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Chloroquine

PubChem CID
2719
Structure
Chloroquine_small.png
Chloroquine_3D_Structure.png
Molecular Formula
Synonyms
  • chloroquine
  • 54-05-7
  • Aralen
  • Chlorochin
  • Chloraquine
Molecular Weight
319.9 g/mol
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Dates
  • Create:
    2005-03-25
  • Modify:
    2025-01-18
Description
Chloroquine is an aminoquinoline that is quinoline which is substituted at position 4 by a [5-(diethylamino)pentan-2-yl]amino group at at position 7 by chlorine. It is used for the treatment of malaria, hepatic amoebiasis, lupus erythematosus, light-sensitive skin eruptions, and rheumatoid arthritis. It has a role as an antimalarial, an antirheumatic drug, a dermatologic drug, an autophagy inhibitor and an anticoronaviral agent. It is an aminoquinoline, a secondary amino compound, a tertiary amino compound and an organochlorine compound. It is a conjugate base of a chloroquine(2+).
Chloroquine is an aminoquinolone derivative first developed in the 1940s for the treatment of malaria. It was the drug of choice to treat malaria until the development of newer antimalarials such as [pyrimethamine], [artemisinin], and [mefloquine]. Chloroquine and its derivative [hydroxychloroquine] have since been repurposed for the treatment of a number of other conditions including HIV, systemic lupus erythematosus, and rheumatoid arthritis. **The FDA emergency use authorization for [hydroxychloroquine] and chloroquine in the treatment of COVID-19 was revoked on 15 June 2020.** Chloroquine was granted FDA Approval on 31 October 1949.
Chloroquine is an Antimalarial.
See also: Chloroquine Phosphate (has salt form); Chloroquine Sulfate (has salt form); Chloroquine Hydrochloride (has salt form) ... View More ...

1 Structures

1.1 2D Structure

Chemical Structure Depiction
Chloroquine.png

1.2 3D Conformer

2 Names and Identifiers

2.1 Computed Descriptors

2.1.1 IUPAC Name

4-N-(7-chloroquinolin-4-yl)-1-N,1-N-diethylpentane-1,4-diamine
Computed by Lexichem TK 2.7.0 (PubChem release 2021.10.14)

2.1.2 InChI

InChI=1S/C18H26ClN3/c1-4-22(5-2)12-6-7-14(3)21-17-10-11-20-18-13-15(19)8-9-16(17)18/h8-11,13-14H,4-7,12H2,1-3H3,(H,20,21)
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.3 InChIKey

WHTVZRBIWZFKQO-UHFFFAOYSA-N
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.4 SMILES

CCN(CC)CCCC(C)NC1=C2C=CC(=CC2=NC=C1)Cl
Computed by OEChem 2.3.0 (PubChem release 2024.12.12)

2.2 Molecular Formula

C18H26ClN3
Computed by PubChem 2.2 (PubChem release 2021.10.14)

2.3 Other Identifiers

2.3.1 CAS

54-05-7

2.3.2 Deprecated CAS

56598-66-4

2.3.3 European Community (EC) Number

2.3.4 UNII

2.3.5 ChEBI ID

2.3.6 ChEMBL ID

2.3.7 DrugBank ID

2.3.8 DSSTox Substance ID

2.3.9 HMDB ID

2.3.10 KEGG ID

2.3.11 Metabolomics Workbench ID

2.3.12 NCI Thesaurus Code

2.3.13 Nikkaji Number

2.3.14 NSC Number

2.3.15 PharmGKB ID

2.3.16 Pharos Ligand ID

2.3.17 RXCUI

2.3.18 Wikidata

2.3.19 Wikipedia

2.4 Synonyms

2.4.1 MeSH Entry Terms

  • Aralen
  • Arechine
  • Arequin
  • Chingamin
  • Chlorochin
  • Chloroquine
  • Chloroquine Sulfate
  • Chloroquine Sulphate
  • Khingamin
  • Nivaquine
  • Sulfate, Chloroquine
  • Sulphate, Chloroquine

2.4.2 Depositor-Supplied Synonyms

3 Chemical and Physical Properties

3.1 Computed Properties

Property Name
Molecular Weight
Property Value
319.9 g/mol
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
XLogP3
Property Value
4.6
Reference
Computed by XLogP3 3.0 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Donor Count
Property Value
1
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Acceptor Count
Property Value
3
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Rotatable Bond Count
Property Value
8
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Exact Mass
Property Value
319.1815255 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Monoisotopic Mass
Property Value
319.1815255 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Topological Polar Surface Area
Property Value
28.2 Ų
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Heavy Atom Count
Property Value
22
Reference
Computed by PubChem
Property Name
Formal Charge
Property Value
0
Reference
Computed by PubChem
Property Name
Complexity
Property Value
309
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Isotope Atom Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Atom Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Undefined Atom Stereocenter Count
Property Value
1
Reference
Computed by PubChem
Property Name
Defined Bond Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Undefined Bond Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Covalently-Bonded Unit Count
Property Value
1
Reference
Computed by PubChem
Property Name
Compound Is Canonicalized
Property Value
Yes
Reference
Computed by PubChem (release 2021.10.14)

3.2 Experimental Properties

3.2.1 Physical Description

Solid

3.2.2 Color / Form

WHITE TO SLIGHTLY YELLOW, CRYSTALLINE POWDER
Osol, A. and J.E. Hoover, et al. (eds.). Remington's Pharmaceutical Sciences. 15th ed. Easton, Pennsylvania: Mack Publishing Co., 1975., p. 1155
Colorless crystals
Lewis, R.J. Sr.; Hawley's Condensed Chemical Dictionary 14th Edition. John Wiley & Sons, Inc. New York, NY 2001., p. 259

