siponimod 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |
| Stem definition | Drug id | CAS RN |
|---|---|---|
| 5326 | 1230487-00-9 |
Description:
| Molecule | Description |
|---|---|
|
Synonyms:
|
Siponimod is a sphingosine-1-phosphate (S1P) receptor modulator. Siponimod binds with high affinity to S1P receptors 1 and 5. Siponimod blocks the capacity of lymphocytes to egress from lymph nodes, reducing the number of lymphocytes in peripheral blood. The mechanism by which siponimod exerts therapeutic effects in multiple sclerosis is unknown, but may involve reduction of lymphocyte migration into the central nervous system.
Legend: OFP - off patent OFM - off market ONP - on patent |
Drug dosage:
None
ADMET properties:
None
Approvals:
| Date | Agency | Company | Orphan |
|---|---|---|---|
| Jan. 13, 2020 | EMA | Novartis Europharm Limited | |
| March 26, 2019 | FDA | NOVARTIS PHARMS CORP | |
| June 29, 2020 | PMDA | Novartis Pharma K.K. |
FDA Adverse Event Reporting System (Female)
| MedDRA adverse event term | Likelihood ratio | Likelihood ratio threshold | Patients taking drug having adverse event | Patients taking drug not having adverse event | Patients not taking drug having adverse event | Patients not taking drug not having adverse event |
|---|---|---|---|---|---|---|
| Lymphocyte count decreased | 223.53 | 29.03 | 78 | 3171 | 26229 | 50575646 |
| Multiple sclerosis relapse | 169.66 | 29.03 | 73 | 3176 | 42891 | 50558984 |
| Lymphopenia | 104.99 | 29.03 | 39 | 3210 | 15582 | 50586293 |
| Gait disturbance | 89.23 | 29.03 | 75 | 3174 | 149930 | 50451945 |
| Expanded disability status scale score increased | 75.36 | 29.03 | 14 | 3235 | 356 | 50601519 |
| Headache | 58.76 | 29.03 | 111 | 3138 | 506424 | 50095451 |
| Basal cell carcinoma | 55.57 | 29.03 | 28 | 3221 | 23328 | 50578547 |
| Multiple sclerosis | 44.19 | 29.03 | 23 | 3226 | 20470 | 50581405 |
| Fatigue | 43.86 | 29.03 | 121 | 3128 | 707480 | 49894395 |
| Dizziness | 42.61 | 29.03 | 78 | 3171 | 346291 | 50255584 |
| Balance disorder | 41.22 | 29.03 | 35 | 3214 | 70555 | 50531320 |
| Vision blurred | 39.91 | 29.03 | 36 | 3213 | 78611 | 50523264 |
| White blood cell count decreased | 38.07 | 29.03 | 42 | 3207 | 116680 | 50485195 |
| Product dose omission issue | 35.68 | 29.03 | 51 | 3198 | 183787 | 50418088 |
| Feeling abnormal | 35.58 | 29.03 | 42 | 3207 | 125450 | 50476425 |
| COVID-19 | 35.45 | 29.03 | 27 | 3222 | 46635 | 50555240 |
| Heart rate decreased | 34.25 | 29.03 | 24 | 3225 | 36473 | 50565402 |
| Visual impairment | 30.27 | 29.03 | 29 | 3220 | 68246 | 50533629 |
| Urinary tract infection | 29.43 | 29.03 | 52 | 3197 | 223968 | 50377907 |
| Drug titration error | 29.35 | 29.03 | 7 | 3242 | 603 | 50601272 |
FDA Adverse Event Reporting System (Male)
| MedDRA adverse event term | Likelihood ratio | Likelihood ratio threshold | Patients taking drug having adverse event | Patients taking drug not having adverse event | Patients not taking drug having adverse event | Patients not taking drug not having adverse event |
|---|---|---|---|---|---|---|
| Multiple sclerosis relapse | 116.02 | 40.02 | 34 | 1064 | 11385 | 29562044 |
| Lymphocyte count decreased | 47.50 | 40.02 | 20 | 1078 | 19251 | 29554178 |
| Lymphopenia | 43.49 | 40.02 | 17 | 1081 | 13516 | 29559913 |
