pitolisant 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |
| Stem definition | Drug id | CAS RN |
|---|---|---|
| histamine H3 receptor antagonists, inverse agonists | 5048 | 362665-56-3 |
Description:
| Molecule | Description |
|---|---|
|
Synonyms:
|
Pitolisant is a potent, orally active histamine H3-receptor antagonist/inverse agonist which, via its blockade of histamine auto-receptors enhances the activity of brain histaminergic neurons, a major arousal system with widespread projections to the whole brain. Pitolisant also modulates various neurotransmitter systems, increasing acetylcholine, noradrenaline and dopamine release in the brain.
Legend: OFP - off patent OFM - off market ONP - on patent |
Drug dosage:
| Dose | Unit | Route |
|---|---|---|
| 18 | mg | O |
ADMET properties:
| Property | Value | Reference |
|---|---|---|
| S (Water solubility) | 66 mg/mL | Bocci G, Oprea TI, Benet LZ |
| BDDCS (Biopharmaceutical Drug Disposition Classification System) | 1 | Bocci G, Oprea TI, Benet LZ |
Approvals:
| Date | Agency | Company | Orphan |
|---|---|---|---|
| March 31, 2016 | EMA | Bioprojet Pharma | |
| Aug. 14, 2019 | FDA | HARMONY |
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 |
|---|---|---|---|---|---|---|
| Splenic infarction | 99.74 | 31.67 | 18 | 930 | 1741 | 63486333 |
| Product administration interrupted | 76.07 | 31.67 | 17 | 931 | 4819 | 63483255 |
| Anxiety | 61.87 | 31.67 | 39 | 909 | 217502 | 63270572 |
| Surgery | 45.94 | 31.67 | 18 | 930 | 35894 | 63452180 |
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 |
|---|---|---|---|---|---|---|
| Product administration interrupted | 57.19 | 54.78 | 10 | 228 | 1805 | 34954888 |
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 |
|---|---|---|---|---|---|---|
| Splenic infarction | 101.48 | 41.33 | 18 | 505 | 3646 | 79740219 |
| Product administration interrupted | 55.85 | 41.33 | 11 | 512 | 3888 | 79739977 |
FDA Adverse Event Reporting System (Pediatric)
None
Pharmacologic Action:
| Source | Code | Description |
|---|---|---|
| ATC | N07XX11 | NERVOUS SYSTEM OTHER NERVOUS SYSTEM DRUGS OTHER NERVOUS SYSTEM DRUGS Other nervous system drugs |
Drug Use | Suggest Off label Use Form| |View source of the data|
| Disease | Relation | SNOMED_ID | DOID |
|---|---|---|---|
| Narcolepsy | indication | 60380001 | DOID:8986 |
🐶 Veterinary Drug Use
None
🐶 Veterinary products
None
Acid dissociation constants calculated using MoKa v3.0.0
| Dissociation level | Dissociation constant | Type (acidic/basic) |
|---|---|---|
| pKa1 | 9.59 | 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 17.8MG BASE | WAKIX | HARMONY | N211150 | Aug. 14, 2019 | RX | TABLET | ORAL | 8354430 | Feb. 6, 2026 | METHOD OF TREATING CATAPLEXY IN PATIENTS WITH NARCOLEPSY |
| EQ 17.8MG BASE | WAKIX | HARMONY | N211150 | Aug. 14, 2019 | RX | TABLET | ORAL | 8354430 | Feb. 6, 2026 | METHOD OF TREATING EXCESSIVE DAYTIME SLEEPINESS IN PATIENTS WITH NARCOLEPSY |
| EQ 4.45MG BASE | WAKIX | HARMONY | N211150 | Aug. 14, 2019 | RX | TABLET | ORAL | 8354430 | Feb. 6, 2026 | METHOD OF TREATING CATAPLEXY IN PATIENTS WITH NARCOLEPSY |
| EQ 4.45MG BASE | WAKIX | HARMONY | N211150 | Aug. 14, 2019 | RX | TABLET | ORAL | 8354430 | Feb. 6, 2026 | METHOD OF TREATING EXCESSIVE DAYTIME SLEEPINESS IN PATIENTS WITH NARCOLEPSY |
| EQ 17.8MG BASE | WAKIX | HARMONY | N211150 | Aug. 14, 2019 | RX | TABLET | ORAL | 8486947 | Sept. 26, 2029 | METHOD OF TREATING CATAPLEXY IN PATIENTS WITH NARCOLEPSY |
| EQ 17.8MG BASE | WAKIX | HARMONY | N211150 | Aug. 14, 2019 | RX | TABLET | ORAL | 8486947 | Sept. 26, 2029 | METHOD OF TREATING EXCESSIVE DAYTIME SLEEPINESS IN PATIENTS WITH NARCOLEPSY |
| EQ 4.45MG BASE | WAKIX | HARMONY | N211150 | Aug. 14, 2019 | RX | TABLET | ORAL | 8486947 | Sept. 26, 2029 | METHOD OF TREATING CATAPLEXY IN PATIENTS WITH NARCOLEPSY |
