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

Stem definition	Drug id	CAS RN
	463	58-08-2

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: anhydrous caffeine peyona caffeine 1,3,7-trimethyl-2,6-dioxopurine 7-methyltheophylline cafalgine cafeina durvitan guaranine thein caffeine citrate caffeine, citrated nymusa	A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes SMOOTH MUSCLE, stimulates CARDIAC MUSCLE, stimulates DIURESIS, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide PHOSPHODIESTERASES, antagonism of ADENOSINE RECEPTORS, and modulation of intracellular calcium handling. Molecular weight: 194.19 Formula: C8H10N4O2 CLOGP: -0.04 LIPINSKI: 0 HAC: 6 HDO: 0 TPSA: 58.44 ALOGS: -1.25 ROTB: 0

Molecule

Description

Molfile Inchi Smiles

Synonyms:

anhydrous caffeine
peyona
caffeine
1,3,7-trimethyl-2,6-dioxopurine
7-methyltheophylline
cafalgine
cafeina
durvitan
guaranine
thein
caffeine citrate
caffeine, citrated
nymusa

A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes SMOOTH MUSCLE, stimulates CARDIAC MUSCLE, stimulates DIURESIS, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide PHOSPHODIESTERASES, antagonism of ADENOSINE RECEPTORS, and modulation of intracellular calcium handling.

Molecular weight: 194.19
Formula: C8H10N4O2
CLOGP: -0.04
LIPINSKI: 0
HAC: 6
HDO: 0
TPSA: 58.44
ALOGS: -1.25
ROTB: 0

Drug dosage:

Dose	Unit	Route
0.40	g	O
0.40	g	P

ADMET properties:

Property	Value	Reference
BDDCS (Biopharmaceutical Drug Disposition Classification System)	1	Benet LZ, Broccatelli F, Oprea TI
S (Water solubility)	21.50 mg/mL	Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine)	1 %	Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose)	51.77 µM/kg/day	Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability)	98 %	Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution)	0.63 L/kg	Lombardo F, Berellini G, Obach RS
CL (Clearance)	1.40 mL/min/kg	Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma)	0.64 %	Lombardo F, Berellini G, Obach RS
t_half (Half-life)	4.90 hours	Lombardo F, Berellini G, Obach RS

Approvals:

