aliskiren 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definition	Drug id	CAS RN
renin inhibitors	119	173334-57-1

Description:

Molecule	Description
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 Status: OFP Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

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

Status: OFP

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

Drug dosage:

Dose	Unit	Route
0.15	g	O

ADMET properties:

Property	Value	Reference
MRTD (Maximum Recommended Therapeutic Daily Dose)	7.77 µM/kg/day	Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BDDCS (Biopharmaceutical Drug Disposition Classification System)	3	Hosey CM, Chan R, Benet LZ
S (Water solubility)	350 mg/mL	Hosey CM, Chan R, Benet LZ
EoM (Fraction excreted unchanged in urine)	25 %	Hosey CM, Chan R, Benet LZ
BA (Bioavailability)	2.50 %	Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H

Approvals:

Date	Agency	Company	Orphan
March 5, 2007	FDA	NOVARTIS

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
Neurologic neglect syndrome	495.08	23.72	105	8840	2093	56281029
Carotid artery thrombosis	492.91	23.72	105	8840	2139	56280983
Personality disorder	489.65	23.72	122	8823	5051	56278071
Hemiplegia	435.49	23.72	123	8822	8281	56274841
Adjustment disorder	416.53	23.72	92	8853	2231	56280891
Affect lability	412.84	23.72	123	8822	10002	56273120
Sensory loss	357.53	23.72	107	8838	8828	56274294
Motor dysfunction	343.00	23.72	105	8840	9352	56273770
Muscle spasticity	327.23	23.72	122	8823	19838	56263284
Coordination abnormal	317.17	23.72	106	8839	12515	56270607
Hemiparesis	304.17	23.72	118	8827	21372	56261750
Aphasia	297.08	23.72	128	8817	30287	56252835
Eating disorder	289.33	23.72	107	8838	16998	56266124
Cerebrovascular accident	260.90	23.72	174	8771	99096	56184026
Dysarthria	243.90	23.72	121	8824	39429	56243693
Dysphagia	213.63	23.72	143	8802	81804	56201318
Blood pressure inadequately controlled	184.44	23.72	55	8890	4469	56278653
Muscular weakness	161.14	23.72	133	8812	104319	56178803
Angioedema	111.85	23.72	74	8871	41379	56241743
Skin haemorrhage	111.17	23.72	44	8901	8369	56274753
Anxiety	105.36	23.72	141	8804	193031	56090091
Diabetes mellitus inadequate control	92.71	23.72	45	8900	13935	56269187
Conjoined twins	90.11	23.72	18	8927	262	56282860
Confusional state	89.95	23.72	136	8809	208019	56075103
Sneezing	79.52	23.72	42	8903	15518	56267604
Respiratory tract congestion	79.44	23.72	42	8903	15549	56267573
Sinus congestion	79.11	23.72	42	8903	15682	56267440
Blood pressure increased	73.04	23.72	102	8843	145074	56138048
Sinus disorder	68.28	23.72	42	8903	20692	56262430
Intestinal malrotation	67.84	23.72	15	8930	364	56282758
Concomitant disease progression	66.52	23.72	21	8924	2061	56281061
Congenital bladder anomaly	66.30	23.72	13	8932	171	56282951
Urachal abnormality	65.75	23.72	13	8932	179	56282943
Impaired work ability	65.16	23.72	36	8909	14536	56268586
Persistent cloaca	64.90	23.72	13	8932	192	56282930
Off label use	59.17	23.72	9	8936	556171	55726951
Skin exfoliation	56.78	23.72	47	8898	36853	56246269
Multiple drug therapy	52.85	23.72	19	8926	2773	56280349
Asthenia	52.84	23.72	146	8799	342827	55940295
Exercise tolerance decreased	51.31	23.72	22	8923	5116	56278006
Fall	49.07	23.72	146	8799	357364	55925758
Cystitis	48.98	23.72	49	8896	48989	56234133
Arterial occlusive disease	46.99	23.72	21	8924	5389	56277733
Angina pectoris	45.91	23.72	37	8908	27939	56255183
Hyperkalaemia	45.68	23.72	48	8897	50817	56232305
Hypertension	42.64	23.72	109	8836	244169	56038953
Blood creatinine increased	41.24	23.72	57	8888	80134	56202988
Gangrene	40.27	23.72	19	8926	5521	56277601
Influenza like illness	40.19	23.72	49	8896	60939	56222183
Anal prolapse	36.14	23.72	7	8938	86	56283036
Rhinorrhoea	34.65	23.72	44	8901	56993	56226129
Drug intolerance	28.75	23.72	4	8941	264814	56018308
Toxicity to various agents	25.32	23.72	3	8942	224561	56058561

