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

Stem definition	Drug id	CAS RN
	4523	130-95-0

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: quinine bisulfate heptahydrate chinine qualaquin quinine quinine sulfate	An alkaloid derived from the bark of the cinchona tree. It is used as an antimalarial drug, and is the active ingredient in extracts of the cinchona that have been used for that purpose since before 1633. Quinine is also a mild antipyretic and analgesic and has been used in common cold preparations for that purpose. It was used commonly and as a bitter and flavoring agent, and is still useful for the treatment of babesiosis. Quinine is also useful in some muscular disorders, especially nocturnal leg cramps and myotonia congenita, because of its direct effects on muscle membrane and sodium channels. The mechanisms of its antimalarial effects are not well understood. Molecular weight: 324.42 Formula: C20H24N2O2 CLOGP: 2.79 LIPINSKI: 0 HAC: 4 HDO: 1 TPSA: 45.59 ALOGS: -2.99 ROTB: 4 Status: OFP Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

quinine bisulfate heptahydrate
chinine
qualaquin
quinine
quinine sulfate

An alkaloid derived from the bark of the cinchona tree. It is used as an antimalarial drug, and is the active ingredient in extracts of the cinchona that have been used for that purpose since before 1633. Quinine is also a mild antipyretic and analgesic and has been used in common cold preparations for that purpose. It was used commonly and as a bitter and flavoring agent, and is still useful for the treatment of babesiosis. Quinine is also useful in some muscular disorders, especially nocturnal leg cramps and myotonia congenita, because of its direct effects on muscle membrane and sodium channels. The mechanisms of its antimalarial effects are not well understood.

Molecular weight: 324.42
Formula: C20H24N2O2
CLOGP: 2.79
LIPINSKI: 0
HAC: 4
HDO: 1
TPSA: 45.59
ALOGS: -2.99
ROTB: 4

Status: OFP

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

Drug dosage:

Dose	Unit	Route
1.50	g	O
1.50	g	P

ADMET properties:

Property	Value	Reference
BDDCS (Biopharmaceutical Drug Disposition Classification System)	1	Benet LZ, Broccatelli F, Oprea TI
S (Water solubility)	111.10 mg/mL	Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine)	12 %	Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose)	71.07 µM/kg/day	Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
Vd (Volume of distribution)	1.80 L/kg	Lombardo F, Berellini G, Obach RS
CL (Clearance)	1.90 mL/min/kg	Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma)	0.30 %	Lombardo F, Berellini G, Obach RS
t_half (Half-life)	11 hours	Lombardo F, Berellini G, Obach RS

Approvals:

Date	Agency	Company	Orphan
Aug. 12, 2005	FDA	MUTUAL PHARM CO INC

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
Drug abuse	200.61	13.61	147	12403	65379	53271137
Labile blood pressure	149.89	13.61	42	12508	1832	53334684
Somatic symptom disorder	89.66	13.61	29	12521	2069	53334447
Sacroiliitis	88.58	13.61	30	12520	2470	53334046
Hepatic ischaemia	77.40	13.61	20	12530	638	53335878
Lipase increased	72.42	13.61	38	12512	9340	53327176
Haematemesis	71.99	13.61	59	12491	30798	53305718
Hepatorenal syndrome	70.34	13.61	24	12526	2021	53334495
Hepatic failure	56.71	13.61	55	12495	35751	53300765
Muscle relaxant therapy	54.49	13.61	12	12538	189	53336327
Coronary artery disease	50.41	13.61	50	12500	33387	53303129
Renal failure	48.34	13.61	94	12456	118358	53218158
Rheumatoid arthritis	46.20	13.61	9	12541	314522	53021994
Coagulopathy	44.54	13.61	37	12513	19661	53316855
Thrombotic microangiopathy	42.96	13.61	27	12523	9310	53327206
Hyponatraemia	42.87	13.61	85	12465	108522	53227994
Drug ineffective	40.87	13.61	82	12468	817163	52519353
Electrocardiogram QT prolonged	39.43	13.61	57	12493	56346	53280170
Toxicity to various agents	38.22	13.61	126	12424	219472	53117044
Hypovolaemia	37.91	13.61	26	12524	10376	53326140
Mood altered	37.59	13.61	29	12521	13872	53322644
Duodenal ulcer	37.46	13.61	23	12527	7613	53328903
Drug hypersensitivity	37.42	13.61	142	12408	265100	53071416
Fear of eating	36.93	13.61	10	12540	383	53336133
Off label use	34.75	13.61	36	12514	472176	52864340
Gastrointestinal haemorrhage	33.05	13.61	64	12486	80266	53256250
Post procedural haemorrhage	31.63	13.61	21	12529	7947	53328569
Product dose omission issue	31.46	13.61	4	12546	191616	53144900
Coronary artery bypass	31.09	13.61	14	12536	2464	53334052
Plasmodium falciparum infection	31.07	13.61	6	12544	47	53336469
Retinal toxicity	29.60	13.61	11	12539	1186	53335330
Cinchonism	26.65	13.61	4	12546	4	53336512
Drug intolerance	26.02	13.61	8	12542	205485	53131031
Swollen tongue	25.60	13.61	34	12516	31046	53305470
Vascular injury	25.40	13.61	9	12541	847	53335669
Fatigue	25.24	13.61	88	12462	730418	52606098
Blood sodium decreased	25.00	13.61	29	12521	23087	53313429
Rhabdomyolysis	24.51	13.61	40	12510	43883	53292633
Vestibular disorder	24.39	13.61	10	12540	1401	53335115
Purpura senile	24.16	13.61	8	12542	614	53335902
Cognitive disorder	23.94	13.61	40	12510	44738	53291778
Tarsal tunnel syndrome	23.88	13.61	8	12542	637	53335879
Infusion related reaction	23.87	13.61	4	12546	155953	53180563
Salivary gland enlargement	23.44	13.61	7	12543	383	53336133
Optic ischaemic neuropathy	23.24	13.61	9	12541	1087	53335429
Pancreatitis	23.06	13.61	40	12510	46102	53290414
Oral cavity fistula	23.02	13.61	8	12542	711	53335805
Myocardial ischaemia	22.75	13.61	21	12529	12823	53323693
Exostosis of jaw	21.96	13.61	9	12541	1260	53335256
Eczema asteatotic	20.89	13.61	6	12544	286	53336230
Muscle necrosis	20.69	13.61	7	12543	574	53335942
Cerebral artery occlusion	20.54	13.61	8	12542	980	53335536
Resorption bone increased	19.42	13.61	8	12542	1134	53335382
Ulcer	19.24	13.61	24	12526	20595	53315921
Fibromyalgia	19.21	13.61	36	12514	44039	53292477
Fall	19.18	13.61	147	12403	358293	52978223
Left ventricular dysfunction	19.18	13.61	18	12532	11219	53325297
Exposed bone in jaw	19.10	13.61	11	12539	3239	53333277
Hiccups	19.08	13.61	9	12541	1761	53334755
Haemolytic uraemic syndrome	18.70	13.61	10	12540	2551	53333965
Abdominal rigidity	18.64	13.61	9	12541	1855	53334661
Product use issue	18.46	13.61	5	12545	139579	53196937
Acute kidney injury	18.26	13.61	112	12438	253756	53082760
Adrenal mass	17.91	13.61	7	12543	866	53335650
Abdominal discomfort	17.20	13.61	16	12534	221046	53115470
Hepatocellular injury	16.31	13.61	27	12523	29959	53306557
Synovitis	16.00	13.61	3	12547	107890	53228626
Hepatic enzyme increased	15.81	13.61	5	12545	126190	53210326
Agitated depression	15.41	13.61	4	12546	130	53336386
Injection site pain	15.11	13.61	4	12546	113387	53223129
Gastritis	15.05	13.61	29	12521	36205	53300311
Muscle spasms	14.88	13.61	67	12483	134728	53201788
Nail infection	14.65	13.61	8	12542	2126	53334390
Myocardial infarction	14.63	13.61	54	12496	99300	53237216
Rectal haemorrhage	14.61	13.61	31	12519	41450	53295066
Somnambulism	14.02	13.61	11	12539	5391	53331125
Cerebrovascular accident	13.72	13.61	55	12495	105119	53231397