Date	Agency	Company	Orphan
Nov. 26, 1948	FDA	NOVARTIS

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	11901.26	39.95	2686	8289	18348	2328762
Toxicity to various agents	11409.04	39.95	2820	8155	29934	2317176
Overdose	3588.97	39.95	1038	9937	18869	2328241
Death	2402.64	39.95	1115	9860	80353	2266757
Intentional overdose	1965.15	39.95	576	10399	10745	2336365
Intentional product misuse	1896.68	39.95	539	10436	8950	2338160
Acute hepatic failure	1538.88	39.95	353	10622	2289	2344821
Metabolic acidosis	1333.93	39.95	371	10604	5627	2341483
Cardio-respiratory arrest	1310.26	39.95	402	10573	8744	2338366
Cardiac arrest	1173.72	39.95	417	10558	14513	2332597
Respiratory arrest	1106.93	39.95	323	10652	5855	2341255
Drug abuse	1087.40	39.95	373	10602	11653	2335457
Suicide attempt	973.36	39.95	338	10637	10944	2336166
Coma	908.89	39.95	304	10671	8752	2338358
Hepatic failure	881.57	39.95	266	10709	5423	2341687
Hepatotoxicity	873.21	39.95	237	10738	3244	2343866
Poisoning	777.83	39.95	207	10768	2613	2344497
Hypotension	640.88	39.95	342	10633	32094	2315016
Coagulopathy	577.57	39.95	165	10810	2744	2344366
Alanine aminotransferase increased	559.35	39.95	240	10735	13792	2333318
Aspartate aminotransferase increased	550.17	39.95	230	10745	12382	2334728
Depressed level of consciousness	549.27	39.95	200	10775	7404	2339706
Liver injury	498.84	39.95	140	10835	2174	2344936
Medication error	486.79	39.95	173	10802	5958	2341152
Accidental overdose	436.34	39.95	143	10832	3829	2343281
Vomiting	431.59	39.95	360	10615	71242	2275868
Drug hypersensitivity	406.22	39.95	292	10683	46351	2300759
Hepatic necrosis	385.72	39.95	98	10877	1012	2346098
Somnolence	381.40	39.95	218	10757	23267	2323843
International normalised ratio increased	367.95	39.95	148	10827	7188	2339922
Exposure via ingestion	366.86	39.95	88	10887	700	2346410
Anion gap	358.99	39.95	64	10911	71	2347039
Tachycardia	357.16	39.95	185	10790	16224	2330886
Acute kidney injury	350.07	39.95	220	10755	27902	2319208
Exposure during pregnancy	313.03	39.95	197	10778	25022	2322088
Drug ineffective	301.94	39.95	347	10628	101277	2245833
Respiratory depression	274.45	39.95	87	10888	2083	2345027
Hepatitis	273.97	39.95	115	10860	6222	2340888
Acidosis	243.36	39.95	74	10901	1536	2345574
Brain oedema	240.83	39.95	80	10895	2230	2344880
Pyroglutamate increased	236.64	39.95	40	10935	22	2347088
Drug-induced liver injury	225.42	39.95	86	10889	3613	2343497
Encephalopathy	225.04	39.95	91	10884	4470	2342640
Nausea	215.73	39.95	309	10666	111880	2235230
Substance abuse	203.20	39.95	51	10924	498	2346612
Prothrombin time prolonged	194.64	39.95	63	10912	1614	2345496
Loss of consciousness	187.19	39.95	128	10847	18639	2328471
Transaminases increased	184.10	39.95	79	10896	4508	2342602
Acute lung injury	179.98	39.95	38	10937	154	2346956
Confusional state	178.95	39.95	138	10837	24206	2322904
Analgesic drug level increased	174.80	39.95	40	10935	252	2346858
Renal failure	172.22	39.95	118	10857	17231	2329879
Blood bilirubin increased	166.24	39.95	77	10898	5268	2341842
Drug interaction	165.18	39.95	142	10833	29021	2318089
Liver function test abnormal	164.28	39.95	85	10890	7405	2339705
Unresponsive to stimuli	163.45	39.95	74	10901	4802	2342308
Multiple organ dysfunction syndrome	159.82	39.95	84	10891	7557	2339553
Drug screen positive	159.41	39.95	47	10928	873	2346237
Abdominal pain	158.42	39.95	149	10826	34225	2312885
Hepatic encephalopathy	153.01	39.95	52	10923	1555	2345555
Pyrexia	151.31	39.95	179	10796	53529	2293581
Agitation	148.64	39.95	91	10884	10960	2336150
Liver transplant	147.06	39.95	40	10935	547	2346563
Lethargy	146.62	39.95	83	10892	8647	2338463
Sinus tachycardia	145.82	39.95	61	10914	3264	2343846
Hepatic function abnormal	144.80	39.95	73	10902	6019	2341091
Blood pH decreased	139.71	39.95	37	10938	454	2346656
Bradycardia	138.87	39.95	84	10891	9897	2337213
Thrombocytopenia	137.35	39.95	107	10868	19024	2328086
Poisoning deliberate	135.18	39.95	44	10931	1147	2345963
Hypothermia	134.65	39.95	51	10924	2097	2345013
Hypoglycaemia	133.32	39.95	77	10898	8330	2338780
Heart rate increased	128.16	39.95	83	10892	11022	2336088
Rhabdomyolysis	126.97	39.95	69	10906	6635	2340475
Seizure	124.18	39.95	112	10863	24354	2322756
Acute respiratory distress syndrome	120.02	39.95	53	10922	3239	2343871
Hepatic enzyme increased	119.88	39.95	76	10899	9726	2337384
Toxic epidermal necrolysis	119.10	39.95	52	10923	3092	2344018
Asphyxia	117.64	39.95	38	10937	966	2346144
Arteriosclerosis coronary artery	115.78	39.95	39	10936	1134	2345976
Drug dependence	114.17	39.95	50	10925	2995	2344115
Brain death	111.50	39.95	32	10943	538	2346572
Product administration error	110.87	39.95	53	10922	3890	2343220
Pain	109.06	39.95	164	10811	61693	2285417
Headache	102.73	39.95	184	10791	79995	2267115
Stevens-Johnson syndrome	101.09	39.95	51	10924	4208	2342902
Mental status changes	96.20	39.95	54	10921	5528	2341582
Haemolysis	95.89	39.95	33	10942	1025	2346085
Abdominal pain upper	94.48	39.95	92	10883	22008	2325102
Blood creatine phosphokinase increased	89.36	39.95	50	10925	5086	2342024
Hepatocellular injury	88.81	39.95	46	10929	4009	2343101
Pulmonary oedema	87.30	39.95	56	10919	7307	2339803
Blood lactic acid increased	86.78	39.95	29	10946	822	2346288
Rheumatoid arthritis	86.18	39.95	82	10893	19058	2328052
Drug level increased	86.16	39.95	40	10935	2747	2344363
Intentional self-injury	85.20	39.95	45	10930	4082	2343028
Anion gap increased	83.74	39.95	22	10953	261	2346849
Hypertension	83.23	39.95	95	10880	27266	2319844
Electrocardiogram QRS complex prolonged	83.18	39.95	30	10945	1072	2346038
Leukocytosis	82.46	39.95	42	10933	3534	2343576
