OZANIMOD
Clinical safety rating: caution
Comprehensive clinical and safety monograph for OZANIMOD (OZANIMOD).
Sphingosine 1-phosphate receptor modulator; binds with high affinity to S1P receptors 1 and 5, causing receptor internalization and degradation, thereby reducing lymphocyte egress from lymph nodes and peripheral blood lymphocyte count.
| Metabolism | Primarily metabolized by CYP2C8 and to a lesser extent by CYP3A4; no active metabolites identified. |
| Excretion | Primarily via fecal excretion (84%) with minor renal excretion (17%). Unchanged drug and metabolites are eliminated mainly through biliary/fecal route. |
| Half-life | Terminal elimination half-life is approximately 10-12 days, allowing once-daily oral dosing. Steady state is achieved in about 4-6 weeks. |
| Protein binding | Approximately 99.7% bound to plasma proteins (primarily albumin and α1-acid glycoprotein). |
| Volume of Distribution | Volume of distribution is approximately 1700 L (about 21 L/kg for a 70 kg adult), indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability is approximately 80-90% with no significant food effect. |
| Onset of Action | Oral: Clinical effect on lymphocyte count reduction observed within 4-6 hours, with maximal reduction by 6-8 hours. Clinical efficacy in relapsing multiple sclerosis may be evident after several weeks. |
| Duration of Action | Duration of pharmacological effect (lymphocyte count suppression) persists for approximately 2-4 weeks after discontinuation. Clinical duration of action for relapse prevention extends throughout continuous therapy. |
0.92 mg orally once daily.
| Dosage form | CAPSULE |
| Renal impairment | No dose adjustment required for mild to severe renal impairment including end-stage renal disease on dialysis. |
| Liver impairment | Contraindicated in patients with moderate (Child-Pugh class B) or severe (Child-Pugh class C) hepatic impairment. Use with caution in mild impairment (Child-Pugh class A); no dose adjustment recommended. |
| Pediatric use | Safety and efficacy in pediatric patients below 18 years have not been established. |
| Geriatric use | No dose adjustment required; however, monitor for adverse effects due to potential age-related renal and hepatic changes. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for OZANIMOD (OZANIMOD).
| Breastfeeding | No human data available. In animal studies, ozanimod and its metabolites are excreted in milk. M/P ratio not determined in humans. Caution advised; consider alternative therapies. |
| Teratogenic Risk | First trimester: Increased risk of congenital malformations including neural tube defects, cardiac anomalies, and orofacial clefts based on animal studies and human case reports. Second and third trimester: Potential for fetal bradycardia, growth restriction, and neurodevelopmental deficits due to S1P receptor modulation. Avoid use during pregnancy unless benefit outweighs risk. |
■ FDA Black Box Warning
WARNING: RISK OF INFECTIONS. OZANIMOD may increase the risk of serious infections, including life-threatening and fatal infections. Obtain a complete blood count (CBC) before initiating treatment. Monitor patients for infections during treatment and consider withholding treatment if a serious infection develops.
| Serious Effects |
["Patients with recent (within last 6 months) myocardial infarction, unstable angina, stroke, transient ischemic attack, decompensated heart failure requiring hospitalization, or certain arrhythmias (e.g., Mobitz type II second-degree or third-degree AV block, sick sinus syndrome, sinoatrial block) unless patient has a functioning pacemaker.","Hypersensitivity to ozanimod or any of its excipients."]
| Precautions | ["Risk of infections (including opportunistic infections); delay initiation in patients with active infection until resolved.","Bradyarrhythmia and atrioventricular conduction delays: observe for 6 hours after first dose with ECG monitoring.","Increased blood pressure: monitor blood pressure regularly.","Respiratory effects: reduce forced expiratory volume over 1 second (FEV1) and diffusing capacity for carbon monoxide (DLCO); assess pulmonary function if clinically indicated.","Hepatotoxicity: monitor liver enzymes; discontinue if serious liver injury occurs.","Fetal risk: advise females of reproductive potential of potential risk to fetus; use effective contraception during and for 3 months after treatment.","Macular edema: perform ophthalmic examination before and 3-4 months after treatment initiation.","Posterior reversible encephalopathy syndrome (PRES): evaluate for vision changes, headache, seizures; discontinue if PRES suspected."] |
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| Fetal Monitoring |
| Baseline and periodic liver function tests, blood pressure monitoring, ophthalmic exam (risk of macular edema), and complete blood count. During pregnancy, fetal ultrasound for growth and anatomy, and nonstress testing in third trimester. |
| Fertility Effects | In animal studies, ozanimod did not impair fertility in males or females at clinically relevant doses. Human data lacking; theoretical risk due to S1P modulation on reproductive function. |