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

Stem definitionDrug idCAS RN
acetylcholinesterase inhibitors 2392 123441-03-2

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • prometax
  • rivastigmine
  • S-Rivastigmine
  • rivastigmine tartrate
  • rivastigmine hydrogen tartrate
  • rivastigmine hexal
  • exelon
A carbamate-derived reversible CHOLINESTERASE INHIBITOR that is selective for the CENTRAL NERVOUS SYSTEM and is used for the treatment of DEMENTIA in ALZHEIMER DISEASE and PARKINSON DISEASE.
  • Molecular weight: 250.34
  • Formula: C14H22N2O2
  • CLOGP: 2.10
  • LIPINSKI: 0
  • HAC: 4
  • HDO: 0
  • TPSA: 32.78
  • ALOGS: -2.09
  • ROTB: 5

  • Status: OFP

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

Drug dosage:

DoseUnitRoute
9 mg O
9.50 mg TD

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 1 Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 0.10 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 0.80 ┬ÁM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 72 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 1.30 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 12 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.60 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 1.40 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
May 12, 1998 EMA
April 21, 2000 FDA NOVARTIS

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
Fall 478.48 40.65 184 1783 46915 2309203
Vomiting 413.60 40.65 187 1780 71415 2284703
Confusional state 360.39 40.65 126 1841 24218 2331900
Death 291.96 40.65 154 1813 81314 2274804
Nausea 290.37 40.65 171 1796 112018 2244100
Application site erythema 289.63 40.65 58 1909 1222 2354896
Application site pruritus 248.13 40.65 48 1919 838 2355280
Dementia Alzheimer's type 225.61 40.65 44 1923 802 2355316
Agitation 209.06 40.65 69 1898 10982 2345136
Bradycardia 207.73 40.65 67 1900 9914 2346204
Hallucination 204.04 40.65 63 1904 8085 2348033
Syncope 195.04 40.65 73 1894 16802 2339316
Dizziness 186.89 40.65 103 1864 58562 2297556
Loss of consciousness 183.94 40.65 72 1895 18695 2337423
Aggression 181.17 40.65 51 1916 4735 2351383
Product adhesion issue 179.99 40.65 39 1928 1213 2354905
Dementia 170.10 40.65 43 1924 2638 2353480
Application site rash 163.79 40.65 32 1935 587 2355531
Malaise 158.91 40.65 91 1876 55494 2300624
Disorientation 158.26 40.65 49 1918 6323 2349795
Parkinson's disease 128.83 40.65 30 1937 1296 2354822
Cognitive disorder 127.76 40.65 40 1927 5341 2350777
Diarrhoea 127.19 40.65 92 1875 83472 2272646
Abnormal behaviour 124.03 40.65 38 1929 4722 2351396
General physical health deterioration 120.08 40.65 49 1918 14090 2342028
Weight decreased 118.79 40.65 60 1907 28311 2327807
Condition aggravated 112.01 40.65 60 1907 31919 2324199
Dehydration 110.73 40.65 53 1914 22242 2333876
Hallucination, visual 104.74 40.65 30 1937 2949 2353169
Decreased appetite 103.37 40.65 55 1912 28836 2327282
Cerebrovascular accident 100.24 40.65 48 1919 20138 2335980
Dysphagia 97.26 40.65 41 1926 12764 2343354
Restlessness 96.20 40.65 31 1936 4532 2351586
Application site hypersensitivity 93.76 40.65 15 1952 78 2356040
Somnolence 84.75 40.65 45 1922 23440 2332678
Cerebral atrophy 81.97 40.65 19 1948 802 2355316
Subileus 77.60 40.65 17 1950 554 2355564
Asthenia 76.37 40.65 54 1913 46872 2309246
Tremor 75.67 40.65 40 1927 20621 2335497
Pneumonia 73.98 40.65 54 1913 49242 2306876
Product administration interrupted 73.31 40.65 11 1956 34 2356084
Memory impairment 71.05 40.65 33 1934 12890 2343228
Wrong technique in product usage process 68.83 40.65 37 1930 19711 2336407
Drug interaction 67.89 40.65 42 1925 29121 2326997
Gait disturbance 66.94 40.65 38 1929 22507 2333611
Delirium 65.24 40.65 24 1943 5199 2350919
Mini mental status examination abnormal 62.77 40.65 9 1958 18 2356100
Speech disorder 60.27 40.65 24 1943 6440 2349678
Vascular encephalopathy 59.58 40.65 10 1957 73 2356045
Application site irritation 58.05 40.65 13 1954 469 2355649
Extrapyramidal disorder 57.95 40.65 18 1949 2329 2353789
Anxiety 57.67 40.65 38 1929 29321 2326797
Abdominal pain 56.86 40.65 40 1927 34334 2321784
Dyskinesia 56.12 40.65 21 1946 4768 2351350
Arrhythmia 54.87 40.65 22 1945 6006 2350112
Rash 54.72 40.65 49 1918 59509 2296609
Femoral neck fracture 54.34 40.65 15 1952 1284 2354834
Skin irritation 53.39 40.65 15 1952 1370 2354748
Femur fracture 52.50 40.65 22 1945 6717 2349401
Urinary tract infection 52.21 40.65 36 1931 29906 2326212
Pancreatitis 51.86 40.65 23 1944 8056 2348062
White blood cell count increased 51.46 40.65 22 1945 7056 2349062
Seizure 51.29 40.65 33 1934 24433 2331685
Hyperhidrosis 51.20 40.65 28 1939 15394 2340724
Hypertension 50.31 40.65 34 1933 27327 2328791
Hypotension 49.61 40.65 36 1931 32400 2323718
Erythema 48.01 40.65 32 1935 25127 2330991
Pleurothotonus 47.95 40.65 10 1957 256 2355862
Balance disorder 47.73 40.65 23 1944 9724 2346394
Gastrointestinal sounds abnormal 45.35 40.65 11 1956 564 2355554
Faecaloma 44.98 40.65 12 1955 903 2355215
Depression 44.78 40.65 32 1935 28100 2328018
Medication error 44.37 40.65 19 1948 6112 2350006
C-reactive protein increased 44.01 40.65 19 1948 6236 2349882
Cardiac arrest 43.81 40.65 25 1942 14905 2341213
Delusion 43.36 40.65 14 1953 2051 2354067
Cardiac failure 43.04 40.65 23 1944 12071 2344047
Dysstasia 42.28 40.65 15 1952 2924 2353194
Incorrect dose administered 41.86 40.65 21 1946 9674 2346444
Gait inability 41.60 40.65 18 1949 5937 2350181
Myocardial infarction 40.70 40.65 26 1941 18987 2337131

