midazolam Indications/Contra | FAERs-F | FAERs-M | Orange Bk | 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

  • Status: OFP

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

Drug dosage:

DoseUnitRoute
15 mg O
15 mg P

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 1 Benet LZ, Broccatelli F, Oprea TI
S (Water solubility) 10.30 mg/mL Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 5.60 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 0.26 ┬ÁM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 44 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 1.10 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 5.30 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.02 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 3.10 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
Dec. 20, 1985 FDA

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
Drug ineffective 579.54 60.10 257 1605 101367 2254856
Hypotension 444.92 60.10 156 1706 32280 2323943
Cardiac arrest 307.88 60.10 98 1764 14832 2341391
Anaphylactic reaction 299.81 60.10 87 1775 9618 2346605
Status epilepticus 212.05 60.10 50 1812 2428 2353795
Toxicity to various agents 196.38 60.10 87 1775 32667 2323556
Tachycardia 186.13 60.10 69 1793 16340 2339883
Oxygen saturation decreased 186.04 60.10 57 1805 7529 2348694
Unresponsive to stimuli 160.34 60.10 46 1816 4830 2351393
Drug interaction 154.05 60.10 71 1791 29092 2327131
Bradycardia 147.05 60.10 51 1811 9930 2346293
Seizure 143.15 60.10 64 1798 24402 2331821
Exposure during pregnancy 134.96 60.10 62 1800 25157 2331066
Anaphylactic shock 134.47 60.10 39 1823 4247 2351976
Agitation 130.74 60.10 48 1814 11003 2345220
Intestinal ischaemia 114.40 60.10 26 1836 1065 2355158
Multiple organ dysfunction syndrome 112.28 60.10 39 1823 7602 2348621
Respiratory failure 110.86 60.10 45 1817 13483 2342740
Circulatory collapse 108.50 60.10 32 1830 3688 2352535
Hypoxia 108.01 60.10 36 1826 6191 2350032
Respiratory depression 106.15 60.10 28 1834 2142 2354081
Generalised tonic-clonic seizure 100.95 60.10 33 1829 5339 2350884
Maternal exposure during pregnancy 96.83 60.10 42 1820 14821 2341402
Delirium 93.77 60.10 31 1831 5192 2351031
Serotonin syndrome 88.31 60.10 27 1835 3513 2352710
Labile blood pressure 87.94 60.10 16 1846 207 2356016
Propofol infusion syndrome 84.46 60.10 14 1848 100 2356123
Anaesthetic complication neurological 84.36 60.10 12 1850 24 2356199
Bronchospasm 83.74 60.10 25 1837 2999 2353224
Respiratory acidosis 83.01 60.10 19 1843 802 2355421
Completed suicide 82.90 60.10 42 1820 20992 2335231
Shock 80.91 60.10 26 1836 3978 2352245
Cardiogenic shock 79.54 60.10 23 1839 2468 2353755
Loss of consciousness 78.42 60.10 39 1823 18728 2337495
Apnoea 77.64 60.10 20 1842 1391 2354832
Sedation 76.91 60.10 24 1838 3338 2352885
Anaesthetic complication 76.56 60.10 16 1846 439 2355784
Mitochondrial DNULL mutation 75.98 60.10 10 1852 7 2356216
Myoclonus 75.18 60.10 22 1840 2461 2353762
Upper airway obstruction 73.98 60.10 13 1849 136 2356087
Drug abuse 71.84 60.10 32 1830 11994 2344229
Foetal death 71.62 60.10 20 1842 1892 2354331
Diabetic macroangiopathy 71.34 60.10 9 1853 2 2356221
Delayed recovery from anaesthesia 70.69 60.10 13 1849 179 2356044
Cardio-respiratory arrest 69.98 60.10 29 1833 9117 2347106
Intra-abdominal pressure increased 69.97 60.10 10 1852 21 2356202
Respiratory arrest 69.87 60.10 26 1836 6152 2350071
Sinus tachycardia 68.85 60.10 22 1840 3303 2352920
Electrocardiogram ST segment depression 67.13 60.10 15 1847 567 2355656
Procedural complication 66.91 60.10 17 1845 1118 2355105
Foetal growth restriction 66.84 60.10 17 1845 1123 2355100
Pneumatosis 66.67 60.10 11 1851 76 2356147
Blood pressure decreased 66.35 60.10 28 1834 9208 2347015
Encephalopathy 65.85 60.10 23 1839 4538 2351685
Somnolence 64.75 60.10 37 1825 23448 2332775
Anaesthetic complication pulmonary 63.96 60.10 9 1853 16 2356207
Unwanted awareness during anaesthesia 63.71 60.10 10 1852 48 2356175
Systemic inflammatory response syndrome 62.74 60.10 15 1847 766 2355457
Diabetes insipidus 61.91 60.10 13 1849 365 2355858
Blood lactic acid increased 61.46 60.10 15 1847 836 2355387
Kounis syndrome 60.57 60.10 12 1850 250 2355973

