Can Zeposia (ozanimod) cause muscle spasms and how should they be managed?

Zeposia (Ozanimod) and Muscle Spasms

Muscle spasms are not a documented side effect of Zeposia (ozanimod) based on the available clinical trial data and safety profiles from both ulcerative colitis and multiple sclerosis studies. 1, 2

Documented Adverse Events from Clinical Trials

The comprehensive safety data from the phase 3 True North trial in ulcerative colitis and multiple sclerosis trials do not list muscle spasms among the treatment-emergent adverse events. 1

The most common adverse events documented with ozanimod include:

• Upper respiratory tract infections (nasopharyngitis being most frequent at approximately 11% of patients) 3, 4
• Hepatic transaminase elevations (though rarely leading to discontinuation at 0.4%) 1
• Fatigue (which can occasionally lead to treatment discontinuation) 5
• Transient nausea (reported in real-world studies) 5
• Headache 4
• Urinary tract infections 3, 4

Cardiovascular Effects (Not Muscle Spasms)

The cardiac effects of ozanimod involve transient reductions in heart rate and atrioventricular conduction, not muscle spasms. 1, 5 These effects:

• Occur within the first 5 hours of initial dosing 1
• Are mitigated by the gradual dose escalation protocol 1
• Bradycardia occurred in only 0.6% of patients during induction 1
• Do not typically require treatment or extended monitoring 1

Important Safety Considerations (Unrelated to Muscle Spasms)

The documented adverse events of special interest include: 1, 5

• Infections (serious infections in ≤1.6% of patients, including appendicitis, gastroenteritis, pyelonephritis) 1, 5
• Lymphopenia (41-45% reduction in absolute lymphocyte count after 10 weeks) 5
• Macular edema (≤0.4% incidence) 1, 5
• Malignancy (≤0.9% incidence) 1, 5
• Hypertensive urgency (rare, one case reported in real-world data) 5

Clinical Pitfall

If a patient on Zeposia reports muscle spasms, investigate alternative etiologies rather than attributing them to the medication, as this is not a recognized adverse effect. Consider:

• Electrolyte abnormalities (particularly given potential for infections and gastrointestinal symptoms in UC patients)
• Underlying disease activity
• Concomitant medications
• Other neurological or musculoskeletal conditions

The extensive safety database from both the 24-week phase 2 RADIANCE trial 4 and the 52-week phase 3 True North trial 1 with over 2,900 patients pooled across studies 3 does not identify muscle spasms as a treatment-related adverse event.