be monitored regularly, especially after initial dosing and dose increases.
• Particular attention should be paid to symptoms of excessive sedation or hypotension.

Potential Interactions

• If the patient is taking other medications that may interact with tizanidine, such as CYP1A2 inhibitors (like ciprofloxacin or fluvoxamine), these combinations should be avoided as they can significantly increase tizanidine levels 2.
• The medication should be taken consistently with or without food, as food can affect its absorption.

Renal Function Assessment

• The patient's GFR of 48 indicates moderate renal impairment, which should be taken into account when initiating tizanidine therapy 3.
• The accuracy of GFR-estimating equations may vary in patients with advanced chronic kidney disease, but the Lund-Malmö equation has been shown to perform well in this population 4.

Monitoring and Titration

• Close monitoring of the patient's response to tizanidine and regular assessment of renal function are crucial to minimize the risk of adverse effects.
• The dose of tizanidine should be titrated gradually to achieve the desired therapeutic effect while minimizing the risk of hypotension and other side effects.