FDA Adverse Event Reporting System (Geriatric)
| MedDRA adverse event term | Likelihood ratio | Likelihood ratio threshold | Patients taking drug having adverse event | Patients taking drug not having adverse event | Patients not taking drug having adverse event | Patients not taking drug not having adverse event |
|---|---|---|---|---|---|---|
| Lymphocyte count decreased | 143.55 | 35.36 | 57 | 2732 | 40642 | 64455301 |
| Basal cell carcinoma | 111.50 | 35.36 | 44 | 2745 | 30794 | 64465149 |
| Multiple sclerosis relapse | 92.87 | 35.36 | 42 | 2747 | 41093 | 64454850 |
| Lymphopenia | 80.25 | 35.36 | 33 | 2756 | 25624 | 64470319 |
| Gait disturbance | 68.98 | 35.36 | 58 | 2731 | 172097 | 64323846 |
| Balance disorder | 62.29 | 35.36 | 41 | 2748 | 83885 | 64412058 |
| Fatigue | 59.27 | 35.36 | 111 | 2678 | 748619 | 63747324 |
| Headache | 54.15 | 35.36 | 88 | 2701 | 529379 | 63966564 |
| Multiple sclerosis | 48.02 | 35.36 | 21 | 2768 | 18920 | 64477023 |
| Expanded disability status scale score increased | 45.80 | 35.36 | 9 | 2780 | 465 | 64495478 |
| Urinary tract infection | 43.99 | 35.36 | 52 | 2737 | 231544 | 64264399 |
| Movement disorder | 41.93 | 35.36 | 20 | 2769 | 21980 | 64473963 |
| Dizziness | 37.89 | 35.36 | 67 | 2722 | 430096 | 64065847 |
| Central nervous system lesion | 36.20 | 35.36 | 15 | 2774 | 11834 | 64484109 |
FDA Adverse Event Reporting System (Pediatric)
None
Pharmacologic Action:
| Source | Code | Description |
|---|---|---|
| ATC | L04AA42 | ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS IMMUNOSUPPRESSANTS IMMUNOSUPPRESSANTS Selective immunosuppressants |
| MeSH PA | D007155 | Immunologic Factors |
| MeSH PA | D007166 | Immunosuppressive Agents |
| MeSH PA | D000081243 | Sphingosine 1 Phosphate Receptor Modulators |
Drug Use | Suggest Off label Use Form| |View source of the data|
| Disease | Relation | SNOMED_ID | DOID |
|---|---|---|---|
| Relapsing remitting multiple sclerosis | indication | 426373005 | DOID:2378 |
| Sick sinus syndrome | contraindication | 36083008 | DOID:13884 |
| Atrioventricular block | contraindication | 233917008 | DOID:0050820 |
🐶 Veterinary Drug Use
None
🐶 Veterinary products
None
Acid dissociation constants calculated using MoKa v3.0.0
| Dissociation level | Dissociation constant | Type (acidic/basic) |
|---|---|---|
| pKa1 | 3.28 | acidic |
| pKa2 | 7.69 | Basic |
Orange Book patent data (new drug applications)
| Formulation strength | Trade name | Applicant | Application number | Approval date | Type | Dose form | Route | Patent number | Patent expiration date | Patent use |
|---|---|---|---|---|---|---|---|---|---|---|
| EQ 0.25MG BASE | MAYZENT | NOVARTIS | N209884 | March 26, 2019 | RX | TABLET | ORAL | 8492441 | Nov. 30, 2030 | A METHOD OF TREATING MULTIPLE SCLEROSIS BY ADMINISTERING SIPONIMOD USING A TITRATION SCHEME TO REACH A MAINTENANCE DOSE |
| EQ 1MG BASE | MAYZENT | NOVARTIS | N209884 | Aug. 24, 2021 | RX | TABLET | ORAL | 8492441 | Nov. 30, 2030 | A METHOD OF TREATING MULTIPLE SCLEROSIS BY ADMINISTERING SIPONIMOD USING A TITRATION SCHEME TO REACH A MAINTENANCE DOSE |
| EQ 2MG BASE | MAYZENT | NOVARTIS | N209884 | March 26, 2019 | RX | TABLET | ORAL | 8492441 | Nov. 30, 2030 | A METHOD OF TREATING MULTIPLE SCLEROSIS BY ADMINISTERING SIPONIMOD USING A TITRATION SCHEME TO REACH A MAINTENANCE DOSE |
