milnacipran Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |
| Stem definition | Drug id | CAS RN |
|---|---|---|
| 1808 | 92623-85-3 |
Description:
| Molecule | Description |
|---|---|
|
Synonyms:
|
A cyclopropanecarboxamide serotonin and norepinephrine reuptake inhibitor (SNRI) that is used in the treatment of FIBROMYALGIA.
Legend: OFP - off patent OFM - off market ONP - on patent |
Drug dosage:
| Dose | Unit | Route |
|---|---|---|
| 0.10 | g | O |
ADMET properties:
| Property | Value | Reference |
|---|---|---|
| BDDCS (Biopharmaceutical Drug Disposition Classification System) | 3 | Benet LZ, Broccatelli F, Oprea TI |
| EoM (Fraction excreted unchanged in urine) | 55 % | Benet LZ, Broccatelli F, Oprea TI |
| MRTD (Maximum Recommended Therapeutic Daily Dose) | 11.60 µM/kg/day | Contrera JF, Matthews EJ, Kruhlak NL, Benz RD |
| BA (Bioavailability) | 84 % | Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H |
| Vd (Volume of distribution) | 4.51 L/kg | Lombardo F, Berellini G, Obach RS |
| CL (Clearance) | 8.17 mL/min/kg | Lombardo F, Berellini G, Obach RS |
| fu (Fraction unbound in plasma) | 0.87 % | Lombardo F, Berellini G, Obach RS |
| t_half (Half-life) | 6.48 hours | Lombardo F, Berellini G, Obach RS |
Approvals:
| Date | Agency | Company | Orphan |
|---|---|---|---|
| Jan. 14, 2009 | FDA | CYPRESS BIOSCIENCE |
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 |
|---|---|---|---|---|---|---|
| Suicidal ideation | 134.84 | 17.59 | 88 | 6677 | 60423 | 53281878 |
| Serotonin syndrome | 108.13 | 17.59 | 57 | 6708 | 26349 | 53315952 |
| Drug hypersensitivity | 97.03 | 17.59 | 142 | 6623 | 265100 | 53077201 |
| Hyperhidrosis | 73.32 | 17.59 | 75 | 6690 | 96718 | 53245583 |
| Somatic delusion | 69.36 | 17.59 | 16 | 6749 | 596 | 53341705 |
| Nausea | 68.49 | 17.59 | 230 | 6535 | 755861 | 52586440 |
| Hot flush | 60.18 | 17.59 | 49 | 6716 | 47111 | 53295190 |
| Headache | 50.77 | 17.59 | 166 | 6599 | 536655 | 52805646 |
| Depression | 47.52 | 17.59 | 84 | 6681 | 182968 | 53159333 |
| Heart rate increased | 45.33 | 17.59 | 54 | 6711 | 82261 | 53260040 |
| Urine odour abnormal | 41.09 | 17.59 | 18 | 6747 | 5528 | 53336773 |
| Insomnia | 39.99 | 17.59 | 79 | 6686 | 186993 | 53155308 |
| Persistent genital arousal disorder | 39.69 | 17.59 | 9 | 6756 | 310 | 53341991 |
| Abnormal faeces | 37.81 | 17.59 | 16 | 6749 | 4518 | 53337783 |
| Blood pressure increased | 37.12 | 17.59 | 65 | 6700 | 140414 | 53201887 |
| Gastrointestinal motility disorder | 36.63 | 17.59 | 16 | 6749 | 4880 | 53337421 |
| Blood thyroid stimulating hormone normal | 34.66 | 17.59 | 7 | 6758 | 137 | 53342164 |
| Anger | 32.48 | 17.59 | 20 | 6745 | 12370 | 53329931 |
| Migraine | 32.09 | 17.59 | 45 | 6720 | 80372 | 53261929 |
| Chromaturia | 30.19 | 17.59 | 21 | 6744 | 15929 | 53326372 |
