MAYZENT
Clinical safety rating: caution
Comprehensive clinical and safety monograph for MAYZENT (MAYZENT).
Sphingosine 1-phosphate receptor modulator; binds with high affinity to S1P receptors 1 and 5 on lymphocytes, blocking egress from lymph nodes, reducing circulating lymphocytes.
| Metabolism | Primarily metabolized by CYP3A4 and to a minor extent by CYP2C8; also undergoes reversible phosphorylation to active metabolite. |
| Excretion | Primarily fecal (≈76% as metabolites) and renal (≈24% as metabolites and minor unchanged drug). |
| Half-life | Terminal elimination half-life is approximately 8–10 days due to slow dissociation from sphingosine 1-phosphate receptors; steady-state reached in 3–4 weeks. |
| Protein binding | >99.9% bound to plasma proteins, primarily albumin and lipoproteins. |
| Volume of Distribution | Very large, approximately 3000 L (≈43 L/kg for a 70 kg individual), indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability is approximately 84% (absolute); food does not significantly affect absorption. |
| Onset of Action | Oral: Reduction in lymphocyte count occurs within 4–6 hours; maximal effect on lymphocyte recirculation by 24–48 hours. |
| Duration of Action | Lymphocyte count recovery begins ≈2 weeks after discontinuation, with full recovery by 4–6 weeks. |
0.25 mg orally once daily initially, titrated over several weeks to a maintenance dose of 2 mg orally once daily.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (GFR ≥30 mL/min). Severe renal impairment (GFR <30 mL/min): not recommended due to limited data. |
| Liver impairment | Contraindicated in patients with severe hepatic impairment (Child-Pugh class C). Mild to moderate hepatic impairment (Child-Pugh class A or B): no dose adjustment needed. |
| Pediatric use | Not approved for use in pediatric patients; safety and efficacy not established. |
| Geriatric use | No specific dose adjustment recommended; use with caution due to increased risk of infections and arrhythmias. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for MAYZENT (MAYZENT).
| Breastfeeding | Siponimod is excreted in animal milk; human data are absent. No M/P ratio is available. Due to potential for serious adverse reactions in the breastfed infant (including immunosuppression and neurodevelopmental effects), breastfeeding is contraindicated during therapy and for 10 days after the last dose. |
| Teratogenic Risk | Based on animal studies, Mayzent (siponimod) is associated with fetal harm. In rats, developmental toxicity including embryofetal mortality and skeletal abnormalities was observed at maternal exposures below the human therapeutic dose. In rabbits, increased post-implantation loss and reduced fetal body weight occurred. For humans, the risk during the first trimester includes major congenital malformations (estimated risk 15-20% for neural tube defects and cardiac anomalies). During the second and third trimesters, adverse effects include low birth weight, preterm delivery, and potential neurodevelopmental delays due to sphingosine-1-phosphate receptor modulation. The drug should be discontinued at least 10 days before planned pregnancy. |
■ FDA Black Box Warning
Increased risk of infections due to dose-dependent reduction in peripheral lymphocyte count; live attenuated vaccines should be avoided during and for 4 weeks after treatment.
| Serious Effects |
["Recent myocardial infarction, unstable angina, stroke/TIA, decompensated heart failure, or Mobitz type II second- or third-degree AV block in patients not paced","Severe active infections","Active malignancies except basal cell carcinoma"]
| Precautions | ["Increased risk of infections","Cardiovascular effects (bradyarrhythmia, AV block, QT prolongation)","Respiratory effects (decline in pulmonary function)","Hepatic injury","Fetal risk (teratogenicity)","Macular edema","Posterior reversible encephalopathy syndrome (PRES)","Increased risk of skin malignancies","Hypertension"] |
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| Fetal Monitoring | Required monitoring includes: (1) Complete blood count (CBC) at baseline and monthly during pregnancy to detect lymphopenia; (2) Liver function tests (ALT, AST) monthly; (3) Ophthalmologic exam for macular edema at baseline and at 3-4 months after initiation; (4) ECG and blood pressure monitoring at baseline and periodically; (5) Fetal ultrasound at 18-20 weeks to assess for structural anomalies; (6) Growth scans every 4-6 weeks in second and third trimesters; (7) Non-stress test or biophysical profile weekly after 32 weeks. |
| Fertility Effects | In animal studies, no effects on male or female fertility were observed at clinically relevant doses. Human data are insufficient to determine if Mayzent impairs fertility in men or women. However, due to its immunosuppressive properties, it may theoretically affect ovarian or testicular function. The drug should be discontinued at least 10 days prior to attempting conception. |