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

Stem definition	Drug id	CAS RN
calcium channel blockers, diltiazem derivatives	897	42399-41-7

Description:

Molecule	Description
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

Molecule

Description

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:

Dose	Unit	Route
0.24	g	O

ADMET properties:

Property	Value	Reference
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 µM/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:

Date	Agency	Company	Orphan
Nov. 5, 1982	FDA	VALEANT INTL

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
Completed suicide	704.44	10.25	1155	94986	144765	46445156
Atrial fibrillation	584.13	10.25	881	95260	102709	46487212
Cardiac failure congestive	272.75	10.25	591	95550	91159	46498762
Bradycardia	224.96	10.25	451	95690	65847	46524074
Rheumatoid arthritis	202.62	10.25	122	96019	240093	46349828
Hypotension	192.59	10.25	967	95174	231622	46358299
Off label use	190.20	10.25	306	95835	379535	46210386
Drug ineffective	189.80	10.25	738	95403	677100	45912821
Maternal exposure during pregnancy	151.55	10.25	17	96124	102532	46487389
Dyspnoea	137.47	10.25	1642	94499	513906	46076015
Exposure during pregnancy	130.89	10.25	31	96110	108181	46481740
Nodal rhythm	113.17	10.25	60	96081	1665	46588256
Sedation complication	112.13	10.25	78	96063	3567	46586354
Creatinine renal clearance decreased	109.13	10.25	100	96041	6820	46583101
Toxicity to various agents	107.33	10.25	775	95366	210991	46378930
Treatment failure	102.54	10.25	32	96109	93055	46496866
Neutropenia	99.50	10.25	89	96052	143115	46446806
Cardiac arrest	92.34	10.25	400	95741	89999	46499922
Atrioventricular block complete	91.72	10.25	95	96046	7532	46582389
Nerve injury	87.36	10.25	93	96048	7612	46582309
Febrile neutropenia	84.03	10.25	45	96096	94582	46495339
Orthostatic hypotension	83.86	10.25	168	95973	24490	46565431
Dyspnoea exertional	81.19	10.25	258	95883	50031	46539890
Fluid retention	77.10	10.25	256	95885	50790	46539131
Synovitis	76.85	10.25	16	96125	61059	46528862
Atrioventricular block second degree	76.26	10.25	63	96078	3736	46586185
Heart rate increased	75.65	10.25	330	95811	74461	46515460
Chronic obstructive pulmonary disease	74.90	10.25	275	95866	57358	46532563
Poisoning	73.01	10.25	115	96026	13879	46576042
Gastrointestinal haemorrhage	71.22	10.25	332	95809	77041	46512880
Pemphigus	70.81	10.25	6	96135	45268	46544653
International normalised ratio increased	68.92	10.25	233	95908	46650	46543271
Sinus bradycardia	67.44	10.25	110	96031	13672	46576249
Chest pain	67.29	10.25	605	95536	175719	46414202
Oedema peripheral	65.62	10.25	557	95584	159149	46430772
Atrioventricular block first degree	63.74	10.25	71	96070	6115	46583806
Therapeutic product effect incomplete	62.59	10.25	42	96099	78111	46511810
Cardiogenic shock	62.27	10.25	117	96024	16267	46573654
Drug intolerance	58.10	10.25	136	96005	146913	46443008
Labile blood pressure	56.06	10.25	38	96103	1665	46588256
Product use issue	55.38	10.25	68	96073	94576	46495345
Contraindicated product administered	55.12	10.25	50	96091	79897	46510024
Systemic lupus erythematosus	54.98	10.25	33	96108	65147	46524774
Pulmonary congestion	54.16	10.25	104	96037	14695	46575226
Abortion spontaneous	53.75	10.25	12	96129	43634	46546287
Rash	53.57	10.25	473	95668	356039	46233882
Leukopenia	53.04	10.25	38	96103	68305	46521616
Therapeutic product effect decreased	50.85	10.25	57	96084	82544	46507377
Injection site erythema	50.77	10.25	47	96094	74380	46515541
Heart rate decreased	50.50	10.25	162	95979	31561	46558360
Atrial flutter	48.86	10.25	76	96065	9072	46580849
Alopecia	48.21	10.25	172	95969	162242	46427679
Hand deformity	47.98	10.25	7	96134	34567	46555354
Pulmonary arterial hypertension	47.42	10.25	139	96002	25789	46564132
Fall	46.60	10.25	943	95198	328154	46261767
Pneumonia	46.45	10.25	1057	95084	375263	46214658
Dizziness	46.09	10.25	969	95172	339445	46250476
Product use in unapproved indication	45.67	10.25	72	96069	90201	46499720
Product complaint	45.47	10.25	86	96055	12015	46577906
Malignant neoplasm progression	44.28	10.25	41	96100	64885	46525036
Cardiac disorder	43.17	10.25	192	95949	43666	46546255
Suspected suicide	42.13	10.25	50	96091	4611	46585310
Coronary artery disease	42.12	10.25	159	95982	33593	46556328
Blood calcium decreased	42.04	10.25	97	96044	15576	46574345
Palpitations	40.55	10.25	335	95806	94924	46494997
Pericardial haemorrhage	40.40	10.25	30	96111	1521	46588400
Supraventricular tachycardia	39.94	10.25	86	96055	13184	46576737
Medication error	39.72	10.25	147	95994	30764	46559157