| Oral discomfort | 27.83 | 17.59 | 16 | 6749 | 8730 | 53333571 |
| Tremor | 26.71 | 17.59 | 53 | 6712 | 125683 | 53216618 |
| Lip swelling | 26.04 | 17.59 | 24 | 6741 | 27177 | 53315124 |
| Musculoskeletal discomfort | 25.92 | 17.59 | 19 | 6746 | 15641 | 53326660 |
| Homicidal ideation | 24.24 | 17.59 | 9 | 6756 | 1805 | 53340496 |
| Palpitations | 24.01 | 17.59 | 45 | 6720 | 102303 | 53239998 |
| Crying | 23.99 | 17.59 | 21 | 6744 | 22241 | 53320060 |
| Aphasia | 23.53 | 17.59 | 24 | 6741 | 30754 | 53311547 |
| Flushing | 23.10 | 17.59 | 36 | 6729 | 70564 | 53271737 |
| Irritability | 21.62 | 17.59 | 23 | 6742 | 30930 | 53311371 |
| Feeling abnormal | 19.65 | 17.59 | 49 | 6716 | 135252 | 53207049 |
| Fibromyalgia | 19.59 | 17.59 | 26 | 6739 | 44049 | 53298252 |
| Ear infection | 19.44 | 17.59 | 20 | 6745 | 25880 | 53316421 |
| Drug withdrawal syndrome | 18.13 | 17.59 | 20 | 6745 | 28002 | 53314299 |
| Suicide attempt | 18.11 | 17.59 | 29 | 6736 | 58139 | 53284162 |
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 |
|---|---|---|---|---|---|---|
| Urinary retention | 55.64 | 26.79 | 26 | 1059 | 35671 | 32476770 |
| Suicidal ideation | 48.03 | 26.79 | 24 | 1061 | 38059 | 32474382 |
| Agoraphobia | 39.59 | 26.79 | 7 | 1078 | 264 | 32512177 |
| Dysuria | 32.20 | 26.79 | 16 | 1069 | 24994 | 32487447 |
| Urinary hesitation | 29.14 | 26.79 | 8 | 1077 | 2333 | 32510108 |
| Neurosis | 29.07 | 26.79 | 5 | 1080 | 160 | 32512281 |
Pharmacologic Action:
| Source | Code | Description |
|---|---|---|
| ATC | N06AX17 | NERVOUS SYSTEM PSYCHOANALEPTICS ANTIDEPRESSANTS Other antidepressants |
| FDA MoA | N0000000102 | Norepinephrine Uptake Inhibitors |
| FDA MoA | N0000000109 | Serotonin Uptake Inhibitors |
| MeSH PA | D000700 | Analgesics |
| MeSH PA | D018712 | Analgesics, Non-Narcotic |
| MeSH PA | D002491 | Central Nervous System Agents |
| MeSH PA | D049990 | Membrane Transport Modulators |
| MeSH PA | D018377 | Neurotransmitter Agents |
| MeSH PA | D014179 | Neurotransmitter Uptake Inhibitors |
| MeSH PA | D018373 | Peripheral Nervous System Agents |
| MeSH PA | D018689 | Sensory System Agents |
| MeSH PA | D000068760 | Serotonin and Noradrenaline Reuptake Inhibitors |
| FDA EPC | N0000175749 | Serotonin and Norepinephrine Reuptake Inhibitor |
Drug Use (View source of the data)
| Disease | Relation | SNOMED_ID | DOID |
|---|---|---|---|
| Fibromyalgia | indication | 203082005 | DOID:631 |
| Tachyarrhythmia | contraindication | 6285003 | |
| Urinary tract obstruction | contraindication | 7163005 | DOID:5200 |
| Alcoholism | contraindication | 7200002 | |
| Hypertensive disorder | contraindication | 38341003 | DOID:10763 |
| Disorder of cardiovascular system | contraindication | 49601007 | DOID:1287 |
| Syndrome of inappropriate vasopressin secretion | contraindication | 55004003 | DOID:3401 |
