aliskiren indications/contra

Stem definitionDrug idCAS RN
renin inhibitors 119 173334-57-1

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • aliskiren
  • rasilez
  • tekturna
  • aliskiren hemifumarate
  • aliskiren fumarate
  • SPP100
Renin is secreted by the kidney in response to decreases in blood volume and renal perfusion. Renin cleaves angiotensinogen to form the inactive decapeptide angiotensin I (Ang I). Ang I is converted to the active octapeptide angiotensin II (Ang II) by ACE and non-ACE pathways. Ang II is a powerful vasoconstrictor and leads to the release of catecholamines from the adrenal medulla and prejunctional nerve endings. It also promotes aldosterone secretion and sodium reabsorption. Together, these effects increase blood pressure. Ang II also inhibits renin release, thus providing a negative feedback to the system. This cycle, from renin through angiotensin to aldosterone and its associated negative feedback loop, is known as the renin-angiotensin-aldosterone system (RAAS). Aliskiren is a direct renin inhibitor, decreasing plasma renin activity (PRA) and inhibiting the conversion of angiotensinogen to Ang I. Whether aliskiren affects other RAAS components, e.g., ACE or non-ACE pathways, is not known.
  • Molecular weight: 551.77
  • Formula: C30H53N3O6
  • CLOGP: 3.51
  • LIPINSKI: 1
  • HAC: 9
  • HDO: 4
  • TPSA: 146.13
  • ALOGS: -5.42
  • ROTB: 19

Drug dosage:

DoseUnitRoute
0.15 g O

Approvals:

DateAgencyCompanyOrphan
March 5, 2007 FDA NOVARTIS

FDA Adverse Event Reporting System

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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
Blood creatinine increased 1032.92 36.97 295 3299 21523 3360742
Blood pressure increased 613.12 36.97 199 3395 22031 3360234
Hyperkalaemia 605.67 36.97 169 3425 11125 3371140
Angioedema 518.29 36.97 160 3434 14975 3367290
Acute kidney injury 480.32 36.97 206 3388 49477 3332788
Concomitant disease progression 474.60 36.97 87 3507 790 3381475
Dyspnoea 462.59 36.97 252 3342 102682 3279583
Cardiac failure 442.11 36.97 152 3442 19953 3362312
Renal impairment 436.51 36.97 147 3447 18114 3364151
Blood pressure inadequately controlled 414.86 36.97 84 3510 1336 3380929
Renal failure 393.09 36.97 159 3435 32781 3349484
Blood urea increased 363.12 36.97 104 3490 7456 3374809
Hypotension 352.33 36.97 166 3428 49348 3332917
Blood potassium increased 303.15 36.97 79 3515 3957 3378308
Hypertension 288.76 36.97 134 3460 38332 3343933
Oedema peripheral 283.95 36.97 128 3466 34233 3348032
Urine albumin/creatinine ratio increased 281.53 36.97 41 3553 59 3382206
Dizziness 247.53 36.97 152 3442 76360 3305905
Chronic kidney disease 232.58 36.97 71 3523 6321 3375944
Glomerular filtration rate decreased 219.69 36.97 55 3539 2336 3379929
Angina pectoris 211.24 36.97 69 3525 7652 3374613
Hyponatraemia 202.48 36.97 84 3510 18275 3363990
Cerebrovascular accident 195.42 36.97 100 3494 35188 3347077
Glycosylated haemoglobin increased 194.26 36.97 52 3542 2880 3379385
Hypertensive crisis 185.96 36.97 51 3543 3096 3379169
Oedema 178.28 36.97 72 3522 14608 3367657
Blood pressure systolic increased 175.92 36.97 49 3545 3150 3379115
Blood pressure diastolic decreased 174.60 36.97 42 3552 1505 3380760
Atrial fibrillation 165.59 36.97 79 3515 23862 3358403
Malaise 159.75 36.97 109 3485 65068 3317197

Pharmacologic Action:

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SourceCodeDescription
ATC C09XA02 CARDIOVASCULAR SYSTEM
AGENTS ACTING ON THE RENIN-ANGIOTENSIN SYSTEM
OTHER AGENTS ACTING ON THE RENIN-ANGIOTENSIN SYSTEM
Renin-inhibitors
ATC C09DX02 CARDIOVASCULAR SYSTEM
AGENTS ACTING ON THE RENIN-ANGIOTENSIN SYSTEM
ANGIOTENSIN II ANTAGONISTS, COMBINATIONS
Angiotensin II antagonists, other combinations
ATC C09XA52 CARDIOVASCULAR SYSTEM
AGENTS ACTING ON THE RENIN-ANGIOTENSIN SYSTEM
OTHER AGENTS ACTING ON THE RENIN-ANGIOTENSIN SYSTEM
Renin-inhibitors
ATC C09XA53 CARDIOVASCULAR SYSTEM
AGENTS ACTING ON THE RENIN-ANGIOTENSIN SYSTEM
OTHER AGENTS ACTING ON THE RENIN-ANGIOTENSIN SYSTEM
Renin-inhibitors
ATC C09XA54 CARDIOVASCULAR SYSTEM
AGENTS ACTING ON THE RENIN-ANGIOTENSIN SYSTEM
OTHER AGENTS ACTING ON THE RENIN-ANGIOTENSIN SYSTEM
Renin-inhibitors
FDA EPC N0000175900 Renin Inhibitor
FDA MoA N0000175899 Renin Inhibitors
CHEBI has role CHEBI:35674 antihypertensive agent

