midazolam Indications/Contra | FAERs | Orange Book | BioActivity |

Stem definitionDrug idCAS RN
diazepam derivatives 1802 59467-70-8

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • buccolam
  • midazolam
  • mezolam
  • midazolam hydrochloride
  • midazolam HCl
A short-acting hypnotic-sedative drug with anxiolytic and amnestic properties. It is used in dentistry, cardiac surgery, endoscopic procedures, as preanesthetic medication, and as an adjunct to local anesthesia. The short duration and cardiorespiratory stability makes it useful in poor-risk, elderly, and cardiac patients. It is water-soluble at pH less than 4 and lipid-soluble at physiological pH.
  • Molecular weight: 325.77
  • Formula: C18H13ClFN3
  • CLOGP: 3.42
  • LIPINSKI: 0
  • HAC: 3
  • HDO: 0
  • TPSA: 30.18
  • ALOGS: -4.52
  • ROTB: 1

Drug dosage:

DoseUnitRoute
15 mg O
15 mg P

Approvals:

DateAgencyCompanyOrphan
Dec. 20, 1985 FDA

FDA Adverse Event Reporting System

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
Drug ineffective 1087.81 56.37 531 3945 185530 4448986
Hypotension 1014.46 56.37 378 4098 67022 4567494
Anaphylactic reaction 633.36 56.37 192 4284 17718 4616798
Oxygen saturation decreased 553.44 56.37 164 4312 13957 4620559
Cardiac arrest 523.59 56.37 195 4281 33812 4600704
Toxicity to various agents 519.60 56.37 240 4236 71800 4562716
Status epilepticus 501.80 56.37 122 4354 4841 4629675
Respiratory depression 408.05 56.37 104 4372 5006 4629510
Sedation 406.59 56.37 113 4363 7604 4626912
Tachycardia 394.16 56.37 155 4321 30990 4603526
Seizure 366.19 56.37 169 4307 50068 4584448
Bradycardia 330.46 56.37 125 4351 22444 4612072
Unresponsive to stimuli 308.51 56.37 97 4379 9996 4624520
Agitation 300.76 56.37 119 4357 24081 4610435
Respiratory arrest 297.01 56.37 101 4375 13319 4621197
Delirium 251.18 56.37 88 4388 12664 4621852
Hypoxia 241.12 56.37 86 4390 13035 4621481
Coma 238.13 56.37 92 4384 17427 4617089
Respiratory failure 236.04 56.37 107 4369 30219 4604297
Drug interaction 234.20 56.37 136 4340 64372 4570144
Drug abuse 221.87 56.37 100 4376 27847 4606669
Apnoea 220.45 56.37 58 4418 3150 4631366
Anaphylactic shock 217.21 56.37 70 4406 7787 4626729
Circulatory collapse 201.55 56.37 66 4410 7719 4626797
Cardio-respiratory arrest 189.90 56.37 81 4395 19741 4614775
Intestinal ischaemia 183.04 56.37 47 4429 2316 4632200
Procedural complication 181.73 56.37 47 4429 2383 4632133
Metabolic acidosis 174.89 56.37 67 4409 12373 4622143
Anaesthetic complication neurological 172.49 56.37 30 4446 204 4634312
Somnolence 171.40 56.37 97 4379 43563 4590953
Depressed level of consciousness 162.07 56.37 67 4409 15087 4619429
Blood pressure decreased 161.06 56.37 70 4406 17830 4616686
Multiple organ dysfunction syndrome 151.50 56.37 68 4408 18688 4615828
Diabetes insipidus 149.31 56.37 33 4443 846 4633670
Hyperthermia malignant 139.94 56.37 30 4446 664 4633852
Loss of consciousness 139.20 56.37 79 4397 35603 4598913
Generalised tonic-clonic seizure 136.87 56.37 53 4423 10057 4624459
Completed suicide 134.14 56.37 82 4394 42363 4592153
Rhabdomyolysis 133.21 56.37 63 4413 19495 4615021
Propofol infusion syndrome 129.77 56.37 25 4451 316 4634200
Exposure during pregnancy 128.59 56.37 73 4403 32898 4601618
Acidosis hyperchloraemic 126.81 56.37 22 4454 147 4634369
Hypoventilation 126.02 56.37 31 4445 1279 4633237
Dyskinesia 123.33 56.37 48 4428 9227 4625289
Bronchospasm 123.05 56.37 42 4434 5564 4628952
Anaesthetic complication 122.19 56.37 28 4448 848 4633668
Delayed recovery from anaesthesia 121.71 56.37 24 4452 345 4634171
Upper airway obstruction 118.93 56.37 23 4453 297 4634219
Drug reaction with eosinophilia and systemic symptoms 115.82 56.37 49 4427 11664 4622852
Pulseless electrical activity 115.12 56.37 32 4444 2135 4632381
Overdose 114.70 56.37 75 4401 43484 4591032
Shock 114.52 56.37 45 4431 8871 4625645
Blood lactic acid increased 113.91 56.37 31 4445 1911 4632605
Kounis syndrome 109.31 56.37 25 4451 750 4633766
Hyperthermia 109.00 56.37 34 4442 3390 4631126