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
Confusional state 363.94 39.34 127 1257 21151 1724246
Fall 272.74 39.34 110 1274 27104 1718293
Aggression 224.46 39.34 70 1314 8045 1737352
Bradycardia 194.71 39.34 67 1317 10467 1734930
Hallucination 186.74 39.34 61 1323 8109 1737288
Death 185.15 39.34 124 1260 87319 1658078
Agitation 180.19 39.34 64 1320 10962 1734435
Application site erythema 164.28 39.34 33 1351 601 1744796
Product adhesion issue 157.12 39.34 29 1355 329 1745068
Malaise 142.57 39.34 72 1312 29493 1715904
Disorientation 137.66 39.34 44 1340 5425 1739972
Abnormal behaviour 135.25 39.34 45 1339 6297 1739100
Syncope 129.75 39.34 54 1330 14115 1731282
Dementia 125.01 39.34 33 1351 2063 1743334
Dementia Alzheimer's type 118.38 39.34 25 1359 586 1744811
Condition aggravated 112.02 39.34 55 1329 21095 1724302
Vomiting 103.97 39.34 64 1320 38251 1707146
Application site pruritus 96.06 39.34 19 1365 317 1745080
Somnolence 92.92 39.34 45 1339 16694 1728703
Sinus bradycardia 89.76 39.34 25 1359 1908 1743489
Parkinson's disease 87.66 39.34 24 1360 1718 1743679
Dizziness 87.03 39.34 55 1329 34306 1711091
Nausea 82.55 39.34 62 1322 51134 1694263
Gait disturbance 79.22 39.34 37 1347 12633 1732764
Hallucination, visual 74.01 39.34 23 1361 2569 1742828
Loss of consciousness 73.57 39.34 37 1347 14838 1730559
Restlessness 69.96 39.34 25 1359 4296 1741101
Application site rash 69.49 39.34 14 1370 257 1745140
Parkinson's disease psychosis 68.71 39.34 9 1375 3 1745394
Delirium 63.98 39.34 26 1358 6336 1739061
Pneumonia 63.56 39.34 51 1333 46131 1699266
Cognitive disorder 62.43 39.34 23 1361 4307 1741090
Asthenia 60.19 39.34 44 1340 34626 1710771
Hyperhidrosis 58.60 39.34 30 1354 12458 1732939
Insomnia 53.81 39.34 31 1353 16245 1729152
Urinary incontinence 52.59 39.34 18 1366 2718 1742679
General physical health deterioration 51.55 39.34 28 1356 13090 1732307
Hypotension 49.98 39.34 37 1347 29617 1715780
Decreased appetite 49.95 39.34 34 1350 23837 1721560
Circulatory collapse 48.43 39.34 18 1366 3449 1741948
Depression 47.88 39.34 29 1355 16640 1728757
Muscle rigidity 46.91 39.34 15 1369 1833 1743564
Blood cholinesterase decreased 46.88 39.34 8 1376 55 1745342
Blood pressure decreased 46.68 39.34 22 1362 7624 1737773
Memory impairment 46.38 39.34 21 1363 6642 1738755
Tremor 46.03 39.34 26 1358 13105 1732292
Pneumonia aspiration 44.42 39.34 19 1365 5247 1740150
Dementia with Lewy bodies 42.42 39.34 8 1376 102 1745295
Salivary hypersecretion 41.78 39.34 13 1371 1452 1743945
Miosis 41.67 39.34 13 1371 1465 1743932
Heart rate decreased 40.75 39.34 15 1369 2794 1742603
Balance disorder 39.44 39.34 18 1366 5794 1739603