Asthenia	39.68	10.25	878	95263	310197	46279724
Pyrexia	39.63	10.25	494	95647	348308	46241613
Renal failure	39.38	10.25	382	95759	113212	46476709
Acute generalised exanthematous pustulosis	39.32	10.25	70	96071	9335	46580586
Sedation	39.23	10.25	120	96021	22790	46567131
Hepatic enzyme increased	37.02	10.25	70	96071	81717	46508204
Hypoxia	36.88	10.25	207	95934	51631	46538290
Foetal exposure during pregnancy	36.77	10.25	9	96132	30738	46559183
Angina pectoris	36.67	10.25	130	96011	26645	46563276
Pulmonary hypertension	36.51	10.25	159	95982	35834	46554087
Respiratory arrest	36.32	10.25	152	95989	33664	46556257
Hyperkalaemia	35.10	10.25	201	95940	50508	46539413
Drug interaction	34.58	10.25	599	95542	202495	46387426
White blood cell count decreased	33.86	10.25	118	96023	112113	46477808
Nodal arrhythmia	33.83	10.25	25	96116	1258	46588663
Inhibitory drug interaction	33.76	10.25	30	96111	1965	46587956
Joint swelling	33.74	10.25	202	95939	165871	46424050
Presyncope	33.72	10.25	119	96022	24335	46565586
Arthropathy	33.70	10.25	78	96063	84622	46505299
Infusion related reaction	33.59	10.25	102	96039	101106	46488815
Pain in jaw	33.36	10.25	162	95979	38210	46551711
Intentional self-injury	33.29	10.25	5	96136	24161	46565760
Balance disorder	33.08	10.25	237	95904	64284	46525637
Musculoskeletal stiffness	33.07	10.25	98	96043	97895	46492026
Blood pressure systolic increased	32.98	10.25	132	96009	28655	46561266
C-reactive protein abnormal	32.77	10.25	3	96138	21267	46568654
Nephrolithiasis	32.76	10.25	145	95996	32906	46557015
Thrombocytopenia	32.49	10.25	142	95999	126439	46463482
Oedema	32.46	10.25	243	95898	66828	46523093
Torsade de pointes	32.35	10.25	75	96066	12079	46577842
Pulseless electrical activity	32.12	10.25	55	96086	7112	46582809
Injection site pain	32.10	10.25	113	96028	107039	46482882
Premature delivery	31.74	10.25	4	96137	22065	46567856
Bezoar	31.59	10.25	25	96116	1394	46588527
Arthralgia	31.12	10.25	546	95595	364057	46225864
Atrioventricular block	30.17	10.25	52	96089	6759	46583162
Respiratory tract congestion	29.93	10.25	75	96066	12689	46577232
Body tinea	28.74	10.25	20	96121	915	46589006
Pulmonary oedema	28.72	10.25	192	95949	50913	46539008
Pregnancy	28.69	10.25	10	96131	27127	46562794
Myocardial infarction	28.59	10.25	317	95824	97211	46492710
Suicidal ideation	28.48	10.25	45	96096	56337	46533584
Glossodynia	27.98	10.25	30	96111	44343	46545578
General physical health deterioration	27.84	10.25	133	96008	115636	46474285
Neutrophil count decreased	26.68	10.25	30	96111	43396	46546525
Ventricular tachycardia	26.42	10.25	86	96055	16881	46573040
Bunion operation	26.33	10.25	18	96123	800	46589121
Product residue present	26.17	10.25	36	96105	3846	46586075
Pancytopenia	25.94	10.25	89	96052	84969	46504952
Intentional product use issue	25.84	10.25	43	96098	52737	46537184
Blood pressure diastolic decreased	25.81	10.25	76	96065	14135	46575786
Cognitive disorder	25.39	10.25	146	95995	36737	46553184
Erythromelalgia	25.28	10.25	10	96131	137	46589784
Transfusion	25.22	10.25	72	96069	13159	46576762
Depressed level of consciousness	25.12	10.25	176	95965	47393	46542528
Injection site pruritus	24.92	10.25	27	96114	39716	46550205
Arrhythmia	24.69	10.25	139	96002	34702	46555219
Alveolitis	24.45	10.25	28	96113	2485	46587436
Seizure	24.29	10.25	151	95990	122903	46467018
Sinus arrhythmia	24.11	10.25	21	96120	1339	46588582
Fluid overload	23.79	10.25	115	96026	27070	46562851
Cardioactive drug level increased	23.60	10.25	25	96116	2034	46587887
Gouty tophus	23.54	10.25	10	96131	166	46589755
Sinus arrest	23.45	10.25	23	96118	1708	46588213
Hepatic ischaemia	23.41	10.25	14	96127	492	46589429
Arteriovenous fistula occlusion	23.17	10.25	12	96129	317	46589604
Colon gangrene	23.01	10.25	5	96136	4	46589917
Death	22.99	10.25	876	95265	334672	46255249
Muscle relaxant therapy	22.97	10.25	9	96132	120	46589801
Mucosal inflammation	22.79	10.25	28	96113	38948	46550973
Erythrodermic psoriasis	22.72	10.25	17	96124	872	46589049
Syncope	22.71	10.25	322	95819	104481	46485440
Blue toe syndrome	22.31	10.25	12	96129	343	46589578
Premature baby	22.26	10.25	5	96136	18107	46571814
Drug hypersensitivity	21.78	10.25	362	95779	243463	46346458
Bladder prolapse	21.71	10.25	23	96118	1871	46588050
C-reactive protein increased	21.69	10.25	56	96085	58534	46531387
Vasoplegia syndrome	21.69	10.25	18	96123	1074	46588847
Rectal prolapse	21.53	10.25	21	96120	1549	46588372
Injection site swelling	21.51	10.25	31	96110	40296	46549625
Epilepsy	21.48	10.25	11	96130	23727	46566194
Blood pressure inadequately controlled	21.33	10.25	35	96106	4371	46585550
Heart rate irregular	21.09	10.25	85	96056	18506	46571415
Rectal haemorrhage	21.06	10.25	143	95998	38112	46551809
BRASH syndrome	21.03	10.25	8	96133	98	46589823
Hospitalisation	20.90	10.25	211	95930	63174	46526747
Cardioversion	20.85	10.25	18	96123	1134	46588787
Nephroangiosclerosis	20.83	10.25	9	96132	156	46589765
Unevaluable event	20.50	10.25	164	95977	46011	46543910
Depression	20.37	10.25	238	95903	169866	46420055
Psoriasis	20.27	10.25	88	96053	78516	46511405
Cerebellar syndrome	20.22	10.25	30	96111	3435	46586486
Cardiac pacemaker insertion	20.13	10.25	31	96110	3668	46586253
Coagulopathy	19.74	10.25	83	96058	18416	46571505
Renal pain	19.52	10.25	38	96103	5423	46584498
Status epilepticus	19.01	10.25	3	96138	13976	46575945
Posterior reversible encephalopathy syndrome	18.97	10.25	4	96137	15137	46574784
Bone marrow failure	18.77	10.25	20	96121	29649	46560272
Thermal burn	18.74	10.25	35	96106	4842	46585079
Prinzmetal angina	18.32	10.25	14	96127	741	46589180
Stent placement	18.24	10.25	29	96112	3527	46586394
Multiple sclerosis relapse	18.23	10.25	37	96104	42088	46547833
Stomatitis	17.89	10.25	76	96065	68221	46521700
Cerebrovascular accident	17.89	10.25	300	95841	100739	46489182
Inappropriate schedule of product administration	17.87	10.25	71	96070	64942	46524979
Anuria	17.85	10.25	58	96083	11373	46578548
Injection site reaction	17.51	10.25	46	96095	47803	46542118
Impaired quality of life	17.41	10.25	27	96114	3215	46586706
Drug resistance	17.35	10.25	7	96134	17361	46572560
Hepatorenal syndrome	17.35	10.25	20	96121	1788	46588133
Sleep disorder	17.11	10.25	45	96096	46750	46543171
Stupor	17.09	10.25	28	96113	3492	46586429
Cytomegalovirus infection	17.04	10.25	8	96133	18136	46571785
Fear of eating	17.02	10.25	10	96131	340	46589581
Disease progression	17.01	10.25	114	96027	91186	46498735
Oxygen therapy	16.91	10.25	20	96121	1837	46588084
Blood pressure increased	16.88	10.25	360	95781	126306	46463615
Blood loss anaemia	16.73	10.25	47	96094	8510	46581411
Limb injury	16.70	10.25	81	96060	19093	46570828
Myopathy	16.61	10.25	48	96093	8833	46581088
Extrasystoles	16.34	10.25	33	96108	4836	46585085
Peak expiratory flow rate abnormal	16.33	10.25	7	96134	119	46589802
Metabolic acidosis	16.28	10.25	136	96005	38644	46551277
Drug-induced liver injury	16.16	10.25	17	96124	25351	46564570
Electrocardiogram QT shortened	16.11	10.25	7	96134	123	46589798
Leukaemoid reaction	16.11	10.25	8	96133	193	46589728
Urticaria	16.10	10.25	160	95981	117732	46472189
Aggression	15.94	10.25	14	96127	22730	46567191
Catheter site erythema	15.83	10.25	29	96112	3954	46585967
Cardiac ablation	15.71	10.25	16	96125	1243	46588678
Psoriatic arthropathy	15.71	10.25	32	96109	36347	46553574
Distributive shock	15.68	10.25	11	96130	510	46589411
Acute lung injury	15.59	10.25	16	96125	1255	46588666
Sinus node dysfunction	15.52	10.25	30	96111	4259	46585662
Sopor	15.41	10.25	11	96130	19817	46570104
Forced expiratory volume decreased	15.27	10.25	33	96108	5071	46584850
Atrioventricular dissociation	15.25	10.25	8	96133	217	46589704
Heart rate abnormal	15.19	10.25	26	96115	3361	46586560
Catheter site haemorrhage	15.16	10.25	23	96118	2686	46587235
Histoplasmosis	15.06	10.25	18	96123	1672	46588249
Red blood cell sedimentation rate increased	14.97	10.25	15	96126	22874	46567047
Productive cough	14.92	10.25	165	95976	50550	46539371
Carbon dioxide increased	14.80	10.25	15	96126	1159	46588762
Exposure via ingestion	14.75	10.25	26	96115	3441	46586480
Pain	14.70	10.25	818	95323	476130	46113791
Activated partial thromboplastin time prolonged	14.63	10.25	39	96102	6850	46583071
Dialysis	14.61	10.25	50	96091	10066	46579855
Hepatotoxicity	14.59	10.25	18	96123	24991	46564930
Pulmonary embolism	14.56	10.25	148	95993	108437	46481484
Anion gap abnormal	14.52	10.25	9	96132	338	46589583
Infection susceptibility increased	14.38	10.25	20	96121	2159	46587762
Respiratory rate increased	14.38	10.25	54	96087	11379	46578542
Disturbance in attention	14.28	10.25	27	96114	31533	46558388
Pericarditis	14.19	10.25	17	96124	23910	46566011
Lower gastrointestinal haemorrhage	14.11	10.25	40	96101	7280	46582641
Cardiac monitoring	13.97	10.25	4	96137	18	46589903
Intra-abdominal haematoma	13.93	10.25	17	96124	1614	46588307
Poor quality sleep	13.69	10.25	65	96076	15188	46574733
Hypertrophic cardiomyopathy	13.68	10.25	15	96126	1269	46588652
Humidity intolerance	13.68	10.25	9	96132	375	46589546
Total lung capacity decreased	13.67	10.25	14	96127	1095	46588826
Oxygen saturation decreased	13.60	10.25	209	95932	68955	46520966
Unresponsive to stimuli	13.59	10.25	113	96028	32061	46557860
Inflammation	13.58	10.25	53	96088	48728	46541193
Renal necrosis	13.55	10.25	5	96136	56	46589865
Nasal congestion	13.46	10.25	155	95986	47958	46541963
Acute myocardial infarction	13.42	10.25	112	96029	31812	46558109
Wrong technique in product usage process	13.38	10.25	62	96079	54360	46535561
Injection site urticaria	13.37	10.25	4	96137	11963	46577958
Anaphylactic reaction	13.36	10.25	60	96081	53052	46536869
Bundle branch block left	13.36	10.25	36	96105	6363	46583558
Arrhythmogenic right ventricular dysplasia	13.31	10.25	4	96137	22	46589899
Sebaceous gland infection	13.29	10.25	6	96135	116	46589805
Acute myeloid leukaemia	13.28	10.25	8	96133	15770	46574151
Sinoatrial block	13.25	10.25	12	96129	806	46589115
Plasma cell myeloma	13.25	10.25	47	96094	44431	46545490
Incision site haemorrhage	13.24	10.25	10	96131	520	46589401
Caesarean section	13.18	10.25	9	96132	16594	46573327
Wound	12.90	10.25	45	96096	42757	46547164
Injection site inflammation	12.85	10.25	23	96118	3079	46586842
Haemodialysis	12.83	10.25	45	96096	9172	46580749
Discomfort	12.80	10.25	51	96090	46619	46543302
Liver disorder	12.74	10.25	37	96104	37209	46552712
Brain natriuretic peptide increased	12.71	10.25	29	96112	4621	46585300
Arteriospasm coronary	12.70	10.25	25	96116	3596	46586325
Osteonecrosis of jaw	12.64	10.25	33	96108	34369	46555552
Rhabdomyolysis	12.63	10.25	137	96004	41772	46548149
Metastases to liver	12.62	10.25	13	96128	19572	46570349
Muscle spasticity	12.47	10.25	4	96137	11436	46578485
Hypochromic anaemia	12.32	10.25	15	96126	1420	46588501
Metastases to central nervous system	12.09	10.25	4	96137	11217	46578704
Bladder disorder	12.05	10.25	37	96104	7041	46582880
Injection site rash	11.99	10.25	9	96132	15804	46574117
Exercise tolerance decreased	11.91	10.25	28	96113	4549	46585372
Duodenal polyp	11.88	10.25	5	96136	81	46589840
Migraine	11.79	10.25	90	96051	69936	46519985
Erythema	11.78	10.25	215	95926	142605	46447316
Night sweats	11.74	10.25	24	96117	27226	46562695
No adverse event	11.71	10.25	34	96107	34197	46555724
Bronchitis	11.58	10.25	293	95848	105686	46484235
Blister	11.48	10.25	50	96091	44581	46545340
Accidental exposure to product	11.45	10.25	16	96125	21065	46568856
Abnormal behaviour	11.42	10.25	16	96125	21042	46568879
Catheter site discharge	11.40	10.25	17	96124	1955	46587966
Upper gastrointestinal haemorrhage	11.35	10.25	66	96075	16672	46573249
Electrocardiogram QRS complex shortened	11.34	10.25	8	96133	374	46589547
Mitral valve incompetence	11.30	10.25	72	96069	18780	46571141
Fibrous histiocytoma	11.26	10.25	9	96132	509	46589412
Ill-defined disorder	11.24	10.25	24	96117	26803	46563118
Mental status changes	11.24	10.25	124	96017	37964	46551957
CREST syndrome	11.21	10.25	8	96133	381	46589540
Electrocardiogram U wave present	11.20	10.25	5	96136	94	46589827
Asthma	11.18	10.25	257	95884	91285	46498636
Pneumocystis jirovecii pneumonia	11.16	10.25	9	96132	15239	46574682
Polyneuropathy	11.14	10.25	5	96136	11639	46578282
Ventricular fibrillation	11.06	10.25	50	96091	11446	46578475
Catheter site inflammation	11.06	10.25	10	96131	670	46589251
Retroperitoneal haemorrhage	11.00	10.25	20	96121	2710	46587211
Brain oedema	10.97	10.25	6	96135	12472	46577449
Blood pressure decreased	10.96	10.25	172	95969	56987	46532934
Metastases to bone	10.81	10.25	12	96129	17464	46572457
Contusion	10.81	10.25	246	95895	87241	46502680
Coronary artery occlusion	10.80	10.25	39	96102	8063	46581858
Hyperbilirubinaemia	10.77	10.25	4	96137	10434	46579487
Intestinal ischaemia	10.69	10.25	35	96106	6890	46583031
Cough	10.68	10.25	578	95563	229671	46360250
Seasonal allergy	10.67	10.25	55	96086	13279	46576642
Palmar-plantar erythrodysaesthesia syndrome	10.63	10.25	16	96125	20435	46569486
Live birth	10.59	10.25	4	96137	10326	46579595
Atrial appendage closure	10.57	10.25	3	96138	13	46589908
Blood count abnormal	10.54	10.25	68	96073	17810	46572111
Aortic stenosis	10.54	10.25	26	96115	4356	46585565
Multiple sclerosis	10.54	10.25	22	96119	24769	46565152
Fracture	10.54	10.25	11	96130	16460	46573461
Hepatic haematoma	10.49	10.25	8	96133	422	46589499
Malignant melanoma	10.43	10.25	4	96137	10230	46579691
Condition aggravated	10.39	10.25	406	95735	244646	46345275
Jaundice	10.35	10.25	28	96113	28817	46561104
Renal injury	10.33	10.25	43	96098	9498	46580423
Gastrointestinal disorder	10.30	10.25	76	96065	59500	46530421
Enlarged uvula	10.28	10.25	5	96136	115	46589806
Gravitational oedema	10.27	10.25	12	96129	1088	46588833
Orthopnoea	10.25	10.25	31	96110	5849	46584072

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
Bradycardia	390.35	10.59	556	57933	64970	29829019
Atrial fibrillation	316.65	10.59	670	57819	107454	29786535
Completed suicide	290.64	10.59	616	57873	98876	29795113
Cardiac failure congestive	143.92	10.59	426	58063	83981	29810008
Hypotension	135.33	10.59	758	57731	199807	29694182
Off label use	134.63	10.59	174	58315	249116	29644873
Cardiac arrest	86.58	10.59	385	58104	92465	29801524
Febrile neutropenia	61.07	10.59	71	58418	106622	29787367
Atrial flutter	60.83	10.59	104	58385	14177	29879812
Dyspnoea	59.76	10.59	947	57542	332348	29561641
Drug ineffective	59.62	10.59	405	58084	339982	29554007
International normalised ratio increased	58.02	10.59	215	58274	47524	29846465
Atrioventricular block complete	56.42	10.59	76	58413	8401	29885588
Atrioventricular block	54.23	10.59	69	58420	7213	29886776
Myocardial infarction	50.88	10.59	419	58070	125206	29768783
Pyrexia	46.84	10.59	360	58129	294129	29599860
Product use in unapproved indication	46.68	10.59	45	58444	73648	29820341
Dizziness	43.18	10.59	575	57914	194334	29699655
Chronic obstructive pulmonary disease	41.98	10.59	190	58299	45936	29848053
Incision site pain	41.28	10.59	33	58456	1971	29892018
Poisoning	40.93	10.59	77	58412	11305	29882684
Prinzmetal angina	39.80	10.59	24	58465	905	29893084
Atrioventricular block first degree	37.86	10.59	51	58438	5637	29888352
Syncope	36.96	10.59	288	58201	84615	29809374
Nodal arrhythmia	36.35	10.59	22	58467	835	29893154
Neutropenia	36.26	10.59	129	58360	128411	29765578
Drug interaction	35.59	10.59	567	57922	199001	29694988
Arterial spasm	34.71	10.59	12	58477	116	29893873
Gastrointestinal haemorrhage	34.11	10.59	279	58210	83167	29810822
Coronary artery disease	32.75	10.59	187	58302	49525	29844464
Nodal rhythm	32.71	10.59	25	58464	1398	29892591
Cardioplegia	31.44	10.59	6	58483	0	29893989
Chest pain	30.71	10.59	358	58131	117269	29776720
Exposure via ingestion	30.06	10.59	31	58458	2580	29891409
Cardiogenic shock	29.52	10.59	86	58403	16775	29877214
Oedema peripheral	29.38	10.59	326	58163	105506	29788483
Angina unstable	28.88	10.59	70	58419	12240	29881749
Tetany	28.28	10.59	18	58471	748	29893241
Heart rate decreased	27.56	10.59	97	58392	20897	29873092
Angina pectoris	26.40	10.59	121	58368	29397	29864592
Red blood cells urine positive	25.83	10.59	23	58466	1594	29892395
Serotonin syndrome	24.58	10.59	3	58486	17888	29876101
Suspected suicide	23.61	10.59	30	58459	3131	29890858
Medication error	23.44	10.59	92	58397	20880	29873109
General physical health deterioration	23.32	10.59	108	58381	99836	29794153
Pancytopenia	22.88	10.59	87	58402	84965	29809024
Blood glucose increased	22.63	10.59	201	58288	61329	29832660
Fluid retention	22.01	10.59	102	58387	24896	29869093
Pulmonary arterial hypertension	21.93	10.59	53	58436	9248	29884741
Product use issue	21.88	10.59	35	58454	45981	29848008
Influenza virus test positive	21.02	10.59	8	58481	104	29893885
Treatment failure	21.00	10.59	22	58467	34657	29859332
Mycotic allergy	20.68	10.59	9	58480	168	29893821
Discharge	20.35	10.59	8	58481	114	29893875
Chondrocalcinosis	19.99	10.59	10	58479	259	29893730
Neutrophil count decreased	19.53	10.59	33	58456	42421	29851568
White blood cell count decreased	19.41	10.59	91	58398	83856	29810133
Injury	19.37	10.59	89	58400	21642	29872347
Atrioventricular block second degree	19.16	10.59	27	58462	3113	29890876
Cerebrovascular accident	18.72	10.59	247	58242	83230	29810759
Myocardial ischaemia	18.57	10.59	75	58414	17242	29876747
Acquired haemophilia	18.47	10.59	14	58475	773	29893216
Electrocardiogram QRS complex shortened	18.40	10.59	8	58481	149	29893840
Thrombocytopenia	18.35	10.59	175	58314	136869	29757120
Mite allergy	18.32	10.59	9	58480	224	29893765
Rheumatoid arthritis	18.06	10.59	33	58456	41164	29852825
Intentional product use issue	18.01	10.59	27	58462	36413	29857576
Atrial thrombosis	17.57	10.59	20	58469	1861	29892128
Malignant neoplasm progression	17.53	10.59	77	58412	72210	29821779
Nephrogenic systemic fibrosis	17.52	10.59	31	58458	4340	29889649
Ventricular fibrillation	17.40	10.59	67	58422	15071	29878918
Pneumocystis jirovecii pneumonia	17.13	10.59	6	58483	17114	29876875
Ischaemic hepatitis	17.03	10.59	18	58471	1541	29892448
Eczema infected	16.97	10.59	5	58484	27	29893962
Gallbladder polyp	16.70	10.59	9	58480	273	29893716
Palpitations	16.35	10.59	117	58372	33456	29860533
Hepatic function abnormal	16.33	10.59	36	58453	41909	29852080
Skin tightness	16.32	10.59	20	58469	2012	29891977
Spirometry abnormal	16.23	10.59	9	58480	289	29893700
Toxic optic neuropathy	15.71	10.59	12	58477	670	29893319
Blood urea increased	15.65	10.59	110	58379	31271	29862718
Protein urine present	15.57	10.59	31	58458	4744	29889245
Lymphocyte count decreased	15.50	10.59	76	58413	18979	29875010
Vitiligo	15.44	10.59	12	58477	688	29893301
Pacemaker generated rhythm	15.30	10.59	5	58484	40	29893949
BRASH syndrome	15.19	10.59	5	58484	41	29893948
Psychotic disorder	14.98	10.59	12	58477	21503	29872486
Hypoxia	14.94	10.59	151	58338	47703	29846286
Toxicity to various agents	14.89	10.59	452	58037	176731	29717258
Pericardial haemorrhage	14.79	10.59	23	58466	2895	29891094
Mesothelioma	14.76	10.59	10	58479	462	29893527
Blood pressure immeasurable	14.64	10.59	13	58476	898	29893091
Cardiac disorder	14.50	10.59	130	58359	39763	29854226
Blood pressure systolic decreased	14.49	10.59	26	58463	3681	29890308
Renal injury	14.38	10.59	53	58436	11676	29882313
Agranulocytosis	14.35	10.59	13	58476	21929	29872060
Product dose omission issue	14.03	10.59	113	58376	91518	29802471
Infection	14.02	10.59	92	58397	77982	29816007
Sinus arrest	13.92	10.59	16	58473	1504	29892485
Device capturing issue	13.65	10.59	3	58486	3	29893986
Subacute cutaneous lupus erythematosus	13.60	10.59	11	58478	668	29893321
Rectal fissure	13.48	10.59	8	58481	293	29893696
Dust allergy	13.44	10.59	9	58480	408	29893581
Sepsis	13.44	10.59	203	58286	146192	29747797
Angina bullosa haemorrhagica	13.42	10.59	5	58484	61	29893928
Fear	13.34	10.59	49	58440	10776	29883213
Ventricular tachycardia	13.31	10.59	86	58403	23776	29870213
Epilepsy	13.13	10.59	12	58477	20157	29873832
Heart rate irregular	13.07	10.59	53	58436	12206	29881783
Anuria	12.97	10.59	47	58442	10269	29883720
Aortic stenosis	12.86	10.59	26	58463	4022	29889967
Bronchopulmonary aspergillosis	12.83	10.59	4	58485	12280	29881709
Cardiospasm	12.79	10.59	3	58486	5	29893984
Eosinophilic pleural effusion	12.73	10.59	7	58482	221	29893768
Blood pressure inadequately controlled	12.67	10.59	20	58469	2550	29891439
Mast cell degranulation present	12.61	10.59	5	58484	73	29893916
Arrhythmia	12.52	10.59	109	58380	33060	29860929
Antiacetylcholine receptor antibody positive	12.46	10.59	4	58485	30	29893959
Septic shock	12.43	10.59	73	58416	63534	29830455
Hyperbilirubinaemia	12.37	10.59	9	58480	16933	29877056
Encephalopathy	12.24	10.59	28	58461	32177	29861812
Osteonecrosis of jaw	12.21	10.59	11	58478	18607	29875382
Product residue present	12.06	10.59	20	58469	2658	29891331
Drug resistance	11.93	10.59	13	58476	20120	29873869
Anticoagulation drug level above therapeutic	11.77	10.59	16	58473	1783	29892206
Abnormal behaviour	11.70	10.59	20	58469	25603	29868386
Emotional distress	11.51	10.59	61	58428	15704	29878285
Conjunctivitis allergic	11.44	10.59	9	58480	525	29893464
Rhabdomyolysis	11.41	10.59	181	58308	63399	29830590
Labyrinthitis	11.39	10.59	11	58478	846	29893143
Cardioactive drug level increased	11.37	10.59	15	58474	1624	29892365
Right ventricular failure	11.31	10.59	38	58451	7998	29885991
Anhedonia	11.27	10.59	39	58450	8330	29885659
Dyspnoea exertional	11.15	10.59	112	58377	35318	29858671
Blood pressure diastolic decreased	11.11	10.59	32	58457	6199	29887790
Iron binding capacity total increased	11.11	10.59	4	58485	44	29893945
Arteriospasm coronary	11.06	10.59	19	58470	2599	29891390
Transaminases increased	11.00	10.59	18	58471	23439	29870550
Lung adenocarcinoma stage IV	10.91	10.59	5	58484	106	29893883
Lower gastrointestinal haemorrhage	10.79	10.59	37	58452	7867	29886122
Unevaluable event	10.75	10.59	102	58387	31683	29862306
Shock	10.75	10.59	79	58410	22780	29871209
Infectious mononucleosis	10.69	10.59	8	58481	433	29893556
Tooth injury	10.68	10.59	10	58479	740	29893249
Inner ear disorder	10.62	10.59	6	58483	200	29893789

Pharmacologic Action:

Source	Code	Description
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
MeSH PA	D014665	Vasodilator Agents
CHEBI has role	CHEBI:35620	vasodilator
CHEBI has role	CHEBI:35674	antihypertensive
CHEBI has role	CHEBI:38215	calcium channel blockers

Drug Use (View source of the data)

Disease	Relation	SNOMED_ID	DOID
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
Anal fissure	off-label use	30037006
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 level	Dissociation constant	Type (acidic/basic)
pKa1	7.63	Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

Formulation strength	Trade name	Applicant	Application number	Approval date	Type	Dose form	Route	Exclusivity date	Description
120MG	DILTIAZEM HYDROCHLORIDE	GLENMARK PHARMS LTD	A212317	March 22, 2021	RX	CAPSULE, EXTENDED RELEASE	ORAL	Sept. 26, 2021	COMPETITIVE GENERIC THERAPY
60MG	DILTIAZEM HYDROCHLORIDE	GLENMARK PHARMS LTD	A212317	March 22, 2021	RX	CAPSULE, EXTENDED RELEASE	ORAL	Sept. 26, 2021	COMPETITIVE GENERIC THERAPY
90MG	DILTIAZEM HYDROCHLORIDE	GLENMARK PHARMS LTD	A212317	March 22, 2021	RX	CAPSULE, EXTENDED RELEASE	ORAL	Sept. 26, 2021	COMPETITIVE GENERIC THERAPY

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Bioact source	MoA source
Voltage-dependent L-type calcium channel subunit alpha-1C	Ion channel	Q13936	CAC1C_HUMAN	BLOCKER	IC50	7.32	WOMBAT-PK	CHEMBL
Voltage-dependent calcium channel gamma-1 subunit	Ion channel	Q06432	CCG1_HUMAN		IC50	6.10	WOMBAT-PK
Cytochrome P450 3A4	Enzyme	P08684	CP3A4_HUMAN		IC50	5.74	DRUG MATRIX
Voltage-dependent T-type calcium channel subunit alpha-1H	Ion channel	O95180	CAC1H_HUMAN		Ki	4.02	WOMBAT-PK
5-hydroxytryptamine receptor 2A	GPCR	P28223	5HT2A_HUMAN		Ki	5.62	PDSP
Multidrug resistance protein 1	Transporter	P08183	MDR1_HUMAN		IC50	4.37	CHEMBL
Solute carrier family 22 member 1	Transporter	O15245	S22A1_HUMAN		IC50	4.91	CHEMBL
Potassium voltage-gated channel subfamily H member 2	Ion channel	Q12809	KCNH2_HUMAN		IC50	4.76	CHEMBL
Voltage-dependent L-type calcium channel subunit alpha-1S	Ion channel	Q13698	CAC1S_HUMAN		Ki	6.42	CHEMBL
Sodium channel alpha subunits; brain (Types I, II, III)	Ion channel	P35498 Q99250 Q9NY46	SCN1A_HUMAN SCN2A_HUMAN SCN3A_HUMAN		IC50	4.35	CHEMBL
5-hydroxytryptamine receptor 3A	Ion channel	P46098	5HT3A_HUMAN	BLOCKER	IC50	4.68	IUPHAR
Voltage-dependent L-type calcium channel subunit alpha-1C	Ion channel		CAC1C_RABIT		IC50	4.52	CHEMBL
Voltage-gated L-type calcium channel	Ion channel		CAC1C_RAT CAC1D_RAT CAC1S_RAT		Ki	7.80	CHEMBL
Voltage-dependent L-type calcium channel subunit alpha-1D	Ion channel		CAC1D_RAT		IC50	7.34	CHEMBL
Voltage-dependent L-type calcium channel subunit alpha-1C	Ion channel		CAC1C_RAT		IC50	7.27	CHEMBL
Potassium voltage-gated channel subfamily C member 1	Unclassified		KCNC1_MOUSE	BLOCKER	IC50	4	IUPHAR
Potassium voltage-gated channel subfamily A member 7	Unclassified		KCNA7_MOUSE	BLOCKER	IC50	4.20	IUPHAR
5-hydroxytryptamine receptor 3A	Ion channel		5HT3A_MOUSE	BLOCKER	IC50	5.26	IUPHAR
Voltage-dependent L-type calcium channel subunit alpha-1F	Unclassified		CAC1F_MOUSE	BLOCKER	IC50	4	IUPHAR

External reference:

ID	Source
4020128	VUID
N0000179650	NUI
D00616	KEGG_DRUG
33286-22-5	SECONDARY_CAS_RN
4018817	VANDF
4019722	VANDF
4020128	VANDF
C0012373	UMLSCUI
CHEBI:101278	CHEBI
C9F	PDB_CHEM_ID
39186	PUBCHEM_CID
CHEMBL23	ChEMBL_ID
CHEMBL1697	ChEMBL_ID
CHEMBL1200805	ChEMBL_ID
DB00343	DRUGBANK_ID
D004110	MESH_DESCRIPTOR_UI
2298	IUPHAR_LIGAND_ID
3433	INN_ID
EE92BBP03H	UNII
203211	RXNORM
1547	MMSL
4604	MMSL
d00045	MMSL
000711	NDDF
004514	NDDF
007237	NDDF
12218006	SNOMEDCT_US
372793000	SNOMEDCT_US
59941008	SNOMEDCT_US

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
Diltiazem Hydrochloride	HUMAN PRESCRIPTION DRUG LABEL	1	0093-0318	TABLET, FILM COATED	30 mg	ORAL	ANDA	18 sections
Diltiazem Hydrochloride	HUMAN PRESCRIPTION DRUG LABEL	1	0093-0319	TABLET, FILM COATED	60 mg	ORAL	ANDA	18 sections
Diltiazem Hydrochloride	HUMAN PRESCRIPTION DRUG LABEL	1	0093-0320	TABLET, FILM COATED	90 mg	ORAL	ANDA	18 sections
Diltiazem Hydrochloride	HUMAN PRESCRIPTION DRUG LABEL	1	0093-0321	TABLET, FILM COATED	120 mg	ORAL	ANDA	18 sections
Cardizem	HUMAN PRESCRIPTION DRUG LABEL	1	0187-0771	TABLET, COATED	30 mg	ORAL	NDA	21 sections
Cardizem	HUMAN PRESCRIPTION DRUG LABEL	1	0187-0772	TABLET, COATED	60 mg	ORAL	NDA	21 sections
Cardizem	HUMAN PRESCRIPTION DRUG LABEL	1	0187-0791	TABLET, COATED	90 mg	ORAL	NDA	21 sections
Cardizem	HUMAN PRESCRIPTION DRUG LABEL	1	0187-0792	TABLET, COATED	120 mg	ORAL	NDA	21 sections
Cardizem CD	HUMAN PRESCRIPTION DRUG LABEL	1	0187-0795	CAPSULE, COATED, EXTENDED RELEASE	120 mg	ORAL	NDA	14 sections
Cardizem CD	HUMAN PRESCRIPTION DRUG LABEL	1	0187-0796	CAPSULE, COATED, EXTENDED RELEASE	180 mg	ORAL	NDA	14 sections
Cardizem CD	HUMAN PRESCRIPTION DRUG LABEL	1	0187-0797	CAPSULE, COATED, EXTENDED RELEASE	240 mg	ORAL	NDA	14 sections
Cardizem CD	HUMAN PRESCRIPTION DRUG LABEL	1	0187-0798	CAPSULE, COATED, EXTENDED RELEASE	300 mg	ORAL	NDA	14 sections
Cardizem CD	HUMAN PRESCRIPTION DRUG LABEL	1	0187-0799	CAPSULE, COATED, EXTENDED RELEASE	360 mg	ORAL	NDA	14 sections
Cardizem LA	HUMAN PRESCRIPTION DRUG LABEL	1	0187-2045	TABLET, EXTENDED RELEASE	120 mg	ORAL	NDA	25 sections
Cardizem LA	HUMAN PRESCRIPTION DRUG LABEL	1	0187-2046	TABLET, EXTENDED RELEASE	180 mg	ORAL	NDA	25 sections
Cardizem LA	HUMAN PRESCRIPTION DRUG LABEL	1	0187-2047	TABLET, EXTENDED RELEASE	240 mg	ORAL	NDA	25 sections
Cardizem LA	HUMAN PRESCRIPTION DRUG LABEL	1	0187-2048	TABLET, EXTENDED RELEASE	300 mg	ORAL	NDA	25 sections
Cardizem LA	HUMAN PRESCRIPTION DRUG LABEL	1	0187-2049	TABLET, EXTENDED RELEASE	360 mg	ORAL	NDA	25 sections
Cardizem LA	HUMAN PRESCRIPTION DRUG LABEL	1	0187-2050	TABLET, EXTENDED RELEASE	420 mg	ORAL	NDA	25 sections
TIAZACEXTENDED RELEASE	HUMAN PRESCRIPTION DRUG LABEL	1	0187-2612	CAPSULE, EXTENDED RELEASE	120 mg	ORAL	NDA	23 sections
TIAZACEXTENDED RELEASE	HUMAN PRESCRIPTION DRUG LABEL	1	0187-2613	CAPSULE, EXTENDED RELEASE	180 mg	ORAL	NDA	23 sections
TIAZACEXTENDED RELEASE	HUMAN PRESCRIPTION DRUG LABEL	1	0187-2614	CAPSULE, EXTENDED RELEASE	240 mg	ORAL	NDA	23 sections
TIAZACEXTENDED RELEASE	HUMAN PRESCRIPTION DRUG LABEL	1	0187-2615	CAPSULE, EXTENDED RELEASE	300 mg	ORAL	NDA	23 sections
TIAZACEXTENDED RELEASE	HUMAN PRESCRIPTION DRUG LABEL	1	0187-2616	CAPSULE, EXTENDED RELEASE	360 mg	ORAL	NDA	23 sections
TIAZACEXTENDED RELEASE	HUMAN PRESCRIPTION DRUG LABEL	1	0187-2617	CAPSULE, EXTENDED RELEASE	420 mg	ORAL	NDA	23 sections
Diltiazem Hydrochloride	HUMAN PRESCRIPTION DRUG LABEL	1	0228-2918	CAPSULE, EXTENDED RELEASE	360 mg	ORAL	ANDA	20 sections
Diltiazem Hydrochloride	HUMAN PRESCRIPTION DRUG LABEL	1	0378-6060	CAPSULE, EXTENDED RELEASE	60 mg	ORAL	ANDA	20 sections
Diltiazem Hydrochloride	HUMAN PRESCRIPTION DRUG LABEL	1	0378-6090	CAPSULE, EXTENDED RELEASE	90 mg	ORAL	ANDA	20 sections
Diltiazem Hydrochloride	HUMAN PRESCRIPTION DRUG LABEL	1	0378-6120	CAPSULE, EXTENDED RELEASE	120 mg	ORAL	ANDA	20 sections
Diltiazem Hydrochloride	HUMAN PRESCRIPTION DRUG LABEL	1	0409-1171	INJECTION, SOLUTION	5 mg	INTRAVENOUS	ANDA	24 sections