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
Concomitant disease progression	287.47	21.30	68	4834	2321	31690121
Cardiac failure	107.80	21.30	96	4806	85857	31606585
Blood creatinine increased	100.95	21.30	94	4808	88984	31603458
Hyperkalaemia	86.87	21.30	75	4827	64276	31628166
Urine albumin/creatinine ratio increased	54.22	21.30	11	4891	179	31692263
Renal impairment	49.91	21.30	64	4838	86285	31606157
Chronic kidney disease	48.62	21.30	43	4859	37932	31654510
Blood pressure inadequately controlled	47.94	21.30	17	4885	2452	31689990
Blood pressure increased	41.32	21.30	56	4846	79577	31612865
Angina pectoris	40.83	21.30	35	4867	29606	31662836
Blood potassium increased	38.67	21.30	26	4876	15319	31677123
Disease progression	35.84	21.30	56	4846	90408	31602034
Angioedema	35.13	21.30	34	4868	33584	31658858
Bundle branch block left	34.74	21.30	17	4885	5501	31686941
Diabetic nephropathy	32.10	21.30	12	4890	2009	31690433
Glycosylated haemoglobin increased	32.05	21.30	20	4882	10380	31682062
Hypotension	30.93	21.30	85	4817	204533	31487909
Cardiac failure acute	30.70	21.30	19	4883	9722	31682720
Oedema peripheral	29.16	21.30	57	4845	109782	31582660
Off label use	28.84	21.30	9	4893	347265	31345177
Post procedural haematoma	28.15	21.30	10	4892	1449	31690993
Bundle branch block right	25.49	21.30	15	4887	7009	31685433
Acute pulmonary oedema	25.38	21.30	15	4887	7061	31685381
Orthopnoea	25.02	21.30	13	4889	4768	31687674
Cardiac failure chronic	24.94	21.30	15	4887	7288	31685154
Dyspnoea	24.27	21.30	111	4791	343368	31349074
Blood urea increased	24.22	21.30	26	4876	28986	31663456
Defect conduction intraventricular	23.34	21.30	6	4896	288	31692154

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
Neurologic neglect syndrome	490.70	21.17	105	10733	2276	70915330
Carotid artery thrombosis	489.30	21.17	106	10732	2440	70915166
Personality disorder	485.77	21.17	122	10716	5426	70912180
Affect lability	412.82	21.17	122	10716	10024	70907582
Adjustment disorder	392.32	21.17	92	10746	3052	70914554
Hemiplegia	375.02	21.17	122	10716	13773	70903833
Muscle spasticity	333.38	21.17	122	10716	19567	70898039
Sensory loss	327.45	21.17	105	10733	11314	70906292
Motor dysfunction	313.53	21.17	105	10733	12965	70904641
Concomitant disease progression	310.62	21.17	77	10761	3238	70914368
Coordination abnormal	299.86	21.17	107	10731	15959	70901647
Eating disorder	284.77	21.17	107	10731	18458	70899148
Hemiparesis	265.04	21.17	118	10720	31351	70886255
Aphasia	258.64	21.17	128	10710	43121	70874485
Dysarthria	206.98	21.17	125	10713	62188	70855418
Dysphagia	192.56	21.17	150	10688	112684	70804922
Cerebrovascular accident	182.84	21.17	161	10677	143309	70774297
Blood pressure inadequately controlled	162.62	21.17	52	10786	5540	70912066
Muscular weakness	129.66	21.17	131	10707	138205	70779401
Angioedema	99.51	21.17	82	10756	66528	70851078
Skin haemorrhage	98.06	21.17	42	10796	10138	70907468
Hyperkalaemia	90.88	21.17	96	10742	106495	70811111
Anxiety	90.85	21.17	138	10700	220192	70697414
Sneezing	80.47	21.17	43	10795	16908	70900698
Sinus congestion	76.70	21.17	42	10796	17331	70900275
Respiratory tract congestion	76.08	21.17	42	10796	17611	70899995
Sinus disorder	73.28	21.17	42	10796	18917	70898689
Cardiac failure	72.41	21.17	99	10739	143442	70774164
Diabetes mellitus inadequate control	68.89	21.17	43	10795	22602	70895004
Off label use	68.63	21.17	15	10823	743045	70174561
Blood creatinine increased	63.78	21.17	93	10745	142908	70774698
Impaired work ability	62.62	21.17	36	10802	16304	70901302
Angina pectoris	60.87	21.17	54	10784	48329	70869277
Confusional state	60.73	21.17	134	10704	284264	70633342
Blood pressure increased	54.76	21.17	101	10737	188416	70729190
Multiple drug therapy	47.45	21.17	18	10820	3174	70914432
Cystitis	44.88	21.17	45	10793	46896	70870710
Asthenia	44.42	21.17	162	10676	457504	70460102
Renal impairment	44.16	21.17	79	10759	143858	70773748
Skin exfoliation	43.55	21.17	45	10793	48581	70869025
Arterial occlusive disease	43.51	21.17	22	10816	7720	70909886
Exercise tolerance decreased	39.36	21.17	21	10817	8227	70909379
Diabetic nephropathy	38.94	21.17	15	10823	2758	70914848
Anal prolapse	37.55	21.17	7	10831	72	70917534
Influenza like illness	37.43	21.17	48	10790	65283	70852323
Chronic kidney disease	36.78	21.17	46	10792	61011	70856595
Toxicity to various agents	36.67	21.17	7	10831	382165	70535441
Gangrene	36.43	21.17	20	10818	8289	70909317
Fall	35.57	21.17	148	10690	443948	70473658
Oedema peripheral	35.28	21.17	95	10743	227996	70689610
Rhinorrhoea	30.77	21.17	44	10794	66327	70851279
Hypertension	29.67	21.17	106	10732	295927	70621679
Neutropenia	26.21	21.17	4	10834	257152	70660454
Cardiac failure acute	24.98	21.17	21	10817	17466	70900140
Bundle branch block left	24.89	21.17	17	10821	10382	70907224
Pharyngeal oedema	24.83	21.17	20	10818	15676	70901930
Renal failure	24.59	21.17	74	10764	188996	70728610
Condition aggravated	24.24	21.17	18	10820	427617	70489989
Post procedural haematoma	23.64	21.17	10	10828	2338	70915268
Rectocele	23.60	21.17	7	10831	579	70917027
Glycosylated haemoglobin increased	23.04	21.17	20	10818	17371	70900235
Cardiac failure chronic	22.73	21.17	16	10822	10253	70907353
Defect conduction intraventricular	21.45	21.17	6	10832	403	70917203
Abortion induced	21.20	21.17	13	10825	6612	70910994

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

Source	Code	Description
ATC	C09DX02	CARDIOVASCULAR SYSTEM AGENTS ACTING ON THE RENIN-ANGIOTENSIN SYSTEM ANGIOTENSIN II RECEPTOR BLOCKERS (ARBs), COMBINATIONS Angiotensin II receptor blockers (ARBs), other combinations
ATC	C09XA02	CARDIOVASCULAR SYSTEM AGENTS ACTING ON THE RENIN-ANGIOTENSIN SYSTEM OTHER AGENTS ACTING ON THE RENIN-ANGIOTENSIN SYSTEM Renin-inhibitors
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 MoA	N0000175899	Renin Inhibitors
FDA EPC	N0000175900	Renin Inhibitor
CHEBI has role	CHEBI:35674	antihypertensive drugs

Drug Use | Suggest Off label Use Form| |View source of the data|

Disease	Relation	SNOMED_ID	DOID
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
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

🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	12.53	acidic
pKa2	9.2	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
Renin	Enzyme	P00797	RENI_HUMAN	INHIBITOR	IC50	9.22	WOMBAT-PK	CHEMBL
Multidrug resistance protein 1	Transporter	P08183	MDR1_HUMAN		Km	5.68	WOMBAT-PK
Cytochrome P450 3A4	Enzyme	P08684	CP3A4_HUMAN		Km	4.61	WOMBAT-PK
Renin	Enzyme		RENI_CALJA		IC50	8.70	CHEMBL
Renin	Enzyme		RENI_MACFA		IC50	8.10	CHEMBL
Renin	Enzyme		RENI_RAT		IC50	7.10	CHEMBL
Renin-1	Enzyme		RENI1_MOUSE		IC50	8.35	CHEMBL
Renin	Enzyme		Q7M3D2_RABIT		IC50	7.96	CHEMBL
Protease	Enzyme		Q9YQ12_9HIV1		Ki	7.12	CHEMBL
Renin	Enzyme		RENI_MACMU		IC50	8.92	CHEMBL

External reference:

ID	Source
4025960	VUID
N0000179765	NUI
D03208	KEGG_DRUG
173334-58-2	SECONDARY_CAS_RN
325646	RXNORM
C1120110	UMLSCUI
CHEBI:601027	CHEBI
C41	PDB_CHEM_ID
CHEMBL1639	ChEMBL_ID
CHEMBL3545059	ChEMBL_ID
CHEMBL1667	ChEMBL_ID
DB09026	DRUGBANK_ID
C446481	MESH_SUPPLEMENTAL_RECORD_UI
4812	IUPHAR_LIGAND_ID
7992	INN_ID
502FWN4Q32	UNII
5493444	PUBCHEM_CID
011991	NDDF
011995	NDDF
425981005	SNOMEDCT_US
426725002	SNOMEDCT_US
427002003	SNOMEDCT_US
4025960	VANDF
4030489	VANDF
108166	MMSL
23512	MMSL
310257	MMSL
34310	MMSL
d06665	MMSL

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
ALISKIREN	HUMAN PRESCRIPTION DRUG LABEL	1	49884-424	TABLET, FILM COATED	150 mg	ORAL	ANDA	29 sections
ALISKIREN	HUMAN PRESCRIPTION DRUG LABEL	1	49884-425	TABLET, FILM COATED	300 mg	ORAL	ANDA	29 sections
Tekturna	HUMAN PRESCRIPTION DRUG LABEL	1	50090-2985	TABLET, FILM COATED	300 mg	ORAL	NDA	29 sections
Tekturna	HUMAN PRESCRIPTION DRUG LABEL	1	50090-2985	TABLET, FILM COATED	300 mg	ORAL	NDA	29 sections
Tekturna	HUMAN PRESCRIPTION DRUG LABEL	1	54868-5772	TABLET, FILM COATED	150 mg	ORAL	NDA	29 sections
Tekturna HCT	HUMAN PRESCRIPTION DRUG LABEL	2	54868-6041	TABLET, FILM COATED	150 mg	ORAL	NDA	28 sections
Tekturna	HUMAN PRESCRIPTION DRUG LABEL	1	54868-6042	TABLET, FILM COATED	300 mg	ORAL	NDA	29 sections
Tekturna HCT	HUMAN PRESCRIPTION DRUG LABEL	2	54868-6103	TABLET, FILM COATED	300 mg	ORAL	NDA	28 sections
Tekturna HCT	HUMAN PRESCRIPTION DRUG LABEL	2	54868-6194	TABLET, FILM COATED	300 mg	ORAL	NDA	28 sections
Aliskiren	HUMAN PRESCRIPTION DRUG LABEL	1	66993-141	TABLET, FILM COATED	150 mg	ORAL	NDA authorized generic	28 sections
Aliskiren	HUMAN PRESCRIPTION DRUG LABEL	1	66993-142	TABLET, FILM COATED	300 mg	ORAL	NDA authorized generic	28 sections
Tekturna HCT	HUMAN PRESCRIPTION DRUG LABEL	2	70839-112	TABLET, FILM COATED	150 mg	ORAL	NDA	29 sections
Tekturna HCT	HUMAN PRESCRIPTION DRUG LABEL	2	70839-112	TABLET, FILM COATED	150 mg	ORAL	NDA	29 sections
Tekturna HCT	HUMAN PRESCRIPTION DRUG LABEL	2	70839-125	TABLET, FILM COATED	150 mg	ORAL	NDA	29 sections
Tekturna HCT	HUMAN PRESCRIPTION DRUG LABEL	2	70839-125	TABLET, FILM COATED	150 mg	ORAL	NDA	29 sections
Tekturna	HUMAN PRESCRIPTION DRUG LABEL	1	70839-150	TABLET, FILM COATED	150 mg	ORAL	NDA	28 sections
Tekturna	HUMAN PRESCRIPTION DRUG LABEL	1	70839-300	TABLET, FILM COATED	300 mg	ORAL	NDA	28 sections
Tekturna HCT	HUMAN PRESCRIPTION DRUG LABEL	2	70839-312	TABLET, FILM COATED	300 mg	ORAL	NDA	29 sections
Tekturna HCT	HUMAN PRESCRIPTION DRUG LABEL	2	70839-312	TABLET, FILM COATED	300 mg	ORAL	NDA	29 sections
Tekturna HCT	HUMAN PRESCRIPTION DRUG LABEL	2	70839-325	TABLET, FILM COATED	300 mg	ORAL	NDA	29 sections
Tekturna HCT	HUMAN PRESCRIPTION DRUG LABEL	2	70839-325	TABLET, FILM COATED	300 mg	ORAL	NDA	29 sections