3.2.3 Odor

ODORLESS
Osol, A. and J.E. Hoover, et al. (eds.). Remington's Pharmaceutical Sciences. 15th ed. Easton, Pennsylvania: Mack Publishing Co., 1975., p. 1155

3.2.4 Taste

Bitter taste
Lewis, R.J. Sr.; Hawley's Condensed Chemical Dictionary 14th Edition. John Wiley & Sons, Inc. New York, NY 2001., p. 259

3.2.5 Melting Point

87-89.5
ChemSpider
87 °C
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 373
289 °C

3.2.6 Solubility

Bitter colorless crystals, dimorphic. Freely soluble in water, less sol in neutral or alkaline pH. Stable to heat in soln pH4 to 6.5. Practically in soluble in alcohol, benzene and chloroform /Diphosphate/
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 373
WHITE CRYSTALLINE POWDER; ODORLESS; BITTER TASTE; FREELY SOL IN WATER;PRACTICALLY INSOL IN ALCOHOL, CHLOROFORM, ETHER; AQ SOLN HAS PH OF ABOUT 4.5; PKA1= 7; PKA2= 9.2 /PHOSPHATE/
Osol, A. and J.E. Hoover, et al. (eds.). Remington's Pharmaceutical Sciences. 15th ed. Easton, Pennsylvania: Mack Publishing Co., 1975., p. 1155
VERY SLIGHTLY SOL IN WATER; SOL IN DIL ACIDS, CHLOROFORM, ETHER
Osol, A. and J.E. Hoover, et al. (eds.). Remington's Pharmaceutical Sciences. 15th ed. Easton, Pennsylvania: Mack Publishing Co., 1975., p. 1155
Insoluble in alcohol, benzene, chloroform, ether.
Lewis, R.J. Sr.; Hawley's Condensed Chemical Dictionary 14th Edition. John Wiley & Sons, Inc. New York, NY 2001., p. 259
1.75e-02 g/L

3.2.7 LogP

4.63
HANSCH,C ET AL. (1995)
log Kow = 4.63
Hansch, C., Leo, A., D. Hoekman. Exploring QSAR - Hydrophobic, Electronic, and Steric Constants. Washington, DC: American Chemical Society., 1995., p. 159
4.3

3.2.8 Stability / Shelf Life

Stable to heat in solutions of pH 4.0 to 6.5 /Chloroquine Diphosphate/
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 373
SENSITIVE TO LIGHT. /PHOSPHATE/
Sunshine, I. (ed.). CRC Handbook of Analytical Toxicology. Cleveland: The Chemical Rubber Co., 1969., p. 28
SENSITIVE TO LIGHT. /SULFATE/
Sunshine, I. (ed.). CRC Handbook of Analytical Toxicology. Cleveland: The Chemical Rubber Co., 1969., p. 28

3.2.9 Dissociation Constants

pKa
10.1
SANGSTER (1994)
pKa = 10.1
Sangster J; LOGKOW Database. A databank of evaluated octanol-water partition coefficients (Log P). Available from, as of May 2, 2006: https://logkow.cisti.nrc.ca/logkow/search.html

3.2.10 Collision Cross Section

176.8 Ų [M+H]+ [CCS Type: TW; Method: Major Mix IMS/Tof Calibration Kit (Waters)]

3.2.11 Kovats Retention Index

Standard non-polar
2600 , 2610 , 2630 , 2637 , 2660 , 2578.2 , 2590 , 2660 , 2642.7
Semi-standard non-polar
2626.3 , 2604 , 2624.8

3.2.12 Other Experimental Properties

USUALLY IS IN A PARTLY HYDRATED FORM
Osol, A. and J.E. Hoover, et al. (eds.). Remington's Pharmaceutical Sciences. 15th ed. Easton, Pennsylvania: Mack Publishing Co., 1975., p. 1155
COLORLESS LIQUID; PH BETWEEN 5.5 & 6.5 /CHLOROQUINE HYDROCHLORIDE INJECTION/
Osol, A. and J.E. Hoover, et al. (eds.). Remington's Pharmaceutical Sciences. 15th ed. Easton, Pennsylvania: Mack Publishing Co., 1975., p. 1155
Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics. 5th ed. New York: Macmillan Publishing Co., Inc., 1975., p. 1050
Upon decomosition emits NOx
Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 10th ed. Volumes 1-3 New York, NY: John Wiley & Sons Inc., 1999., p. 899

3.3 Chemical Classes

3.3.1 Drugs

Pharmaceuticals
S10 | SWISSPHARMA | Pharmaceutical List with Consumption Data | DOI:10.5281/zenodo.2623484
3.3.1.1 Human Drugs
Breast Feeding; Lactation; Milk, Human; Anti-infective Agents; Antiparasitic Agents; Antimalarials; Antirheumatic Agents; Antiprotozoal Agents
Human drug -> Discontinued
Pharmaceuticals
S72 | NTUPHTW | Pharmaceutically Active Substances from National Taiwan University | DOI:10.5281/zenodo.3955664

Antimalarial medicines > For chemoprevention

Antimalarial medicines > For curative treatment

Disease-modifying anti-rheumatic drugs (DMARDs)

4 Spectral Information

4.1 1D NMR Spectra

4.1.1 13C NMR Spectra

1 of 2
Copyright
Copyright © 2016-2024 W. Robien, Inst. of Org. Chem., Univ. of Vienna. All Rights Reserved.
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2 of 2
Instrument Name
Bruker AM-400
Copyright
Copyright © 2002-2024 Wiley-VCH Verlag GmbH & Co. KGaA. All Rights Reserved.
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4.2 Mass Spectrometry

4.2.1 GC-MS

1 of 12
View All
Spectra ID
Instrument Type
CI-B
Ionization Mode
positive
Top 5 Peaks

320.0 99.99

322.0 34

321.0 21

323.0 7

319.0 5

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Notes
instrument=Unknown
2 of 12
View All
MoNA ID
MS Category
Experimental
MS Type
GC-MS
MS Level
MS1
Instrument
Unknown
Instrument Type
CI-B
Ionization Mode
positive
Top 5 Peaks

320 99.99

322 34

321 21

323 7

319 5

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License
CC BY-NC-SA

4.2.2 MS-MS

1 of 6
View All
Spectra ID
Ionization Mode
Positive
Top 5 Peaks

86.09948 100

179.04067 87.90

191.04087 54.50

247.10326 46.80

69.07272 35.80

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2 of 6
View All
Spectra ID
Ionization Mode
Positive
Top 5 Peaks

247.10443 100

142.16265 37.10

320.19279 15.20

86.10002 3.50

179.04165 2.40

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4.2.3 LC-MS

1 of 25
View All
Authors
Kevin S. Jewell; Björn Ehlig; Arne Wick
Instrument
TripleTOF 6600 SCIEX
Instrument Type
LC-ESI-QTOF
MS Level
MS2
Ionization Mode
POSITIVE
Ionization
ESI
Collision Energy
60
Fragmentation Mode
CID
Column Name
Zorbax Eclipse Plus C18 2.1 mm x 150 mm, 3.5 um, Agilent
Retention Time
4.84 min
Precursor m/z
320.1888
Precursor Adduct
[M+H]+
Top 5 Peaks

179.0373 999

191.0371 487

86.0965 481

156.0682 223

144.0686 202

Thumbnail
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License
dl-de/by-2-0
2 of 25
View All
Authors
Kevin S. Jewell; Björn Ehlig; Arne Wick
Instrument
TripleTOF 6600 SCIEX
Instrument Type
LC-ESI-QTOF
MS Level
MS2
Ionization Mode
POSITIVE
Ionization
ESI
Collision Energy
40
Fragmentation Mode
CID
Column Name
Zorbax Eclipse Plus C18 2.1 mm x 150 mm, 3.5 um, Agilent
Retention Time
4.84 min
Precursor m/z
320.1888
Precursor Adduct
[M+H]+
Top 5 Peaks

247.0999 999

179.0369 398

142.1588 330

191.0368 264

86.0962 261

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License
dl-de/by-2-0

4.2.4 Other MS

1 of 4
View All
Authors
YOSHIZUMI H, FAC. OF PHARMACY, MEIJO UNIV.
Instrument
Unknown
Instrument Type
CI-B
MS Level
MS
Ionization Mode
POSITIVE
Top 5 Peaks

320 999

322 340

321 210

323 70

319 50

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License
CC BY-NC-SA
2 of 4
View All
MS Category
Experimental
MS Type
Other
MS Level
MS2
Precursor Type
[M+H]+
Precursor m/z
320.18595515645575
Ionization Mode
positive
Retention Time
2.24
Top 5 Peaks

247.10081794858803 100

142.16200341467243 41.36

179.04096756783338 37.45

191.039162402852 28.27

320.1952506959025 26.92

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4.3 Other Spectra

Intense mass spectral peaks: 58 m/z, 86 m/z, 245 m/z, 290 m/z, 319 m/z
Pfleger, K., H. Maurer and A. Weber. Mass Spectral and GC Data of Drugs, Poisons and their Metabolites. Parts I and II. Mass Spectra Indexes. Weinheim, Federal Republic of Germany. 1985., p. 561

6 Chemical Vendors

7 Drug and Medication Information

7.1 Drug Indication

Chloroquine is indicated to treat infections of _P. vivax_, _P. malariae_, _P. ovale_, and susceptible strains of _P. falciparum_. It is also used to treat extraintestinal amebiasis. Chloroquine is also used off label for the treatment of rheumatic diseases, as well as treatment and prophylaxis of Zika virus. Chloroquine is currently undergoing clinical trials for the treatment of COVID-19.

7.2 LiverTox Summary

Chloroquine is an aminoquinoline used for the prevention and therapy of malaria. It is also effective in extraintestinal amebiasis and as an antiinflammatory agent for therapy of rheumatoid arthritis and lupus erythematosus. Chloroquine is not associated with serum enzyme elevations and is an extremely rare cause of clinically apparent acute liver injury.

7.3 Drug Classes

Breast Feeding; Lactation; Milk, Human; Anti-infective Agents; Antiparasitic Agents; Antimalarials; Antirheumatic Agents; Antiprotozoal Agents
Antimalarial Agents

7.4 WHO Essential Medicines

Drug
Drug Classes
Antimalarial medicines > For chemoprevention
Formulation
(1) Oral - Liquid: 50 mg per 5 mL syrup (as phosphate or sulfate); (2) Oral - Solid: 150 mg tablet (as phosphate or sulfate)
Indication
(1) Malaria due to Plasmodium falciparum; (2) Malaria due to Plasmodium vivax; (3) Malaria due to Plasmodium ovale; (4) Malaria due to Plasmodium malariae
Drug
Drug Classes
Antimalarial medicines > For curative treatment
Formulation
(1) Parenteral - General injections - IV: 40 mg per mL in 5 mL ampoule (as hydrochloride, phosphate or sulfate); (2) Oral - Liquid: 50 mg per 5 mL syrup (as phosphate or sulfate); (3) Oral - Solid: 150 mg tablet (as phosphate or sulfate); 100 mg tablet (as phosphate or sulfate)
Indication
(1) Malaria due to Plasmodium falciparum; (2) Malaria due to Plasmodium vivax
Drug
Drug Classes
Disease-modifying anti-rheumatic drugs (DMARDs)
Formulation
Oral - Solid: 100 mg tablet (as phosphate or sulfate); 150 mg tablet (as phosphate or sulfate)
Indication
Rheumatoid arthritis

7.5 Clinical Trials

7.5.1 ClinicalTrials.gov

7.5.2 EU Clinical Trials Register

7.6 Therapeutic Uses

Mesh Heading: Amebicides, antimalarials, antirheumatic Agents
National Library of Medicine, SIS; ChemIDplus Record for Chloroquine. (54-05-7). Available from, as of April 17, 2006: https://chem.sis.nlm.nih.gov/chemidplus/chemidlite.jsp
Antimalarial; antiamebic; antirheumatic. Lupus erythematosus suppressant.
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 373
Chloroquine is indicated in the suppressive treatment and the treatment of acute attacks of malaria caused by plasmodium vivax, Plasmodium malariae, Plasmodium ovale, chlrorquine-susceptible strains of P. falciparum. /Included in the US product label/
Thomson.Micromedex. Drug Information for the Health Care Professional. 25th ed. Volume 1. Plus Updates. Content Reviewed by the United States Pharmacopeial Convention, Inc. Greenwood Village, CO. 2005., p. 837
Chloroquine is indicated for the treatment of amebic liver abscess, usually in combination with and effective intestinal amebicide. However, it is not considered a primary drug. /Included in the US product label/
Thomson.Micromedex. Drug Information for the Health Care Professional. 25th ed. Volume 1. Plus Updates. Content Reviewed by the United States Pharmacopeial Convention, Inc. Greenwood Village, CO. 2005., p. 837
For more Therapeutic Uses (Complete) data for CHLOROQUINE (13 total), please visit the HSDB record page.

7.7 Drug Warnings

Chloroquine is contraindicated in patients who are hypersensitive to 4-aminoquinoline derivatives.
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 858
Ophthalmologic examinations, including slit lamp, funduscopic, and visual field tests, should be performed prior to initiation of chloroquine therapy and periodically during therapy whenever long term use of the drug is contemplated. Chloroquine should be discontinued immediately and the patient observed for possible progression if there is any indication of abnormalities in visual acuity or visual field, abnormalities in the retinal macular area such as pigmentary changes or loss of foveal reflex, or if any other visual symptoms such as light flashes and streaks occur which are not fully explainable by difficulties of accommodation or corneal opacities.
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 858
Because chloroquine may concentrate in the liver, the drug should be used with caution in patients with hepatic disease or alcoholism and in patients receiving other hepatotoxic drugs.
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 858
Complete blood cell counts should be performed periodically in patients receiving prolonged therapy with chloroquine. Chloroquine should be discontinued if there is evidence of adverse hematologic effects that are severe and not attributable to the disease being treated. The manufacturer states that chloroquine should be administered with caution to patients with glucose-6-phosphate dehydrogenase deficiency.
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 858
For more Drug Warnings (Complete) data for CHLOROQUINE (21 total), please visit the HSDB record page.

7.8 Reported Fatal Dose

... The lethal dose of chloroquine for an adult is estimated at 30 to 50 mg/kg.
Olson, K.R. (Ed.); Poisoning & Drug Overdose. 4th ed. Lange Medical Books/McGraw-Hill. New York, N.Y. 2004., p. 166
Chloroquine doses of more than 5 g given parenterally usually are fatal.
Hardman, J.G., L.E. Limbird, P.B., A.G. Gilman. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 10th ed. New York, NY: McGraw-Hill, 2001., p. 1079
... Fatal dose ... of chloroquine phosphate (2 to 3 g, adult) ... /Chloroquine phosphate/
WHO; Poisons Information Monographs (PIMs) 030: Amodiaquine. Available from, as of July 24, 2006: https://www.inchem.org/pages/pims.html

7.9 Drug Tolerance

Although there are a few areas where chloroquine is still effective, parenteral chloroquine is no longer recommended for the treatment of severe malaria because of widespread resistance.
WHO; WHO Guidelines for the Treatment of Malaria (2006). Available from, as of July 31, 2006: https://www.who.int/malaria/docs/TreatmentGuidelines2006.pdf
Resistance to antimalarials has been documented for P. falciparum, P. vivax and, recently, P. malariae. In P. falciparum, resistance has been observed to almost all currently used antimalarials (amodiaquine, chloroquine, mefloquine, quinine and sulfadoxine - pyrimethamine) except for artemisinin and its derivatives. The geographical distributions and rates of spread have varied considerably. P. vivax has developed resistance rapidly to sulfadoxine -pyrimethamine in many areas. Chloroquine resistance is confined largely to Indonesia, East Timor, Papua New Guinea and other parts of Oceania. There are also documented reports from Peru. P. vivax remains sensitive to chloroquine in South-East Asia, the Indian subcontinent, the Korean peninsula, the Middle East, north-east Africa, and most of South and Central America.
WHO; WHO Guidelines for the Treatment of Malaria (2006). Available from, as of July 31, 2006: https://www.who.int/malaria/docs/TreatmentGuidelines2006.pdf