Drug Use (View source of the data)

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DiseaseRelationSNOMED_IDDOID
Hypertensive disorder indication 38341003 DOID:10763
Anuria contraindication 2472002 DOID:2983
Hypercholesterolemia contraindication 13644009
Hyperkalemia contraindication 14140009
Secondary angle-closure glaucoma contraindication 21571006
Hypovolemia contraindication 28560003
Obstruction of bile duct contraindication 30144000 DOID:13580
Dehydration contraindication 34095006
Hyperuricemia contraindication 35885006 DOID:1920
Angioedema contraindication 41291007 DOID:1558
Hypokalemia contraindication 43339004
Low blood pressure contraindication 45007003
Systemic lupus erythematosus contraindication 55464009 DOID:9074
Sympathectomy contraindication 57071006
Acute nephropathy contraindication 58574008
Hepatic failure contraindication 59927004
Hypercalcemia contraindication 66931009 DOID:12678
Hyperparathyroidism contraindication 66999008 DOID:13543
Hypochloremic alkalosis contraindication 70134007
Hepatic coma contraindication 72836002 DOID:12550
Diabetes mellitus contraindication 73211009 DOID:9351
Chronic idiopathic constipation contraindication 82934008
Hyponatremia contraindication 89627008
Gout contraindication 90560007 DOID:13189
Hypomagnesemia contraindication 190855004
Acute pancreatitis contraindication 197456007 DOID:2913
Impaired renal function disorder contraindication 197663003
Disease of liver contraindication 235856003 DOID:409
Neonatal hyperbilirubinemia contraindication 281610001
Pregnancy, function contraindication 289908002
Renal artery stenosis contraindication 302233006
Neutropenic disorder contraindication 303011007 DOID:1227
Azotemia contraindication 445009001
Severe Aortic Valve Stenosis contraindication

Acid dissociation constants calculated using MoKa v3.0.0

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Dissociation levelDissociation constantType (acidic/basic)
pKa1 12.53 acidic
pKa2 9.2 Basic

Orange Book patent data (new drug applications)

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Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
EQ 150MG BASE TEKTURNA NODEN PHARMA N021985 March 5, 2007 RX TABLET ORAL 5559111 July 21, 2018 TREATMENT OF HYPERTENSION
EQ 300MG BASE TEKTURNA NODEN PHARMA N021985 March 5, 2007 RX TABLET ORAL 5559111 July 21, 2018 TREATMENT OF HYPERTENSION
EQ 150MG BASE TEKTURNA HCT NODEN PHARMA N022107 Jan. 18, 2008 RX TABLET ORAL 5559111 July 21, 2018 TREATMENT OF HYPERTENSION
EQ 300MG BASE TEKTURNA HCT NODEN PHARMA N022107 Jan. 18, 2008 RX TABLET ORAL 5559111 July 21, 2018 TREATMENT OF HYPERTENSION
EQ 150MG BASE VALTURNA NOVARTIS N022217 Sept. 16, 2009 DISCN TABLET ORAL 5559111 July 21, 2018 TREATMENT OF HYPERTENSION
EQ 300MG BASE VALTURNA NOVARTIS N022217 Sept. 16, 2009 DISCN TABLET ORAL 5559111 July 21, 2018 TREATMENT OF HYPERTENSION
EQ 150MG BASE TEKAMLO NOVARTIS N022545 Aug. 26, 2010 DISCN TABLET ORAL 5559111 July 21, 2018 TREATMENT OF HYPERTENSION
EQ 300MG BASE TEKAMLO NOVARTIS N022545 Aug. 26, 2010 DISCN TABLET ORAL 5559111 July 21, 2018 TREATMENT OF HYPERTENSION
EQ 150MG BASE AMTURNIDE NOVARTIS N200045 Dec. 21, 2010 DISCN TABLET ORAL 5559111 July 21, 2018 TREATMENT OF HYPERTENSION
EQ 300MG BASE AMTURNIDE NOVARTIS N200045 Dec. 21, 2010 DISCN TABLET ORAL 5559111 July 21, 2018 TREATMENT OF HYPERTENSION

