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chlorothiazide 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |
| Stem definition | Drug id | CAS RN |
|---|---|---|
| diuretics, chlorothiazide derivatives | 609 | 58-94-6 |
Description:
| Molecule | Description |
|---|---|
|
Synonyms:
|
A thiazide diuretic with actions and uses similar to those of HYDROCHLOROTHIAZIDE. (From Martindale, The Extra Pharmacopoeia, 30th ed, p812)
Legend: OFP - off patent OFM - off market ONP - on patent |
Drug dosage:
| Dose | Unit | Route |
|---|---|---|
| 0.50 | g | O |
| 0.50 | g | O |
ADMET properties:
| Property | Value | Reference |
|---|---|---|
| BDDCS (Biopharmaceutical Drug Disposition Classification System) | 4 | Benet LZ, Broccatelli F, Oprea TI |
| S (Water solubility) | 0.70 mg/mL | Bocci G, Oprea TI, Benet LZ |
| EoM (Fraction excreted unchanged in urine) | 92 % | Benet LZ, Broccatelli F, Oprea TI |
| MRTD (Maximum Recommended Therapeutic Daily Dose) | 112.60 µM/kg/day | Contrera JF, Matthews EJ, Kruhlak NL, Benz RD |
| BA (Bioavailability) | 13 % | Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H |
Predicted pharmacokinetic/toxicological properties (PK-AZ):
| Property | Description | Value | Unit | Confidence | Similarity |
|---|---|---|---|---|---|
| azlogd74 | LogD at pH 7.4 | -1.154 | High | 1 | |
| caco2-efflux | Caco-2 efflux ratio (BA/AB) | 7.852 | High | 1 | |
| caco2-intrinsic-papp | Caco-2 intrinsic apparent permeability | 0.261 | 10^-6 cm/s | High | 1 |
| dh-clint | Dog hepatocyte intrinsic clearance | 3.459 | uL/min/10^6 cells | High | 1 |
| dppb | Dog plasma protein binding (% unbound) | 40.950 | % | High | 1 |
| fcs-ppb | Fetal calf serum protein binding (% unbound) | 19.060 | % | High | 1 |
| herg | hERG pIC50 | 4.027 | pIC50 | High | 1 |
| hh-clint | Human hepatocyte intrinsic clearance | 1.213 | uL/min/10^6 cells | High | 1 |
| hlm-clint | Human liver microsomal intrinsic clearance | 3.105 | uL/min/mg protein | High | 1 |
| hppb | Human plasma protein binding (% unbound) | 31.620 | % | High | 1 |
| kinase-safety-class | ACVR2A,ACVR2B,AURKA,AXL,BRAF,BTK,CAMK2B,CAMK2D,CDK5,CDK9,DDR1,DYRK1B,EGFR,EIF2AK3,EPHB4,ERBB2,FLT3,GRK2,GRK3,GSK3B,IKBKB,ITK,JAK1,JAK2,MAP2K6,MAP3K21,MAP3K7,MAPK10,MAPK12,MAPK7,MAPK9,MAPKAPK2,MTOR,NTRK2,PDK1,PDK2,PDPK1,PIK3CB,PIK3CD,PIK3CG,PIM2,PRKDC,SIK2,SIK3,STK33,SYK,TEK,TGFBR1,TTK,ULK1,ZAP70 | 51 | |||
| kinase-selectivity-class | GRK2,MAP2K6,PDK1,PDK2,TEK,UHMK1,ZAP70 | 7 | |||
| mdck-mdr1-bcrp-efflux | MDCK-MDR1-BCRP efflux ratio | 1.052 | High | 1 | |
| mdck-mdr1-efflux | MDCK-MDR1 efflux ratio | 0.628 | High | 1 | |
| mh-clint | Mouse hepatocyte intrinsic clearance | 5.861 | High | 1 | |
| mppb | Mouse plasma protein binding (% unbound) | 41.170 | High | 1 | |
| nih-mdck-mdr1-efflux | NIH MDCK-MDR1 efflux ratio | 0.385 | High | 1 | |
| pfas-class | PFAS structural alert (1 = True, 0 = False) | 0 | |||
| pppb | Pig plasma protein binding (% unbound) | 31.370 | % | High | 1 |
| rat-kpuu-brain | Rat brain Kpuu | 0.012 | % | High | 1 |
| rh-clint | Rat hepatocyte intrinsic clearance | 3.388 | uL/min/10^6 cells | High | 1 |
| rh-fuinc | Rat hepatocyte fraction unbound in incubation | 92.990 | % | High | 1 |
| rppb | Rat plasma protein binding (% unbound) | 20.410 | % | High | 1 |
| solubility-dd | Solubility at pH 7.4 in DMSO | 950.605 | uM | High | 1 |
Approvals:
| Date | Agency | Company | Orphan |
|---|---|---|---|
| Sept. 4, 1958 | FDA | OAK PHARMS AKORN |
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 |
|---|---|---|---|---|---|---|
| Pulmonary vein stenosis | 36.61 | 29.42 | 5 | 1134 | 92 | 90627216 |
| Respiratory failure | 36.24 | 29.42 | 21 | 1118 | 118397 | 90508911 |