8 Pharmacology and Biochemistry

8.1 Pharmacodynamics

Chloroquine inhibits the action of heme polymerase, which causes the buildup of toxic heme in _Plasmodium_ species. It has a long duration of action as the half life is 20-60 days. Patients should be counselled regarding the risk of retinopathy with long term usage or high dosage, muscle weakness, and toxicity in children.

8.2 MeSH Pharmacological Classification

Antimalarials
Agents used in the treatment of malaria. They are usually classified on the basis of their action against plasmodia at different stages in their life cycle in the human. (From AMA, Drug Evaluations Annual, 1992, p1585) (See all compounds classified as Antimalarials.)
Amebicides
Agents which are destructive to amebae, especially the parasitic species causing AMEBIASIS in man and animal. (See all compounds classified as Amebicides.)
Antirheumatic Agents
Drugs that are used to treat RHEUMATOID ARTHRITIS. (See all compounds classified as Antirheumatic Agents.)

8.3 FDA Pharmacological Classification

FDA UNII
886U3H6UFF
Active Moiety
CHLOROQUINE
Pharmacological Classes
Established Pharmacologic Class [EPC] - Antimalarial
FDA Pharmacology Summary
Chloroquine is an Antimalarial.

8.4 ATC Code

P - Antiparasitic products, insecticides and repellents

P01 - Antiprotozoals

P01B - Antimalarials

P01BA - Aminoquinolines

P01BA01 - Chloroquine

P01BA01

8.5 Absorption, Distribution and Excretion

Absorption
Chloroquine oral solution has a bioavailability of 52-102% and oral tablets have a bioavailability of 67-114%. Intravenous chloroquine reaches a Cmax of 650-1300µg/L and oral chloroquine reaches a Cmax of 65-128µg/L with a Tmax of 0.5h.
Route of Elimination
Chloroquine is predominantly eliminated in the urine. 50% of a dose is recovered in the urine as unchanged chloroquine, with 10% of the dose recovered in the urine as desethylchloroquine.
Volume of Distribution
The volume of distribution of chloroquine is 200-800L/kg.
Clearance
Chloroquine has a total plasma clearance of 0.35-1L/h/kg.
Chloroquine is rapidly and almost completely absorbed from the GI tract following oral administration, and peak plasma concn of the drug are generally attained within 1-2 hr. Considerable interindividual variations in serum concn of chloroquine have been reported. Oral administration of 310 mg of chloroquine daily reportedly results in peak plasma concn of about 0.125 ug/mL. If 500 mg of chloroquine is administered once weekly, peak plasma concn of the drug reportedly range from 0.15-0.25 ug/mL and trough plasma concn reportedly range from 0.02-0.04 ug/mL. Results of one study indicate that chloroquine may exhibit nonlinear dose dependent pharmacokinetics. In this study, administration of a single 500 mg oral dose of chloroquine resulted in a peak serum concentration of 0.12 ug/mL, and administration of a single 1 g oral dose of the drug resulted in a peak serum concentration of 0.34 ug/mL.
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 859
Results of one cross-over study in healthy adults indicate that the bioavailability of chloroquine is greater when the drug is administered with food than when the drug is administered in the fasting state. In this study, the rate of absorption of chloroquine was unaffected by the presence of food in the GI tract however, peak plasma concn of chloroquine and areas under the plasma concentration-time curves were higher when 600 mg of the drug was administered with food than when the same dose was administered without food.
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 859
Chloroquine is widely distributed into body tissues. The drug has an apparent volume of distribution of 116-285 L/kg in healthy adults. Animal studies indicate that concn of chloroquine in liver, spleen, kidney, and lung are at least 200-700 times higher than those in plasma, and concentration of the drug in brain and spinal cord are at least 10-30 times higher than those in plasma. Chloroquine binds to melanin containing cells in the eyes and skin; skin concn of the drug are considerably higher than plasma concentration. Animal studies indicate that the drug is concentrated in the iris and choroid and, to a lesser extent, in the cornea, retina, and sclera and is found in these tissues in higher concentration than in other tissues.
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 859
Chloroquine is also concentrated in erythrocytes and binds to platelets and granulocytes. Serum concentrations of chloroquine are higher than those in plasma, presumably because the drug is released from platelets during coagulation, and plasma concentrations are 10 to 15% lower than whole blood concentration of the drug.
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 859
For more Absorption, Distribution and Excretion (Complete) data for CHLOROQUINE (16 total), please visit the HSDB record page.