Condition aggravated	80.78	39.95	101	10874	31878	2315232
Rash	80.46	39.95	140	10835	59418	2287692
Analgesic drug level above therapeutic	79.51	39.95	15	10960	28	2347082
Visual impairment	78.40	39.95	63	10912	11692	2335418
Gamma-glutamyltransferase increased	77.81	39.95	47	10928	5515	2341595
Body temperature increased	75.32	39.95	38	10937	3133	2343977
Generalised tonic-clonic seizure	71.57	39.95	44	10931	5328	2341782
Photophobia	71.21	39.95	33	10942	2256	2344854
Ventricular arrhythmia	70.84	39.95	23	10952	594	2346516
Body temperature decreased	70.77	39.95	28	10947	1295	2345815
Electrocardiogram QT prolonged	70.09	39.95	50	10925	7764	2339346
Pruritus	69.37	39.95	110	10865	43230	2303880
Blood creatinine increased	69.28	39.95	56	10919	10477	2336633
Renal impairment	69.24	39.95	55	10920	10037	2337073
Respiratory failure	68.70	39.95	62	10913	13466	2333644
Gastrointestinal haemorrhage	67.14	39.95	59	10916	12376	2334734
Blood alkaline phosphatase increased	66.00	39.95	45	10930	6500	2340610
Mydriasis	65.96	39.95	31	10944	2188	2344922
Toxicologic test abnormal	65.81	39.95	16	10959	135	2346975
Jaundice	65.55	39.95	42	10933	5466	2341644
Peripheral swelling	65.52	39.95	68	10907	17529	2329581
Drug abuser	64.52	39.95	24	10951	937	2346173
Premature labour	64.39	39.95	30	10945	2076	2345034
Haemoglobin decreased	63.77	39.95	68	10907	18083	2329027
Premature baby	63.49	39.95	34	10941	3170	2343940
Self-medication	63.42	39.95	21	10954	578	2346532
Accidental death	62.80	39.95	18	10957	301	2346809
Product use issue	62.24	39.95	56	10919	12113	2334997
Maternal exposure during pregnancy	61.85	39.95	61	10914	14802	2332308
Shock	61.65	39.95	36	10939	3968	2343142
Joint swelling	60.84	39.95	64	10911	16755	2330355
Drug reaction with eosinophilia and systemic symptoms	60.58	39.95	40	10935	5478	2341632
Gastrointestinal sounds abnormal	60.24	39.95	20	10955	555	2346555
Oliguria	59.83	39.95	25	10950	1332	2345778
Alcohol use	59.56	39.95	19	10956	463	2346647
Blood bicarbonate decreased	58.77	39.95	19	10956	484	2346626
Cholestasis	58.74	39.95	34	10941	3687	2343423
Pneumonia aspiration	58.56	39.95	34	10941	3708	2343402
Synovial fluid analysis	58.49	39.95	11	10964	20	2347090
Respiratory distress	58.30	39.95	38	10937	5091	2342019
Renal papillary necrosis	58.21	39.95	12	10963	42	2347068
Night sweats	57.97	39.95	33	10942	3467	2343643
Dilatation intrahepatic duct acquired	57.77	39.95	13	10962	75	2347035
Hepatitis fulminant	57.63	39.95	20	10955	637	2346473
Loss of personal independence in daily activities	57.10	39.95	38	10937	5273	2341837
Respiratory rate increased	57.10	39.95	25	10950	1495	2345615
Urticaria	57.08	39.95	74	10901	24187	2322923
Respiratory alkalosis	56.84	39.95	17	10958	332	2346778
Suicidal ideation	56.65	39.95	51	10924	11036	2336074
Incorrect dose administered	56.37	39.95	48	10927	9647	2337463
Brain herniation	55.89	39.95	19	10956	568	2346542
Muscle spasticity	55.08	39.95	25	10950	1628	2345482
Insomnia	55.05	39.95	75	10900	25712	2321398
Ammonia increased	54.81	39.95	20	10955	739	2346371
Bursitis	54.70	39.95	26	10949	1882	2345228
Drug intolerance	54.68	39.95	55	10920	13662	2333448
Activated partial thromboplastin time prolonged	54.40	39.95	23	10952	1262	2345848
White blood cell count increased	53.81	39.95	41	10934	7037	2340073
Blood sodium decreased	53.43	39.95	30	10945	3070	2344040
Bradypnoea	53.19	39.95	17	10958	417	2346693
Agranulocytosis	52.80	39.95	31	10944	3451	2343659
Asthenia	52.79	39.95	102	10873	46824	2300286
Hyperthermia	51.45	39.95	23	10952	1445	2345665
Contraindicated product administered	51.43	39.95	29	10946	2992	2344118
Pancreatitis	51.11	39.95	42	10933	8037	2339073
Tachypnoea	50.86	39.95	26	10949	2203	2344907
Dyspnoea	50.53	39.95	137	10838	78596	2268514
Migraine	50.52	39.95	47	10928	10606	2336504
Hepatitis cholestatic	49.95	39.95	21	10954	1136	2345974
Antidepressant drug level above therapeutic	49.88	39.95	11	10964	57	2347053
Fatigue	49.86	39.95	143	10832	84730	2262380
Lower respiratory tract infection	49.31	39.95	35	10940	5389	2341721
Conjunctivitis	49.12	39.95	26	10949	2367	2344743
Malaise	48.67	39.95	109	10866	55476	2291634
Foetal death	48.61	39.95	24	10951	1888	2345222
Pancreatitis acute	47.39	39.95	30	10945	3823	2343287
Coma hepatic	47.36	39.95	13	10962	184	2346926
Tenosynovitis stenosans	47.26	39.95	12	10963	123	2346987
Pneumonia	46.94	39.95	100	10875	49196	2297914
Product use in unapproved indication	46.65	39.95	46	10929	11154	2335956
Drug level above therapeutic	46.24	39.95	16	10959	505	2346605
Ulcer	46.03	39.95	23	10952	1857	2345253
Foetal exposure during pregnancy	45.70	39.95	33	10942	5219	2341891
Lactic acidosis	45.26	39.95	33	10942	5297	2341813
Hallucination	44.65	39.95	39	10936	8109	2339001
Serotonin syndrome	44.63	39.95	28	10947	3512	2343598
Blood pressure decreased	44.28	39.95	41	10934	9195	2337915
Disorientation	44.28	39.95	35	10940	6337	2340773
Renal tubular necrosis	43.55	39.95	21	10954	1569	2345541
Accidental exposure to product	43.23	39.95	39	10936	8458	2338652
Inflammation	42.90	39.95	34	10941	6179	2340931
PCO2 decreased	42.58	39.95	13	10962	273	2346837
Crepitations	42.40	39.95	16	10959	650	2346460
Back pain	42.10	39.95	74	10901	31585	2315525
Face oedema	41.84	39.95	28	10947	3920	2343190
Scleritis	41.63	39.95	13	10962	295	2346815
Respiratory disorder	41.48	39.95	28	10947	3976	2343134
Blood glucose increased	41.32	39.95	45	10930	12245	2334865
Emphysema	41.25	39.95	18	10957	1067	2346043
Hyperbilirubinaemia	41.04	39.95	20	10955	1529	2345581
Hypoxia	40.70	39.95	33	10942	6194	2340916
Anaphylactic reaction	40.67	39.95	40	10935	9665	2337445
Alcohol poisoning	40.21	39.95	13	10962	331	2346779

