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

Stem definition	Drug id	CAS RN
N-methylated xanthine derivatives	2620	58-55-9

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: aminophyllin aminophylline theophylline 1,3-Dimethylxanthine armophylline cetraphylline chronophyllin duraphyllin elixophyllin elixophylline etheophyl lanophyllin pseudotheophylline theophyllin throphylline xanthium theophylline anhydrous aminophylline dihydrate theophylline sodium glycinate theophylline monohydrate	A plant genus of the family ASTERACEAE. The name "prickly burweed" is sometimes used but causes confusion with AMSINCKIA. Molecular weight: 180.17 Formula: C7H8N4O2 CLOGP: -0.03 LIPINSKI: 0 HAC: 6 HDO: 1 TPSA: 69.30 ALOGS: -0.80 ROTB: 0 Status: OFP Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

aminophyllin
aminophylline
theophylline
1,3-Dimethylxanthine
armophylline
cetraphylline
chronophyllin
duraphyllin
elixophyllin
elixophylline
etheophyl
lanophyllin
pseudotheophylline
theophyllin
throphylline
xanthium
theophylline anhydrous
aminophylline dihydrate
theophylline sodium glycinate
theophylline monohydrate

A plant genus of the family ASTERACEAE. The name "prickly burweed" is sometimes used but causes confusion with AMSINCKIA.

Molecular weight: 180.17
Formula: C7H8N4O2
CLOGP: -0.03
LIPINSKI: 0
HAC: 6
HDO: 1
TPSA: 69.30
ALOGS: -0.80
ROTB: 0

Status: OFP

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

Drug dosage:

Dose	Unit	Route
0.40	g	O
0.40	g	P
0.40	g	R
0.60	g	O
0.60	g	P
0.60	g	R

ADMET properties:

Property	Value	Reference
BDDCS (Biopharmaceutical Drug Disposition Classification System)	1	Benet LZ, Broccatelli F, Oprea TI
S (Water solubility)	8.30 mg/mL	Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine)	18 %	Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose)	48.12 µM/kg/day	Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
Vd (Volume of distribution)	0.51 L/kg	Lombardo F, Berellini G, Obach RS
CL (Clearance)	0.86 mL/min/kg	Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma)	0.61 %	Lombardo F, Berellini G, Obach RS
t_half (Half-life)	7.20 hours	Lombardo F, Berellini G, Obach RS

Approvals:

