Is tachycardia a contraindication to using Zeposia (ozanimod)?

Is Tachycardia a Contraindication to Zeposia (Ozanimod)?

No, tachycardia is not listed as a contraindication to Zeposia (ozanimod). The drug's cardiovascular contraindications are specifically limited to bradyarrhythmias and conduction blocks, not tachyarrhythmias.

Specific Cardiac Contraindications

Ozanimod is contraindicated only in the following cardiac conditions 1:

• Mobitz type II second-degree atrioventricular block
• Third-degree atrioventricular block
• Sick sinus syndrome
• Sino-atrial block (unless patient has a functioning pacemaker)
• Recent major cardiovascular events: myocardial infarction, unstable angina, stroke, or TIA within the last 6 months 2
• Decompensated heart failure requiring hospitalization or Class III/IV heart failure 3

Why Bradycardia, Not Tachycardia, Is the Concern

The mechanism of ozanimod explains this distinction 1:

• S1P receptor modulators cause transient reductions in heart rate, not increases, due to S1P receptor binding in the heart
• The drug's lack of affinity for S1P3 receptors is specifically relevant to its favorable cardiovascular safety profile, as S1P3 modulation is associated with cardiac conduction abnormalities 1
• First-dose effects show maximum heart rate reduction of less than 2 beats per minute within the first 6 hours, with no patient experiencing heart rate below 45 bpm 4
• The built-in dose escalation regimen (starting at 0.23-0.25 mg and titrating up over 7-8 days) mitigates these bradycardic effects 5, 4

Clinical Trial Safety Data

Real-world and clinical trial evidence demonstrates 1, 5:

• Only 0.2% of UC patients and 0.6% of MS patients experienced cardiac-related adverse events on Day 1
• No cases of second- or third-degree AV block were observed in clinical trials
• Among patients with pre-existing cardiac disorders (6.9% in UC trials, 5.4% in MS trials), cardiac events on Day 1 were rare and manageable 5
• Cardiac adverse events overall were ≤2.2% in phase 3 trials 1

Important Caveat: Hypertensive Risk

While tachycardia itself is not a contraindication, be aware that 1, 2, 3:

• One patient with pre-existing hypertension developed hypertensive urgency and discontinued ozanimod in real-world data 1
• Ozanimod inhibits monoamine oxidase-B, creating risk for hypertensive crisis when combined with sympathomimetic drugs, MAO inhibitors, or high tyramine intake 2, 3

Practical Recommendation

Proceed with ozanimod in patients with tachycardia, but:

• Obtain baseline ECG to rule out the actual contraindications (conduction blocks) 1
• If tachycardia is secondary to uncontrolled hypertension, optimize blood pressure control first
• Avoid concomitant medications that could precipitate hypertensive crisis (sympathomimetics, MAO inhibitors) 2, 3
• Consider cardiology consultation if patient is on Class Ia/III antiarrhythmics, QTc-prolonging drugs, calcium channel blockers, or beta-blockers 1