| Acute nephropathy | contraindication | 58574008 | |
| Blood coagulation disorder | contraindication | 64779008 | DOID:1247 |
| Hyponatremia | contraindication | 89627008 | |
| Seizure disorder | contraindication | 128613002 | |
| Liver function tests abnormal | contraindication | 166603001 | |
| Mania | contraindication | 231494001 | |
| Hypomania | contraindication | 231496004 | |
| Disease of liver | contraindication | 235856003 | DOID:409 |
| Suicidal | contraindication | 267073005 | |
| Serotonin syndrome | contraindication | 371089000 | |
| Angle-closure glaucoma | contraindication | 392291006 | DOID:13550 |
Acid dissociation constants calculated using MoKa v3.0.0
| Dissociation level | Dissociation constant | Type (acidic/basic) |
|---|---|---|
| pKa1 | 10.64 | 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 | SAVELLA | ALLERGAN | N022256 | Jan. 14, 2009 | RX | TABLET | ORAL | 6602911 | Jan. 14, 2023 | MANAGEMENT OF FIBROMYALGIA (FM) |
| 12.5MG | SAVELLA | ALLERGAN | N022256 | Jan. 14, 2009 | RX | TABLET | ORAL | 6602911 | Jan. 14, 2023 | MANAGEMENT OF FIBROMYALGIA (FM) |
| 25MG | SAVELLA | ALLERGAN | N022256 | Jan. 14, 2009 | RX | TABLET | ORAL | 6602911 | Jan. 14, 2023 | MANAGEMENT OF FIBROMYALGIA (FM) |
| 50MG | SAVELLA | ALLERGAN | N022256 | Jan. 14, 2009 | RX | TABLET | ORAL | 6602911 | Jan. 14, 2023 | MANAGEMENT OF FIBROMYALGIA (FM) |
| 100MG | SAVELLA | ALLERGAN | N022256 | Jan. 14, 2009 | RX | TABLET | ORAL | 7994220 | Sept. 19, 2029 | MANAGEMENT OF FIBROMYALGIA |
| 12.5MG | SAVELLA | ALLERGAN | N022256 | Jan. 14, 2009 | RX | TABLET | ORAL | 7994220 | Sept. 19, 2029 | MANAGEMENT OF FIBROMYALGIA |
| 25MG | SAVELLA | ALLERGAN | N022256 | Jan. 14, 2009 | RX | TABLET | ORAL | 7994220 | Sept. 19, 2029 | MANAGEMENT OF FIBROMYALGIA |
| 50MG | SAVELLA | ALLERGAN | N022256 | Jan. 14, 2009 | RX | TABLET | ORAL | 7994220 | Sept. 19, 2029 | MANAGEMENT OF FIBROMYALGIA |
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 |
|---|---|---|---|---|---|---|---|---|---|
| Sodium-dependent serotonin transporter | Transporter | INHIBITOR | Ki | 7.29 | WOMBAT-PK | CHEMBL | |||
| Sodium-dependent noradrenaline transporter | Transporter | INHIBITOR | Ki | 7.60 | WOMBAT-PK | CHEMBL | |||
| Sodium-dependent dopamine transporter | Transporter | IC50 | 5.21 | CHEMBL | |||||
| Glutamate receptor ionotropic, NMDA 2A | Ion channel | IC50 | 5.20 | WOMBAT-PK | |||||
| Sodium-dependent serotonin transporter | Transporter | IC50 | 7.33 | CHEMBL | |||||
| Sodium-dependent dopamine transporter | Transporter | IC50 | 4.43 | CHEMBL | |||||
| Transporter | Transporter | IC50 | 7.52 | CHEMBL |
External reference:
| ID | Source |
|---|---|
| 4025253 | VUID |
| N0000179785 | NUI |
| D01107 | KEGG_DRUG |
| 101152-94-7 | SECONDARY_CAS_RN |