Date	Agency	Company	Orphan
April 19, 1940	FDA	GD SEARLE LLC

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
Asthma	709.22	12.50	463	20226	91079	46574294
Wheezing	288.48	12.50	217	20472	53169	46612204
Chronic obstructive pulmonary disease	168.85	12.50	165	20524	57468	46607905
Dyspnoea	122.68	12.50	501	20188	515047	46150326
Productive cough	108.80	12.50	123	20566	50592	46614781
Forced expiratory volume decreased	104.02	12.50	49	20640	5055	46660318
Sputum discoloured	99.38	12.50	65	20624	12713	46652660
Rales	87.37	12.50	54	20635	9577	46655796
Hypercapnia	77.97	12.50	39	20650	4587	46660786
Breath sounds abnormal	76.48	12.50	46	20643	7769	46657604
Status asthmaticus	69.78	12.50	23	20666	913	46664460
Sinus tachycardia	63.35	12.50	62	20627	21587	46643786
Rheumatoid arthritis	62.26	12.50	15	20674	240200	46425173
Chest discomfort	59.90	12.50	127	20562	90142	46575231
Obstructive airways disorder	54.11	12.50	46	20643	13366	46652007
Bronchitis chronic	52.73	12.50	29	20660	4138	46661235
Neurosensory hypoacusis	50.92	12.50	14	20675	295	46665078
Toxicity to various agents	46.22	12.50	201	20488	211565	46453808
Cough	44.62	12.50	211	20478	230038	46435335
Respiratory rate increased	43.66	12.50	38	20651	11395	46653978
Lung hyperinflation	42.87	12.50	17	20672	1152	46664221
Airway peak pressure increased	42.33	12.50	12	20677	284	46665089
Occupational asthma	41.11	12.50	10	20679	127	46665246
Pneumonia	40.43	12.50	295	20394	376025	46289348
Drug interaction	39.98	12.50	187	20502	202907	46462466
Bronchial neoplasm	39.74	12.50	11	20678	238	46665135
Acute respiratory failure	39.12	12.50	56	20633	29082	46636291
PCO2 increased	38.32	12.50	16	20673	1238	46664135
Nasal turbinate hypertrophy	37.93	12.50	12	20677	417	46664956
Increased viscosity of bronchial secretion	37.75	12.50	11	20678	288	46665085
Nasal congestion	37.00	12.50	72	20617	48041	46617332
Bronchospasm	36.93	12.50	40	20649	15667	46649706
Emphysema	36.41	12.50	31	20658	9023	46656350
Bronchial haemorrhage	36.19	12.50	11	20678	334	46665039
Lower respiratory tract infection	35.93	12.50	77	20612	55012	46610361
Respiratory failure	35.14	12.50	107	20582	94709	46570664
Prolonged expiration	35.09	12.50	11	20678	371	46665002
Heart sounds	35.02	12.50	10	20679	243	46665130
Lipohypertrophy	34.63	12.50	13	20676	759	46664614
Vital capacity decreased	34.61	12.50	12	20677	557	46664816
Respiratory tract inflammation	33.20	12.50	11	20678	444	46664929
Respiratory acidosis	33.15	12.50	25	20664	6123	46659250
Congestive cardiomyopathy	32.52	12.50	24	20665	5689	46659684
Eosinophilic granulomatosis with polyangiitis	32.48	12.50	16	20673	1820	46663553
PO2 decreased	32.21	12.50	15	20674	1507	46663866
Oesophageal dilatation	32.11	12.50	10	20679	330	46665043
Stress cardiomyopathy	32.02	12.50	27	20662	7757	46657616
Tachycardia	31.09	12.50	106	20583	99516	46565857
Decreased bronchial secretion	30.97	12.50	7	20682	63	46665310
Arteriosclerosis coronary artery	30.92	12.50	27	20662	8129	46657244
Joint swelling	30.32	12.50	18	20671	166055	46499318
Infective exacerbation of chronic obstructive airways disease	29.30	12.50	13	20676	1167	46664206
Pain	29.12	12.50	111	20578	476837	46188536
Alopecia	29.10	12.50	18	20671	162396	46502977
Sinus pain	28.97	12.50	15	20674	1895	46663478
Endometrial ablation	28.57	12.50	11	20678	689	46664684
Blood bicarbonate decreased	28.27	12.50	17	20672	2868	46662505
Breast neoplasm	28.14	12.50	13	20676	1282	46664091
Drug level above therapeutic	27.64	12.50	18	20671	3491	46661882
Bronchial disorder	27.63	12.50	12	20677	1023	46664350
Middle insomnia	27.36	12.50	27	20662	9488	46655885
Blood pH decreased	27.10	12.50	16	20673	2611	46662762
Drug level increased	27.07	12.50	37	20652	18404	46646969
Dyspnoea exertional	26.91	12.50	65	20624	50224	46615149
Antasthmatic drug level above therapeutic	26.89	12.50	4	20685	0	46665373
Rhonchi	26.89	12.50	15	20674	2200	46663173
Female sterilisation	26.61	12.50	10	20679	586	46664787
Asthmatic crisis	26.50	12.50	13	20676	1465	46663908
Treatment failure	25.73	12.50	5	20684	93082	46572291
Adrenal suppression	25.31	12.50	11	20678	940	46664433
Urogenital haemorrhage	25.09	12.50	7	20682	156	46665217
Bronchial obstruction	24.82	12.50	12	20677	1310	46664063
Ligament pain	24.48	12.50	7	20682	171	46665202
Blood immunoglobulin E increased	24.27	12.50	13	20676	1760	46663613
