What are the side effects of Zepbound (ozanimod)?

Side Effects of Zepbound (Ozanimod)

Zepbound (ozanimod) has several important side effects including cardiovascular effects, immunosuppression, and potential drug interactions that require careful monitoring and management. 1, 2

Common Side Effects

• Upper respiratory tract infections are among the most common adverse reactions reported with ozanimod treatment 2, 3
• Hepatic transaminase elevation is frequently observed and requires periodic liver enzyme monitoring 2, 3
• Headache is a common side effect reported in clinical trials 2
• Fatigue may occur and in some cases can lead to treatment discontinuation 1
• Transient nausea has been reported in real-world studies 1

Cardiovascular Effects

• Transient reductions in heart rate and atrioventricular conduction may occur due to S1P receptor binding in the heart 1

  • This effect is mitigated with the upward titration dosing schedule included in the starter pack 1
  • First-dose cardiac monitoring is not required in the US, unlike with some other S1P modulators 3

• Contraindicated in patients with:

  • Myocardial infarction, unstable angina, stroke, or TIA within the last 6 months 1, 2
  • Decompensated heart failure requiring hospitalization or Class III/IV heart failure 1, 2
  • Mobitz type II second-degree or third-degree AV block, sick sinus syndrome, or sino-atrial block (unless patient has functioning pacemaker) 1, 2

• Blood pressure increases may occur and should be monitored during treatment 2

Immunological Effects

• Reduction in absolute lymphocyte count (ALC) is an expected pharmacodynamic effect 1

  • Mean reduction of 41-45% after 10 weeks of treatment 1
  • ALC typically returns to normal within 30 days after discontinuation 1
  • Treatment should be discontinued if ALC falls below 0.2 × 10^9/L 1

• Increased susceptibility to infections due to immunosuppressive effects 1

  • Complete blood count should be obtained prior to treatment initiation 1
  • Patients should be monitored for infections during treatment and for 3 months after discontinuation 2

Hepatic Effects

• Liver enzyme elevations may occur during treatment 2, 3
  • Baseline and periodic liver function tests are recommended 2
  • Treatment should be discontinued if there is evidence of liver injury without other cause 2

Ocular Effects

• Macular edema risk is increased, particularly in patients with diabetes mellitus or uveitis 2
  • Baseline evaluation of the fundus is recommended near the start of treatment 2
  • Periodic evaluations should be conducted during therapy 2
  • Consider discontinuation if macular edema develops 2

Respiratory Effects

• Decline in pulmonary function may occur 2
  • Pulmonary function assessment (e.g., spirometry) should be performed if clinically indicated 2

Dermatological Effects

• Cutaneous malignancies risk may be increased 2
  • Skin examination prior to or shortly after starting treatment and periodically thereafter is recommended 2
  • Suspicious skin lesions should be evaluated 2

Drug Interactions

• Monoamine oxidase inhibitors (MAOIs) are contraindicated due to risk of hypertensive crisis 4, 2

• Tyramine-containing foods in high amounts (>150 mg) should be avoided due to potential for severe hypertension 1

  • This is based on in vitro findings that ozanimod inhibits monoamine oxidase-B 1
  • Moderate consumption of tyramine-containing foods is likely safe 1

• Opioid drugs (meperidine, methadone, tramadol, etc.) may cause serious adverse reactions including hypertensive crisis 1

• Serotonergic/adrenergic drugs (SSRIs, SNRIs, tricyclics) may cause serious adverse reactions 1

• Sympathomimetic drugs (pseudoephedrine, amphetamines, etc.) may cause hypertensive crisis 1

• CYP2C8 inhibitors (gemfibrozil, clopidogrel) may increase exposure to active metabolites of ozanimod 1

Special Considerations

• Pregnancy risk: Women of childbearing potential should use effective contraception during treatment and for 3 months after stopping 2

• Live vaccines should be avoided during and for up to 3 months after treatment 2

• Progressive Multifocal Leukoencephalopathy (PML): Treatment should be withheld at the first sign or symptom suggestive of PML 2

• Hepatic impairment: Dosage adjustment is needed for patients with mild or moderate hepatic impairment; not recommended in severe hepatic impairment 2