Pharmacologic Action:

SourceCodeDescription
ATC N06DA03 NERVOUS SYSTEM
PSYCHOANALEPTICS
ANTI-DEMENTIA DRUGS
Anticholinesterases
FDA EPC N0000175723 Cholinesterase Inhibitor
CHEBI has role CHEBI:63726 neuroprotective agent
CHEBI has role CHEBI:38323 cholinergic drug
MeSH PA D002491 Central Nervous System Agents
MeSH PA D018678 Cholinergic Agents
MeSH PA D002800 Cholinesterase Inhibitors
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D018696 Neuroprotective Agents
MeSH PA D018377 Neurotransmitter Agents
MeSH PA D020011 Protective Agents

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Alzheimer's disease indication 26929004 DOID:10652
Dementia associated with Parkinson's Disease indication 425390006
Diffuse Lewy body disease off-label use 80098002
Moderate to Severe Alzheimer's Type Dementia off-label use
Urinary tract obstruction contraindication 7163005 DOID:5200
Chronic obstructive lung disease contraindication 13645005 DOID:3083
Parkinsonism contraindication 32798002
Sick sinus syndrome contraindication 36083008 DOID:13884
Gastrointestinal ulcer contraindication 40845000
Conduction disorder of the heart contraindication 44808001
Neuromuscular block, function contraindication 55394004
Anorexia nervosa contraindication 56882008 DOID:8689
Diarrhea contraindication 62315008
Gastrointestinal hemorrhage contraindication 74474003
Extrapyramidal disease contraindication 76349003
Weight loss contraindication 89362005
Seizure disorder contraindication 128613002
Asthma contraindication 195967001 DOID:2841
Atrioventricular block contraindication 233917008 DOID:0050820
Vomiting contraindication 422400008
Nausea contraindication 422587007

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 8.32 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Cholinesterase Enzyme INHIBITOR IC50 7.52 CHEMBL IUPHAR
Acetylcholinesterase Enzyme INHIBITOR IC50 7.43 CHEMBL IUPHAR
Acetylcholinesterase Enzyme IC50 5.74 CHEMBL
Acetylcholinesterase Enzyme IC50 5.95 CHEMBL
Butyrylcholinesterase; Protein Bche Enzyme IC50 6.46 CHEMBL
Cholinesterase Enzyme IC50 5.80 CHEMBL
Cholinesterase Enzyme IC50 6.08 CHEMBL
Acetylcholinesterase Enzyme IC50 6.21 CHEMBL
Butyrylcholinesterase Enzyme IC50 6.80 CHEMBL
Acetylcholinesterase Enzyme IC50 5.38 CHEMBL

External reference:

IDSource
D000068836 MESH_DESCRIPTOR_UI
4021219 VUID
N0000148665 NUI
C0649350 UMLSCUI
D03822 KEGG_DRUG
d04537 MMSL
183379 RXNORM
395868008 SNOMEDCT_US
4021219 VANDF
323368009 SNOMEDCT_US
23978 MMSL
007559 NDDF
79573 MMSL
9IY2357JPE UNII
129101-54-8 SECONDARY_CAS_RN
CHEBI:8874 CHEBI
CHEMBL636 ChEMBL_ID
CHEMBL215645 ChEMBL_ID
DB00989 DRUGBANK_ID
7562 INN_ID
77991 PUBCHEM_CID
6602 IUPHAR_LIGAND_ID

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Exelon HUMAN PRESCRIPTION DRUG LABEL 1 0078-0323 CAPSULE 1.50 mg ORAL NDA 17 sections
Exelon HUMAN PRESCRIPTION DRUG LABEL 1 0078-0324 CAPSULE 3 mg ORAL NDA 17 sections
Exelon HUMAN PRESCRIPTION DRUG LABEL 1 0078-0325 CAPSULE 4.50 mg ORAL NDA 17 sections
Exelon HUMAN PRESCRIPTION DRUG LABEL 1 0078-0326 CAPSULE 6 mg ORAL NDA 17 sections
Exelon HUMAN PRESCRIPTION DRUG LABEL 1 0078-0501 PATCH, EXTENDED RELEASE 4.60 mg TRANSDERMAL NDA 18 sections
Exelon HUMAN PRESCRIPTION DRUG LABEL 1 0078-0502 PATCH, EXTENDED RELEASE 9.50 mg TRANSDERMAL NDA 18 sections
Exelon HUMAN PRESCRIPTION DRUG LABEL 1 0078-0503 PATCH, EXTENDED RELEASE 13.30 mg TRANSDERMAL NDA 18 sections
Rivastigmine HUMAN PRESCRIPTION DRUG LABEL 1 0378-9070 PATCH 4.60 mg TRANSDERMAL ANDA 17 sections
Rivastigmine HUMAN PRESCRIPTION DRUG LABEL 1 0378-9071 PATCH 9.50 mg TRANSDERMAL ANDA 17 sections
Rivastigmine HUMAN PRESCRIPTION DRUG LABEL 1 0378-9072 PATCH 13.30 mg TRANSDERMAL ANDA 17 sections
Rivastigmine Tartrate HUMAN PRESCRIPTION DRUG LABEL 1 0591-3208 CAPSULE 1.50 mg ORAL ANDA 16 sections
Rivastigmine Tartrate HUMAN PRESCRIPTION DRUG LABEL 1 0591-3209 CAPSULE 3 mg ORAL ANDA 16 sections
Rivastigmine Tartrate HUMAN PRESCRIPTION DRUG LABEL 1 0591-3210 CAPSULE 4.50 mg ORAL ANDA 16 sections
Rivastigmine Tartrate HUMAN PRESCRIPTION DRUG LABEL 1 0591-3211 CAPSULE 6 mg ORAL ANDA 16 sections
Rivastigmine Tartrate HUMAN PRESCRIPTION DRUG LABEL 1 0781-2614 CAPSULE 1.50 mg ORAL NDA AUTHORIZED GENERIC 17 sections
Rivastigmine Tartrate HUMAN PRESCRIPTION DRUG LABEL 1 0781-2615 CAPSULE 3 mg ORAL NDA AUTHORIZED GENERIC 17 sections
Rivastigmine Tartrate HUMAN PRESCRIPTION DRUG LABEL 1 0781-2616 CAPSULE 4.50 mg ORAL NDA AUTHORIZED GENERIC 17 sections
Rivastigmine Tartrate HUMAN PRESCRIPTION DRUG LABEL 1 0781-2617 CAPSULE 6 mg ORAL NDA AUTHORIZED GENERIC 17 sections
Rivastigmine HUMAN PRESCRIPTION DRUG LABEL 1 0781-7304 PATCH, EXTENDED RELEASE 4.60 mg TRANSDERMAL NDA authorized generic 17 sections
Rivastigmine HUMAN PRESCRIPTION DRUG LABEL 1 0781-7309 PATCH, EXTENDED RELEASE 9.50 mg TRANSDERMAL NDA authorized generic 17 sections
Rivastigmine HUMAN PRESCRIPTION DRUG LABEL 1 0781-7313 PATCH, EXTENDED RELEASE 13.30 mg TRANSDERMAL NDA authorized generic 17 sections
Rivastigmine Tartrate HUMAN PRESCRIPTION DRUG LABEL 1 0904-6587 CAPSULE 1.50 mg ORAL ANDA 16 sections
Rivastigmine HUMAN PRESCRIPTION DRUG LABEL 1 16714-115 PATCH, EXTENDED RELEASE 4.60 mg TRANSDERMAL ANDA 18 sections
Rivastigmine HUMAN PRESCRIPTION DRUG LABEL 1 16714-116 PATCH, EXTENDED RELEASE 9.50 mg TRANSDERMAL ANDA 18 sections
Rivastigmine HUMAN PRESCRIPTION DRUG LABEL 1 16714-117 PATCH, EXTENDED RELEASE 13.30 mg TRANSDERMAL ANDA 18 sections
Exelon HUMAN PRESCRIPTION DRUG LABEL 1 21695-357 PATCH, EXTENDED RELEASE 4.60 mg TRANSDERMAL NDA 16 sections
RIVASTIGMINE TARTRATE HUMAN PRESCRIPTION DRUG LABEL 1 27241-090 CAPSULE 1.50 mg ORAL ANDA 16 sections
RIVASTIGMINE TARTRATE HUMAN PRESCRIPTION DRUG LABEL 1 27241-091 CAPSULE 3 mg ORAL ANDA 16 sections
RIVASTIGMINE TARTRATE HUMAN PRESCRIPTION DRUG LABEL 1 27241-092 CAPSULE 4.50 mg ORAL ANDA 16 sections
RIVASTIGMINE TARTRATE HUMAN PRESCRIPTION DRUG LABEL 1 27241-093 CAPSULE 6 mg ORAL ANDA 16 sections