Left ventricular failure	24.08	12.50	19	20670	4971	46660402
Kyphosis	23.70	12.50	14	20675	2287	46663086
Lung opacity	23.00	12.50	11	20678	1173	46664200
Fatigue	22.93	12.50	167	20522	608530	46056843
Diabetes mellitus	22.92	12.50	61	20628	50004	46615369
Hypoventilation	22.80	12.50	17	20672	4093	46661280
Dyspnoea at rest	22.54	12.50	16	20673	3572	46661801
Multiple drug therapy	22.50	12.50	10	20679	901	46664472
Rhabdomyolysis	22.24	12.50	54	20635	41855	46623518
Blood lactic acid increased	22.00	12.50	19	20670	5638	46659735
Heart rate increased	21.95	12.50	78	20611	74713	46590660
Cyanosis	21.88	12.50	31	20658	15940	46649433
Paranasal sinus hypersecretion	21.70	12.50	15	20674	3209	46662164
Off label use	21.50	12.50	91	20598	379750	46285623
Exercise tolerance decreased	21.18	12.50	17	20672	4560	46660813
Macrocytosis	21.10	12.50	13	20676	2290	46663083
Presbyacusis	21.07	12.50	14	20675	2808	46662565
Allergic cough	20.98	12.50	8	20681	488	46664885
Respiratory tract congestion	20.87	12.50	27	20662	12737	46652636
Spleen congestion	20.74	12.50	6	20683	153	46665220
Febrile neutropenia	20.71	12.50	8	20681	94619	46570754
Arthropathy	20.56	12.50	6	20683	84694	46580679
Rash	20.43	12.50	85	20604	356427	46308946
Painful respiration	19.95	12.50	13	20676	2524	46662849
Eye paraesthesia	19.72	12.50	5	20684	76	46665297
Pertussis	19.53	12.50	8	20681	590	46664783
Viral infection	19.40	12.50	42	20647	30193	46635180
Neutropenia	19.28	12.50	21	20668	143183	46522190
Systemic lupus erythematosus	19.11	12.50	3	20686	65177	46600196
Drug ineffective	18.87	12.50	201	20488	677637	45987736
Glossitis	18.77	12.50	13	20676	2790	46662583
Abdominal discomfort	18.40	12.50	24	20665	151141	46514232
Sleep disorder due to a general medical condition	18.36	12.50	14	20675	3485	46661888
Hypokalaemia	17.98	12.50	82	20607	87942	46577431
Contraindicated product prescribed	17.90	12.50	8	20681	731	46664642
Anaphylactic reaction	17.88	12.50	58	20631	53054	46612319
Pulmonary congestion	17.78	12.50	27	20662	14772	46650601
Product use issue	17.63	12.50	10	20679	94634	46570739
Granuloma	17.35	12.50	14	20675	3784	46661589
Pleural rub	17.32	12.50	4	20685	40	46665333
Respiration abnormal	17.21	12.50	15	20674	4506	46660867
Increased bronchial secretion	17.09	12.50	10	20679	1604	46663769
Bronchitis	16.87	12.50	92	20597	105887	46559486
Rhinitis	16.63	12.50	19	20670	7887	46657486
Medication error	16.58	12.50	40	20649	30871	46634502
Blood count abnormal	16.56	12.50	29	20660	17849	46647524
Myopathy	16.46	12.50	20	20669	8861	46656512
Ventricular tachycardia	16.34	12.50	28	20661	16939	46648434
Depressive symptom	16.34	12.50	12	20677	2824	46662549
Parakeratosis	16.08	12.50	5	20684	164	46665209
Depressed level of consciousness	16.06	12.50	52	20637	47517	46617856
Musculoskeletal stiffness	16.02	12.50	12	20677	97981	46567392
Staphylococcus test positive	15.92	12.50	13	20676	3571	46661802
Injection site hypoaesthesia	15.88	12.50	6	20683	357	46665016
Oropharyngeal candidiasis	15.85	12.50	8	20681	958	46664415
Atopy	15.48	12.50	5	20684	186	46665187
Respiratory disorder	15.37	12.50	36	20653	27264	46638109
Haemoptysis	15.25	12.50	35	20654	26154	46639219
Diarrhoea	15.12	12.50	167	20522	559435	46105938
Tremor	14.93	12.50	95	20594	115544	46549829
Aortic valve calcification	14.93	12.50	6	20683	421	46664952
Wrong technique in product usage process	14.88	12.50	3	20686	54419	46610954
Escherichia infection	14.82	12.50	21	20668	10796	46654577
Cushingoid	14.80	12.50	16	20673	6250	46659123
Neonatal tachycardia	14.64	12.50	3	20686	16	46665357
Stress urinary incontinence	14.61	12.50	10	20679	2106	46663267
Generalised tonic-clonic seizure	14.44	12.50	35	20654	27087	46638286
Scratch	14.36	12.50	14	20675	4848	46660525
Supraventricular tachycardia	14.26	12.50	23	20666	13247	46652126
Contraindicated product administered	14.11	12.50	9	20680	79938	46585435
Injection site pain	14.10	12.50	16	20673	107136	46558237
Oxygen saturation decreased	13.80	12.50	64	20625	69100	46596273
Blood pressure inadequately controlled	13.60	12.50	13	20676	4393	46660980
Mental disability	13.47	12.50	4	20685	112	46665261
Product dose omission issue	13.19	12.50	35	20654	168485	46496888
Vasodilation procedure	12.99	12.50	3	20686	30	46665343
Diabetes mellitus inadequate control	12.98	12.50	22	20667	13192	46652181
Weaning failure	12.88	12.50	5	20684	320	46665053
Death	12.61	12.50	92	20597	335456	46329917