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
Hypotension 456.06 51.49 177 1687 29477 1715440
Drug ineffective 383.80 51.49 197 1667 63604 1681313
Anaphylactic reaction 283.03 51.49 84 1780 6029 1738888
Toxicity to various agents 261.16 51.49 119 1745 29022 1715895
Sedation 249.01 51.49 67 1797 3350 1741567
Respiratory depression 221.29 51.49 56 1808 2191 1742726
Oxygen saturation decreased 198.67 51.49 63 1801 5612 1739305
Cardiac arrest 180.64 51.49 77 1787 15853 1729064
Coma 171.76 51.49 60 1804 7202 1737715
Status epilepticus 167.29 51.49 44 1820 2002 1742915
Tachycardia 166.46 51.49 68 1796 12560 1732357
Seizure 165.31 51.49 78 1786 20363 1724554
Bradycardia 164.09 51.49 64 1800 10470 1734447
Respiratory arrest 156.51 51.49 53 1811 5786 1739131
Drug abuse 138.08 51.49 61 1803 13628 1731289
Agitation 130.39 51.49 55 1809 10971 1733946
Hyperthermia malignant 126.33 51.49 25 1839 304 1744613
Respiratory failure 122.10 51.49 57 1807 14448 1730469
Delirium 118.13 51.49 44 1820 6318 1738599
Cardio-respiratory arrest 115.32 51.49 48 1816 9245 1735672
Unresponsive to stimuli 108.33 51.49 38 1826 4591 1740326
Anaesthetic complication neurological 100.45 51.49 15 1849 23 1744894
Anaphylactic shock 96.35 51.49 31 1833 2868 1742049
Pulseless electrical activity 93.26 51.49 24 1840 996 1743921
Dyskinesia 91.81 51.49 32 1832 3787 1741130
Metabolic acidosis 91.66 51.49 35 1829 5367 1739550
Drug reaction with eosinophilia and systemic symptoms 90.18 51.49 34 1830 5036 1739881
Blood pressure decreased 89.79 51.49 38 1826 7608 1737309
Procedural complication 86.35 51.49 23 1841 1093 1743824
Rhabdomyolysis 85.28 51.49 41 1823 11049 1733868
Depressed level of consciousness 84.91 51.49 35 1829 6557 1738360
Circulatory collapse 83.13 51.49 29 1835 3438 1741479
Somnolence 82.85 51.49 46 1818 16693 1728224
Hyperthermia 81.25 51.49 24 1840 1667 1743250
Acidosis hyperchloraemic 78.83 51.49 13 1851 49 1744868
Hypoxia 74.54 51.49 31 1833 5932 1738985
Apnoea 71.51 51.49 21 1843 1428 1743489
Confusional state 70.11 51.49 45 1819 21233 1723684
Diabetes insipidus 64.40 51.49 15 1849 407 1744510
Intestinal ischaemia 64.22 51.49 18 1846 1035 1743882
Neonatal respiratory depression 62.77 51.49 11 1853 64 1744853
Mental status changes 60.82 51.49 27 1837 6048 1738869
Product administered to patient of inappropriate age 59.17 51.49 16 1848 804 1744113
Post procedural complication 57.38 51.49 20 1844 2360 1742557
Drug interaction 56.80 51.49 44 1820 27914 1717003
Aggression 56.31 51.49 28 1836 8087 1736830
Rash maculo-papular 55.69 51.49 22 1842 3681 1741236
Hypoventilation 55.53 51.49 14 1850 533 1744384
Ventricular fibrillation 54.51 51.49 20 1844 2736 1742181
Overdose 54.16 51.49 35 1829 16666 1728251
Respiratory distress 51.86 51.49 23 1841 5134 1739783

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