| Rhinovirus infection | 34.20 | 29.42 | 9 | 1130 | 5954 | 90621354 |
| Hypervolaemia | 32.36 | 29.42 | 13 | 1126 | 32744 | 90594564 |
| Heparin-induced thrombocytopenia | 30.38 | 29.42 | 8 | 1131 | 5304 | 90622004 |
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 |
|---|---|---|---|---|---|---|
| Pulmonary hypertension | 45.71 | 26.89 | 20 | 1397 | 23549 | 42596369 |
| Respiratory failure | 45.45 | 26.89 | 36 | 1381 | 128096 | 42491822 |
| Hyperparathyroidism secondary | 41.05 | 26.89 | 10 | 1407 | 1832 | 42618086 |
| Respiratory distress | 32.18 | 26.89 | 19 | 1398 | 41801 | 42578117 |
FDA Adverse Event Reporting System (Geriatric)
| 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 |
|---|---|---|---|---|---|---|
| Respiratory failure | 61.24 | 24.12 | 44 | 2263 | 215288 | 110371704 |
| Respiratory distress | 53.78 | 24.12 | 27 | 2280 | 68847 | 110518145 |
| Hyperparathyroidism secondary | 39.86 | 24.12 | 10 | 2297 | 3294 | 110583698 |
| Pulmonary vein stenosis | 38.87 | 24.12 | 6 | 2301 | 157 | 110586835 |
| Pulmonary hypertension | 38.32 | 24.12 | 20 | 2287 | 55200 | 110531792 |
| Hospitalisation | 37.91 | 24.12 | 28 | 2279 | 142465 | 110444527 |
| Hypoxia | 35.69 | 24.12 | 26 | 2281 | 129489 | 110457503 |
| Pulmonary arterial hypertension | 35.28 | 24.12 | 16 | 2291 | 32552 | 110554440 |
| Hypervolaemia | 31.72 | 24.12 | 17 | 2290 | 49443 | 110537549 |
| Rhinovirus infection | 31.08 | 24.12 | 11 | 2296 | 11778 | 110575214 |
| Catheterisation cardiac | 29.34 | 24.12 | 9 | 2298 | 6182 | 110580810 |
| Oxygen saturation decreased | 29.19 | 24.12 | 25 | 2282 | 156957 | 110430035 |
| Cardiac arrest | 28.08 | 24.12 | 27 | 2280 | 196726 | 110390266 |
| Cardiac operation | 25.41 | 24.12 | 8 | 2299 | 5987 | 110581005 |
| Acute respiratory failure | 25.12 | 24.12 | 17 | 2290 | 75243 | 110511749 |
| Aspartate aminotransferase increased | 24.82 | 24.12 | 23 | 2284 | 159913 | 110427079 |
| Tracheitis | 24.76 | 24.12 | 6 | 2301 | 1715 | 110585277 |
| Heart disease congenital | 24.48 | 24.12 | 5 | 2302 | 657 | 110586335 |
FDA Adverse Event Reporting System (Pediatric)
None
Pharmacologic Action:
| Source | Code | Description |
|---|---|---|
| ATC | C03AA04 | CARDIOVASCULAR SYSTEM DIURETICS LOW-CEILING DIURETICS, THIAZIDES Thiazides, plain |
| ATC | C03AB04 | CARDIOVASCULAR SYSTEM DIURETICS LOW-CEILING DIURETICS, THIAZIDES Thiazides and potassium in combination |
| ATC | C03AH01 | CARDIOVASCULAR SYSTEM DIURETICS LOW-CEILING DIURETICS, THIAZIDES Thiazides, combinations with psycholeptics and/or analgesics |
| FDA CS | M0471776 | Thiazides |
| FDA PE | N0000175359 | Increased Diuresis |
| FDA EPC | N0000175419 | Thiazide Diuretic |
| CHEBI has role | CHEBI:35498 | diuretic |
| CHEBI has role | CHEBI:35674 | antihypertensive agent |
| MeSH PA | D000959 | Antihypertensive Agents |
| MeSH PA | D002317 | Cardiovascular Agents |
| MeSH PA | D004232 | Diuretics |
| MeSH PA | D045283 | Natriuretic Agents |
| MeSH PA | D049990 | Membrane Transport Modulators |
| MeSH PA | D049993 | Sodium Chloride Symporter Inhibitors |
Related Drugs by ATC class:
C03AA Thiazides, plain 9 drugs
C03AB Thiazides and potassium in combination 8 drugs
C03AH Thiazides, combinations with psycholeptics and/or analgesics 1 drug
Drug Use | Suggest Off label Use Form| |View source of the data|
| Disease | Relation | SNOMED_ID | DOID |
|---|---|---|---|
| Hypertensive disorder | indication | 38341003 | DOID:10763 |
| Chronic heart failure | indication | 48447003 | |
| Edema | indication | 267038008 | |
| Hypertensive urgency | indication | 443482000 | |
| Edema due to Nephrotic Syndrome | indication | ||
| Edema due to Hepatic Cirrhosis | indication | ||
