From the Guidelines
The concomitant use of tizanidine and ciprofloxacin is a contraindication due to the significant risk of severe hypotension, sedation, and potentially life-threatening adverse effects. This combination creates a dangerous drug interaction, as ciprofloxacin is a strong CYP1A2 inhibitor that dramatically increases tizanidine blood levels, resulting in a significant increase in tizanidine exposure 1. The interaction can cause rapid and severe drops in blood pressure, excessive sedation, dizziness, and respiratory depression. In a hospital setting, this combination could lead to falls, syncope, or cardiorespiratory compromise requiring emergency intervention.
Some key points to consider when evaluating this interaction include:
- Ciprofloxacin's long half-life, which can persist throughout the duration of therapy, making the interaction a prolonged risk 1
- The interaction is not dose-dependent and occurs even with standard doses of both medications, making it particularly dangerous in vulnerable hospitalized patients with multiple comorbidities
- Alternative muscle relaxants like baclofen or methocarbamol should be considered for patients requiring ciprofloxacin
- If tizanidine is absolutely necessary, ciprofloxacin should be switched to a non-interacting antibiotic
The most recent and highest quality study, published in 2021, highlights the significance of this interaction and the need for caution when prescribing these medications together 1. Therefore, it is essential to avoid this combination to prevent severe adverse effects and ensure patient safety.
From the FDA Drug Label
In a pharmacokinetic study, systemic exposure of tizanidine (4 mg single dose) was significantly increased (Cmax 7-fold, AUC 10-fold) when the drug was given concomitantly with ciprofloxacin (500 mg bid for 3 days). The hypotensive and sedative effects of tizanidine were also potentiated Concomitant administration of tizanidine and ciprofloxacin is contraindicated.
The concomitant use of tizanidine (Zanaflex) and ciprofloxacin (Cipro) is a contraindication because ciprofloxacin significantly increases the systemic exposure of tizanidine, potentiating its hypotensive and sedative effects. This increased exposure can lead to enhanced and potentially dangerous side effects of tizanidine 2.
From the Research
Concomitant Use of Tizanidine and Ciprofloxacin
The concomitant use of tizanidine (Zanaflex) and ciprofloxacin (Cipro) is a contraindication due to the increased risk of adverse events. Some key points to consider include:
- Tizanidine is extensively metabolized via cytochrome P450 (CYP) 1A2, and ciprofloxacin is a potent inhibitor of this enzyme 3, 4, 5, 6.
- The inhibition of CYP1A2 by ciprofloxacin can lead to increased plasma concentrations of tizanidine, resulting in enhanced hypotensive and sedative effects 6.
- The concomitant use of tizanidine and ciprofloxacin has been associated with an increased risk of hypotension, bradycardia, syncope, shock, cardiorespiratory arrest, and falls or fractures 3, 4, 5.
- Studies have shown that the coadministration of tizanidine and ciprofloxacin can result in a significant increase in the area under the plasma concentration-time curve (AUC) of tizanidine, leading to a higher risk of adverse events 6.
- The interaction between tizanidine and ciprofloxacin can be serious, and healthcare providers should exercise caution when prescribing these medications together 7.
Mechanism of Interaction
The mechanism of interaction between tizanidine and ciprofloxacin is primarily due to the inhibition of CYP1A2 by ciprofloxacin, which leads to:
- Increased plasma concentrations of tizanidine
- Enhanced hypotensive and sedative effects of tizanidine
- Increased risk of adverse events, such as hypotension, bradycardia, and syncope 3, 4, 5, 6.
Clinical Implications
The concomitant use of tizanidine and ciprofloxacin is contraindicated due to the increased risk of adverse events. Healthcare providers should: