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

Stem definitionDrug idCAS RN
2612 62989-33-7

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • sapropterin hydrochloride
  • tetrahydrobiopterin
  • sapropterin
  • sapropterin dihydrochloride
  • kuvan
  • sapropterin HCl
  • Molecular weight: 241.25
  • Formula: C9H15N5O3
  • CLOGP: -1.17
  • 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:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 1 Hosey CM, Chan R, Benet LZ

Approvals:

DateAgencyCompanyOrphan
Dec. 2, 2008 EMA
Dec. 13, 2007 FDA BIOMARIN PHARM

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Amino acid level increased 360.49 46.15 45 945 258 53347818
Maternal exposure during pregnancy 226.38 46.15 90 900 155549 53192527
Abortion spontaneous 53.56 46.15 23 967 46612 53301464
Amino acid level decreased 46.55 46.15 6 984 45 53348031

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Amino acid level increased 172.23 42.76 24 521 388 32512593
Amino acid level decreased 72.39 42.76 9 536 55 32512926

Pharmacologic Action:

SourceCodeDescription
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 Nutritional supplement
CHEBI has role CHEBI:77746 H. sapiens metabolites
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 (View source of the data)

DiseaseRelationSNOMED_IDDOID
Classical phenylketonuria indication 7573000
Neutropenic disorder contraindication 303011007 DOID:1227

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 11.23 acidic
pKa2 5.42 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent 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:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Phenylalanine-4-hydroxylase Enzyme ACTIVATOR Ki 5.40 IUPHAR CHEMBL
Nitric oxide synthase, brain Enzyme Kd 5.95 CHEMBL

External reference:

IDSource
4027166 VUID
N0000176128 NUI
D01798 KEGG_DRUG
69056-38-8 SECONDARY_CAS_RN
4027166 VANDF
4027167 VANDF
C0048897 UMLSCUI
CHEBI:59560 CHEBI
BH4 PDB_CHEM_ID
H4B PDB_CHEM_ID
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:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
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