| Hypertension with Left Ventricular Hypertrophy | indication | ||
| Pulmonary Edema due to Chronic Heart Failure | indication | ||
| Peripheral Edema due to Chronic Heart Failure | indication | ||
| Nephrogenic diabetes insipidus | off-label use | 111395007 | DOID:12387 |
| Calcium renal calculus | off-label use | 427649000 | |
| Anuria | contraindication | 2472002 | DOID:2983 |
| Bronchospasm | contraindication | 4386001 | |
| Suicidal thoughts | contraindication | 6471006 | |
| Psoriasis | contraindication | 9014002 | DOID:8893 |
| Peptic ulcer | contraindication | 13200003 | DOID:750 |
| Hypercholesterolemia | contraindication | 13644009 | |
| Hyperkalemia | contraindication | 14140009 | |
| Chronic disease of respiratory system | contraindication | 17097001 | |
| Metabolic acidosis, normal anion gap, acidifying salts | contraindication | 18104000 | |
| Jaundice | contraindication | 18165001 | |
| Cirrhosis of liver | contraindication | 19943007 | DOID:5082 |
| Secondary angle-closure glaucoma | contraindication | 21571006 | |
| Electroconvulsive therapy | contraindication | 23835007 | |
| Acute vomiting | contraindication | 23971007 | |
| Complete atrioventricular block | contraindication | 27885002 | |
| Hypovolemia | contraindication | 28560003 | |
| Acute cerebrovascular insufficiency | contraindication | 29322000 | |
| Obstruction of bile duct | contraindication | 30144000 | |
| Parkinsonism | contraindication | 32798002 | |
| Dehydration | contraindication | 34095006 | |
| Depressive disorder | contraindication | 35489007 | |
| Hyperuricemia | contraindication | 35885006 | DOID:1920 |
| Sick sinus syndrome | contraindication | 36083008 | DOID:13884 |
| Acute hepatitis | contraindication | 37871000 | |
| Immunosuppression | contraindication | 38013005 | |
| Anaphylaxis | contraindication | 39579001 | |
| Angioedema | contraindication | 41291007 | DOID:1558 |
| Hypokalemia | contraindication | 43339004 | |
| Diabetes mellitus type 2 | contraindication | 44054006 | DOID:9352 |
| Conduction disorder of the heart | contraindication | 44808001 | |
| Low blood pressure | contraindication | 45007003 | |
| Diabetes mellitus type 1 | contraindication | 46635009 | DOID:9744 |
| Sinus bradycardia | contraindication | 49710005 | |
| Cough | contraindication | 49727002 | |
| Acidosis | contraindication | 51387008 | |
| Syndrome of inappropriate vasopressin secretion | contraindication | 55004003 | DOID:3401 |
| Systemic lupus erythematosus | contraindication | 55464009 | DOID:9074 |
| Sympathectomy | contraindication | 57071006 | |
| Acute nephropathy | contraindication | 58574008 | |
| Hepatic failure | contraindication | 59927004 | |
| Aortic valve stenosis | contraindication | 60573004 | DOID:1712 |
| Chronic bronchitis | contraindication | 63480004 | DOID:6132 |
| Ulcerative colitis | contraindication | 64766004 | DOID:8577 |
| Hypercalcemia | contraindication | 66931009 | DOID:12678 |
| Hyperparathyroidism | contraindication | 66999008 | DOID:13543 |
| Benign intracranial hypertension | contraindication | 68267002 | DOID:11459 |
| Hypochloremic alkalosis | contraindication | 70134007 | |
| Hepatic coma | contraindication | 72836002 | DOID:12550 |
| Diabetes mellitus | contraindication | 73211009 | DOID:9351 |
| Wolff-Parkinson-White pattern | contraindication | 74390002 | DOID:384 |
| Transplantation | contraindication | 77465005 | |
| Chronic idiopathic constipation | contraindication | 82934008 | |
| Hereditary angioneurotic edema | contraindication | 82966003 | DOID:14735 |
| Oliguria | contraindication | 83128009 | |
| Epilepsy | contraindication | 84757009 | DOID:1826 |
