What are the contraindications and precautions when using tizanidine (Zanaflex) with cipro (ciprofloxacin)?

Contraindications and Precautions When Using Tizanidine with Ciprofloxacin

Concomitant use of tizanidine (Zanaflex) with ciprofloxacin is absolutely contraindicated due to potentially dangerous increases in tizanidine plasma levels that can cause severe hypotension and excessive sedation. 1

Mechanism of Interaction

• Ciprofloxacin is a strong inhibitor of cytochrome P450 1A2 (CYP1A2), the primary metabolic pathway for tizanidine
• This inhibition leads to:
  • 10-fold increase in tizanidine area under the curve (AUC) 2
  • 7-fold increase in peak plasma concentration 2
  • Prolonged elimination half-life (from 1.5 to 1.8 hours) 2

Clinical Consequences of Co-administration

Cardiovascular Effects

• Severe hypotension (43% increased risk compared to tizanidine alone) 3
  • Systolic blood pressure can drop by up to 35 mmHg (vs 15 mmHg with tizanidine alone) 2
  • Diastolic blood pressure can drop by up to 24 mmHg (vs 11 mmHg with tizanidine alone) 2
• Risk of bradycardia and syncope 4
• Potential for cardiovascular collapse in severe cases

Central Nervous System Effects

• Significantly increased sedation and drowsiness 2
• Impaired cognitive function and psychomotor performance 2
• Increased risk of falls and fractures 4

Evidence from Pharmacovigilance Data

• The WHO pharmacovigilance database shows that despite the contraindication, co-administration occurs in clinical practice 5
• Most adverse reactions affect the nervous and cardiovascular systems 5
• Fatal outcomes have been reported 5
• The FDA Adverse Event Reporting System shows a reporting odds ratio of 28.1 for hypotension when tizanidine is used with ciprofloxacin 4

Clinical Recommendations

1. Never co-administer tizanidine and ciprofloxacin under any circumstances 1
2. If a patient is on tizanidine and requires an antibiotic:
   • Choose an alternative antibiotic that does not inhibit CYP1A2
   • If a fluoroquinolone is necessary, consider alternatives to tizanidine for muscle relaxation
3. If a patient is on ciprofloxacin and requires a muscle relaxant:
   • Select an alternative muscle relaxant that is not primarily metabolized by CYP1A2
   • Wait at least 5 half-lives (approximately 24 hours) after discontinuing ciprofloxacin before starting tizanidine

Risk Mitigation if Inadvertent Co-administration Occurs

• Immediately discontinue one or both medications
• Monitor blood pressure, heart rate, and level of consciousness closely
• Position patient supine if hypotension occurs
• Provide supportive care as needed
• Consider IV fluids for hypotension
• Be prepared to manage severe adverse effects in an emergency setting

Special Populations at Higher Risk

• Elderly patients (increased sensitivity to hypotensive and sedative effects) 6
• Patients with pre-existing cardiovascular disease
• Patients with hepatic or renal impairment (reduced clearance of both drugs) 6
• Patients on other medications with CNS depressant or hypotensive effects 6

This contraindication is absolute and not dose-dependent - even small doses of tizanidine combined with ciprofloxacin can lead to dangerous adverse effects due to the potent inhibition of tizanidine metabolism.