| 4025253 | VANDF |
| 4028372 | VANDF |
| C1533126 | UMLSCUI |
| CHEBI:135005 | CHEBI |
| CHEMBL252923 | ChEMBL_ID |
| CHEMBL259209 | ChEMBL_ID |
| DB04896 | DRUGBANK_ID |
| CHEMBL4297064 | ChEMBL_ID |
| D000078764 | MESH_DESCRIPTOR_UI |
| 5701 | INN_ID |
| 65833 | PUBCHEM_CID |
| 7436 | IUPHAR_LIGAND_ID |
| G56VK1HF36 | UNII |
| 30003 | RXNORM |
| 26139 | MMSL |
| d06635 | MMSL |
| 008263 | NDDF |
| 008264 | NDDF |
| 441641002 | SNOMEDCT_US |
| 442542004 | SNOMEDCT_US |
| 442642007 | SNOMEDCT_US |
| CHEMBL1237129 | ChEMBL_ID |
Pharmaceutical products:
| Product | Category | Ingredients | NDC | Form | Quantity | Route | Marketing | Label |
|---|---|---|---|---|---|---|---|---|
| Savella | HUMAN PRESCRIPTION DRUG LABEL | 1 | 0456-1510 | TABLET, FILM COATED | 100 mg | ORAL | NDA | 37 sections |
| Savella | HUMAN PRESCRIPTION DRUG LABEL | 1 | 0456-1512 | TABLET, FILM COATED | 12.50 mg | ORAL | NDA | 37 sections |
| Savella | HUMAN PRESCRIPTION DRUG LABEL | 1 | 0456-1525 | TABLET, FILM COATED | 25 mg | ORAL | NDA | 37 sections |
| Savella | HUMAN PRESCRIPTION DRUG LABEL | 1 | 0456-1550 | TABLET, FILM COATED | 50 mg | ORAL | NDA | 37 sections |
| SAVELLA | HUMAN PRESCRIPTION DRUG LABEL | 1 | 16590-845 | TABLET, FILM COATED | 25 mg | ORAL | NDA | 35 sections |
| SAVELLA | HUMAN PRESCRIPTION DRUG LABEL | 1 | 16590-846 | TABLET, FILM COATED | 50 mg | ORAL | NDA | 35 sections |
| SAVELLA | HUMAN PRESCRIPTION DRUG LABEL | 1 | 16590-847 | TABLET, FILM COATED | 100 mg | ORAL | NDA | 35 sections |
| Savella | HUMAN PRESCRIPTION DRUG LABEL | 1 | 21695-650 | TABLET, FILM COATED | 25 mg | ORAL | NDA | 34 sections |
| Savella | HUMAN PRESCRIPTION DRUG LABEL | 1 | 21695-651 | TABLET, FILM COATED | 50 mg | ORAL | NDA | 34 sections |
| Savella | HUMAN PRESCRIPTION DRUG LABEL | 1 | 35356-545 | TABLET, FILM COATED | 50 mg | ORAL | NDA | 33 sections |
| Savella | HUMAN PRESCRIPTION DRUG LABEL | 1 | 50436-9993 | TABLET, FILM COATED | 25 mg | ORAL | NDA | 33 sections |
| Savella | HUMAN PRESCRIPTION DRUG LABEL | 1 | 54868-6024 | TABLET, FILM COATED | 100 mg | ORAL | NDA | 33 sections |
| Savella | HUMAN PRESCRIPTION DRUG LABEL | 1 | 54868-6043 | TABLET, FILM COATED | 50 mg | ORAL | NDA | 33 sections |
| Savella | HUMAN PRESCRIPTION DRUG LABEL | 1 | 55154-4626 | TABLET, FILM COATED | 50 mg | ORAL | NDA | 33 sections |
| Milnacipran HCl | HUMAN PRESCRIPTION DRUG LABEL | 1 | 65162-091 | TABLET | 12.50 mg | ORAL | ANDA | 20 sections |
| Milnacipran HCl | HUMAN PRESCRIPTION DRUG LABEL | 1 | 65162-092 | TABLET | 25 mg | ORAL | ANDA | 20 sections |
| Milnacipran HCl | HUMAN PRESCRIPTION DRUG LABEL | 1 | 65162-093 | TABLET | 50 mg | ORAL | ANDA | 20 sections |
| Milnacipran HCl | HUMAN PRESCRIPTION DRUG LABEL | 1 | 65162-094 | TABLET | 100 mg | ORAL | ANDA | 20 sections |