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
Toxicity to various agents	5648.69	46.31	1549	4563	27592	1713077
Completed suicide	5232.48	46.31	1300	4812	15012	1725657
Overdose	2018.23	46.31	627	5485	16074	1724595
Intentional product misuse	1129.46	46.31	334	5778	7024	1733645
Drug abuse	940.78	46.31	338	5774	13351	1727318
Intentional overdose	931.53	46.31	291	5821	7379	1733290
Death	915.54	46.31	587	5525	86856	1653813
Cardio-respiratory arrest	836.59	46.31	281	5831	9012	1731657
Acute hepatic failure	744.87	46.31	184	5928	1859	1738810
Respiratory arrest	577.96	46.31	190	5922	5649	1735020
Cardiac arrest	547.80	46.31	239	5873	15691	1724978
Accidental overdose	462.54	46.31	148	5964	4016	1736653
Metabolic acidosis	459.75	46.31	157	5955	5245	1735424
Hepatotoxicity	453.81	46.31	136	5976	2948	1737721
Coma	382.01	46.31	148	5964	7114	1733555
Suicide attempt	358.51	46.31	142	5970	7239	1733430
Hypotension	342.26	46.31	214	5898	29440	1711229
Coagulopathy	329.87	46.31	104	6008	2677	1737992
Poisoning	318.31	46.31	99	6013	2433	1738236
Hepatic failure	309.18	46.31	120	5992	5783	1734886
Alanine aminotransferase increased	265.34	46.31	134	5978	12144	1728525
Medication error	264.64	46.31	101	6011	4642	1736027
Aspartate aminotransferase increased	260.90	46.31	127	5985	10629	1730040
Depressed level of consciousness	258.95	46.31	109	6003	6483	1734186
International normalised ratio increased	256.89	46.31	116	5996	8183	1732486
Substance abuse	245.99	46.31	66	6046	937	1739732
Liver injury	225.62	46.31	71	6041	1811	1738858
Hepatic necrosis	221.23	46.31	57	6055	684	1739985
Acute kidney injury	217.31	46.31	173	5939	34771	1705898
Toxic epidermal necrolysis	197.76	46.31	68	6044	2303	1738366
Anion gap	193.07	46.31	35	6077	53	1740616
Respiratory depression	177.94	46.31	62	6050	2185	1738484
Exposure via ingestion	167.89	46.31	45	6067	635	1740034
Vomiting	161.46	46.31	152	5960	38163	1702506
Stevens-Johnson syndrome	153.70	46.31	62	6050	3295	1737374
Drug interaction	151.62	46.31	128	5984	27830	1712839
Rhabdomyolysis	137.32	46.31	84	6028	11006	1729663
Tachycardia	137.14	46.31	88	6024	12540	1728129
Transaminases increased	128.18	46.31	57	6055	3860	1736809
Brain oedema	126.79	46.31	48	6064	2148	1738521
Multiple organ dysfunction syndrome	119.51	46.31	72	6040	9170	1731499
Prothrombin time prolonged	117.89	46.31	42	6070	1579	1739090
Agitation	112.70	46.31	74	6038	10952	1729717
Pulmonary oedema	111.03	46.31	61	6051	6525	1734144
Unresponsive to stimuli	110.02	46.31	54	6058	4575	1736094
Pulmonary congestion	109.81	46.31	41	6071	1764	1738905
Somnolence	106.03	46.31	84	6028	16655	1724014
Acidosis	105.89	46.31	38	6074	1459	1739210
Renal failure	100.91	46.31	88	6024	19929	1720740
Hepatic encephalopathy	100.30	46.31	41	6071	2251	1738418
Hepatic function abnormal	98.97	46.31	58	6054	7016	1733653
Lethargy	98.13	46.31	58	6054	7126	1733543
Hepatitis	95.00	46.31	50	6062	4905	1735764
Blood pH decreased	91.49	46.31	26	6086	460	1740209
Encephalopathy	91.29	46.31	47	6065	4405	1736264
Brain death	91.02	46.31	26	6086	469	1740200
Mental status changes	88.12	46.31	51	6061	6024	1734645
Liver function test abnormal	85.53	46.31	49	6063	5677	1734992
Seizure	83.71	46.31	80	6032	20361	1720308
Drug screen positive	82.99	46.31	29	6083	1028	1739641
Drug hypersensitivity	81.22	46.31	69	6043	15066	1725603
Thrombocytopenia	79.22	46.31	79	6033	21170	1719499
Pneumonia aspiration	78.47	46.31	45	6067	5221	1735448
Blood creatinine increased	75.68	46.31	64	6048	13882	1726787
Drug level increased	73.84	46.31	35	6077	2742	1737927
Cholestasis	73.14	46.31	38	6074	3627	1737042
Confusional state	70.05	46.31	74	6038	21204	1719465
Pyrexia	69.40	46.31	109	6003	46291	1694378
Ammonia increased	69.24	46.31	24	6088	830	1739839
Liver transplant	68.99	46.31	22	6090	584	1740085
Hepatocellular injury	68.80	46.31	35	6077	3196	1737473
Anion gap increased	67.32	46.31	18	6094	251	1740418
Methaemoglobinaemia	66.39	46.31	19	6093	345	1740324
Leukocytosis	65.85	46.31	35	6077	3498	1737171
Jaundice	65.10	46.31	42	6070	6020	1734649
Loss of consciousness	64.25	46.31	60	6052	14815	1725854
Hepatic enzyme increased	64.11	46.31	43	6069	6578	1734091
Abdominal pain	62.46	46.31	70	6042	21420	1719249
Incorrect dose administered	62.04	46.31	44	6068	7365	1733304
Bradycardia	60.56	46.31	50	6062	10484	1730185
Drug-induced liver injury	60.14	46.31	32	6080	3205	1737464
Heart rate increased	59.98	46.31	41	6071	6469	1734200
Shock	57.85	46.31	34	6078	4127	1736542
Blood bilirubin increased	56.95	46.31	39	6073	6171	1734498
Hypoglycaemia	56.92	46.31	44	6068	8394	1732275
Hypothermia	55.74	46.31	25	6087	1723	1738946
Blood bicarbonate decreased	54.97	46.31	17	6095	407	1740262
Alcohol use	54.20	46.31	20	6092	831	1739838
Brain injury	53.99	46.31	21	6091	1010	1739659
Arteriosclerosis coronary artery	53.85	46.31	25	6087	1867	1738802
Environmental exposure	52.34	46.31	11	6101	48	1740621
Electrocardiogram QRS complex prolonged	52.27	46.31	19	6093	756	1739913
Analgesic drug level increased	51.25	46.31	12	6100	93	1740576
Anaphylactic reaction	50.47	46.31	36	6076	6077	1734592
Drug abuser	50.19	46.31	22	6090	1435	1739234
Hepatitis acute	49.96	46.31	21	6091	1236	1739433
Aggression	49.75	46.31	40	6072	8075	1732594
Haemodialysis	48.98	46.31	26	6086	2590	1738079
Blood alkaline phosphatase increased	48.52	46.31	33	6079	5162	1735507
Gastrointestinal haemorrhage	47.58	46.31	50	6062	14217	1726452