Haemodynamic instability 107.71 56.37 32 4444 2707 4631809
Myoclonus 106.35 56.37 37 4439 5187 4629329
Medication error 106.05 56.37 49 4427 14367 4620149
Serotonin syndrome 105.76 56.37 40 4436 7112 4627404
Respiratory acidosis 105.07 56.37 28 4448 1593 4632923
Respiratory distress 104.92 56.37 45 4431 11071 4623445
Acute respiratory distress syndrome 103.85 56.37 40 4436 7473 4627043
Foetal exposure during pregnancy 103.14 56.37 56 4420 23113 4611403
Death 102.75 56.37 137 4339 198026 4436490
Confusional state 102.27 56.37 73 4403 48761 4585755
Maternal exposure during pregnancy 101.07 56.37 50 4426 17043 4617473
Intentional product misuse 100.25 56.37 51 4425 18442 4616074
Arrhythmia 96.12 56.37 45 4431 13587 4620929
Post procedural complication 95.29 56.37 35 4441 5736 4628780
Renal failure 93.94 56.37 65 4411 41304 4593212
Necrosis ischaemic 92.53 56.37 17 4459 163 4634353
Cardiogenic shock 90.09 56.37 33 4443 5365 4629151
Brain oedema 89.89 56.37 32 4444 4795 4629721
Encephalopathy 89.56 56.37 39 4437 9948 4624568
Off label use 88.80 56.37 103 4373 129010 4505506
Laryngospasm 88.16 56.37 23 4453 1204 4633312
Ventricular tachycardia 86.99 56.37 35 4441 7329 4627187
Carcinoid crisis 86.29 56.37 14 4462 58 4634458
Cognitive disorder 84.55 56.37 38 4438 10443 4624073
Product administered to patient of inappropriate age 84.10 56.37 25 4451 2117 4632399
Ventricular fibrillation 83.08 56.37 31 4445 5306 4629210
Erythema 81.62 56.37 60 4416 41880 4592636
Rash maculo-papular 78.73 56.37 34 4442 8495 4626021
Labile blood pressure 78.49 56.37 17 4459 395 4634121
Sinus tachycardia 78.40 56.37 31 4445 6203 4628313
Systemic inflammatory response syndrome 78.28 56.37 23 4453 1870 4632646
Pyrexia 77.87 56.37 88 4388 107056 4527460
Altered state of consciousness 77.61 56.37 33 4443 7938 4626578
Heart rate increased 77.48 56.37 43 4433 18499 4616017
Vomiting 76.47 56.37 92 4384 119607 4514909
Mitochondrial DNA mutation 75.53 56.37 11 4465 17 4634499
Anaesthetic complication pulmonary 73.72 56.37 11 4465 22 4634494
Urticaria 73.37 56.37 55 4421 39518 4594998
Hyperhidrosis 72.59 56.37 49 4427 29868 4604648
Mental status changes 72.53 56.37 36 4440 12340 4622176
Stevens-Johnson syndrome 71.84 56.37 32 4444 8607 4625909
Cyanosis 71.51 56.37 29 4447 6193 4628323
Foetal death 71.51 56.37 23 4453 2529 4631987
Aggression 71.44 56.37 37 4439 13862 4620654
Diabetic macroangiopathy 70.59 56.37 10 4466 11 4634505
Drug resistance 70.43 56.37 31 4445 8105 4626411
Tryptase increased 70.35 56.37 13 4463 129 4634387
Hyperkalaemia 69.66 56.37 38 4438 15799 4618717
Disseminated intravascular coagulation 69.66 56.37 30 4446 7443 4627073
Therapeutic product effect incomplete 69.42 56.37 39 4437 17169 4617347
Poisoning 69.20 56.37 28 4448 5946 4628570
Unwanted awareness during anaesthesia 68.88 56.37 13 4463 146 4634370
Pneumothorax 68.29 56.37 27 4449 5398 4629118
Electrocardiogram QRS complex prolonged 68.08 56.37 21 4455 2015 4632501
Toxic skin eruption 66.56 56.37 25 4451 4355 4630161
Paradoxical drug reaction 66.48 56.37 18 4458 1087 4633429
Toxic epidermal necrolysis 64.84 56.37 27 4449 6165 4628351
Condition aggravated 64.41 56.37 60 4416 58111 4576405
Premature baby 64.16 56.37 31 4445 10020 4624496
Neonatal respiratory depression 63.56 56.37 12 4464 135 4634381
Drug hypersensitivity 63.44 56.37 64 4412 68336 4566180
Intra-abdominal pressure increased 62.97 56.37 10 4466 35 4634481
Epilepsy 62.71 56.37 30 4446 9488 4625028
Electrocardiogram ST segment depression 60.87 56.37 17 4459 1152 4633364
Multiple-drug resistance 60.17 56.37 15 4461 653 4633863
Electrocardiogram QT prolonged 59.89 56.37 34 4442 15261 4619255
Aspiration 59.76 56.37 22 4454 3623 4630893
Drug use disorder 59.22 56.37 16 4460 958 4633558
Rash 59.07 56.37 77 4399 108311 4526205
Obstructive airways disorder 58.92 56.37 20 4456 2600 4631916
Blood pH decreased 57.97 56.37 16 4460 1038 4633478
Anuria 57.69 56.37 22 4454 3993 4630523
Acute kidney injury 56.52 56.37 61 4415 70370 4564146