| Megaloblastic anemia due to folate deficiency | contraindication | 85649008 | DOID:14026 |
| Pulmonary emphysema | contraindication | 87433001 | |
| Cardiogenic shock | contraindication | 89138009 | |
| Hyponatremia | contraindication | 89627008 | |
| Gout | contraindication | 90560007 | DOID:13189 |
| Kidney disease | contraindication | 90708001 | DOID:557 |
| Myasthenia gravis | contraindication | 91637004 | DOID:437 |
| Kidney stone | contraindication | 95570007 | |
| Disorder of connective tissue | contraindication | 105969002 | DOID:65 |
| Diabetic renal disease | contraindication | 127013003 | |
| Disorder of muscle | contraindication | 129565002 | DOID:423 |
| Liver function tests abnormal | contraindication | 166603001 | |
| Hypomagnesemia | contraindication | 190855004 | |
| Angina pectoris | contraindication | 194828000 | |
| Partial atrioventricular block | contraindication | 195039008 | |
| Second degree atrioventricular block | contraindication | 195042002 | |
| Decompensated cardiac failure | contraindication | 195111005 | |
| Asthma | contraindication | 195967001 | DOID:2841 |
| Acute hepatic failure | contraindication | 197270009 | |
| Acute pancreatitis | contraindication | 197456007 | DOID:2913 |
| Impaired renal function disorder | contraindication | 197663003 | |
| Cerebrovascular accident | contraindication | 230690007 | |
| Hypertrophic cardiomyopathy | contraindication | 233873004 | DOID:11984 |
| Disease of liver | contraindication | 235856003 | DOID:409 |
| Hypoglycemic disorder | contraindication | 237630007 | |
| Disorder of electrolytes | contraindication | 237840007 | |
| Lupus erythematosus and erythema multiforme-like syndrome | contraindication | 238926009 | |
| Rhabdomyolysis | contraindication | 240131006 | |
| Raynaud's phenomenon | contraindication | 266261006 | |
| Calculus in biliary tract | contraindication | 266474003 | |
| Anemia | contraindication | 271737000 | DOID:2355 |
| Neonatal hyperbilirubinemia | contraindication | 281610001 | |
| Pregnancy, function | contraindication | 289908002 | |
| Renal artery stenosis | contraindication | 302233006 | |
| Pheochromocytoma | contraindication | 302835009 | |
| Hypertriglyceridemia | contraindication | 302870006 | |
| Neutropenic disorder | contraindication | 303011007 | DOID:1227 |
| Bone marrow depression | contraindication | 307762000 | |
| Severe chronic obstructive pulmonary disease | contraindication | 313299006 | |
| Right ventricular failure | contraindication | 367363000 | |
| Surgical procedure | contraindication | 387713003 | |
| Peripheral arterial occlusive disease | contraindication | 399957001 | |
| Peripheral vascular disease | contraindication | 400047006 | |
| Severe diarrhea | contraindication | 409587002 | |
| Autoimmune hemolytic anemia | contraindication | 413603009 | DOID:718 |
| Disorder of coronary artery | contraindication | 414024009 | |
| Myocardial ischemia | contraindication | 414795007 | DOID:3393 |
| Myocardial infarction in recovery phase | contraindication | 418044006 | |
| Porphyria | contraindication | 418470004 | |
| Intraoperative floppy iris syndrome | contraindication | 418801006 | |
| Poor metabolizer due to cytochrome p450 CYP2D6 variant | contraindication | 423629005 | |
| Slow acetylator due to N-acetyltransferase enzyme variant | contraindication | 425079005 | |
| Azotemia | contraindication | 445009001 | |
| Smokes tobacco daily | contraindication | 449868002 | |
| Acute exacerbation of asthma | contraindication | 708038006 | |
| Severe Cerebrovascular Disease | contraindication | ||
| Hemodialysis with High-Flux Membrane | contraindication | ||
| Head and Neck Angioedema | contraindication | ||
