sapropterin 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definition	Drug id	CAS RN
pteridine derivatives	2612	62989-33-7

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: sapropterin hydrochloride tetrahydrobiopterin sapropterin sapropterin dihydrochloride kuvan sapropterin HCl	Molecular weight: 241.25 Formula: C9H15N5O3 CLOGP: -0.77 LIPINSKI: 1 HAC: 8 HDO: 6 TPSA: 132 ALOGS: -2.07 ROTB: 2 Status: OFP Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

sapropterin hydrochloride
tetrahydrobiopterin
sapropterin
sapropterin dihydrochloride
kuvan
sapropterin HCl

Molecular weight: 241.25
Formula: C9H15N5O3
CLOGP: -0.77
LIPINSKI: 1
HAC: 8
HDO: 6
TPSA: 132
ALOGS: -2.07
ROTB: 2

Status: OFP

Legend:
OFP - off patent
OFM - off market
ONP - on patent

Drug dosage:

None

ADMET properties:

Property	Value	Reference
BDDCS (Biopharmaceutical Drug Disposition Classification System)	1	Hosey CM, Chan R, Benet LZ
S (Water solubility)	2 mg/mL	Bocci G, Oprea TI, Benet LZ

Approvals:

Date	Agency	Company	Orphan
Dec. 2, 2008	EMA
Dec. 13, 2007	FDA	BIOMARIN PHARM

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
Amino acid level increased	354.90	44.17	45	975	351	63487651
Maternal exposure during pregnancy	205.33	44.17	89	931	219973	63268029
Abortion spontaneous	56.49	44.17	23	997	47172	63440830
Amino acid level decreased	47.78	44.17	6	1014	42	63487960
Anxiety	45.02	44.17	33	987	217508	63270494

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
Amino acid level increased	171.48	45.15	24	539	418	34955950
Amino acid level decreased	67.32	45.15	9	554	108	34956260

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
Maternal exposure during pregnancy	140.92	42.74	51	682	136487	79607168
Amino acid level increased	124.38	42.74	18	715	710	79742945
Amino acid level decreased	51.39	42.74	6	727	40	79743615
Abortion spontaneous	49.68	42.74	16	717	29491	79714164

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

Source	Code	Description
ATC	A16AX07	ALIMENTARY TRACT AND METABOLISM OTHER ALIMENTARY TRACT AND METABOLISM PRODUCTS OTHER ALIMENTARY TRACT AND METABOLISM PRODUCTS Various alimentary tract and metabolism products
CHEBI has role	CHEBI:23354	coenzymes
CHEBI has role	CHEBI:26348	prosthetic groups
CHEBI has role	CHEBI:50733	Dietary Supplement
CHEBI has role	CHEBI:77746	Homo sapiens metabolite
FDA MoA	N0000185503	P-Glycoprotein Inhibitors
FDA MoA	N0000190113	Breast Cancer Resistance Protein Inhibitors
FDA MoA	N0000190482	Phenylalanine Hydroxylase Activators
FDA EPC	N0000190483	Phenylalanine Hydroxylase Activator
CHEBI has role	CHEBI:33295	diagnostic aid
CHEBI has role	CHEBI:23357	cofactor

Drug Use | Suggest Off label Use Form| |View source of the data|

Disease	Relation	SNOMED_ID	DOID
Classical phenylketonuria	indication	7573000
Tetrahydrobiopterin deficiency	indication	68724006
Neutropenic disorder	contraindication	303011007	DOID:1227

🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	11.23	acidic
pKa2	5.42	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
100MG	KUVAN	BIOMARIN PHARM	N022181	Dec. 13, 2007	RX	TABLET	ORAL	7566714	Nov. 17, 2024	FOR REDUCING BLOOD PHENYLALANINE LEVELS IN A HUMAN SUFFERING FROM HYPERPHENYLALANINEMIA
100MG	KUVAN	BIOMARIN PHARM	N022181	Dec. 13, 2007	RX	TABLET	ORAL	7612073	Nov. 17, 2024	TO REDUCE BLOOD PHENYLALANINE LEVELS IN PATIENTS WITH HYPERPHENYLALANINEMIA DUE TO TETRA HYDROBIOPTERIN RESPONSIVE PHENYLKETONURIA. KUVAN SHOULD BE TAKEN ORALLY WITH FOOD TO INCREASE ABSORPTION
100MG	KUVAN	BIOMARIN PHARM	N022181	Dec. 13, 2007	RX	TABLET	ORAL	8067416	Nov. 17, 2024	FOR REDUCING BLOOD PHENYLALANINE LEVELS IN A HUMAN SUFFERING FROM HYPERPHENYLALANINEMIA
100MG	KUVAN	BIOMARIN PHARM	N022181	Dec. 13, 2007	RX	TABLET	ORAL	9433624	Nov. 17, 2024	METHOD OF USE FOR REDUCING BLOOD PHENYLALANINE LEVELS IN A HUMAN SUFFERING FROM HYPERPHENYLALANINEMIA
100MG	KUVAN	BIOMARIN PHARM	N022181	Dec. 13, 2007	RX	TABLET	ORAL	RE43797	Nov. 17, 2024	TO REDUCE BLOOD PHENYLALANINE (PHE) LEVELS IN PATIENTS WITH HYPERPHENYLALANINEMIA (HPA)
100MG/PACKET	KUVAN	BIOMARIN PHARM	N205065	Dec. 19, 2013	RX	POWDER	ORAL	7566714	Nov. 17, 2024	METHOD OF USE FOR REDUCING BLOOD PHENYLALANINE LEVELS IN A HUMAN SUFFERING FROM HYPERPHENYLALANINEMIA
100MG/PACKET	KUVAN	BIOMARIN PHARM	N205065	Dec. 19, 2013	RX	POWDER	ORAL	7612073	Nov. 17, 2024	TO REDUCE BLOOD PHENYLALANINE LEVELS IN PATIENTS WITH HYPERPHENYLALANINEMIA DUE TO TETRA HYDROBIOPTERIN RESPONSIVE PHENYLKETONURIA. KUVAN SHOULD BE TAKEN ORALLY WITH FOOD TO INCREASE ABSORPTION
100MG/PACKET	KUVAN	BIOMARIN PHARM	N205065	Dec. 19, 2013	RX	POWDER	ORAL	8067416	Nov. 17, 2024	METHOD OF USE FOR REDUCING BLOOD PHENYLALANINE LEVELS IN A HUMAN SUFFERING FROM HYPERPHENYLALANINEMIA
100MG/PACKET	KUVAN	BIOMARIN PHARM	N205065	Dec. 19, 2013	RX	POWDER	ORAL	9433624	Nov. 17, 2024	METHOD OF USE FOR REDUCING BLOOD PHENYLALANINE LEVELS IN A HUMAN SUFFERING FROM HYPERPHENYLALANINEMIA
100MG/PACKET	KUVAN	BIOMARIN PHARM	N205065	Dec. 19, 2013	RX	POWDER	ORAL	RE43797	Nov. 17, 2024	KUVAN IS INDICATED TO REDUCE BLOOD PHENYLALANINE LEVELS IN PATIENTS WITH HYPERPHENYLALANINEMIA
500MG/PACKET	KUVAN	BIOMARIN PHARM	N205065	Oct. 27, 2015	RX	POWDER	ORAL	7566714	Nov. 17, 2024	METHOD OF USE FOR REDUCING BLOOD PHENYLALANINE LEVELS IN A HUMAN SUFFERING FROM HYPERPHENYLALANINEMIA
500MG/PACKET	KUVAN	BIOMARIN PHARM	N205065	Oct. 27, 2015	RX	POWDER	ORAL	7612073	Nov. 17, 2024	TO REDUCE BLOOD PHENYLALANINE LEVELS IN PATIENTS WITH HYPERPHENYLALANINEMIA DUE TO TETRA HYDROBIOPTERIN RESPONSIVE PHENYLKETONURIA. KUVAN SHOULD BE TAKEN ORALLY WITH FOOD TO INCREASE ABSORPTION
500MG/PACKET	KUVAN	BIOMARIN PHARM	N205065	Oct. 27, 2015	RX	POWDER	ORAL	8067416	Nov. 17, 2024	METHOD OF USE FOR REDUCING BLOOD PHENYLALANINE LEVELS IN A HUMAN SUFFERING FROM HYPERPHENYLALANINEMIA
500MG/PACKET	KUVAN	BIOMARIN PHARM	N205065	Oct. 27, 2015	RX	POWDER	ORAL	9433624	Nov. 17, 2024	METHOD OF USE FOR REDUCING BLOOD PHENYLALANINE LEVELS IN A HUMAN SUFFERING FROM HYPERPHENYLALANINEMIA
500MG/PACKET	KUVAN	BIOMARIN PHARM	N205065	Oct. 27, 2015	RX	POWDER	ORAL	RE43797	Nov. 17, 2024	KUVAN IS INDICATED TO REDUCE BLOOD PHENYLALANINE LEVELS IN PATIENTS WITH HYPERPHENYLALANINEMIA