Orange Book exclusivity data (new drug applications)

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Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
EQ 37.5MG BASE TEKTURNA NODEN PHARMA N210709 Nov. 14, 2017 RX CAPSULE, PELLET ORAL Nov. 14, 2020 NEW PRODUCT
EQ 37.5MG BASE TEKTURNA NODEN PHARMA N210709 Nov. 14, 2017 RX CAPSULE, PELLET ORAL May 14, 2021 PEDIATRIC EXCLUSIVITY

Bioactivity Summary:

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TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Renin Enzyme INHIBITOR IC50 9.22 WOMBAT-PK CHEMBL
Multidrug resistance protein 1 Transporter Km 5.68 WOMBAT-PK
Cytochrome P450 3A4 Enzyme Km 4.61 WOMBAT-PK
Renin Enzyme IC50 8.70 CHEMBL
Renin Enzyme IC50 7.96 CHEMBL
Renin Enzyme IC50 8.10 CHEMBL
Renin-1 Enzyme IC50 8.35 CHEMBL
Renin Enzyme IC50 7.10 CHEMBL
Protease Enzyme Ki 7.12 CHEMBL

External reference:

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IDSource
4812 IUPHAR_LIGAND_ID
4025960 VUID
N0000179765 NUI
C1120110 UMLSCUI
D03208 KEGG_DRUG
502FWN4Q32 UNII
7992 INN_ID
325646 RXNORM
23512 MMSL
d06665 MMSL
4025960 VANDF
426725002 SNOMEDCT_US
427002003 SNOMEDCT_US
N0000176084 NDFRT
N0000179765 NDFRT
011991 NDDF
5493444 PUBCHEM_CID
CHEMBL1639 ChEMBL_ID
173334-58-2 SECONDARY_CAS_RN
DB09026 DRUGBANK_ID
CHEMBL3545059 ChEMBL_ID
C446481 MESH_SUPPLEMENTAL_RECORD_UI
CHEBI:601027 CHEBI
C41 PDB_CHEM_ID

Pharmaceutical products:

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ProductCategoryIngredientsNDCFormQuantityRoute MarketingLabel
Tekturna HUMAN PRESCRIPTION DRUG LABEL 1 0078-0485 TABLET, FILM COATED 150 mg ORAL NDA 19 sections
Tekturna HUMAN PRESCRIPTION DRUG LABEL 1 0078-0486 TABLET, FILM COATED 300 mg ORAL NDA 19 sections
Tekturna HUMAN PRESCRIPTION DRUG LABEL 1 50090-1250 TABLET, FILM COATED 300 mg ORAL NDA 19 sections
Tekturna HUMAN PRESCRIPTION DRUG LABEL 1 54868-5772 TABLET, FILM COATED 150 mg ORAL NDA 19 sections
Tekturna HCT HUMAN PRESCRIPTION DRUG LABEL 2 54868-6041 TABLET, FILM COATED 150 mg ORAL NDA 19 sections
Tekturna HUMAN PRESCRIPTION DRUG LABEL 1 54868-6042 TABLET, FILM COATED 300 mg ORAL NDA 19 sections
Tekturna HCT HUMAN PRESCRIPTION DRUG LABEL 2 54868-6103 TABLET, FILM COATED 300 mg ORAL NDA 19 sections
Tekturna HCT HUMAN PRESCRIPTION DRUG LABEL 2 54868-6194 TABLET, FILM COATED 300 mg ORAL NDA 19 sections
Tekturna HUMAN PRESCRIPTION DRUG LABEL 1 69189-0485 TABLET, FILM COATED 150 mg ORAL NDA 19 sections
Tekturna HCT HUMAN PRESCRIPTION DRUG LABEL 2 70839-112 TABLET, FILM COATED 150 mg ORAL NDA 19 sections
Tekturna HCT HUMAN PRESCRIPTION DRUG LABEL 2 70839-125 TABLET, FILM COATED 150 mg ORAL NDA 19 sections
Tekturna HUMAN PRESCRIPTION DRUG LABEL 1 70839-150 TABLET, FILM COATED 150 mg ORAL NDA 18 sections
Tekturna HUMAN PRESCRIPTION DRUG LABEL 1 70839-300 TABLET, FILM COATED 300 mg ORAL NDA 18 sections
Tekturna HCT HUMAN PRESCRIPTION DRUG LABEL 2 70839-312 TABLET, FILM COATED 300 mg ORAL NDA 19 sections
Tekturna HCT HUMAN PRESCRIPTION DRUG LABEL 2 70839-325 TABLET, FILM COATED 300 mg ORAL NDA 19 sections