| EQ 4.45MG BASE | WAKIX | HARMONY | N211150 | Aug. 14, 2019 | RX | TABLET | ORAL | 8486947 | Sept. 26, 2029 | METHOD OF TREATING EXCESSIVE DAYTIME SLEEPINESS IN PATIENTS WITH NARCOLEPSY |
Orange Book exclusivity data (new drug applications)
| Formulation strength | Trade name | Applicant | Application number | Approval date | Type | Dose form | Route | Exclusivity date | Description |
|---|---|---|---|---|---|---|---|---|---|
| EQ 17.8MG BASE | WAKIX | HARMONY | N211150 | Aug. 14, 2019 | RX | TABLET | ORAL | Oct. 13, 2023 | TREATMENT OF CATAPLEXY IN ADULT PATIENTS WITH NACROLEPSY |
| EQ 4.45MG BASE | WAKIX | HARMONY | N211150 | Aug. 14, 2019 | RX | TABLET | ORAL | Oct. 13, 2023 | TREATMENT OF CATAPLEXY IN ADULT PATIENTS WITH NACROLEPSY |
| EQ 17.8MG BASE | WAKIX | HARMONY | N211150 | Aug. 14, 2019 | RX | TABLET | ORAL | Aug. 14, 2024 | NEW CHEMICAL ENTITY |
| EQ 4.45MG BASE | WAKIX | HARMONY | N211150 | Aug. 14, 2019 | RX | TABLET | ORAL | Aug. 14, 2024 | NEW CHEMICAL ENTITY |
| EQ 17.8MG BASE | WAKIX | HARMONY | N211150 | Aug. 14, 2019 | RX | TABLET | ORAL | Aug. 14, 2026 | INDICATED FOR THE TREATMENT OF EXCESSIVE DAYTIME SLEEPINESS (EDS) IN ADULT PATIENTS WITH NARCOLEPSY |
| EQ 4.45MG BASE | WAKIX | HARMONY | N211150 | Aug. 14, 2019 | RX | TABLET | ORAL | Aug. 14, 2026 | INDICATED FOR THE TREATMENT OF EXCESSIVE DAYTIME SLEEPINESS (EDS) IN ADULT PATIENTS WITH NARCOLEPSY |
| EQ 17.8MG BASE | WAKIX | HARMONY | N211150 | Aug. 14, 2019 | RX | TABLET | ORAL | Oct. 13, 2027 | TREATMENT OF CATAPLEXY IN ADULT PATIENTS WITH NACROLEPSY |
| EQ 4.45MG BASE | WAKIX | HARMONY | N211150 | Aug. 14, 2019 | RX | TABLET | ORAL | Oct. 13, 2027 | TREATMENT OF CATAPLEXY IN ADULT PATIENTS WITH NACROLEPSY |
Bioactivity Summary:
| Target | Class | Pharos | UniProt | Action | Type | Activity value (-log[M]) | Mechanism action | Bioact source | MoA source |
|---|---|---|---|---|---|---|---|---|---|
| Histamine H3 receptor | GPCR | INVERSE AGONIST | Ki | 9.80 | SCIENTIFIC LITERATURE | SCIENTIFIC LITERATURE | |||
| Histamine H1 receptor | GPCR | Ki | 5.94 | CHEMBL | |||||
| Histamine H2 receptor | GPCR | ANTAGONIST | Ki | 4.96 | IUPHAR | ||||
| Potassium voltage-gated channel subfamily H member 2 | Ion channel | IC50 | 5.77 | CHEMBL | |||||
| Histamine H3 receptor | GPCR | Ki | 7.77 | CHEMBL | |||||
| Histamine H3 receptor | GPCR | Ki | 7.85 | CHEMBL | |||||
| Histamine H3 receptor | GPCR | Ki | 9.80 | CHEMBL | |||||
| Cholinesterase | Enzyme | IC50 | 5.08 | CHEMBL |
External reference:
| ID | Source |
|---|---|
| 4BC83L4PIY | UNII |
| 903576-44-3 | SECONDARY_CAS_RN |
| 4038743 | VANDF |
| 4038744 | VANDF |
| C3529928 | UMLSCUI |
| CHEBI:134709 | CHEBI |
| CHEMBL462605 | ChEMBL_ID |
| 9948102 | PUBCHEM_CID |
| DB11642 | DRUGBANK_ID |
| CHEMBL4164059 | ChEMBL_ID |
| 8952 | INN_ID |
| C516975 | MESH_SUPPLEMENTAL_RECORD_UI |
| 8924 | IUPHAR_LIGAND_ID |
| 2197878 | RXNORM |
| 247019 | MMSL |
| 32128 | MMSL |
| d08498 | MMSL |
| 017799 | NDDF |
| 017884 | NDDF |
| 421000220103 | SNOMEDCT_US |
| 716308007 | SNOMEDCT_US |
| 789360005 | SNOMEDCT_US |
Pharmaceutical products:
| Product | Category | Ingredients | NDC | Form | Quantity | Route | Marketing | Label |
|---|---|---|---|---|---|---|---|---|
| Wakix | HUMAN PRESCRIPTION DRUG LABEL | 1 | 72028-045 | TABLET, FILM COATED | 4.45 mg | ORAL | NDA | 29 sections |
| Wakix | HUMAN PRESCRIPTION DRUG LABEL | 1 | 72028-045 | TABLET, FILM COATED | 4.45 mg | ORAL | NDA | 29 sections |
| Wakix | HUMAN PRESCRIPTION DRUG LABEL | 1 | 72028-045 | TABLET, FILM COATED | 4.45 mg | ORAL | NDA | 29 sections |
| Wakix | HUMAN PRESCRIPTION DRUG LABEL | 1 | 72028-178 | TABLET, FILM COATED | 17.80 mg | ORAL | NDA | 29 sections |
| Wakix | HUMAN PRESCRIPTION DRUG LABEL | 1 | 72028-178 | TABLET, FILM COATED | 17.80 mg | ORAL | NDA | 29 sections |
| Wakix | HUMAN PRESCRIPTION DRUG LABEL | 1 | 72028-178 | TABLET, FILM COATED | 17.80 mg | ORAL | NDA | 29 sections |