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
Asthma	467.25	12.88	253	12796	35921	29903508
Chronic obstructive pulmonary disease	304.28	12.88	210	12839	45916	29893513
Forced expiratory volume decreased	119.11	12.88	47	13002	3203	29936226
Wheezing	108.19	12.88	97	12952	30841	29908588
Dyspnoea	96.83	12.88	341	12708	332954	29606475
Obstructive airways disorder	88.70	12.88	53	12996	9006	29930423
Respiratory failure	69.09	12.88	142	12907	100500	29838929
Vital capacity decreased	60.84	12.88	17	13032	388	29939041
Sputum discoloured	57.56	12.88	36	13013	6632	29932797
Foetal malformation	55.71	12.88	13	13036	139	29939290
Mental disability	54.06	12.88	10	13039	28	29939401
Forced vital capacity decreased	53.99	12.88	18	13031	754	29938675
Trisomy 18	49.65	12.88	13	13036	230	29939199
Pulmonary function test decreased	41.70	12.88	25	13024	4270	29935159
Tachycardia foetal	41.21	12.88	12	13037	319	29939110
Productive cough	38.69	12.88	56	12993	29897	29909532
Foetal distress syndrome	38.66	12.88	15	13034	976	29938453
Eosinophilic granulomatosis with polyangiitis	37.86	12.88	16	13033	1299	29938130
Total lung capacity abnormal	37.72	12.88	10	13039	186	29939243
Pneumonia	35.08	12.88	257	12792	334049	29605380
Cough	33.99	12.88	126	12923	125516	29813913
Chest discomfort	30.93	12.88	64	12985	45416	29894013
Lung hyperinflation	30.12	12.88	12	13037	838	29938591
Tachycardia	28.01	12.88	83	12966	73656	29865773
Epidural lipomatosis	26.94	12.88	8	13041	228	29939201
Lung opacity	26.40	12.88	11	13038	862	29938567
Supraventricular tachycardia	26.02	12.88	27	13022	10245	29929184
Supraventricular extrasystoles	24.25	12.88	16	13033	3228	29936201
Sputum increased	23.91	12.88	13	13036	1844	29937585
Wolff-Parkinson-White syndrome	23.66	12.88	7	13042	197	29939232
Conduction disorder	23.31	12.88	13	13036	1938	29937491
Eosinophil count increased	23.30	12.88	22	13027	7451	29931978
Dyspnoea exertional	23.08	12.88	49	13000	35381	29904048
Drug level increased	21.80	12.88	33	13016	18321	29921108
Blood count abnormal	21.57	12.88	26	13023	11626	29927803
Carbon dioxide increased	21.54	12.88	10	13039	1015	29938414
Gastrooesophageal reflux disease	21.46	12.88	45	13004	32210	29907219
Sleep disorder due to a general medical condition	20.67	12.88	11	13038	1496	29937933
Arrhythmia	20.60	12.88	45	13004	33124	29906305
Status asthmaticus	20.45	12.88	7	13042	318	29939111
Atrial fibrillation	20.27	12.88	97	12952	108027	29831402
Tachyarrhythmia	20.26	12.88	14	13035	3047	29936382
Tonic convulsion	20.06	12.88	9	13040	844	29938585
Hypoxia	19.25	12.88	55	12994	47799	29891630
Ventricular extrasystoles	18.67	12.88	24	13025	11450	29927979
Perfume sensitivity	18.02	12.88	5	13044	111	29939318
Rhinitis perennial	17.98	12.88	5	13044	112	29939317
Lipid metabolism disorder	17.89	12.88	6	13043	256	29939173
Electrocardiogram abnormal	17.71	12.88	17	13032	5875	29933554
Hypercapnia	17.47	12.88	14	13035	3810	29935619
Somnambulism	17.37	12.88	13	13036	3201	29936228
Gastrointestinal necrosis	17.11	12.88	13	13036	3276	29936153
Blood immunoglobulin E increased	16.61	12.88	10	13039	1720	29937709
Unmasking of previously unidentified disease	16.30	12.88	7	13042	591	29938838
Off label use	16.30	12.88	55	12994	249235	29690194
Ventricular arrhythmia	16.07	12.88	14	13035	4274	29935155
Accelerated idioventricular rhythm	15.96	12.88	4	13045	59	29939370
Emphysema	15.82	12.88	20	13029	9382	29930047
Vitamin D increased	15.37	12.88	4	13045	69	29939360
Pancytopenia	15.35	12.88	9	13040	85043	29854386
Electrocardiogram repolarisation abnormality	15.28	12.88	7	13042	689	29938740
Fatigue	15.24	12.88	80	12969	320593	29618836
Diarrhoea	14.98	12.88	85	12964	334018	29605411
Diverticulum intestinal haemorrhagic	14.86	12.88	10	13039	2085	29937344
Bronchial wall thickening	14.70	12.88	6	13043	446	29938983
Nikolsky's sign	14.65	12.88	5	13044	225	29939204
Febrile neutropenia	14.56	12.88	15	13034	106678	29832751
Neutropenia	14.45	12.88	21	13028	128519	29810910
Circulatory collapse	14.39	12.88	29	13020	20185	29919244
Bronchospasm	14.33	12.88	20	13029	10318	29929111
Eye infection	14.27	12.88	11	13038	2831	29936598
Small intestinal perforation	14.23	12.88	9	13040	1690	29937739
Electrocardiogram ST segment depression	13.77	12.88	10	13039	2352	29937077
Clonic convulsion	13.66	12.88	6	13043	535	29938894
Therapeutic product effect prolonged	13.59	12.88	5	13044	281	29939148
Respiratory alkalosis	13.24	12.88	8	13041	1386	29938043