8.6 Metabolism / Metabolites

Chloroquine is N-dealkylated primarily by CYP2C8 and CYP3A4 to N-desethylchloroquine. It is N-dealkylated to a lesser extent by CYP3A5, CYP2D6, and to an ever lesser extent by CYP1A1. N-desethylchloroquine can be further N-dealkylated to N-bidesethylchloroquine, which is further N-dealkylated to 7-chloro-4-aminoquinoline.
Chloroquine is partially metabolized; the major metabolite is desethylchloroquine. Desethylchloroquine also has antiplasmodial activity, but is slightly less active than chloroquine. Bisdesethylchloroquine, which is a carboxylic acid derivative, and several other unidentified metabolites are also formed in small amounts.
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 860
Hepatic (partially), to active de-ethylated metabolites. Principal metabolite is desethylchloroquine
Thomson.Micromedex. Drug Information for the Health Care Professional. 25th ed. Volume 1. Plus Updates. Content Reviewed by the United States Pharmacopeial Convention, Inc. Greenwood Village, CO. 2005., p. 837
Completely absorbed from gastrointestinal tract. Chloroquine is partially metabolized; the major metabolite is desethylchloroquine. Desethylchloroquine also has antiplasmodial activity, but is slightly less active than chloroquine. Bisdesethylchloroquine, which is a carboxylic acid derivative, and several other unidentified metabolites are also formed in small amounts (A625). Route of Elimination: Excretion of chloroquine is quite slow, but is increased by acidification of the urine. Half Life: 1-2 months
A625: Kojima T, Matsumoto M, Togashi H, Tachibana K, Kemmotsu O, Yoshioka M: Fluvoxamine suppresses the long-term potentiation in the hippocampal CA1 field of anesthetized rats: an effect mediated via 5-HT1A receptors. Brain Res. 2003 Jan 3;959(1):165-8. PMID:12480170

8.7 Biological Half-Life

The half life of chloroquine is 20-60 days.
The plasma half-life of chloroquine in healthy individuals is generally reported to be 72-120 hr. In one study, serum concentrations of chloroquine appeared to decline in a biphasic manner and the serum half-life of the terminal phase increased with higher dosage of the drug. In this study, the terminal half-life of chloroquine was 3.1 hr after a single 250 mg oral dose, 42.9 hr after a single 500 mg oral dose, and 312 hr after a single 1 g oral dose of the drug.
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 860
Terminal elimination half-life is 1 to 2 months.
Thomson.Micromedex. Drug Information for the Health Care Professional. 25th ed. Volume 1. Plus Updates. Content Reviewed by the United States Pharmacopeial Convention, Inc. Greenwood Village, CO. 2005., p. 837
... extremely slow elimination, with a terminal elimination half-life of 200 to 300 hours)
Haddad, L.M. (Ed). Clinical Management of Poisoning and Drug Overdose 3rd Edition. Saunders, Philadelphia, PA. 1998., p. 711

8.8 Mechanism of Action

Chloroquine inhibits the action of heme polymerase in malarial trophozoites, preventing the conversion of heme to hemazoin. _Plasmodium_ species continue to accumulate toxic heme, killing the parasite. Chloroquine passively diffuses through cell membranes and into endosomes, lysosomes, and Golgi vesicles; where it becomes protonated, trapping the chloroquine in the organelle and raising the surrounding pH. The raised pH in endosomes, prevent virus particles from utilizing their activity for fusion and entry into the cell. Chloroquine does not affect the level of ACE2 expression on cell surfaces, but inhibits terminal glycosylation of ACE2, the receptor that SARS-CoV and SARS-CoV-2 target for cell entry. ACE2 that is not in the glycosylated state may less efficiently interact with the SARS-CoV-2 spike protein, further inhibiting viral entry.
The exact mechanism of antimalarial activity of chloroquine has not been determined. The 4-aminoquinoline derivatives appear to bind to nucleoproteins and interfere with protein synthesis in susceptible organisms; the drugs intercalate readily into double-stranded DNA and inhibit both DNA and RNA polymerase. In addition, studies using chloroquine indicate that the drug apparently concentrates in parasite digestive vacuoles, increases the pH of the vacuoles, and interferes with the parasite's ability to metabolize and utilize erythrocyte hemoglobin. Plasmodial forms that do not have digestive vacuoles and do not utilize hemoglobin, such as exoerythrocytic forms, are not affected by chloroquine.
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 859
The 4-aminoquinoline derivatives, including chloroquine, also have anti-inflammatory activity; however, the mechanism(s) of action of the drugs in the treatment of rheumatoid arthritis and lupus erythematosus has not been determined. Chloroquine reportedly antagonizes histamine in vitro, has antiserotonin effects, and inhibits prostaglandin effects in mammalian cells presumably by inhibiting conversion of arachidonic acid to prostaglandin F2. In vitro studies indicate that chloroquine also inhibits chemotaxis of polymorphonuclear leukocytes, macrophages, and eosinophils.
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 859
Antiprotozoal-Malaria: /Mechanism of action/ may be based on ability of chloroquine to bind and alter the properties of DNA. Chloroquine also is taken up into the acidic food vacuoles of the parasite in the erythrocyte. It increases the pH of the acid vesicles, interfering with vesicle functions and possibly inhibiting phospholipid metabolism. In suppressive treatment, chloroquine inhibits the erythrocytic stage of development of plasmodia. In acute attacks of malaria, chloroquine interrupts erythrocytic schizogony of the parasite. its ability to concentrate in parasitized erythrocytes may account for its selective toxicity against the erythrocytic stages of plasmodial infection.
Thomson.Micromedex. Drug Information for the Health Care Professional. 25th ed. Volume 1. Plus Updates. Content Reviewed by the United States Pharmacopeial Convention, Inc. Greenwood Village, CO. 2005., p. 837
Antirheumatic-Chloroquine is though to act as a mild immunosuppressant, inhibiting the production of rheumatoid factor and acute phase reactants. It also accumulates in white blood cells, stabilizing lysosomal membranes and inhibiting the activity of many enzymes, including collagenase and the proteases that cause cartilage breakdown.
Thomson.Micromedex. Drug Information for the Health Care Professional. 25th ed. Volume 1. Plus Updates. Content Reviewed by the United States Pharmacopeial Convention, Inc. Greenwood Village, CO. 2005., p. 837

