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

Stem definitionDrug idCAS RN
calcium channel blockers, diltiazem derivatives 897 42399-41-7

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • (+)-Diltiazem
  • dilzem
  • d-Diltiazem
  • d-cis-Diltiazem
  • diltiazem hydrochloride
  • diltiazem malate
  • diltiazem
  • diltiazem HCl
A benzothiazepine derivative with vasodilating action due to its antagonism of the actions of CALCIUM ion on membrane functions.
  • Molecular weight: 414.52
  • Formula: C22H26N2O4S
  • CLOGP: 3.65
  • LIPINSKI: 0
  • HAC: 6
  • HDO: 0
  • TPSA: 59.08
  • ALOGS: -4.39
  • ROTB: 7

  • Status: OFP

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

Drug dosage:

DoseUnitRoute
0.24 g O

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 1 Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 2 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 19.30 ┬ÁM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 38 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 4.10 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 13 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.18 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 5.60 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
Nov. 5, 1982 FDA VALEANT INTL

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
Completed suicide 3044.41 44.45 654 1549 20380 2335502
Toxicity to various agents 697.67 44.45 228 1975 32526 2323356
Bradycardia 503.44 44.45 136 2067 9845 2346037
Poisoning 492.88 44.45 105 2098 2715 2353167
Cardiac arrest 436.34 44.45 133 2070 14797 2341085
Hypotension 385.32 44.45 147 2056 32289 2323593
Drug interaction 359.94 44.45 136 2067 29027 2326855
Respiratory arrest 305.07 44.45 83 2120 6095 2349787
Overdose 304.90 44.45 109 2094 19798 2336084
Sinus bradycardia 292.06 44.45 65 2138 2051 2353831
Drug hypersensitivity 245.30 44.45 119 2084 46524 2309358
Nodal rhythm 241.93 44.45 42 2161 340 2355542
Intentional overdose 199.63 44.45 69 2134 11252 2344630
Medication error 188.42 44.45 57 2146 6074 2349808
Acute generalised exanthematous pustulosis 169.88 44.45 40 2163 1618 2354264
Atrioventricular block complete 165.45 44.45 38 2165 1376 2354506
Drug abuse 165.42 44.45 61 2142 11965 2343917
Death 161.25 44.45 110 2093 81358 2274524
Intentional product misuse 160.09 44.45 56 2147 9433 2346449
Cardiogenic shock 148.87 44.45 39 2164 2452 2353430
Atrial fibrillation 126.02 44.45 52 2151 13716 2342166
Dizziness 115.15 44.45 79 2124 58586 2297296
Cardio-respiratory arrest 109.66 44.45 42 2161 9104 2346778
Exposure via ingestion 107.41 44.45 24 2179 764 2355118
Asthenia 105.97 44.45 69 2134 46857 2309025
Syncope 103.20 44.45 48 2155 16827 2339055
Poisoning deliberate 102.63 44.45 25 2178 1166 2354716
Metabolic acidosis 95.69 44.45 34 2169 5964 2349918
Anuria 92.06 44.45 25 2178 1799 2354083
Product complaint 88.93 44.45 30 2173 4508 2351374
Rhabdomyolysis 88.32 44.45 33 2170 6671 2349211
Heart rate decreased 86.88 44.45 28 2175 3648 2352234
Renal failure 86.77 44.45 43 2160 17306 2338576
Nodal arrhythmia 83.36 44.45 16 2187 235 2355647
Acute kidney injury 82.72 44.45 49 2154 28073 2327809
Presyncope 81.90 44.45 27 2176 3776 2352106
Blood pressure decreased 81.43 44.45 34 2169 9202 2346680
Labile blood pressure 78.95 44.45 15 2188 208 2355674
Myopathy 77.16 44.45 21 2182 1522 2354360
Atrioventricular block first degree 76.73 44.45 19 2184 948 2354934
Atrioventricular block second degree 72.79 44.45 17 2186 660 2355222
Nausea 70.61 44.45 79 2124 112110 2243772
Hyperkalaemia 70.35 44.45 27 2176 5866 2350016
Sinus arrest 68.16 44.45 14 2189 295 2355587
Pulmonary oedema 67.90 44.45 28 2175 7335 2348547
Atrioventricular block 62.89 44.45 17 2186 1200 2354682
Blood creatinine increased 61.33 44.45 29 2174 10504 2345378
Product residue present 59.32 44.45 16 2187 1120 2354762
Acidosis 58.18 44.45 17 2186 1593 2354289
Hypokalaemia 57.97 44.45 28 2175 10626 2345256
Fall 57.75 44.45 48 2155 47051 2308831
Confusional state 57.71 44.45 37 2166 24307 2331575
Palpitations 57.19 44.45 32 2171 16424 2339458
Loss of consciousness 53.27 44.45 32 2171 18735 2337147
Electrocardiogram QT prolonged 53.24 44.45 24 2179 7790 2348092
Blood potassium increased 52.98 44.45 17 2186 2179 2353703
Torsade de pointes 52.60 44.45 17 2186 2229 2353653
Blood urea increased 52.06 44.45 19 2184 3586 2352296
Dyspnoea 50.31 44.45 56 2147 78677 2277205
Blood creatine phosphokinase increased 48.92 44.45 20 2183 5116 2350766
Left ventricular dysfunction 48.83 44.45 14 2189 1226 2354656
Depressed level of consciousness 47.54 44.45 22 2181 7582 2348300
Renal impairment 47.39 44.45 24 2179 10068 2345814
Malaise 47.07 44.45 46 2157 55539 2300343
Sinus node dysfunction 46.92 44.45 12 2191 682 2355200
Shock 46.53 44.45 18 2185 3986 2351896
Sinus arrhythmia 45.99 44.45 10 2193 279 2355603
Haemodialysis 45.77 44.45 15 2188 2054 2353828
Suicide attempt 44.87 44.45 24 2179 11258 2344624