Pharmacologic Action:

Source	Code	Description
ATC	N06BC01	NERVOUS SYSTEM PSYCHOANALEPTICS PSYCHOSTIMULANTS, AGENTS USED FOR ADHD AND NOOTROPICS Xanthine derivatives
ATC	V04CG30	VARIOUS DIAGNOSTIC AGENTS OTHER DIAGNOSTIC AGENTS Tests for gastric secretion
FDA PE	N0000175729	Central Nervous System Stimulation
FDA EPC	N0000175790	Methylxanthine
FDA Chemical/Ingredient	N0000008118	Xanthines
CHEBI has role	CHEBI:35471	psychotropic drug
CHEBI has role	CHEBI:35498	diuretic
CHEBI has role	CHEBI:64047	food additive
CHEBI has role	CHEBI:60809	adjuvant
CHEBI has role	CHEBI:35337	central nervous system stimulant
MeSH PA	D002491	Central Nervous System Agents
MeSH PA	D000697	Central Nervous System Stimulants
MeSH PA	D004791	Enzyme Inhibitors
MeSH PA	D018377	Neurotransmitter Agents
MeSH PA	D010726	Phosphodiesterase Inhibitors
MeSH PA	D058914	Purinergic Antagonists
MeSH PA	D058915	Purinergic P1 Receptor Antagonists

Drug Use (View source of the data)

Disease	Relation	SNOMED_ID	DOID
Sinus headache	indication	4969004
Apnea in the newborn	indication	13094009
Pain	indication	22253000
Migraine	indication	37796009	DOID:6364
Joint pain	indication	57676002
Allergic rhinitis	indication	61582004
Nasal discharge	indication	64531003
Nasal congestion	indication	68235000
Common cold	indication	82272006	DOID:10459
Vascular headache	indication	128187005
Backache	indication	161891005
Cluster headache syndrome	indication	193031009
Spasticity	indication	221360009
Headache disorder	indication	230461009
Dysmenorrhea	indication	266599000
Influenza-like symptoms	indication	315642008
Tension-type headache	indication	398057008
Cluster Headache Prevention	indication
Fatigue	off-label use	84229001
Urinary incontinence	off-label use	165232002
Obesity	off-label use	414916001	DOID:9970
Brain damage	contraindication	2470005
Necrotizing enterocolitis in fetus OR newborn	contraindication	2707005
Ocular hypertension	contraindication	4210003	DOID:9282
Gastritis	contraindication	4556007	DOID:4029
Hypophosphatemia	contraindication	4996001
Tachyarrhythmia	contraindication	6285003
Suicidal thoughts	contraindication	6471006
Dependent drug abuse	contraindication	6525002
Urinary tract obstruction	contraindication	7163005	DOID:5200
Alcoholism	contraindication	7200002
Alcohol withdrawal delirium	contraindication	8635005
Hyperammonemia	contraindication	9360008
Peptic ulcer	contraindication	13200003	DOID:750
Chronic obstructive lung disease	contraindication	13645005	DOID:3083
Asthenia	contraindication	13791008
Hepatic encephalopathy	contraindication	13920009	DOID:13413
Hyperkalemia	contraindication	14140009
Severe chronic ulcerative colitis	contraindication	14311001
Constipation	contraindication	14760008	DOID:2089
Chronic disease of respiratory system	contraindication	17097001
Mood swings	contraindication	18963009
Myocardial infarction	contraindication	22298006	DOID:5844
Glaucoma	contraindication	23986001	DOID:1686
Inflammatory bowel disease	contraindication	24526004	DOID:0050589
Ventricular tachycardia	contraindication	25569003
Alcohol intoxication	contraindication	25702006
Complete atrioventricular block	contraindication	27885002
Shock	contraindication	27942005
Toxic megacolon	contraindication	28536002	DOID:1770
Hypovolemia	contraindication	28560003
Orthostatic hypotension	contraindication	28651003
Acute cerebrovascular insufficiency	contraindication	29322000
Atony of colon	contraindication	29479008
Hypercapnia	contraindication	29596007
Dehydration	contraindication	34095006
Hyperthyroidism	contraindication	34486009	DOID:7998
Depressive disorder	contraindication	35489007
Acute hepatitis	contraindication	37871000
Hypertensive disorder	contraindication	38341003	DOID:10763
Disorder of gallbladder	contraindication	39621005	DOID:0060262
Gastrointestinal ulcer	contraindication	40845000
Hypothyroidism	contraindication	40930008	DOID:1459
Complete trisomy 21 syndrome	contraindication	41040004	DOID:14250
Hypokalemia	contraindication	43339004
Body fluid retention	contraindication	43498006
Hyperactive behavior	contraindication	44548000
Fecal impaction	contraindication	44635007
Conduction disorder of the heart	contraindication	44808001
Low blood pressure	contraindication	45007003
Achalasia of esophagus	contraindication	45564002	DOID:9164
Chronic heart failure	contraindication	48447003
Bradycardia	contraindication	48867003
Retroperitoneal fibrosis	contraindication	49120005
Disorder of cardiovascular system	contraindication	49601007	DOID:1287
Acidosis	contraindication	51387008
Fibrosis of lung	contraindication	51615001	DOID:3770
Gastrointestinal perforation	contraindication	51875005
Vitamin K deficiency	contraindication	52675005	DOID:11249
Nasal polyp	contraindication	52756005
Gastrectomy	contraindication	53442002
Paralytic ileus	contraindication	55525008	DOID:8442
Peptic reflux disease	contraindication	57643001
Congenital myotonia, autosomal dominant form	contraindication	57938005
Acute nephropathy	contraindication	58574008
Leber's optic atrophy	contraindication	58610003	DOID:705
Hepatic failure	contraindication	59927004
Diarrhea	contraindication	62315008
Thrombophlebitis	contraindication	64156001	DOID:3875
Ulcerative colitis	contraindication	64766004	DOID:8577
Blood coagulation disorder	contraindication	64779008	DOID:1247
Arterial thrombosis	contraindication	65198009
Drug AND/OR toxin-induced diarrhea	contraindication	65979008
Substance abuse	contraindication	66214007
Hypermagnesemia	contraindication	66978005
Benign intracranial hypertension	contraindication	68267002	DOID:11459
Hemorrhoids	contraindication	70153002	DOID:9746
Poisoning by acetaminophen	contraindication	70273001
Agoraphobia	contraindication	70691001	DOID:593
Arteriosclerotic vascular disease	contraindication	72092001
Hepatic coma	contraindication	72836002	DOID:12550
Diabetes mellitus	contraindication	73211009	DOID:9351
Sleep apnea	contraindication	73430006	DOID:0050847
Factor II deficiency	contraindication	73975000
Reye's syndrome	contraindication	74351001	DOID:14525
Gastrointestinal hemorrhage	contraindication	74474003
Urethral stricture	contraindication	76618002
Thrombotic thrombocytopenic purpura	contraindication	78129009	DOID:10772
Spastic paralysis	contraindication	78403003
Disturbance of salivary secretion	contraindication	78948009
Decreased respiratory function	contraindication	80954004
Injury of head	contraindication	82271004
Chronic idiopathic constipation	contraindication	82934008
Cor pulmonale	contraindication	83291003	DOID:8515
Hiatal hernia	contraindication	84089009	DOID:12642
Atrophic gastritis	contraindication	84568007	DOID:8929
Epilepsy	contraindication	84757009	DOID:1826
Pulmonary emphysema	contraindication	87433001
Gout	contraindication	90560007	DOID:13189
Chronic renal failure syndrome	contraindication	90688005
Kidney disease	contraindication	90708001	DOID:557
Thyrotoxicosis	contraindication	90739004	DOID:7997
Hemophilia	contraindication	90935002
Myasthenia gravis	contraindication	91637004	DOID:437
Obstruction of duodenum	contraindication	95532008	DOID:3558
Disorder of biliary tract	contraindication	105997008	DOID:9741
Anemia due to enzyme deficiency	contraindication	111577008
Prolonged QT interval	contraindication	111975006
Acute abdominal pain	contraindication	116290004
Procedure on urinary system	contraindication	118677009
Gastrointestinal obstruction	contraindication	126765001
Neoplasm of brain	contraindication	126952004	DOID:1319
von Willebrand disorder	contraindication	128105004	DOID:12531
Seizure disorder	contraindication	128613002
Autonomic dysreflexia	contraindication	129618003
Bleeding	contraindication	131148009
Prolonged PR interval	contraindication	164947007
Drug-induced psychosis	contraindication	191483003	DOID:1742
Obsessive-compulsive disorder	contraindication	191736004	DOID:10933
Insomnia	contraindication	193462001
Partial atrioventricular block	contraindication	195039008
Decompensated cardiac failure	contraindication	195111005
Acute pancreatitis	contraindication	197456007	DOID:2913
Impaired renal function disorder	contraindication	197663003
Coronary artery bypass graft	contraindication	232717009
Myocardial dysfunction	contraindication	233928007
Peripheral ischemia	contraindication	233958001
Gastroesophageal reflux disease	contraindication	235595009	DOID:8534
Gastroparesis	contraindication	235675006
Disease of liver	contraindication	235856003	DOID:409
Chronic diarrhea	contraindication	236071009
Hyporeninemic hypoaldosteronism	contraindication	236464008
Aluminum intoxication	contraindication	236546003
Bladder outflow obstruction	contraindication	236645006
Morbid obesity	contraindication	238136002	DOID:11981
Sepsis syndrome	contraindication	238150007
Pyloric obstruction	contraindication	244815007
Sleep automatism	contraindication	247962006
Raynaud's phenomenon	contraindication	266261006
Benign prostatic hyperplasia	contraindication	266569009
Retention of urine	contraindication	267064002
Anemia	contraindication	271737000	DOID:2355
Drowsy	contraindication	271782001
Exacerbation of asthma	contraindication	281239006
Cerebral ischemia	contraindication	287731003
Pregnancy, function	contraindication	289908002
Lesion of brain	contraindication	301766008
Thrombocytopenic disorder	contraindication	302215000	DOID:1588
Neutropenic disorder	contraindication	303011007	DOID:1227
Familial hyperkalemic periodic paralysis	contraindication	304737009	DOID:14451
Panic disorder	contraindication	371631005	DOID:594
Coma	contraindication	371632003
Primary adrenocortical insufficiency	contraindication	373662000
Operation on gastrointestinal tract	contraindication	386621005
Hypoxia	contraindication	389086002
Angle-closure glaucoma	contraindication	392291006	DOID:13550
Cardiovascular event risk	contraindication	395112001
Pseudomembranous enterocolitis	contraindication	397683000
Gastric ulcer	contraindication	397825006	DOID:10808
Peripheral vascular disease	contraindication	400047006
Respiratory insufficiency	contraindication	409623005
Breastfeeding (mother)	contraindication	413712001
Chronic lung disease	contraindication	413839001
Chronic myocardial ischemia	contraindication	413844008	DOID:3393
Disorder of coronary artery	contraindication	414024009
Myocardial ischemia	contraindication	414795007	DOID:3393
Myocardial infarction in recovery phase	contraindication	418044006
Central nervous system depression	contraindication	418072004
Porphyria	contraindication	418470004
Ultrarapid metabolizer due to cytochrome p450 CYP2D6 variant	contraindication	422681000
Dysfunction of sphincter of Oddi	contraindication	430887001
Fibrosis of pleura	contraindication	442110002
Congenital long QT syndrome	contraindication	442917000
Hypertensive urgency	contraindication	443482000
Acute erosive gastritis	contraindication	444926003
Smokes tobacco daily	contraindication	449868002
Severe dehydration	contraindication	450316000
Acute exacerbation of asthma	contraindication	708038006
Ergot Alkaloid Toxicity	contraindication
Acute Thromboembolic Stroke	contraindication
Organic Cardiac Disease	contraindication
Severe Pruritus	contraindication

