amiloride 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |
| Stem definition | Drug id | CAS RN |
|---|---|---|
| epithelial sodium channel (ENaC) inhibitors, amiloride derivatives | 158 | 2609-46-3 |
Description:
| Molecule | Description |
|---|---|
|
Synonyms:
|
A pyrazine compound inhibiting SODIUM reabsorption through SODIUM CHANNELS in renal EPITHELIAL CELLS. This inhibition creates a negative potential in the luminal membranes of principal cells, located in the distal convoluted tubule and collecting duct. Negative potential reduces secretion of potassium and hydrogen ions. Amiloride is used in conjunction with DIURETICS to spare POTASSIUM loss. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p705)
Legend: OFP - off patent OFM - off market ONP - on patent |
Drug dosage:
| Dose | Unit | Route |
|---|---|---|
| 10 | mg | O |
ADMET properties:
| Property | Value | Reference |
|---|---|---|
| BDDCS (Biopharmaceutical Drug Disposition Classification System) | 3 | Benet LZ, Broccatelli F, Oprea TI |
| S (Water solubility) | 50 mg/mL | Benet LZ, Broccatelli F, Oprea TI |
| EoM (Fraction excreted unchanged in urine) | 49 % | Benet LZ, Broccatelli F, Oprea TI |
| MRTD (Maximum Recommended Therapeutic Daily Dose) | 0.47 µM/kg/day | Contrera JF, Matthews EJ, Kruhlak NL, Benz RD |
| BA (Bioavailability) | 50 % | Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H |
Approvals:
| Date | Agency | Company | Orphan |
|---|---|---|---|
| Oct. 5, 1981 | FDA | PADDOCK 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 |
|---|---|---|---|---|---|---|
| Hyperkalaemia | 58.91 | 19.69 | 36 | 3244 | 54167 | 63431575 |
| Hypokalaemia | 52.09 | 19.69 | 43 | 3237 | 103761 | 63381981 |
| Corneal abrasion | 36.46 | 19.69 | 9 | 3271 | 1115 | 63484627 |
| Granulomatous liver disease | 34.40 | 19.69 | 8 | 3272 | 770 | 63484972 |
| Acute kidney injury | 34.29 | 19.69 | 54 | 3226 | 263361 | 63222381 |
| Hypomagnesaemia | 33.55 | 19.69 | 20 | 3260 | 28717 | 63457025 |
| Hyponatraemia | 32.14 | 19.69 | 34 | 3246 | 111866 | 63373876 |
| Partial seizures with secondary generalisation | 27.86 | 19.69 | 6 | 3274 | 407 | 63485335 |
| Neurological symptom | 25.42 | 19.69 | 10 | 3270 | 5773 | 63479969 |
| Gingival oedema | 23.51 | 19.69 | 4 | 3276 | 76 | 63485666 |
| Disinhibition | 23.33 | 19.69 | 6 | 3274 | 877 | 63484865 |
| Leukoencephalopathy | 20.70 | 19.69 | 8 | 3272 | 4405 | 63481337 |
| Pyroglutamic acidosis | 20.17 | 19.69 | 5 | 3275 | 630 | 63485112 |
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 |
|---|---|---|---|---|---|---|
| Interstitial granulomatous dermatitis | 52.92 | 23.27 | 9 | 1774 | 173 | 34954975 |
| Hyperkalaemia | 35.72 | 23.27 | 29 | 1754 | 69360 | 34885788 |
| Dyskinesia oesophageal | 24.92 | 23.27 | 4 | 1779 | 53 | 34955095 |
| Mania | 23.85 | 23.27 | 11 | 1772 | 9500 | 34945648 |
| Diffuse alopecia | 23.56 | 23.27 | 4 | 1779 | 76 | 34955072 |