Pharmacologic Action:

SourceCodeDescription
ATC N05CD08 NERVOUS SYSTEM
PSYCHOLEPTICS
HYPNOTICS AND SEDATIVES
Benzodiazepine derivatives
MeSH PA D000759 Adjuvants, Anesthesia
FDA EPC N0000175694 Benzodiazepine
FDA CS M0002356 Benzodiazepines
MeSH PA D000777 Anesthetics
MeSH PA D018686 Anesthetics, Intravenous
CHEBI has role CHEBI:91016 GABAA receptor agonist
CHEBI has role CHEBI:35623 anticonvulsant
CHEBI has role CHEBI:35474 anxiolytic drug
CHEBI has role CHEBI:35610 antineoplastic agent
CHEBI has role CHEBI:51371 muscle relaxant
CHEBI has role CHEBI:35717 sedative
CHEBI has role CHEBI:38869 general anaesthetic
CHEBI has role CHEBI:35488 central nervous system depressant
MeSH PA D014151 Anti-Anxiety Agents
MeSH PA D002491 Central Nervous System Agents
MeSH PA D002492 Central Nervous System Depressants
MeSH PA D018682 GABA Agents
MeSH PA D018757 GABA Modulators
MeSH PA D006993 Hypnotics and Sedatives
MeSH PA D018377 Neurotransmitter Agents
MeSH PA D011619 Psychotropic Drugs
MeSH PA D014149 Tranquilizing Agents

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Feeling agitated indication 24199005
Anxiety indication 48694002
General anesthesia indication 50697003
Sedation indication 72641008
Conscious sedation indication 314271007
Local anesthesia indication 386761002
Induce Anterograde Amnesia indication
Sedation in Intubated Patients indication
Preoperative Anxiety indication
Sedation as Adjunct to Anesthesia indication
Insomnia off-label use 193462001
Status epilepticus off-label use 230456007 DOID:1824
Cocaine-Associated Acute Ischemic Heart Disease off-label use
Chronic obstructive lung disease contraindication 13645005 DOID:3083
Cirrhosis of liver contraindication 19943007 DOID:5082
Shock contraindication 27942005
End stage renal disease contraindication 46177005 DOID:784
Chronic heart failure contraindication 48447003
Pregnancy, function contraindication 289908002
Coma contraindication 371632003
Angle-closure glaucoma contraindication 392291006 DOID:13550
Hemodynamic instability contraindication 422773005
Peripheral Vasoconstriction contraindication