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Mechanism action	Bioact source	MoA source
Phenylalanine-4-hydroxylase	Enzyme	P00439	PH4H_HUMAN	ACTIVATOR	Ki	5.40		IUPHAR	CHEMBL
Nitric oxide synthase, brain	Enzyme	P29475	NOS1_HUMAN		Kd	5.95		CHEMBL

External reference:

ID	Source
4027166	VUID
N0000176128	NUI
D01798	KEGG_DRUG
69056-38-8	SECONDARY_CAS_RN
4027166	VANDF
4027167	VANDF
C0048897	UMLSCUI
CHEBI:59560	CHEBI
THB	PDB_CHEM_ID
CHEMBL1201774	ChEMBL_ID
CHEMBL1201775	ChEMBL_ID
DB00360	DRUGBANK_ID
C003402	MESH_SUPPLEMENTAL_RECORD_UI
5276	IUPHAR_LIGAND_ID
6553	INN_ID
EGX657432I	UNII
135398654	PUBCHEM_CID
751628	RXNORM
129793	MMSL
24913	MMSL
339312	MMSL
d07068	MMSL
007099	NDDF
012473	NDDF
012474	NDDF
432857000	SNOMEDCT_US
432859002	SNOMEDCT_US
434239009	SNOMEDCT_US

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
sapropterin dihydrochloride	HUMAN PRESCRIPTION DRUG LABEL	1	31722-045	TABLET	100 mg	ORAL	ANDA	26 sections
Sapropterin dihydrochloride	HUMAN PRESCRIPTION DRUG LABEL	1	31722-047	POWDER, FOR SOLUTION	100 mg	ORAL	ANDA	26 sections
Sapropterin dihydrochloride	HUMAN PRESCRIPTION DRUG LABEL	1	31722-048	POWDER, FOR SOLUTION	500 mg	ORAL	ANDA	26 sections
JAVYGTOR	HUMAN PRESCRIPTION DRUG LABEL	1	43598-096	TABLET	100 mg	ORAL	ANDA	25 sections
JAVYGTOR	HUMAN PRESCRIPTION DRUG LABEL	1	43598-097	POWDER, FOR SOLUTION	100 mg	ORAL	ANDA	26 sections
Sapropterin Dihydrochloride	HUMAN PRESCRIPTION DRUG LABEL	1	43598-162	POWDER, FOR SOLUTION	500 mg	ORAL	ANDA	25 sections
Sapropterin Dihydrochloride	HUMAN PRESCRIPTION DRUG LABEL	1	43598-162	POWDER, FOR SOLUTION	500 mg	ORAL	ANDA	25 sections
Sapropterin Dihydrochloride	HUMAN PRESCRIPTION DRUG LABEL	1	43598-477	POWDER, FOR SOLUTION	100 mg	ORAL	ANDA	26 sections
Sapropterin Dihydrochloride	HUMAN PRESCRIPTION DRUG LABEL	1	43598-749	TABLET	100 mg	ORAL	NDA	26 sections
sapropterin dihydrochloride	HUMAN PRESCRIPTION DRUG LABEL	1	49884-720	TABLET	100 mg	ORAL	ANDA	25 sections
SAPROPTERIN DIHYDROCHLORIDE	HUMAN PRESCRIPTION DRUG LABEL	1	49884-873	POWDER, FOR SOLUTION	500 mg	ORAL	ANDA	27 sections
SAPROPTERIN DIHYDROCHLORIDE	HUMAN PRESCRIPTION DRUG LABEL	1	49884-948	POWDER, FOR SOLUTION	100 mg	ORAL	ANDA	28 sections
Kuvan	HUMAN PRESCRIPTION DRUG LABEL	1	68135-300	TABLET	100 mg	ORAL	NDA	25 sections
Kuvan	HUMAN PRESCRIPTION DRUG LABEL	1	68135-301	POWDER, FOR SOLUTION	100 mg	ORAL	NDA	25 sections
Kuvan	HUMAN PRESCRIPTION DRUG LABEL	1	68135-482	POWDER, FOR SOLUTION	500 mg	ORAL	NDA	25 sections