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	1.86	Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Bioact source	MoA source
Adenosine receptor A2b	GPCR	P29275	AA2BR_HUMAN	ANTAGONIST	Ki	4.77	WOMBAT-PK	CHEMBL
Adenosine receptor A1	GPCR	P30542	AA1R_HUMAN	ANTAGONIST	Ki	4.97	IUPHAR	CHEMBL
Adenosine receptor A2a	GPCR	P29274	AA2AR_HUMAN	ANTAGONIST	Ki	5.61	CHEMBL	CHEMBL
Acetylcholinesterase	Enzyme	P22303	ACES_HUMAN		IC50	5.14	CHEMBL
Potassium voltage-gated channel subfamily H member 2	Ion channel	Q12809	KCNH2_HUMAN		IC50	5.31	CHEMBL
Adenosine receptor A3	GPCR	P0DMS8	AA3R_HUMAN	ANTAGONIST	Ki	4.33	WOMBAT-PK
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform	Kinase	O00329	PK3CD_HUMAN		IC50	4.12	CHEMBL
Guanine deaminase	Enzyme	Q9Y2T3	GUAD_HUMAN		Ki	4.99	CHEMBL
Adenosine receptor A1	GPCR		AA1R_BOVIN		Ki	4.54	CHEMBL
Adenosine receptor A1	GPCR		AA1R_RAT		Ki	4.77	CHEMBL
Adenosine A2a receptor	Unclassified		AA2AR_CAVPO		Ki	4.10	CHEMBL
Adenosine receptor A2a	GPCR		AA2AR_RAT		Ki	5.03	CHEMBL
Adenosine A2 receptor	GPCR		AA2AR_RAT AA2BR_RAT		Ki	4.57	CHEMBL
Glycogen phosphorylase, muscle form	Enzyme		PYGM_RABIT		IC50	4.13	CHEMBL
Adenosine receptor A1	GPCR		AA1R_CAVPO		Ki	4	CHEMBL
Adenosine receptor	GPCR		AA1R_RAT AA2AR_RAT AA2BR_RAT AA3R_RAT		Ki	4.22	CHEMBL
Adenosine receptor A2b	Unclassified		AA2BR_MOUSE	ANTAGONIST	Ki	4.89	IUPHAR

External reference:

ID	Source
D002110	MESH_DESCRIPTOR_UI
4017537	VUID
N0000145919	NUI
C0006644	UMLSCUI
D00528	KEGG_DRUG
3G6A5W338E	UNII
91107009	SNOMEDCT_US
4017537	VANDF
000600	NDDF
4939	MMSL
1886	RXNORM
255641001	SNOMEDCT_US
4318	MMSL
d00801	MMSL
2519	PUBCHEM_CID
CHEBI:27732	CHEBI
CHEMBL113	ChEMBL_ID
DB00201	DRUGBANK_ID
CHEMBL1200569	ChEMBL_ID
69-22-7	SECONDARY_CAS_RN
CFF	PDB_CHEM_ID
407	IUPHAR_LIGAND_ID
C026189	MESH_SUPPLEMENTAL_RECORD_UI