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 |
|---|---|---|---|---|---|---|
| Hyperkalaemia | 103.72 | 17.80 | 71 | 4601 | 114327 | 79625389 |
| Hypokalaemia | 58.66 | 17.80 | 56 | 4616 | 143984 | 79595732 |
| Interstitial granulomatous dermatitis | 49.10 | 17.80 | 9 | 4663 | 233 | 79739483 |
| Acute kidney injury | 45.19 | 17.80 | 96 | 4576 | 519308 | 79220408 |
| Hyponatraemia | 42.20 | 17.80 | 52 | 4620 | 177796 | 79561920 |
| Hypomagnesaemia | 35.23 | 17.80 | 26 | 4646 | 46885 | 79692831 |
| Corneal abrasion | 34.46 | 17.80 | 9 | 4663 | 1230 | 79738486 |
| Granulomatous liver disease | 24.55 | 17.80 | 7 | 4665 | 1326 | 79738390 |
| Partial seizures with secondary generalisation | 24.48 | 17.80 | 6 | 4666 | 635 | 79739081 |
| Dyskinesia oesophageal | 23.90 | 17.80 | 4 | 4668 | 60 | 79739656 |
| Drug level increased | 23.28 | 17.80 | 19 | 4653 | 39632 | 79700084 |
| Blood creatinine increased | 22.73 | 17.80 | 36 | 4636 | 155021 | 79584695 |
| Azotaemia | 20.76 | 17.80 | 10 | 4662 | 8266 | 79731450 |
| Neurological symptom | 20.19 | 17.80 | 10 | 4662 | 8773 | 79730943 |
| Neuromyopathy | 19.21 | 17.80 | 6 | 4666 | 1552 | 79738164 |
| Leukoencephalopathy | 18.15 | 17.80 | 9 | 4663 | 7920 | 79731796 |
| Vitamin B12 decreased | 17.91 | 17.80 | 7 | 4665 | 3498 | 79736218 |
FDA Adverse Event Reporting System (Pediatric)
None
Pharmacologic Action:
| Source | Code | Description |
|---|---|---|
| ATC | C03DB01 | CARDIOVASCULAR SYSTEM DIURETICS ALDOSTERONE ANTAGONISTS AND OTHER POTASSIUM-SPARING AGENTS Other potassium-sparing agents |
| FDA PE | N0000008859 | Decreased Renal K+ Excretion |
| FDA PE | N0000175359 | Increased Diuresis |
| FDA EPC | N0000175418 | Potassium-sparing Diuretic |
| CHEBI has role | CHEBI:35498 | diuretics |
| CHEBI has role | CHEBI:38633 | sodium channel blockers |
| MeSH PA | D062646 | Acid Sensing Ion Channel Blockers |
| MeSH PA | D004232 | Diuretics |
| MeSH PA | D062686 | Epithelial Sodium Channel Blockers |
| MeSH PA | D049990 | Membrane Transport Modulators |
| MeSH PA | D045283 | Natriuretic Agents |
| MeSH PA | D026941 | Sodium Channel Blockers |
Drug Use | Suggest Off label Use Form| |View source of the data|
| Disease | Relation | SNOMED_ID | DOID |
|---|---|---|---|
| Hypertensive disorder | indication | 38341003 | DOID:10763 |
| Edema | indication | 267038008 | |
| Hypokalemia Prevention | indication | ||
| Hypercalcemia | off-label use | 66931009 | DOID:12678 |
| Nephrogenic diabetes insipidus | off-label use | 111395007 | DOID:12387 |
| Peripheral Edema due to Chronic Heart Failure | off-label use | ||
| Pulmonary Edema due to Chronic Heart Failure | off-label use | ||
| Anuria | contraindication | 2472002 | DOID:2983 |
| Hypercholesterolemia | contraindication | 13644009 | |
| Hyperkalemia | contraindication | 14140009 | |
| Secondary angle-closure glaucoma | contraindication | 21571006 | |
| Hypovolemia | contraindication | 28560003 | |
| Dehydration | contraindication | 34095006 | |