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
Drug abuse	1071.78	16.58	465	6944	79778	32426339
Toxicity to various agents	242.66	16.58	247	7162	177794	32328323
Poisoning	86.97	16.58	45	7364	11113	32495004
Exposure via ingestion	56.55	16.58	21	7388	2336	32503781
Intentional product misuse	54.16	16.58	53	7356	35998	32470119
Compartment syndrome	47.67	16.58	19	7390	2558	32503559
Electrocardiogram U wave present	42.53	16.58	7	7402	19	32506098
Atrioventricular block	35.53	16.58	22	7387	7633	32498484
Cinchonism	34.00	16.58	5	7404	4	32506113
Muscle spasms	33.99	16.58	59	7350	70359	32435758
Toxic neuropathy	31.01	16.58	9	7400	460	32505657
Hypomagnesaemia	30.78	16.58	29	7380	18776	32487341
Mouth swelling	29.35	16.58	12	7397	1724	32504393
Urine sodium decreased	28.57	16.58	7	7402	185	32505932
Agitated depression	26.99	16.58	7	7402	234	32505883
Nephrogenic systemic fibrosis	24.07	16.58	14	7395	4338	32501779
Lower respiratory tract infection	23.36	16.58	31	7378	29212	32476905
Drug ineffective	22.45	16.58	33	7376	383444	32122673
Cerebral malaria	22.16	16.58	3	7406	0	32506117
Malaria	21.14	16.58	6	7403	283	32505834
Blood sodium decreased	20.68	16.58	22	7387	16452	32489665
Infected skin ulcer	20.66	16.58	9	7400	1512	32504605
Alveolar proteinosis	20.02	16.58	6	7403	343	32505774
Increased bronchial secretion	19.40	16.58	9	7400	1752	32504365
Hypocalcaemia	19.28	16.58	25	7384	23029	32483088
Body mass index decreased	19.11	16.58	5	7404	173	32505944
Cutaneous extramedullary haemopoiesis	18.87	16.58	3	7406	6	32506111
Lethargy	17.89	16.58	33	7376	41195	32464922
Skin induration	17.39	16.58	9	7400	2219	32503898
Bradycardia	17.04	16.58	45	7364	71517	32434600
Restless legs syndrome	16.96	16.58	14	7395	7610	32498507

Pharmacologic Action:

Source	Code	Description
ATC	M09AA72	MUSCULO-SKELETAL SYSTEM OTHER DRUGS FOR DISORDERS OF THE MUSCULO-SKELETAL SYSTEM OTHER DRUGS FOR DISORDERS OF THE MUSCULO-SKELETAL SYSTEM Quinine and derivatives
ATC	P01BC01	ANTIPARASITIC PRODUCTS, INSECTICIDES AND REPELLENTS ANTIPROTOZOALS ANTIMALARIALS Methanolquinolines
FDA EPC	N0000175482	Antimalarial
MeSH PA	D000700	Analgesics
MeSH PA	D018712	Analgesics, Non-Narcotic
MeSH PA	D000890	Anti-Infective Agents
MeSH PA	D000962	Antimalarials
MeSH PA	D000977	Antiparasitic Agents
MeSH PA	D000981	Antiprotozoal Agents
MeSH PA	D002491	Central Nervous System Agents
MeSH PA	D009125	Muscle Relaxants, Central
MeSH PA	D009465	Neuromuscular Agents
MeSH PA	D018373	Peripheral Nervous System Agents
MeSH PA	D018689	Sensory System Agents
CHEBI has role	CHEBI:38068	antimalarials
CHEBI has role	CHEBI:51371	muscle relaxants

Drug Use (View source of the data)