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
Completed suicide 1372.59 45.28 350 1456 15962 1729013
Bradycardia 967.50 45.28 244 1562 10290 1734685
Hypotension 619.50 45.28 219 1587 29435 1715540
Drug abuse 475.28 45.28 149 1657 13540 1731435
Toxicity to various agents 443.00 45.28 171 1635 28970 1716005
Cardiac arrest 377.17 45.28 130 1676 15800 1729175
Poisoning 291.44 45.28 71 1735 2461 1742514
Drug interaction 215.58 45.28 102 1704 27856 1717119
Overdose 182.85 45.28 78 1728 16623 1728352
Intentional overdose 174.28 45.28 61 1745 7609 1737366
Acute kidney injury 165.81 45.28 92 1714 34852 1710123
Atrial fibrillation 147.00 45.28 65 1741 15046 1729929
Heart rate decreased 145.88 45.28 42 1764 2767 1742208
Atrioventricular block complete 132.69 45.28 34 1772 1437 1743538
Exposure via ingestion 119.84 45.28 27 1779 653 1744322
Dizziness 116.67 45.28 73 1733 34288 1710687
Rhabdomyolysis 115.14 45.28 50 1756 11040 1733935
Nodal rhythm 114.14 45.28 23 1783 319 1744656
Death 111.08 45.28 103 1703 87340 1657635
Intentional product misuse 109.73 45.28 43 1763 7315 1737660
Syncope 88.52 45.28 45 1761 14124 1730851
Respiratory arrest 86.56 45.28 34 1772 5805 1739170
Atrioventricular block 82.38 45.28 23 1783 1348 1743627
Cardiogenic shock 81.36 45.28 26 1780 2428 1742547
Atrioventricular block first degree 81.26 45.28 21 1785 915 1744060
Pulmonary oedema 79.21 45.28 33 1773 6553 1738422
Metabolic acidosis 74.97 45.28 30 1776 5372 1739603
Somnolence 73.29 45.28 42 1764 16697 1728278
Atrioventricular block second degree 68.77 45.28 17 1789 617 1744358
Vomiting 68.22 45.28 55 1751 38260 1706715
Drug hypersensitivity 66.29 45.28 38 1768 15097 1729878
Shock 64.35 45.28 25 1781 4136 1740839
Dyspnoea 63.05 45.28 60 1746 51999 1692976
Sinus arrest 61.65 45.28 14 1792 350 1744625
Blood creatinine increased 61.02 45.28 35 1771 13911 1731064
Acute generalised exanthematous pustulosis 59.15 45.28 17 1789 1105 1743870
Sinus bradycardia 58.02 45.28 19 1787 1914 1743061
Suicide attempt 53.57 45.28 26 1780 7355 1737620
Cardio-respiratory arrest 53.57 45.28 28 1778 9265 1735710
Nodal arrhythmia 52.08 45.28 11 1795 194 1744781
Loss of consciousness 51.20 45.28 32 1774 14843 1730132
Medication error 51.10 45.28 22 1784 4721 1740254
Multiple organ dysfunction syndrome 48.05 45.28 26 1780 9216 1735759
Ventricular fibrillation 47.76 45.28 18 1788 2738 1742237
Blood glucose increased 47.43 45.28 27 1779 10557 1734418
Pulseless electrical activity 47.33 45.28 14 1792 1006 1743969
Hyperkalaemia 47.11 45.28 25 1781 8522 1736453
Fall 46.07 45.28 38 1768 27176 1717799
Bundle branch block left 45.69 45.28 13 1793 814 1744161

Pharmacologic Action:

SourceCodeDescription
ATC C05AE03 CARDIOVASCULAR SYSTEM
VASOPROTECTIVES
AGENTS FOR TREATMENT OF HEMORRHOIDS AND ANAL FISSURES FOR TOPICAL USE
Muscle relaxants
ATC C08DB01 CARDIOVASCULAR SYSTEM
CALCIUM CHANNEL BLOCKERS
SELECTIVE CALCIUM CHANNEL BLOCKERS WITH DIRECT CARDIAC EFFECTS
Benzothiazepine derivatives
FDA MoA N0000000069 Calcium Channel Antagonists
FDA EPC N0000175566 Calcium Channel Blocker
MeSH PA D000959 Antihypertensive Agents
MeSH PA D002121 Calcium Channel Blockers
MeSH PA D000077264 Calcium-Regulating Hormones and Agents
MeSH PA D002317 Cardiovascular Agents
MeSH PA D049990 Membrane Transport Modulators
CHEBI has role CHEBI:35620 vasodilator agent
CHEBI has role CHEBI:35674 antihypertensive agent
MeSH PA D014665 Vasodilator Agents

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Hypertensive disorder indication 38341003 DOID:10763
Atrial fibrillation indication 49436004 DOID:0060224
Paroxysmal supraventricular tachycardia indication 67198005
Prinzmetal angina indication 87343002
Angina pectoris indication 194828000
Supraventricular arrhythmia off-label use 72654001
Diastolic heart failure off-label use 418304008 DOID:9775
Hyperkalemia contraindication 14140009
Ventricular tachycardia contraindication 25569003
Complete atrioventricular block contraindication 27885002
Acute cerebrovascular insufficiency contraindication 29322000
Sick sinus syndrome contraindication 36083008 DOID:13884
Immunosuppression contraindication 38013005
Angioedema contraindication 41291007 DOID:1558
Low blood pressure contraindication 45007003
Bradycardia contraindication 48867003
Lown-Ganong-Levine syndrome contraindication 55475008 DOID:13087
Aortic valve stenosis contraindication 60573004 DOID:1712
Wolff-Parkinson-White pattern contraindication 74390002 DOID:384
Transplantation contraindication 77465005
Chronic idiopathic constipation contraindication 82934008
Hereditary angioneurotic edema contraindication 82966003 DOID:14735
Cardiogenic shock contraindication 89138009
Hyponatremia contraindication 89627008
Kidney disease contraindication 90708001 DOID:557
Disorder of connective tissue contraindication 105969002 DOID:65
Second degree atrioventricular block contraindication 195042002
Decompensated cardiac failure contraindication 195111005
Hypertrophic cardiomyopathy contraindication 233873004 DOID:11984
Disease of liver contraindication 235856003 DOID:409
Pregnancy, function contraindication 289908002
Renal artery stenosis contraindication 302233006
Neutropenic disorder contraindication 303011007 DOID:1227
Bone marrow depression contraindication 307762000
Left ventricular cardiac dysfunction contraindication 429589006
Hemodialysis with High-Flux Membrane contraindication

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 7.63 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
Voltage-dependent L-type calcium channel subunit alpha-1C Ion channel BLOCKER IC50 7.32 WOMBAT-PK CHEMBL
Voltage-dependent calcium channel gamma-1 subunit Ion channel IC50 6.10 WOMBAT-PK
Cytochrome P450 3A4 Enzyme IC50 5.74 DRUG MATRIX
Voltage-dependent T-type calcium channel subunit alpha-1H Ion channel Ki 4.02 WOMBAT-PK
5-hydroxytryptamine receptor 2A GPCR Ki 5.62 PDSP
Multidrug resistance protein 1 Transporter IC50 4.37 CHEMBL
Solute carrier family 22 member 1 Transporter IC50 4.91 CHEMBL
Potassium voltage-gated channel subfamily H member 2 Ion channel IC50 4.76 CHEMBL
Voltage-dependent L-type calcium channel subunit alpha-1S Ion channel Ki 6.42 CHEMBL
Sodium channel alpha subunits; brain (Types I, II, III) Ion channel IC50 4.35 CHEMBL
5-hydroxytryptamine receptor 3A Ion channel BLOCKER IC50 4.68 IUPHAR
Voltage-dependent L-type calcium channel subunit alpha-1C Ion channel IC50 4.52 CHEMBL
Voltage-gated L-type calcium channel Ion channel Ki 7.80 CHEMBL
Voltage-dependent L-type calcium channel subunit alpha-1D Ion channel IC50 7.34 CHEMBL
Voltage-dependent L-type calcium channel subunit alpha-1C Ion channel IC50 7.27 CHEMBL
Potassium voltage-gated channel subfamily C member 1 Unclassified BLOCKER IC50 4 IUPHAR
Potassium voltage-gated channel subfamily A member 7 Unclassified BLOCKER IC50 4.20 IUPHAR
5-hydroxytryptamine receptor 3A Ion channel BLOCKER IC50 5.26 IUPHAR
Voltage-dependent L-type calcium channel subunit alpha-1F Unclassified BLOCKER IC50 4 IUPHAR

External reference:

IDSource
D004110 MESH_DESCRIPTOR_UI
4020128 VUID
N0000179650 NUI
C0700579 UMLSCUI
D00616 KEGG_DRUG
14Y6444DRP UNII
144604-00-2 SECONDARY_CAS_RN
3443 RXNORM
372793000 SNOMEDCT_US
59941008 SNOMEDCT_US
4019722 VANDF
004514 NDDF
d00045 MMSL
CHEMBL23 ChEMBL_ID
DB00343 DRUGBANK_ID
CHEMBL1697 ChEMBL_ID
CHEMBL1200805 ChEMBL_ID
3433 INN_ID
CHEBI:101278 CHEBI
2298 IUPHAR_LIGAND_ID
39186 PUBCHEM_CID

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Diltiazem Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0093-0318 TABLET, FILM COATED 30 mg ORAL ANDA 11 sections
Diltiazem Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0093-0319 TABLET, FILM COATED 60 mg ORAL ANDA 11 sections
Diltiazem Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0093-0320 TABLET, FILM COATED 90 mg ORAL ANDA 11 sections
Diltiazem Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0093-0321 TABLET, FILM COATED 120 mg ORAL ANDA 11 sections
Cardizem HUMAN PRESCRIPTION DRUG LABEL 1 0187-0771 TABLET, COATED 30 mg ORAL NDA 12 sections
Cardizem HUMAN PRESCRIPTION DRUG LABEL 1 0187-0772 TABLET, COATED 60 mg ORAL NDA 12 sections
Cardizem HUMAN PRESCRIPTION DRUG LABEL 1 0187-0791 TABLET, COATED 90 mg ORAL NDA 12 sections
Cardizem HUMAN PRESCRIPTION DRUG LABEL 1 0187-0792 TABLET, COATED 120 mg ORAL NDA 12 sections
Cardizem CD HUMAN PRESCRIPTION DRUG LABEL 1 0187-0795 CAPSULE, COATED, EXTENDED RELEASE 120 mg ORAL NDA 12 sections
Cardizem CD HUMAN PRESCRIPTION DRUG LABEL 1 0187-0796 CAPSULE, COATED, EXTENDED RELEASE 180 mg ORAL NDA 12 sections
Cardizem CD HUMAN PRESCRIPTION DRUG LABEL 1 0187-0797 CAPSULE, COATED, EXTENDED RELEASE 240 mg ORAL NDA 12 sections
Cardizem CD HUMAN PRESCRIPTION DRUG LABEL 1 0187-0798 CAPSULE, COATED, EXTENDED RELEASE 300 mg ORAL NDA 12 sections
Cardizem CD HUMAN PRESCRIPTION DRUG LABEL 1 0187-0799 CAPSULE, COATED, EXTENDED RELEASE 360 mg ORAL NDA 12 sections
Cardizem LA HUMAN PRESCRIPTION DRUG LABEL 1 0187-2045 TABLET, EXTENDED RELEASE 120 mg ORAL NDA 16 sections
Cardizem LA HUMAN PRESCRIPTION DRUG LABEL 1 0187-2046 TABLET, EXTENDED RELEASE 180 mg ORAL NDA 16 sections
Cardizem LA HUMAN PRESCRIPTION DRUG LABEL 1 0187-2047 TABLET, EXTENDED RELEASE 240 mg ORAL NDA 16 sections
Cardizem LA HUMAN PRESCRIPTION DRUG LABEL 1 0187-2048 TABLET, EXTENDED RELEASE 300 mg ORAL NDA 16 sections
Cardizem LA HUMAN PRESCRIPTION DRUG LABEL 1 0187-2049 TABLET, EXTENDED RELEASE 360 mg ORAL NDA 16 sections
Cardizem LA HUMAN PRESCRIPTION DRUG LABEL 1 0187-2050 TABLET, EXTENDED RELEASE 420 mg ORAL NDA 16 sections
TIAZAC HUMAN PRESCRIPTION DRUG LABEL 1 0187-2612 CAPSULE, EXTENDED RELEASE 120 mg ORAL NDA 12 sections
TIAZAC HUMAN PRESCRIPTION DRUG LABEL 1 0187-2613 CAPSULE, EXTENDED RELEASE 180 mg ORAL NDA 12 sections
TIAZAC HUMAN PRESCRIPTION DRUG LABEL 1 0187-2614 CAPSULE, EXTENDED RELEASE 240 mg ORAL NDA 12 sections
TIAZAC HUMAN PRESCRIPTION DRUG LABEL 1 0187-2615 CAPSULE, EXTENDED RELEASE 300 mg ORAL NDA 12 sections
TIAZAC HUMAN PRESCRIPTION DRUG LABEL 1 0187-2616 CAPSULE, EXTENDED RELEASE 360 mg ORAL NDA 12 sections
TIAZAC HUMAN PRESCRIPTION DRUG LABEL 1 0187-2617 CAPSULE, EXTENDED RELEASE 420 mg ORAL NDA 12 sections
Diltiazem Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0228-2918 CAPSULE, EXTENDED RELEASE 360 mg ORAL ANDA 12 sections
Diltiazem Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0378-0023 TABLET, FILM COATED 30 mg ORAL ANDA 11 sections
Diltiazem Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0378-0045 TABLET, FILM COATED 60 mg ORAL ANDA 11 sections
Diltiazem Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0378-0135 TABLET, FILM COATED 90 mg ORAL ANDA 11 sections
Diltiazem Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0378-0525 TABLET, FILM COATED 120 mg ORAL ANDA 11 sections