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
Fiorinal with Codeine	HUMAN PRESCRIPTION DRUG LABEL	4	0023-6010	CAPSULE	40 mg	ORAL	NDA	20 sections
Fiorinal	HUMAN PRESCRIPTION DRUG LABEL	3	0023-6146	CAPSULE	40 mg	ORAL	NDA	12 sections
Excedrin	HUMAN OTC DRUG LABEL	3	0067-2000	TABLET, FILM COATED	65 mg	ORAL	OTC monograph not final	9 sections
Excedrin	HUMAN OTC DRUG LABEL	3	0067-2001	TABLET, FILM COATED	65 mg	ORAL	OTC monograph not final	9 sections
Excedrin	HUMAN OTC DRUG LABEL	3	0067-2021	TABLET, COATED	65 mg	ORAL	OTC monograph not final	9 sections
Excedrin	HUMAN OTC DRUG LABEL	3	0067-2035	TABLET, COATED	65 mg	ORAL	NDA	10 sections
EXCEDRIN	HUMAN OTC DRUG LABEL	3	0067-2039	TABLET, FILM COATED	65 mg	ORAL	NDA	9 sections
Excedrin	HUMAN OTC DRUG LABEL	2	0067-8139	TABLET, FILM COATED	65 mg	ORAL	OTC monograph not final	9 sections
Excedrin PM Triple Action Caplets and Excedrin Tension Headache	HUMAN OTC DRUG LABEL	5	0067-8147	KIT	65 mg	None	OTC monograph not final	9 sections
Excedrin PM Triple Action Caplets and Excedrin Extra Strength Pain Reliever	HUMAN OTC DRUG LABEL	6	0067-8148	KIT	65 mg	None	OTC monograph not final	9 sections
Excedrin Extra Strength and Excedrin Tension Headache	HUMAN OTC DRUG LABEL	5	0067-8151	KIT	65 mg	None	OTC monograph not final	9 sections
Excedrin Extra Strength and Excedrin Tension Headache	HUMAN OTC DRUG LABEL	5	0067-8151	KIT	65 mg	None	OTC monograph not final	9 sections
EXCEDRIN	HUMAN OTC DRUG LABEL	3	0067-8201	TABLET, FILM COATED	65 mg	ORAL	NDA	9 sections
Excedrin	HUMAN OTC DRUG LABEL	3	0067-8202	TABLET, FILM COATED	65 mg	ORAL	OTC monograph not final	9 sections
good sense migraine formula	HUMAN OTC DRUG LABEL	3	0113-0374	TABLET, FILM COATED	65 mg	ORAL	ANDA	9 sections
good sense stay awake	HUMAN OTC DRUG LABEL	1	0113-0409	TABLET	200 mg	ORAL	OTC monograph final	9 sections
basic care migraine relief	HUMAN OTC DRUG LABEL	3	0113-7374	TABLET, FILM COATED	65 mg	ORAL	ANDA	9 sections
PANADOL	HUMAN OTC DRUG LABEL	2	0135-0620	TABLET, FILM COATED	65 mg	ORAL	OTC monograph not final	9 sections
Butalbital, Acetaminophen, and Caffeine	HUMAN PRESCRIPTION DRUG LABEL	3	0143-0170	CAPSULE	40 mg	ORAL	ANDA	14 sections
Butalbital, Acetaminophen and Caffeine	HUMAN PRESCRIPTION DRUG LABEL	3	0143-1787	TABLET	40 mg	ORAL	ANDA	13 sections
ERGOTAMINE	HUMAN PRESCRIPTION DRUG LABEL	2	0143-2120	TABLET, FILM COATED	100 mg	ORAL	ANDA	14 sections
Bayer Back and Body	HUMAN OTC DRUG LABEL	2	0280-2150	TABLET	35.50 mg	ORAL	OTC monograph not final	15 sections
Midol Complete	HUMAN OTC DRUG LABEL	3	0280-8005	TABLET	60 mg	ORAL	OTC monograph not final	9 sections
Midol Complete	HUMAN OTC DRUG LABEL	3	0280-8015	TABLET, COATED	60 mg	ORAL	OTC monograph not final	16 sections
Extra Strength Headache Relief	HUMAN OTC DRUG LABEL	3	0363-0021	CAPSULE	65 mg	ORAL	OTC monograph not final	9 sections
Headache Relief	HUMAN OTC DRUG LABEL	3	0363-0159	TABLET, FILM COATED	65 mg	ORAL	OTC MONOGRAPH NOT FINAL	9 sections
Stay Awake	HUMAN OTC DRUG LABEL	1	0363-0226	TABLET	200 mg	ORAL	OTC MONOGRAPH FINAL	9 sections
Menstrual Relief	HUMAN OTC DRUG LABEL	3	0363-0252	TABLET	60 mg	ORAL	OTC MONOGRAPH NOT FINAL	9 sections
migraine relief	HUMAN OTC DRUG LABEL	3	0363-0374	TABLET, FILM COATED	65 mg	ORAL	ANDA	9 sections
Tension Headache Relief	HUMAN OTC DRUG LABEL	2	0363-0428	TABLET, FILM COATED	65 mg	ORAL	OTC MONOGRAPH NOT FINAL	9 sections