Disease	Relation	SNOMED_ID	DOID
Falciparum malaria	indication	62676009	DOID:14067
Chloroquine Resistant Plasmodium Falciparum Malaria	indication
Babesiosis	off-label use	21061004	DOID:9643
Atrial flutter	contraindication	5370000
Torsades de pointes	contraindication	31722008
End stage renal disease	contraindication	46177005	DOID:784
Atrial fibrillation	contraindication	49436004	DOID:0060224
Neuromuscular block, function	contraindication	55394004
Black water fever	contraindication	56625005	DOID:14068
Acute nephropathy	contraindication	58574008
Optic neuritis	contraindication	66760008	DOID:1210
Thrombotic thrombocytopenic purpura	contraindication	78129009	DOID:10772
Myasthenia gravis	contraindication	91637004	DOID:437
Hemolytic uremic syndrome	contraindication	111407006	DOID:12554
Anemia due to enzyme deficiency	contraindication	111577008
Prolonged QT interval	contraindication	111975006
Disease of liver	contraindication	235856003	DOID:409
Hypoglycemic disorder	contraindication	237630007
Thrombocytopenic disorder	contraindication	302215000	DOID:1588
Congenital long QT syndrome	contraindication	442917000

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	12.44	acidic
pKa2	8.02	Basic
pKa3	4.1	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
Potassium voltage-gated channel subfamily H member 2	Ion channel	Q12809	KCNH2_HUMAN				WOMBAT-PK
Multidrug resistance protein 1	Transporter	P08183	MDR1_HUMAN		Ki	4.92	CHEMBL
Hemoglobin subunit alpha	Secreted	P69905	HBA_HUMAN				WOMBAT-PK
Potassium voltage-gated channel subfamily B member 2	Ion channel	Q92953	KCNB2_HUMAN	BLOCKER	IC50	4.90	IUPHAR
Solute carrier family 22 member 1	Transporter	O15245	S22A1_HUMAN		IC50	4.29	CHEMBL
Sodium channel alpha subunits; brain (Types I, II, III)	Ion channel	P35498 Q99250 Q9NY46	SCN1A_HUMAN SCN2A_HUMAN SCN3A_HUMAN		IC50	5.36	CHEMBL
Equilibrative nucleoside transporter 4	Transporter	Q7RTT9	S29A4_HUMAN	INHIBITOR	Ki	4.57	IUPHAR

External reference:

ID	Source
D08460	KEGG_DRUG
6183-68-2	SECONDARY_CAS_RN
4018620	VANDF
4019926	VANDF
CHEBI:15854	CHEBI
QI9	PDB_CHEM_ID
CHEMBL170	ChEMBL_ID
CHEMBL2359966	ChEMBL_ID
2510	IUPHAR_LIGAND_ID
DB00468	DRUGBANK_ID
A7V27PHC7A	UNII
3034034	PUBCHEM_CID
647128	RXNORM
5023	MMSL
5405	MMSL
84102	MMSL
d00366	MMSL
002934	NDDF
002935	NDDF
373497008	SNOMEDCT_US
47065008	SNOMEDCT_US
47857006	SNOMEDCT_US
D011803	MESH_DESCRIPTOR_UI
C0034417	UMLSCUI

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
Quinine Sulfate	HUMAN PRESCRIPTION DRUG LABEL	1	0093-3002	CAPSULE	324 mg	ORAL	ANDA	31 sections
Qualaquin	HUMAN PRESCRIPTION DRUG LABEL	1	13310-153	CAPSULE	324 mg	ORAL	NDA	32 sections
QUALAQUIN	HUMAN PRESCRIPTION DRUG LABEL	1	16590-595	CAPSULE	324 mg	ORAL	NDA	32 sections
Qualaquin	HUMAN PRESCRIPTION DRUG LABEL	1	49708-153	CAPSULE	324 mg	ORAL	NDA	32 sections
QUININE SULFATE	HUMAN PRESCRIPTION DRUG LABEL	1	50742-238	CAPSULE	324 mg	ORAL	ANDA	21 sections
Quinine Sulfate	HUMAN PRESCRIPTION DRUG LABEL	1	53489-700	CAPSULE	324 mg	ORAL	NDA authorized generic	32 sections
Quinine Sulfate	HUMAN PRESCRIPTION DRUG LABEL	1	65162-811	CAPSULE	324 mg	ORAL	ANDA	20 sections
Quinine Sulfate	HUMAN PRESCRIPTION DRUG LABEL	1	68084-947	CAPSULE	324 mg	ORAL	NDA authorized generic	31 sections
QUININE SULFATE	HUMAN PRESCRIPTION DRUG LABEL	1	68180-560	CAPSULE	324 mg	ORAL	ANDA	20 sections