Pharmacologic Action:

Source	Code	Description
ATC	R03DA04	RESPIRATORY SYSTEM DRUGS FOR OBSTRUCTIVE AIRWAY DISEASES OTHER SYSTEMIC DRUGS FOR OBSTRUCTIVE AIRWAY DISEASES Xanthines
ATC	R03DA05	RESPIRATORY SYSTEM DRUGS FOR OBSTRUCTIVE AIRWAY DISEASES OTHER SYSTEMIC DRUGS FOR OBSTRUCTIVE AIRWAY DISEASES Xanthines
ATC	R03DA54	RESPIRATORY SYSTEM DRUGS FOR OBSTRUCTIVE AIRWAY DISEASES OTHER SYSTEMIC DRUGS FOR OBSTRUCTIVE AIRWAY DISEASES Xanthines
ATC	R03DA55	RESPIRATORY SYSTEM DRUGS FOR OBSTRUCTIVE AIRWAY DISEASES OTHER SYSTEMIC DRUGS FOR OBSTRUCTIVE AIRWAY DISEASES Xanthines
ATC	R03DA74	RESPIRATORY SYSTEM DRUGS FOR OBSTRUCTIVE AIRWAY DISEASES OTHER SYSTEMIC DRUGS FOR OBSTRUCTIVE AIRWAY DISEASES Xanthines
ATC	R03DB04	RESPIRATORY SYSTEM DRUGS FOR OBSTRUCTIVE AIRWAY DISEASES OTHER SYSTEMIC DRUGS FOR OBSTRUCTIVE AIRWAY DISEASES Xanthines and adrenergics
ATC	R03DB05	RESPIRATORY SYSTEM DRUGS FOR OBSTRUCTIVE AIRWAY DISEASES OTHER SYSTEMIC DRUGS FOR OBSTRUCTIVE AIRWAY DISEASES Xanthines and adrenergics
FDA CS	M0023046	Xanthines
FDA EPC	N0000175790	Methylxanthine
CHEBI has role	CHEBI:35523	bronchodilator agents
CHEBI has role	CHEBI:38147	cardiotonic drugs
MeSH PA	D018927	Anti-Asthmatic Agents
MeSH PA	D001993	Bronchodilator Agents
MeSH PA	D002316	Cardiotonic Agents
MeSH PA	D002317	Cardiovascular Agents
MeSH PA	D004791	Enzyme Inhibitors
MeSH PA	D018377	Neurotransmitter Agents
MeSH PA	D018373	Peripheral Nervous System Agents
MeSH PA	D010726	Phosphodiesterase Inhibitors
MeSH PA	D020011	Protective Agents
MeSH PA	D058914	Purinergic Antagonists
MeSH PA	D058915	Purinergic P1 Receptor Antagonists
MeSH PA	D019141	Respiratory System Agents
MeSH PA	D014665	Vasodilator Agents
CHEBI has role	CHEBI:35620	vasodilator
CHEBI has role	CHEBI:49103	drug metabolites
CHEBI has role	CHEBI:49167	anti-asthmatic agents
CHEBI has role	CHEBI:50218	phosphodiesterase inhibitors
CHEBI has role	CHEBI:50846	biomodulator
CHEBI has role	CHEBI:51371	muscle relaxants
CHEBI has role	CHEBI:67079	antiinflammatory agents
CHEBI has role	CHEBI:71232	adenosine receptor antagonists
CHEBI has role	CHEBI:76946	fungal metabolites
CHEBI has role	CHEBI:85234	human blood serum metabolites

Drug Use (View source of the data)