| Hyperuricemia | contraindication | 35885006 | DOID:1920 |
| Hypokalemia | contraindication | 43339004 | |
| Acidosis | contraindication | 51387008 | |
| Systemic lupus erythematosus | contraindication | 55464009 | DOID:9074 |
| Sympathectomy | contraindication | 57071006 | |
| Hyperparathyroidism | contraindication | 66999008 | DOID:13543 |
| Hypochloremic alkalosis | contraindication | 70134007 | |
| Hepatic coma | contraindication | 72836002 | DOID:12550 |
| Diabetes mellitus | contraindication | 73211009 | DOID:9351 |
| Oliguria | contraindication | 83128009 | |
| Hyponatremia | contraindication | 89627008 | |
| Gout | contraindication | 90560007 | DOID:13189 |
| Kidney disease | contraindication | 90708001 | DOID:557 |
| Diabetic renal disease | contraindication | 127013003 | |
| Hypomagnesemia | contraindication | 190855004 | |
| Acute pancreatitis | contraindication | 197456007 | DOID:2913 |
| Disease of liver | contraindication | 235856003 | DOID:409 |
| Neonatal hyperbilirubinemia | contraindication | 281610001 | |
| Azotemia | contraindication | 445009001 |
🐶 Veterinary Drug Use
None
🐶 Veterinary products
None
Acid dissociation constants calculated using MoKa v3.0.0
| Dissociation level | Dissociation constant | Type (acidic/basic) |
|---|---|---|
| pKa1 | 8.64 | Basic |
| pKa2 | 4.41 | Basic |
| pKa3 | 0.72 | 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 |
|---|---|---|---|---|---|---|---|---|---|
| Amiloride-sensitive sodium channel, ENaC | Ion channel | BLOCKER | IC50 | 6.70 | CHEMBL | CHEMBL | |||
| Urokinase-type plasminogen activator | Enzyme | Ki | 5.16 | WOMBAT-PK | |||||
| Adenosine receptor A2a | GPCR | Ki | 5.48 | WOMBAT-PK | |||||
| Amine oxidase [flavin-containing] A | Enzyme | IC50 | 5.41 | DRUG MATRIX | |||||
| Sodium/hydrogen exchanger 1 | Transporter | IC50 | 4.22 | CHEMBL | |||||
| Solute carrier family 22 member 1 | Transporter | IC50 | 4.24 | CHEMBL | |||||
| Acid-sensing ion channel 2 | Ion channel | BLOCKER | IC50 | 4.60 | IUPHAR | ||||
| Acid-sensing ion channel 1 | Ion channel | IC50 | 5 | CHEMBL | |||||
| Acid-sensing ion channel 3 | Ion channel | IC50 | 5.36 | CHEMBL | |||||
| Sodium/hydrogen exchanger 5 | Transporter | INHIBITOR | Ki | 4.68 | IUPHAR | ||||
| Amiloride-sensitive sodium channel subunit alpha | Ion channel | IC50 | 6.11 | CHEMBL | |||||
| Membrane primary amine oxidase | Enzyme | Ki | 5 | CHEMBL | |||||
| Sodium/hydrogen exchanger | Transporter | IC50 | 4.01 | CHEMBL | |||||
| Sodium/hydrogen exchanger 1 | Transporter | INHIBITOR | Ki | 6 | IUPHAR | ||||
| Sodium/hydrogen exchanger 2 | Transporter | Ki | 6 | CHEMBL | |||||
| Urokinase-type plasminogen activator | Enzyme | Ki | 5.64 | CHEMBL | |||||
| Acid-sensing ion channel 1 | Ion channel | IC50 | 4.52 | CHEMBL |
External reference:
| ID | Source |
|---|---|
| 4019603 | VUID |
| N0000147699 | NUI |
| D00649 | KEGG_DRUG |
| 17440-83-4 | SECONDARY_CAS_RN |
