ZEPOSIA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ZEPOSIA (ZEPOSIA).
Sphingosine 1-phosphate receptor modulator; binds with high affinity to S1P receptors 1 and 5, blocking lymphocyte egress from lymph nodes, reducing circulating lymphocytes.
| Metabolism | Primarily metabolized by CYP3A4 and to a minor extent by CYP2C8; also undergoes hydroxylation via non-CYP enzymes. |
| Excretion | Primarily fecal (approximately 78% of dose) via biliary excretion of unchanged drug and oxidative metabolites; renal excretion accounts for approximately 15% of dose, with <1% excreted unchanged in urine. |
| Half-life | Terminal elimination half-life is approximately 21 hours (range 14–30 hours) in healthy subjects, supporting once-daily dosing without need for loading dose. |
| Protein binding | >99% bound to plasma proteins, primarily to albumin and lipoproteins. |
| Volume of Distribution | Volume of distribution is approximately 22 L (0.3 L/kg for a 70 kg adult), indicating extensive tissue distribution. |
| Bioavailability | Absolute oral bioavailability is approximately 73% (90% CI 68–79%) under fasted conditions; no significant food effect observed. |
| Onset of Action | Reduction in peripheral lymphocyte count occurs within 4–6 hours after a single oral dose, with maximal effect observed by 24 hours. |
| Duration of Action | Lymphocyte counts begin to recover within 3–4 days after discontinuation and return to normal range within 4–6 weeks in most patients. |
0.92 mg orally once daily with or without food.
| Dosage form | CAPSULE |
| Renal impairment | No dose adjustment required for mild to severe renal impairment (CrCl ≥15 mL/min). Not recommended in end-stage renal disease (CrCl <15 mL/min) or on dialysis. |
| Liver impairment | Contraindicated in severe hepatic impairment (Child-Pugh class C). No dose adjustment needed for mild to moderate hepatic impairment (Child-Pugh class A or B). |
| Pediatric use | Not approved for pediatric patients; safety and efficacy not established. |
| Geriatric use | No specific dose adjustment for elderly. Use with caution due to age-related decrease in organ function and comorbidities. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ZEPOSIA (ZEPOSIA).
| Breastfeeding | There is no information regarding the presence of ozanimod or its active metabolites in human milk, the effects on the breastfed infant, or the effects on milk production. In animal studies, ozanimod and its metabolites were excreted in rat milk. Because of the potential for serious adverse reactions in breastfed infants, including bradycardia, infection, and respiratory depression, advise women not to breastfeed during treatment with ZEPOSIA and for 3 months after the last dose. |
| Teratogenic Risk | ZEPOSIA (ozanimod) is a sphingosine 1-phosphate receptor modulator. Based on animal studies, there is a risk of fetal harm, including structural malformations and embryolethality, when administered to pregnant women. In rats, oral administration during organogenesis resulted in increased post-implantation loss, reduced fetal body weight, and increased fetal skeletal and visceral malformations at maternal exposures similar to the clinical dose. In rabbits, embryofetal mortality and malformations were observed at maternal exposures similar to the clinical dose. Because there are no adequate and well-controlled studies in pregnant women, ZEPOSIA should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment and for 3 months after the last dose. |
■ FDA Black Box Warning
WARNING: INFECTIONS; BRADYARRHYTHMIA AND AV CONDUCTION DELAYS; MACULAR EDEMA; RESPIRATORY EFFECTS; HEPATIC INJURY; FETAL RISK; INCREASED BLOOD PRESSURE; MALIGNANCIES; SEVERE EXACERBATION OF MULTIPLE SCLEROSIS AFTER DISCONTINUATION; PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME.
| Serious Effects |
Patients who have had a myocardial infarction, unstable angina, stroke, transient ischemic attack, decompensated heart failure, or Class III/IV heart failure within the last 6 months; presence of Mobitz type II 2nd or 3rd degree AV block, sick sinus syndrome, or sinoatrial block unless pacemaker is placed; severe untreated sleep apnea; concurrent use of MAO inhibitors; known hypersensitivity to ozanimod or any of its excipients.
| Precautions | Increased risk of infections (including PML and herpes); bradyarrhythmia and AV block; macular edema (monitor ophthalmologic exams); respiratory effects (decline in FEV1 and DLCO); hepatic injury (monitor LFTs); fetal risk based on animal studies; increased blood pressure; malignancies (skin cancers); severe exacerbation of MS after discontinuation; PML; PRES; immune system effects after switching from other MS therapies. |
Loading safety data…
| Fetal Monitoring | Monitor fetal growth and development via ultrasound as clinically indicated. No specific maternal or fetal monitoring for ZEPOSIA is mandated, but given the potential for bradycardia and AV conduction delays, consider fetal heart rate monitoring if maternal bradycardia occurs. After delivery, monitor the infant for signs of bradycardia, infection, and respiratory depression. |
| Fertility Effects | Based on animal studies, ZEPOSIA may impair male and female fertility. In male rats, reduced sperm count and motility and increased abnormal sperm were observed at exposures similar to the clinical dose. In female rats, prolonged estrous cycles and reduced fertility indices were noted. The clinical relevance of these findings is unknown. Advise patients about potential effects on fertility. |