| First Degree Atrioventricular Heart Block | contraindication | ||
| Intestinal Angioedema | contraindication | ||
| Severe Aortic Valve Stenosis | contraindication |
🐶 Veterinary Drug Use
| Species | Use | Relation |
|---|---|---|
| Dogs | Congestive heart failure | Indication |
| Dogs | Renal edema | Indication |
🐶 Veterinary products
| Product | Applicant | Ingredients |
|---|---|---|
| Diuril Tablet | Boehringer lngelheim Animal Health USA Inc. | 1 |
| Diuril | Boehringer lngelheim Animal Health USA Inc. | 1 |
Acid dissociation constants calculated using MoKa v3.0.0
| Dissociation level | Dissociation constant | Type (acidic/basic) |
|---|---|---|
| pKa1 | 6.53 | acidic |
| pKa2 | 9.74 | acidic |
| pKa3 | 4.58 | 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]) | Mechanism action | Bioact source | MoA source |
|---|---|---|---|---|---|---|---|---|---|
| Solute carrier family 12 member 3 | Transporter | INHIBITOR | A2 | 5.43 | WOMBAT-PK | CHEMBL | |||
| Carbonic anhydrase 2 | Enzyme | WOMBAT-PK | |||||||
| Carbonic anhydrase 1 | Enzyme | IC50 | 6.34 | CHEMBL |
External reference:
| ID | Source |
|---|---|
| 4017731 | VUID |
| N0000146099 | NUI |
| D00519 | KEGG_DRUG |
| 7085-44-1 | SECONDARY_CAS_RN |
| 2396 | RXNORM |
| C0008273 | UMLSCUI |
| CHEBI:3640 | CHEBI |
| CHEMBL842 | ChEMBL_ID |
| DB00880 | DRUGBANK_ID |
| CHEMBL1200616 | ChEMBL_ID |
| D002740 | MESH_DESCRIPTOR_UI |
| 2720 | PUBCHEM_CID |
| 4835 | IUPHAR_LIGAND_ID |
| 636 | INN_ID |
| 77W477J15H | UNII |
| 169210 | MMSL |
| 3950 | MMSL |
| 4419 | MMSL |
| 4420 | MMSL |
| d00190 | MMSL |
| 002292 | NDDF |
| 002293 | NDDF |
| 372782002 | SNOMEDCT_US |
| 5786005 | SNOMEDCT_US |
| 8252004 | SNOMEDCT_US |
| 4017731 | VANDF |
| 4017732 | VANDF |
| 77W477J15H | INXIGHT DRUGS |
Pharmaceutical products:
| Product | Category | Ingredients | NDC | Form | Quantity | Route | Marketing | Label |
|---|---|---|---|---|---|---|---|---|
| Chlorothiazide Sodium | HUMAN PRESCRIPTION DRUG LABEL | 1 | 0517-1820 | INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION | 500 mg | INTRAVENOUS | ANDA | 24 sections |
| Chlorothiazide Sodium | HUMAN PRESCRIPTION DRUG LABEL | 1 | 17478-419 | INJECTION | 500 mg | INTRAVENOUS | NDA authorized generic | 25 sections |
| chlorothiazide sodium | HUMAN PRESCRIPTION DRUG LABEL | 1 | 25021-305 | INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION | 500 mg | INTRAVENOUS | ANDA | 25 sections |
| chlorothiazide sodium | HUMAN PRESCRIPTION DRUG LABEL | 1 | 25021-305 | INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION | 500 mg | INTRAVENOUS | ANDA | 25 sections |
| CHLOROTHIAZIDE SODIUM | Human Prescription Drug Label | 1 | 47335-330 | INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION | 500 mg | INTRAVENOUS | ANDA | 21 sections |
| Chlorothiazide | HUMAN PRESCRIPTION DRUG LABEL | 1 | 63323-658 | INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION | 500 mg | INTRAVENOUS | ANDA | 13 sections |
| Chlorothiazide | HUMAN PRESCRIPTION DRUG LABEL | 1 | 63323-658 | INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION | 500 mg | INTRAVENOUS | ANDA | 13 sections |
| Chlorothiazide | HUMAN PRESCRIPTION DRUG LABEL | 1 | 63323-658 | INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION | 500 mg | INTRAVENOUS | ANDA | 13 sections |
| DIURIL | HUMAN PRESCRIPTION DRUG LABEL | 1 | 65649-311 | SUSPENSION | 250 mg | ORAL | NDA | 23 sections |
| Chlorothiazide sodium | Human Prescription Drug Label | 1 | 68083-614 | INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION | 500 mg | INTRAVENOUS | ANDA | 19 sections |
| Sodium Diuril | HUMAN PRESCRIPTION DRUG LABEL | 1 | 76478-711 | INJECTION | 0.50 mg | INTRAVENOUS | NDA | 24 sections |