| 2016-88-8 | SECONDARY_CAS_RN |
| 1298837 | RXNORM |
| C0002502 | UMLSCUI |
| CHEBI:2639 | CHEBI |
| AMR | PDB_CHEM_ID |
| CHEMBL945 | ChEMBL_ID |
| DB00594 | DRUGBANK_ID |
| CHEMBL1398126 | ChEMBL_ID |
| D000584 | MESH_DESCRIPTOR_UI |
| 16231 | PUBCHEM_CID |
| 2421 | IUPHAR_LIGAND_ID |
| 2352 | INN_ID |
| 7DZO8EB0Z3 | UNII |
| 2658 | MMSL |
| 4166 | MMSL |
| 4167 | MMSL |
| 71823 | MMSL |
| d00169 | MMSL |
| 1268944002 | SNOMEDCT_US |
| 387503008 | SNOMEDCT_US |
| 387516008 | SNOMEDCT_US |
| 412082007 | SNOMEDCT_US |
| 87395005 | SNOMEDCT_US |
| 4017935 | VANDF |
| 4019603 | VANDF |
| 002316 | NDDF |
| 004861 | NDDF |
Pharmaceutical products:
| Product | Category | Ingredients | NDC | Form | Quantity | Route | Marketing | Label |
|---|---|---|---|---|---|---|---|---|
| Amiloride Hydrochloride and Hydrochlorothiazide | HUMAN PRESCRIPTION DRUG LABEL | 2 | 0378-0577 | TABLET | 5 mg | ORAL | ANDA | 23 sections |
| Amiloride Hydrochloride and Hydrochlorothiazide | HUMAN PRESCRIPTION DRUG LABEL | 2 | 0555-0483 | TABLET | 5 mg | ORAL | ANDA | 17 sections |
| amiloride hydrocloride | HUMAN PRESCRIPTION DRUG LABEL | 1 | 0574-0292 | TABLET | 5 mg | ORAL | NDA | 22 sections |
| amiloride hydrocloride | HUMAN PRESCRIPTION DRUG LABEL | 1 | 0574-0292 | TABLET | 5 mg | ORAL | NDA | 22 sections |
| Amiloride Hydrochloride | HUMAN PRESCRIPTION DRUG LABEL | 1 | 42794-005 | TABLET | 5 mg | ORAL | ANDA | 18 sections |
| Amiloride Hydrochloride | HUMAN PRESCRIPTION DRUG LABEL | 1 | 42794-005 | TABLET | 5 mg | ORAL | ANDA | 18 sections |
| Amiloride Hydrochloride | HUMAN PRESCRIPTION DRUG LABEL | 1 | 49884-117 | TABLET | 5 mg | ORAL | ANDA | 18 sections |
| Amiloride Hydrochloride and Hydrochlorothiazide | HUMAN PRESCRIPTION DRUG LABEL | 2 | 50090-0513 | TABLET | 5 mg | ORAL | ANDA | 17 sections |
| Amiloride Hydrochloride and Hydrochlorothiazide | HUMAN PRESCRIPTION DRUG LABEL | 2 | 50090-0513 | TABLET | 5 mg | ORAL | ANDA | 17 sections |
| Amiloride Hydrochloride and Hydrochlorothiazide | HUMAN PRESCRIPTION DRUG LABEL | 2 | 54868-0667 | TABLET | 5 mg | ORAL | ANDA | 12 sections |
| AMILORIDE HYDROCHLORIDE | HUMAN PRESCRIPTION DRUG LABEL | 1 | 54868-5214 | TABLET | 5 mg | ORAL | NDA | 22 sections |
| amiloride hydrochloride | HUMAN PRESCRIPTION DRUG LABEL | 1 | 57721-671 | TABLET | 5 mg | ORAL | ANDA | 18 sections |
| Amiloride Hydrochloride | HUMAN PRESCRIPTION DRUG LABEL | 1 | 60429-275 | TABLET | 5 mg | ORAL | ANDA | 18 sections |
| Amiloride Hydrochloride | HUMAN PRESCRIPTION DRUG LABEL | 1 | 60429-275 | TABLET | 5 mg | ORAL | ANDA | 18 sections |
| Amiloride Hydrochloride | HUMAN PRESCRIPTION DRUG LABEL | 1 | 63629-2114 | TABLET | 5 mg | ORAL | ANDA | 18 sections |
| Amiloride Hydrochloride | HUMAN PRESCRIPTION DRUG LABEL | 1 | 63629-2114 | TABLET | 5 mg | ORAL | ANDA | 18 sections |
| Amiloride Hydrochloride | HUMAN PRESCRIPTION DRUG LABEL | 1 | 68151-0162 | TABLET | 5 mg | ORAL | ANDA | 18 sections |