8.9 Human Metabolite Information

8.9.1 Cellular Locations

  • Cytoplasm
  • Extracellular
  • Membrane

9 Use and Manufacturing

9.1 Uses

MEDICATION
Antimalarial, antiamebic, antitheuratic, Lupus erthematus supressant
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 373
Mesh Heading: Amebicides, antimalarials, antirheumatic Agents
National Library of Medicine, SIS; ChemIDplus Record for Chloroquine. (54-05-7). Available from, as of April 17, 2006: https://chem.sis.nlm.nih.gov/chemidplus/chemidlite.jsp

Use (kg; approx.) in Germany (2009): >750

Consumption (g per capita; approx.) in Germany (2009): 0.00916

Excretion rate: 0.7

Calculated removal (%): 78.6

For the suppressive treatment and for acute attacks of malaria due to P. vivax, P.malariae, P. ovale, and susceptible strains of P. falciparum, Second-line agent in treatment of Rheumatoid Arthritis (A308).
A308: Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. PMID:18048412

9.1.1 Use Classification

Pharmaceuticals
S72 | NTUPHTW | Pharmaceutically Active Substances from National Taiwan University | DOI:10.5281/zenodo.3955664

9.2 Methods of Manufacturing

H. Andersag et al., US 2233970 (1941 to Winthrop)
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 373
Condensation of 4,7-dichloroquinoline with 1-diethylamino-4-aminopentane: German patent 683692 (1939);
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 373

9.3 Formulations / Preparations

Chloroquine phosphate, USP ... is available as tablets containing either 250 or 500 mg of diphosphate. Approximately 60% of diphosphate represents base. /Chloroquine phosphate/
Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990., p. 982
Arechin; Avloclor; Imagon; Malaquin; Resochin; Tresochin. /Chloroquine diphosphate/
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 373
Nivaquine. /Chloroquine Sulfate/
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001., p. 373
Tablets (as the phosphate), 500 mg. Vials (as the dihydrochloride), 50 mg/ml.
Hussar, D.A. (ed.). Modell's Drugs in Current Use and New Drugs. 38th ed. New York, NY: Springer Publishing Co., 1992., p. 37
Chloroquine Phosphate: Oral tablets 300 mg or 150 mg (of chloroquine).
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 860

9.4 U.S. Production

(1977) PROBABLY MORE THAN 4.5X10+5 G /PHOSPHATE/
SRI
(1979) PROBABLY MORE THAN 4.5X10+5 G /PHOSPHATE/
SRI

9.5 U.S. Imports

(1977) 6X10+5 G-PRINCPL CUSTMS DISTS /PHOSPHATE/
SRI
(1979) 3X10+5 G-PRINCPL CUSTMS DISTS /PHOSPHATE/
SRI

9.6 General Manufacturing Information

Usually dispensed as the phosphate.
Lewis, R.J. Sr.; Hawley's Condensed Chemical Dictionary 14th Edition. John Wiley & Sons, Inc. New York, NY 2001., p. 259

10 Identification

10.1 Analytic Laboratory Methods

GENERAL SAMPLE, FLUOROMETRY (EXCITATION= 350, EMISSION= 405).
Sunshine, I. (ed.). CRC Handbook of Analytical Toxicology. Cleveland: The Chemical Rubber Co., 1969., p. 28
Analyte: chloroquine; matrix: chemical identification; procedure: infrared absorption spectrophotometry with comparison to standards
U.S. Pharmacopeia. The United States Pharmacopeia, USP 29/The National Formulary, NF 24; Rockville, MD: U.S. Pharmacopeial Convention, Inc., p480 (2006)
Analyte: chloroquine; matrix: chemical identification; procedure: ultraviolet absorption spectrophotometry with comparison to standards
U.S. Pharmacopeia. The United States Pharmacopeia, USP 29/The National Formulary, NF 24; Rockville, MD: U.S. Pharmacopeial Convention, Inc., p480 (2006)
Analyte: chloroquine; matrix: chemical purity; procedure: dissolution in glacial acetic acid; addition of crystal violet indicator; titration with perchloric acid
U.S. Pharmacopeia. The United States Pharmacopeia, USP 29/The National Formulary, NF 24; Rockville, MD: U.S. Pharmacopeial Convention, Inc., p480 (2006)
For more Analytic Laboratory Methods (Complete) data for CHLOROQUINE (20 total), please visit the HSDB record page.