Disease	Relation	SNOMED_ID	DOID
Bronchospasm	indication	4386001
Disorder of lung	indication	19829001	DOID:850
Bronchitis	indication	32398004	DOID:6132
Pulmonary emphysema	indication	87433001
Asthma	indication	195967001	DOID:2841
Asthma night-time symptoms	indication	395022009
Asthma management	indication	406162001
Acute exacerbation of asthma	indication	708038006
Asthma-chronic obstructive pulmonary disease overlap syndrome	indication	10692761000119107
COPD Associated with Chronic Bronchitis	indication
Chronic Obstructive Pulmonary Disease with Bronchospasms	indication
Apnea in the newborn	off-label use	13094009
Neonatal Mixed Apnea	off-label use
Goiter	contraindication	3716002	DOID:12176
Tachyarrhythmia	contraindication	6285003
Suicidal thoughts	contraindication	6471006
Alcoholism	contraindication	7200002
Hyperammonemia	contraindication	9360008
Peptic ulcer	contraindication	13200003	DOID:750
Hepatic encephalopathy	contraindication	13920009	DOID:13413
Hyperkalemia	contraindication	14140009
Pulmonary edema	contraindication	19242006	DOID:11396
Hashimoto thyroiditis	contraindication	21983002
Myocardial infarction	contraindication	22298006	DOID:5844
Acute tuberculosis	contraindication	25629007
Shock	contraindication	27942005
Hyperthyroidism	contraindication	34486009	DOID:7998
Depressive disorder	contraindication	35489007
Acute hepatitis	contraindication	37871000
Hypertensive disorder	contraindication	38341003	DOID:10763
Hypothyroidism	contraindication	40930008	DOID:1459
Third trimester pregnancy	contraindication	41587001
Conduction disorder of the heart	contraindication	44808001
Chronic heart failure	contraindication	48447003
Disorder of cardiovascular system	contraindication	49601007	DOID:1287
Coronary arteriosclerosis	contraindication	53741008	DOID:3393
Multiple organ failure	contraindication	57653000
Hepatic failure	contraindication	59927004
Poisoning by phenobarbital	contraindication	64921004
Substance abuse	contraindication	66214007
Psychotic disorder	contraindication	69322001
Hepatic coma	contraindication	72836002	DOID:12550
Diabetes mellitus	contraindication	73211009	DOID:9351
Sleep apnea	contraindication	73430006	DOID:0050847
Chronic idiopathic constipation	contraindication	82934008
Cor pulmonale	contraindication	83291003	DOID:8515
Open-angle glaucoma	contraindication	84494001	DOID:1067
Kidney disease	contraindication	90708001	DOID:557
Dermatitis herpetiformis	contraindication	111196000	DOID:8505
Seizure disorder	contraindication	128613002
Cystic fibrosis	contraindication	190905008	DOID:1485
Angina pectoris	contraindication	194828000
Disease of liver	contraindication	235856003	DOID:409
Bladder outflow obstruction	contraindication	236645006
Sepsis syndrome	contraindication	238150007
Hypocomplementemic urticarial vasculitis	contraindication	239945009
Benign prostatic hyperplasia	contraindication	266569009
Dyspnea	contraindication	267036007
Retention of urine	contraindication	267064002
Anemia	contraindication	271737000	DOID:2355
Continuous fever	contraindication	271751000
Pregnancy, function	contraindication	289908002
Thrombocytopenic disorder	contraindication	302215000	DOID:1588
Neutropenic disorder	contraindication	303011007	DOID:1227
Smoking cessation assistance	contraindication	384742004
Angle-closure glaucoma	contraindication	392291006	DOID:13550
Breastfeeding (mother)	contraindication	413712001
Chronic myocardial ischemia	contraindication	413844008	DOID:3393
Disorder of coronary artery	contraindication	414024009
Myocardial ischemia	contraindication	414795007	DOID:3393
Porphyria	contraindication	418470004
Hypertensive urgency	contraindication	443482000
Smokes tobacco daily	contraindication	449868002
Severe Hypoxemia	contraindication
Theophylline Toxicity	contraindication

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	7.46	acidic
pKa2	3.01	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 A1	GPCR	P30542	AA1R_HUMAN	ANTAGONIST	Ki	9.22	CHEMBL	CHEMBL
Adenosine receptor A2b	GPCR	P29275	AA2BR_HUMAN	ANTAGONIST	Ki	5.57	CHEMBL	CHEMBL
cGMP-inhibited 3',5'-cyclic phosphodiesterase A	Enzyme	Q14432	PDE3A_HUMAN	INHIBITOR	Ki	3.85	WOMBAT-PK	CHEMBL
Adenosine receptor A2a	GPCR	P29274	AA2AR_HUMAN	ANTAGONIST	Ki	9.22	CHEMBL	CHEMBL
cAMP-specific 3',5'-cyclic phosphodiesterase 4A	Enzyme	P27815	PDE4A_HUMAN	INHIBITOR	Ki	4.11	WOMBAT-PK	CHEMBL
Alkaline phosphatase, tissue-nonspecific isozyme	Enzyme	P05186	PPBT_HUMAN		Ki	4.09	CHEMBL
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform	Kinase	O00329	PK3CD_HUMAN		IC50	4.12	CHEMBL
Adenosine receptor A3	GPCR	P0DMS8	AA3R_HUMAN	ANTAGONIST	Ki	7.85	CHEMBL
Adenosine A2a receptor	Unclassified		AA2AR_CAVPO		Ki	4.89	CHEMBL
Adenosine receptor A2a	GPCR		AA2AR_RAT		Ki	5.17	CHEMBL
Adenosine A2 receptor	GPCR		AA2AR_RAT AA2BR_RAT		Ki	5.88	CHEMBL
Heart phosphodiesterase	Enzyme		E1BN64_BOVIN PDE1A_BOVIN PDE1B_BOVIN		IC50	4.04	CHEMBL
Adenosine receptor A3	GPCR		AA3R_RAT		Ki	4.07	CHEMBL
Uncharacterized protein	Enzyme		E1BN64_BOVIN		Ki	4.11	CHEMBL
Adenosine A2b receptor	GPCR		AA2BR_RAT		Ki	4.82	CHEMBL
Adenosine receptor A1	GPCR		AA1R_CAVPO		Ki	5.01	CHEMBL
Adenosine receptor	GPCR		AA1R_RAT AA2AR_RAT AA2BR_RAT AA3R_RAT		Ki	4.70	CHEMBL
Adenosine receptor A2b	Unclassified		AA2BR_MOUSE	ANTAGONIST	Ki	5.25	IUPHAR
Adenosine receptor A1	GPCR		AA1R_BOVIN		Ki	5.42	CHEMBL
Adenosine receptor A1	GPCR		AA1R_RAT		Ki	6.15	CHEMBL

External reference:

ID	Source
27Y3KJK423	UNII
4018056	VUID
N0000146397	NUI
D00227	KEGG_DRUG
317-34-0	SECONDARY_CAS_RN
4018055	VANDF
4018056	VANDF
4018129	VANDF
4018130	VANDF
4018132	VANDF
C0039771	UMLSCUI
CHEBI:28177	CHEBI
TEP	PDB_CHEM_ID
CHEMBL1370561	ChEMBL_ID
2153	PUBCHEM_CID
CHEMBL190	ChEMBL_ID
DB00277	DRUGBANK_ID
DB01223	DRUGBANK_ID
CHEMBL1200578	ChEMBL_ID
D000628	MESH_DESCRIPTOR_UI
D013806	MESH_DESCRIPTOR_UI
376	INN_ID
D031210	MESH_DESCRIPTOR_UI
413	IUPHAR_LIGAND_ID
10438	RXNORM
2086	MMSL
3058	MMSL
4172	MMSL
4173	MMSL
4175	MMSL
5563	MMSL
5564	MMSL
674	MMSL
72114	MMSL
72147	MMSL
d00142	MMSL
d00758	MMSL
000602	NDDF
000603	NDDF
000607	NDDF
000608	NDDF
111131008	SNOMEDCT_US
372810006	SNOMEDCT_US
373508009	SNOMEDCT_US
387431001	SNOMEDCT_US
45940009	SNOMEDCT_US
55867006	SNOMEDCT_US
66493003	SNOMEDCT_US

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
THEOPHYLLINE	HUMAN PRESCRIPTION DRUG LABEL	1	0121-0820	SOLUTION	80 mg	ORAL	ANDA	25 sections
Theophylline	HUMAN PRESCRIPTION DRUG LABEL	1	0121-4794	SOLUTION	80 mg	ORAL	ANDA	25 sections
THEOPHYLLINE	HUMAN PRESCRIPTION DRUG LABEL	1	0121-4820	SOLUTION	80 mg	ORAL	ANDA	25 sections
Theophylline in Dextrose	HUMAN PRESCRIPTION DRUG LABEL	2	0264-9554	INJECTION, SOLUTION	80 mg	INTRAVENOUS	NDA	27 sections
Theophylline(Anhydrous)	HUMAN PRESCRIPTION DRUG LABEL	1	0378-0486	TABLET, EXTENDED RELEASE	400 mg	ORAL	ANDA	22 sections
Theophylline(Anhydrous)	HUMAN PRESCRIPTION DRUG LABEL	1	0378-0487	TABLET, EXTENDED RELEASE	600 mg	ORAL	ANDA	22 sections
Aminophylline	HUMAN PRESCRIPTION DRUG LABEL	1	0409-5921	INJECTION, SOLUTION	25 mg	INTRAVENOUS	ANDA	22 sections
Aminophylline	HUMAN PRESCRIPTION DRUG LABEL	1	0409-5922	INJECTION, SOLUTION	25 mg	INTRAVENOUS	ANDA	22 sections
Theophylline Extended Release	HUMAN PRESCRIPTION DRUG LABEL	1	0615-1590	TABLET, EXTENDED RELEASE	300 mg	ORAL	ANDA	23 sections
Theophylline Extended Release	HUMAN PRESCRIPTION DRUG LABEL	1	0615-2503	TABLET, EXTENDED RELEASE	200 mg	ORAL	ANDA	23 sections
Theophylline	HUMAN PRESCRIPTION DRUG LABEL	1	10135-604	SOLUTION	80 mg	ORAL	ANDA	22 sections
Theophylline	HUMAN PRESCRIPTION DRUG LABEL	1	17856-0038	SOLUTION	80 mg	ORAL	ANDA	13 sections
ELIXOPHYLLIN	Human Prescription Drug Label	1	17856-0644	LIQUID	80 mg	ORAL	ANDA	21 sections
Theophylline	HUMAN PRESCRIPTION DRUG LABEL	1	27808-033	SOLUTION	80 mg	ORAL	ANDA	13 sections
Theophylline(Anhydrous)	HUMAN PRESCRIPTION DRUG LABEL	1	29033-001	TABLET, EXTENDED RELEASE	400 mg	ORAL	ANDA	22 sections
Theophylline(Anhydrous)	HUMAN PRESCRIPTION DRUG LABEL	1	29033-002	TABLET, EXTENDED RELEASE	600 mg	ORAL	ANDA	22 sections
TheophyllineAnhydrous	HUMAN PRESCRIPTION DRUG LABEL	1	42858-701	TABLET, EXTENDED RELEASE	400 mg	ORAL	ANDA	25 sections
TheophyllineAnhydrous	HUMAN PRESCRIPTION DRUG LABEL	1	42858-702	TABLET, EXTENDED RELEASE	600 mg	ORAL	ANDA	25 sections
Theophylline	Human Prescription Drug Label	1	46708-025	TABLET, EXTENDED RELEASE	300 mg	ORAL	ANDA	21 sections
Theophylline	Human Prescription Drug Label	1	46708-026	TABLET, EXTENDED RELEASE	450 mg	ORAL	ANDA	21 sections
Theophylline(Anhydrous)	HUMAN PRESCRIPTION DRUG LABEL	1	51407-318	TABLET, EXTENDED RELEASE	400 mg	ORAL	ANDA	22 sections
Theophylline(Anhydrous)	HUMAN PRESCRIPTION DRUG LABEL	1	51407-319	TABLET, EXTENDED RELEASE	600 mg	ORAL	ANDA	22 sections
AMINOPHYLLINE	HUMAN PRESCRIPTION DRUG LABEL	1	51662-1204	INJECTION, SOLUTION	25 mg	INTRAVENOUS	ANDA	12 sections
AMINOPHYLLINE	HUMAN PRESCRIPTION DRUG LABEL	1	51662-1341	INJECTION, SOLUTION	25 mg	INTRAVENOUS	ANDA	12 sections
Theo-24	HUMAN PRESCRIPTION DRUG LABEL	1	52244-100	CAPSULE, EXTENDED RELEASE	100 mg	ORAL	ANDA	25 sections
Theo-24	HUMAN PRESCRIPTION DRUG LABEL	1	52244-200	CAPSULE, EXTENDED RELEASE	200 mg	ORAL	ANDA	25 sections
Theo-24	HUMAN PRESCRIPTION DRUG LABEL	1	52244-300	CAPSULE, EXTENDED RELEASE	300 mg	ORAL	ANDA	25 sections
Theo-24	HUMAN PRESCRIPTION DRUG LABEL	1	52244-400	CAPSULE, EXTENDED RELEASE	400 mg	ORAL	ANDA	25 sections
Aminophylline	HUMAN PRESCRIPTION DRUG LABEL	1	52584-921	INJECTION, SOLUTION	25 mg	INTRAVENOUS	ANDA	12 sections
Aminophylline	HUMAN PRESCRIPTION DRUG LABEL	1	52584-922	INJECTION, SOLUTION	25 mg	INTRAVENOUS	ANDA	12 sections