Orange Book exclusivity data (new drug applications)
| Formulation strength | Trade name | Applicant | Application number | Approval date | Type | Dose form | Route | Exclusivity date | Description |
|---|---|---|---|---|---|---|---|---|---|
| EQ 0.25MG BASE | MAYZENT | NOVARTIS | N209884 | March 26, 2019 | RX | TABLET | ORAL | March 26, 2024 | NEW CHEMICAL ENTITY |
| EQ 1MG BASE | MAYZENT | NOVARTIS | N209884 | Aug. 24, 2021 | RX | TABLET | ORAL | March 26, 2024 | NEW CHEMICAL ENTITY |
| EQ 2MG BASE | MAYZENT | NOVARTIS | N209884 | March 26, 2019 | RX | TABLET | ORAL | March 26, 2024 | NEW CHEMICAL ENTITY |
| EQ 0.25MG BASE | MAYZENT | NOVARTIS | N209884 | March 26, 2019 | RX | TABLET | ORAL | March 1, 2025 | REVISIONS TO THE LABELING TO INCLUDE RESULTS FROM CLINICAL STUDY CBAF312A2130 |
| EQ 1MG BASE | MAYZENT | NOVARTIS | N209884 | Aug. 24, 2021 | RX | TABLET | ORAL | March 1, 2025 | REVISIONS TO THE LABELING TO INCLUDE RESULTS FROM CLINICAL STUDY CBAF312A2130 |
| EQ 2MG BASE | MAYZENT | NOVARTIS | N209884 | March 26, 2019 | RX | TABLET | ORAL | March 1, 2025 | REVISIONS TO THE LABELING TO INCLUDE RESULTS FROM CLINICAL STUDY CBAF312A2130 |
Bioactivity Summary:
| Target | Class | Pharos | UniProt | Action | Type | Activity value (-log[M]) | Mechanism action | Bioact source | MoA source |
|---|---|---|---|---|---|---|---|---|---|
| Sphingosine 1-phosphate receptor 1 | GPCR | MODULATOR | EC50 | 9.41 | SCIENTIFIC LITERATURE | SCIENTIFIC LITERATURE | |||
| Sphingosine 1-phosphate receptor 5 | GPCR | MODULATOR | EC50 | 9.01 | SCIENTIFIC LITERATURE | SCIENTIFIC LITERATURE | |||
| Sphingosine 1-phosphate receptor 4 | GPCR | MODULATOR | EC50 | 6.13 | SCIENTIFIC LITERATURE | ||||
| Sphingosine 1-phosphate receptor 3 | GPCR | MODULATOR | EC50 | 3 | SCIENTIFIC LITERATURE | ||||
| Sphingosine 1-phosphate receptor 2 | GPCR | MODULATOR | EC50 | 4 | SCIENTIFIC LITERATURE |
External reference:
| ID | Source |
|---|---|
| RR6P8L282I | UNII |
| C3657824 | UMLSCUI |
| J8C | PDB_CHEM_ID |
| CHEMBL2336071 | ChEMBL_ID |
| 44599207 | PUBCHEM_CID |
| DB12371 | DRUGBANK_ID |
| CHEMBL4298150 | ChEMBL_ID |
| D11072 | KEGG_DRUG |
| 9289 | IUPHAR_LIGAND_ID |
| 2121085 | RXNORM |
| 312581 | MMSL |
| 36617 | MMSL |
| d09219 | MMSL |
| 786997005 | SNOMEDCT_US |
| 787019001 | SNOMEDCT_US |
| 4038283 | VANDF |
| 017942 | NDDF |
| 017943 | NDDF |
| C578989 | MESH_SUPPLEMENTAL_RECORD_UI |
| 9491 | INN_ID |
| 1230487-00-9 | SECONDARY_CAS_RN |
Pharmaceutical products:
| Product | Category | Ingredients | NDC | Form | Quantity | Route | Marketing | Label |
|---|---|---|---|---|---|---|---|---|
| MAYZENT | HUMAN PRESCRIPTION DRUG LABEL | 1 | 0078-0979 | TABLET, FILM COATED | 0.25 mg | ORAL | NDA | 29 sections |
| MAYZENT | HUMAN PRESCRIPTION DRUG LABEL | 1 | 0078-0979 | TABLET, FILM COATED | 0.25 mg | ORAL | NDA | 29 sections |
| MAYZENT | HUMAN PRESCRIPTION DRUG LABEL | 1 | 0078-0986 | TABLET, FILM COATED | 2 mg | ORAL | NDA | 29 sections |
| MAYZENT | HUMAN PRESCRIPTION DRUG LABEL | 1 | 0078-0986 | TABLET, FILM COATED | 2 mg | ORAL | NDA | 29 sections |
| MAYZENT | HUMAN PRESCRIPTION DRUG LABEL | 1 | 0078-1014 | TABLET, FILM COATED | 1 mg | ORAL | NDA | 29 sections |