10.2 Clinical Laboratory Methods

Determination of chloroquine in blood, plasma, red cells, or urine specimen using spectrophotometer with UV absorption spectrum at 0.0 to 0.1 absorbance range. Recovery is about 90 + or - 2%.
Sunshine, Irving (ed.) Methodology for Analytical Toxicology. Cleveland: CRC Press, Inc., 1975., p. 83
A high-performance liquid chromatography method with fluorescence detection is described for the simultaneous measurement of quinine, chloroquine and mono- and bidesethylchloroquine in human plasma, erythrocytes and urine ... The limit of detection was ca 5 ng/mL of chloroquine and ca 23 ng/mL for quinine ...
Chaulet JF et al; J Chromatogr Biomed Appl 613 (2): 303-10 (1993)
Two new methods for the simultaneous detn of chloroquine and its two main metabolites (monodesethylchloroquine and bisdesethylchloroquine) in biol samples, RIA and ELISA, are described ... Sensitivity limits are, respectively, 0.70 nM (3 pg of chloroquine sulfate measured in 10 uLof plasma sample) for RIA, and 10 nM (22 pg of chloroquine sulfate measured in 5 uL of plasma sample) for ELISA. The interassay coefficients of variation are, respectively, <10 and <16% for RIA and ELISA in the range 14 to 410 nM (6 to 180 ng/mL) ...
Escande C et al; J Pharm Sci 79 (1): 23-7 (1990)
Analyte: chloroquine; matrix: blood (whole, plasma); procedure: high-performance liquid chromatography with ultraviolet detection at 229 nm; limit of detection: <120 ng/mL
Tracqui A et al; J Forensic Sci 40: 254-262 (1995). As cited in: Lunn G, Schmuff N; HPLC Methods for Pharmaceutical Analysis. New York, NY: John Wiley & Sons, 1997., p.459
For more Clinical Laboratory Methods (Complete) data for CHLOROQUINE (17 total), please visit the HSDB record page.

11 Safety and Hazards

11.1 Hazards Identification

11.1.1 GHS Classification

Pictogram(s)
Irritant
Signal
Warning
GHS Hazard Statements
H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]
Precautionary Statement Codes

P264, P270, P301+P317, P330, and P501

(The corresponding statement to each P-code can be found at the GHS Classification page.)

ECHA C&L Notifications Summary

Aggregated GHS information provided per 40 reports by companies from 2 notifications to the ECHA C&L Inventory.

Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown.

11.1.2 Hazard Classes and Categories

Acute Tox. 4 (100%)

11.1.3 Skin, Eye, and Respiratory Irritations

Eleven cases of macular degeneration occurring between the ages of 22 yr and 40 yr are presented. All the patients gave positive history of chloroquine intake and outdoor activity. In 4 of the 11 cases, pterygium was an associated ocular finding. The female to male ratio was 3 to 1. The macular lesions were bilateral and symmetrical in all the cases. It is postulated that the effect of chronic chloroquine ingestion exacerbated by chronic light toxicity might be responsible for this type of macular degeneration presenting in adults.
Obikili AG; East Afr Med J 67 (9): 614-21 (1990)

11.2 Accidental Release Measures

11.2.1 Disposal Methods

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

11.3 Regulatory Information

11.3.1 FDA Requirements

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl chloroquine phosphate, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Chloroquine phosphate/
DHHS/FDA; Electronic Orange Book-Approved Drug Products with Therapeutic Equivalence Evaluations. Available from, as of July 26, 2006: https://www.fda.gov/cder/ob/

11.4 Other Safety Information

Chemical Assessment

IMAP assessments - 1,4-Pentanediamine, N4-(7-chloro-4-quinolinyl)-N1,N1-diethyl-: Human health tier I assessment

IMAP assessments - 1,4-Pentanediamine, N4-(7-chloro-4-quinolinyl)-N1,N1-diethyl-: Environment tier I assessment

11.4.1 Special Reports

Fitch CD; Ferriprotoporphyrin IX: role in chloroquine susceptibility and resistance in malaria.; Prog Clin Biol Res 313: 45-52 (1989). A review of all available evidence supports the hypothesis that ferriprotoporphyrin is the receptor for chloroquine and mediator of its antimalarial activity.
Ochsendorf FR, Runne U; Chloroquine and hydroxychloroquine: side effect profile of important therapeutic drugs; Hautarzt 42 (3): 140-6 (1991). Precise knowledge of the undesirable effects of chloroquine and hydroxychloroquine allows better exploitation of their therapeutic effects.

12 Toxicity

12.1 Toxicological Information

12.1.1 Toxicity Summary

IDENTIFICATION: Chloroquine is a white or slightly yellow, odorless crystalline powder with a bitter taste. Very slightly soluble in water, soluble in chloroform, ether and dilute acids. Chloroquine diphosphate is a white, bitter, crystalline powder. Chloroquine sulfate is a white, odorless, bitter, crystalline powder. Hydroxychloride chloroquine is a colorless liquid. Uses: Indications: Malaria: Chloroquine is the drug of choice for the prophylaxis and treatment of malaria caused by Plasmodium vivax. P. ovale, P. malariae and sensitive P. falciparum. Amebiasis: Chloroquine is used for the treatment of extraintestinal amebiasis (usually in combination with amebicides). Treatment of discoid lupus erythematosis and rheumatoid arthritis (acute and chronic). Chloroquine may be used for the treatment of these conditions. Other less common indications are: amebic liver abscess, porphyria cutanea tarda, solar urticaria, chronic cutaneous vasculitis. HUMAN EXPOSURE: Main risks and target organs: The main toxic effects of chloroquine are related to its quinidine-like (membrane stabilizing) actions on the heart. Other acute effects are respiratory depression and severe gastro-intestinal irritation. Summary of clinical effects: Toxic manifestations appear rapidly within one to three hours after ingestion and include: Cardiac disturbances: circulatory arrest, shock, conduction disturbances, ventricular arrhythmias. Neurological symptoms: drowsiness, coma and sometimes convulsions. Visual disturbances not uncommon. Respiratory symptoms: apnea. