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

Stem definitionDrug idCAS RN
N-methylated xanthine derivatives 2620 58-55-9

Description:

MoleculeDescription

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

Drug dosage:

DoseUnitRoute
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:

PropertyValueReference
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:

DateAgencyCompanyOrphan
April 19, 1940 FDA GD SEARLE LLC

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Toxicity to various agents 354.91 51.60 102 560 32652 2324771
Asthma 273.94 51.60 67 595 11247 2346176
Vomiting 172.44 51.60 73 589 71529 2285894
Tachycardia 153.22 51.60 46 616 16363 2341060
Dyspnoea 139.96 51.60 65 597 78668 2278755
Drug hypersensitivity 129.96 51.60 53 609 46590 2310833
Hypokalaemia 112.84 51.60 33 629 10621 2346802
Intentional overdose 110.86 51.60 33 629 11288 2346135
Respiratory acidosis 109.23 51.60 20 642 801 2356622
Lung hyperinflation 105.88 51.60 15 647 109 2357314
Wheezing 105.28 51.60 28 634 6356 2351067
Drug level increased 100.84 51.60 23 639 2764 2354659
Spleen congestion 99.32 51.60 13 649 47 2357376
Aortic valve calcification 95.10 51.60 13 649 70 2357353
Airway peak pressure increased 94.71 51.60 12 650 31 2357392
Drug interaction 94.24 51.60 37 625 29126 2328297
Overdose 92.55 51.60 33 629 19874 2337549
PCO2 increased 92.17 51.60 14 648 172 2357251
Blood bicarbonate decreased 91.60 51.60 16 646 487 2356936
Blood lactic acid increased 89.44 51.60 17 645 834 2356589
Status asthmaticus 86.49 51.60 13 649 148 2357275
PO2 decreased 84.58 51.60 14 648 306 2357117
Hypercapnia 83.50 51.60 15 647 537 2356886
Blood pH decreased 78.60 51.60 14 648 477 2356946
Seizure 75.26 51.60 30 632 24436 2332987
Pulmonary congestion 75.25 51.60 17 645 1948 2355475
Respiratory rate increased 73.94 51.60 16 646 1504 2355919
Respiratory failure 72.63 51.60 25 637 13503 2343920
Cardiomegaly 71.90 51.60 17 645 2379 2355044
Rhabdomyolysis 71.85 51.60 21 641 6683 2350740
Sinus tachycardia 71.30 51.60 18 644 3307 2354116
Somnolence 69.44 51.60 28 634 23457 2333966
Blood creatine phosphokinase increased 68.11 51.60 19 643 5117 2352306
Nausea 65.84 51.60 45 617 112144 2245279
Hypotension 63.90 51.60 29 633 32407 2325016
Dehydration 63.89 51.60 26 636 22269 2335154
Aortic valve stenosis 63.05 51.60 11 651 331 2357092
Toxic epidermal necrolysis 62.37 51.60 16 646 3128 2354295
Skin infection 57.97 51.60 13 649 1437 2355986
Cyanosis 57.31 51.60 15 647 3170 2354253
Depressed level of consciousness 56.57 51.60 18 644 7586 2349837
Peritonitis bacterial 55.39 51.60 11 651 676 2356747
Oxygen saturation decreased 52.50 51.60 17 645 7569 2349854

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Toxicity to various agents 151.53 54.91 55 440 29086 1717200
Tachycardia 147.23 54.91 44 451 12584 1733702
Asthma 146.75 54.91 36 459 4868 1741418
Dyspnoea 111.07 54.91 52 443 52007 1694279
Seizure 103.47 54.91 38 457 20403 1725883
Hypotension 86.39 54.91 37 458 29617 1716669
Foetal malformation 77.94 54.91 10 485 22 1746264
Trisomy 18 74.10 54.91 10 485 37 1746249
Mental disability 73.89 54.91 10 485 38 1746248
Completed suicide 66.59 54.91 26 469 16286 1730000
Supraventricular tachycardia 63.89 54.91 15 480 1648 1744638
Tachyarrhythmia 61.88 54.91 12 483 527 1745759
Vomiting 59.37 54.91 31 464 38284 1708002
Atrial fibrillation 57.80 54.91 23 472 15088 1731198
Tachycardia foetal 55.53 54.91 8 487 52 1746234

Pharmacologic Action:

SourceCodeDescription
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 EPC N0000175790 Methylxanthine
FDA CS M0023046 Xanthines
CHEBI has role CHEBI:51371 muscle relaxant
CHEBI has role CHEBI:35523 bronchodilator agent
CHEBI has role CHEBI:35620 vasodilator agent
CHEBI has role CHEBI:50846 immunomodulator
CHEBI has role CHEBI:67079 anti-inflammatory agent
CHEBI has role CHEBI:49167 anti-asthmatic drug
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

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
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 levelDissociation constantType (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:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Adenosine receptor A1 GPCR ANTAGONIST Ki 9.22 CHEMBL CHEMBL
Adenosine receptor A2b GPCR ANTAGONIST Ki 5.57 CHEMBL CHEMBL
cGMP-inhibited 3',5'-cyclic phosphodiesterase A Enzyme INHIBITOR Ki 3.85 WOMBAT-PK CHEMBL
Adenosine receptor A2a GPCR ANTAGONIST Ki 9.22 CHEMBL CHEMBL
cAMP-specific 3',5'-cyclic phosphodiesterase 4A Enzyme INHIBITOR Ki 4.11 WOMBAT-PK CHEMBL
Alkaline phosphatase, tissue-nonspecific isozyme Enzyme Ki 4.09 CHEMBL
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform Kinase IC50 4.12 CHEMBL
Adenosine receptor A3 GPCR ANTAGONIST Ki 7.85 CHEMBL
Adenosine A2a receptor Unclassified Ki 4.89 CHEMBL
Adenosine receptor A2a GPCR Ki 5.17 CHEMBL
Adenosine A2 receptor GPCR Ki 5.88 CHEMBL
Heart phosphodiesterase Enzyme IC50 4.04 CHEMBL
Adenosine receptor A3 GPCR Ki 4.07 CHEMBL
Uncharacterized protein Enzyme Ki 4.11 CHEMBL
Adenosine A2b receptor GPCR Ki 4.82 CHEMBL
Adenosine receptor A1 GPCR Ki 5.01 CHEMBL
Adenosine receptor GPCR Ki 4.70 CHEMBL
Adenosine receptor A2b Unclassified ANTAGONIST Ki 5.25 IUPHAR
Adenosine receptor A1 GPCR Ki 5.42 CHEMBL
Adenosine receptor A1 GPCR Ki 6.15 CHEMBL

External reference:

IDSource
D000628 MESH_DESCRIPTOR_UI
4018056 VUID
N0000146397 NUI
C0002575 UMLSCUI
D00227 KEGG_DRUG
0I55128JYK UNII
376 INN_ID
317-34-0 SECONDARY_CAS_RN
66493003 SNOMEDCT_US
4018129 VANDF
2086 MMSL
10438 RXNORM
372810006 SNOMEDCT_US
5563 MMSL
d00142 MMSL
4173 MMSL
000602 NDDF
2153 PUBCHEM_CID
CHEBI:28177 CHEBI
CHEMBL190 ChEMBL_ID
DB00277 DRUGBANK_ID
CHEMBL1200578 ChEMBL_ID
TEP PDB_CHEM_ID
CHEMBL1370561 ChEMBL_ID
D013806 MESH_DESCRIPTOR_UI
D031210 MESH_DESCRIPTOR_UI
413 IUPHAR_LIGAND_ID
DB01223 DRUGBANK_ID

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
THEOPHYLLINE HUMAN PRESCRIPTION DRUG LABEL 1 0121-0820 SOLUTION 80 mg ORAL ANDA 12 sections
Theophylline HUMAN PRESCRIPTION DRUG LABEL 1 0121-4794 SOLUTION 80 mg ORAL ANDA 12 sections
THEOPHYLLINE HUMAN PRESCRIPTION DRUG LABEL 1 0121-4820 SOLUTION 80 mg ORAL ANDA 12 sections
Theophylline in Dextrose HUMAN PRESCRIPTION DRUG LABEL 2 0264-9554 INJECTION, SOLUTION 80 mg INTRAVENOUS NDA 13 sections
Theophylline HUMAN PRESCRIPTION DRUG LABEL 1 0378-0486 TABLET, EXTENDED RELEASE 400 mg ORAL ANDA 12 sections
Theophylline HUMAN PRESCRIPTION DRUG LABEL 1 0378-0487 TABLET, EXTENDED RELEASE 600 mg ORAL ANDA 12 sections
Aminophylline HUMAN PRESCRIPTION DRUG LABEL 1 0409-5921 INJECTION, SOLUTION 25 mg INTRAVENOUS ANDA 12 sections
Aminophylline HUMAN PRESCRIPTION DRUG LABEL 1 0409-5922 INJECTION, SOLUTION 25 mg INTRAVENOUS ANDA 12 sections
Theophylline Extended Release HUMAN PRESCRIPTION DRUG LABEL 1 0615-1590 TABLET, EXTENDED RELEASE 300 mg ORAL ANDA 12 sections
Theophylline Extended Release HUMAN PRESCRIPTION DRUG LABEL 1 0615-2503 TABLET, EXTENDED RELEASE 200 mg ORAL ANDA 12 sections
Theophylline HUMAN PRESCRIPTION DRUG LABEL 1 10135-604 SOLUTION 80 mg ORAL ANDA 12 sections
Theophylline HUMAN PRESCRIPTION DRUG LABEL 1 17856-0038 SOLUTION 80 mg ORAL ANDA 11 sections
ELIXOPHYLLIN HUMAN PRESCRIPTION DRUG LABEL 1 17856-0644 LIQUID 80 mg ORAL ANDA 10 sections
Theophylline HUMAN PRESCRIPTION DRUG LABEL 1 27808-033 SOLUTION 80 mg ORAL ANDA 11 sections
Theophylline HUMAN PRESCRIPTION DRUG LABEL 1 29033-001 TABLET, EXTENDED RELEASE 400 mg ORAL ANDA 12 sections
Theophylline HUMAN PRESCRIPTION DRUG LABEL 1 29033-002 TABLET, EXTENDED RELEASE 600 mg ORAL ANDA 12 sections
Theophylline HUMAN PRESCRIPTION DRUG LABEL 1 42858-701 TABLET, EXTENDED RELEASE 400 mg ORAL ANDA 13 sections
Theophylline HUMAN PRESCRIPTION DRUG LABEL 1 42858-702 TABLET, EXTENDED RELEASE 600 mg ORAL ANDA 13 sections
Theophylline HUMAN PRESCRIPTION DRUG LABEL 1 46708-025 TABLET, EXTENDED RELEASE 300 mg ORAL ANDA 11 sections
Theophylline HUMAN PRESCRIPTION DRUG LABEL 1 46708-026 TABLET, EXTENDED RELEASE 450 mg ORAL ANDA 11 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 12 sections
Theo-24 HUMAN PRESCRIPTION DRUG LABEL 1 52244-200 CAPSULE, EXTENDED RELEASE 200 mg ORAL ANDA 12 sections
Theo-24 HUMAN PRESCRIPTION DRUG LABEL 1 52244-300 CAPSULE, EXTENDED RELEASE 300 mg ORAL ANDA 12 sections
Theo-24 HUMAN PRESCRIPTION DRUG LABEL 1 52244-400 CAPSULE, EXTENDED RELEASE 400 mg ORAL ANDA 12 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
Theophylline HUMAN PRESCRIPTION DRUG LABEL 1 53808-0315 TABLET, EXTENDED RELEASE 200 mg ORAL ANDA 12 sections
Theophylline HUMAN PRESCRIPTION DRUG LABEL 1 53808-0316 TABLET, EXTENDED RELEASE 300 mg ORAL ANDA 12 sections