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 6.07 Basic
pKa2 2.36 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
5MG/SPRAY NAYZILAM UCB INC N211321 May 17, 2019 RX SPRAY NASAL 8217033 Jan. 18, 2028 ACUTE TREATMENT OF INTERMITTENT, STEREOTYPIC EPISODES OF FREQUENT SEIZURE ACTIVITY (I.E., SEIZURE CLUSTERS, ACUTE REPETITIVE SEIZURES) THAT ARE DISTINCT FROM A PATIENT'S USUAL SEIZURE PATTERN IN PATIENTS WITH EPILEPSY 12 YEARS OF AGE AND OLDER
5MG/SPRAY NAYZILAM UCB INC N211321 May 17, 2019 RX SPRAY NASAL 9289432 Jan. 18, 2028 ACUTE TREATMENT OF INTERMITTENT, STEREOTYPIC EPISODES OF FREQUENT SEIZURE ACTIVITY (I.E., SEIZURE CLUSTERS, ACUTE REPETITIVE SEIZURES) THAT ARE DISTINCT FROM A PATIENT'S USUAL SEIZURE PATTERN IN PATIENTS WITH EPILEPSY 12 YEARS OF AGE AND OLDER
5MG/SPRAY NAYZILAM UCB INC N211321 May 17, 2019 RX SPRAY NASAL 9687495 Jan. 18, 2028 ACUTE TREATMENT OF INTERMITTENT, STEREOTYPIC EPISODES OF FREQUENT SEIZURE ACTIVITY (I.E., SEIZURE CLUSTERS, ACUTE REPETITIVE SEIZURES) THAT ARE DISTINCT FROM A PATIENT'S USUAL SEIZURE PATTERN IN PATIENTS WITH EPILEPSY 12 YEARS OF AGE AND OLDER

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
5MG/SPRAY NAYZILAM UCB INC N211321 May 17, 2019 RX SPRAY NASAL May 21, 2022 NEW PRODUCT
EQ 50MG BASE/10ML (EQ 5MG BASE/ML) SEIZALAM MERIDIAN MEDCL TECHN N209566 Sept. 14, 2018 RX SOLUTION INTRAMUSCULAR Sept. 14, 2025 TREATMENT OF STATUS EPILEPTICUS IN ADULTS
5MG/SPRAY NAYZILAM UCB INC N211321 May 17, 2019 RX SPRAY NASAL May 17, 2026 ACUTE TREATMENT OF INTERMITTENT, STEREOTYPIC EPISODES OF FREQUENT SEIZURE ACTIVITY (I.E., SEIZURE CLUSTERS, ACUTE REPETITIVE SEIZURES) THAT ARE DISTINCT FROM A PATIENT'S USUAL SEIZURE PATTERN IN PATIENTS WITH EPILEPSY 12 YEARS OF AGE AND OLDER

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
GABA-A receptor alpha-1/beta-2/gamma-2 Ion channel POSITIVE ALLOSTERIC MODULATOR Ki 8.74 WOMBAT-PK CHEMBL
GABA A receptor alpha-3/beta-2/gamma-2 Ion channel POSITIVE ALLOSTERIC MODULATOR Ki 8.44 WOMBAT-PK CHEMBL
GABA A receptor alpha-5/beta-3/gamma-3 Ion channel POSITIVE ALLOSTERIC MODULATOR Ki 8.26 WOMBAT-PK CHEMBL
GABA-A receptor alpha-5/beta-3/gamma-2 Ion channel POSITIVE ALLOSTERIC MODULATOR Ki 9.12 WOMBAT-PK CHEMBL
GABA A receptor alpha-3/beta-2/gamma-3 Ion channel POSITIVE ALLOSTERIC MODULATOR Ki 7.61 WOMBAT-PK CHEMBL
GABA-A receptor alpha-1/beta-2/gamma-3 Ion channel POSITIVE ALLOSTERIC MODULATOR Ki 7.75 WOMBAT-PK CHEMBL
GABA A receptor alpha-5/beta-2/gamma-2 Ion channel POSITIVE ALLOSTERIC MODULATOR Ki 9.12 WOMBAT-PK CHEMBL
GABA A receptor alpha-5/beta-2/gamma-3 Ion channel POSITIVE ALLOSTERIC MODULATOR Ki 8.26 WOMBAT-PK CHEMBL
Multidrug resistance protein 1 Transporter Km 4.35 WOMBAT-PK
Cytochrome P450 3A4 Enzyme Km 6 WOMBAT-PK
Thyrotropin-releasing hormone receptor GPCR ANTAGONIST Ki 5.49 IUPHAR
GABA-A receptor; anion channel Ion channel Ki 8.70 CHEMBL
Translocator protein Membrane receptor Ki 8.70 CHEMBL

External reference:

IDSource
4019839 VUID
N0000147927 NUI
C0026056 UMLSCUI
D00550 KEGG_DRUG
26800000 SNOMEDCT_US
4019839 VANDF
6960 RXNORM
373476007 SNOMEDCT_US
d00301 MMSL
130935 MMSL
24970 MMSL
004585 NDDF
CHEMBL655 ChEMBL_ID
DB00683 DRUGBANK_ID
CHEMBL1200420 ChEMBL_ID
R60L0SM5BC UNII
4497 INN_ID
08J PDB_CHEM_ID
CHEBI:6931 CHEBI
59467-96-8 SECONDARY_CAS_RN
4192 PUBCHEM_CID
D008874 MESH_DESCRIPTOR_UI
3342 IUPHAR_LIGAND_ID

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Midazolam Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0054-3566 SYRUP 2 mg ORAL ANDA 14 sections
MIDAZOLAM HYDROCHLORIDE HUMAN PRESCRIPTION DRUG LABEL 1 0409-2305 INJECTION, SOLUTION 1 mg INTRAMUSCULAR ANDA 15 sections
Midazolam Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0409-2306 INJECTION, SOLUTION 1 mg INTRAMUSCULAR ANDA 15 sections
Midazolam Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0409-2307 INJECTION, SOLUTION 5 mg INTRAMUSCULAR ANDA 15 sections
MIDAZOLAM HYDROCHLORIDE HUMAN PRESCRIPTION DRUG LABEL 1 0409-2308 INJECTION, SOLUTION 5 mg INTRAMUSCULAR ANDA 15 sections
Midazolam Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0409-2587 INJECTION, SOLUTION 1 mg INTRAMUSCULAR ANDA 15 sections
Midazolam Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0409-2596 INJECTION, SOLUTION 5 mg INTRAMUSCULAR ANDA 15 sections
Midazolam Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0574-0150 SYRUP 2 mg ORAL ANDA 15 sections
Midazolam HUMAN PRESCRIPTION DRUG LABEL 1 0641-6056 INJECTION 1 mg INTRAMUSCULAR ANDA 16 sections
Midazolam HUMAN PRESCRIPTION DRUG LABEL 1 0641-6057 INJECTION 1 mg INTRAMUSCULAR ANDA 16 sections
Midazolam HUMAN PRESCRIPTION DRUG LABEL 1 0641-6059 INJECTION 1 mg INTRAMUSCULAR ANDA 16 sections
Midazolam HUMAN PRESCRIPTION DRUG LABEL 1 0641-6060 INJECTION 5 mg INTRAMUSCULAR ANDA 16 sections
Midazolam HUMAN PRESCRIPTION DRUG LABEL 1 0641-6061 INJECTION 5 mg INTRAMUSCULAR ANDA 16 sections
Midazolam HUMAN PRESCRIPTION DRUG LABEL 1 0641-6063 INJECTION 5 mg INTRAMUSCULAR ANDA 16 sections
Midazolam HUMAN PRESCRIPTION DRUG LABEL 1 0641-6190 INJECTION 5 mg INTRAMUSCULAR ANDA 15 sections
Midazolam HUMAN PRESCRIPTION DRUG LABEL 1 0641-6209 INJECTION 1 mg INTRAMUSCULAR ANDA 16 sections
Midazolam HUMAN PRESCRIPTION DRUG LABEL 1 0641-6210 INJECTION 1 mg INTRAMUSCULAR ANDA 16 sections
Midazolam HUMAN PRESCRIPTION DRUG LABEL 1 0641-6211 INJECTION 5 mg INTRAMUSCULAR ANDA 16 sections
Seizalam HUMAN PRESCRIPTION DRUG LABEL 1 11704-650 INJECTION, SOLUTION 5 mg INTRAMUSCULAR NDA 18 sections
Midazolam HUMAN PRESCRIPTION DRUG LABEL 1 17478-523 INJECTION 1 mg INTRAVENOUS ANDA 15 sections
Midazolam HUMAN PRESCRIPTION DRUG LABEL 1 17478-524 INJECTION 5 mg INTRAVENOUS ANDA 15 sections
Midazolam Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 17856-0146 SYRUP 2 mg ORAL ANDA 15 sections
Midazolam Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 17856-0205 SYRUP 2 mg ORAL ANDA 12 sections
Midazolam Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 17856-3566 SYRUP 2 mg ORAL ANDA 13 sections
Midazolam hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 23155-600 INJECTION, SOLUTION 1 mg INTRAMUSCULAR ANDA 14 sections
Midazolam hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 23155-601 INJECTION, SOLUTION 5 mg INTRAVENOUS ANDA 14 sections
Midazolam HUMAN PRESCRIPTION DRUG LABEL 1 47781-588 INJECTION, SOLUTION 2 mg INTRAVENOUS ANDA 15 sections
Midazolam HUMAN PRESCRIPTION DRUG LABEL 1 47781-589 INJECTION, SOLUTION 5 mg INTRAVENOUS ANDA 15 sections
Midazolam HUMAN PRESCRIPTION DRUG LABEL 1 50090-0683 INJECTION 5 mg INTRAMUSCULAR ANDA 16 sections
Midazolam HUMAN PRESCRIPTION DRUG LABEL 1 50090-0738 INJECTION 1 mg INTRAMUSCULAR ANDA 16 sections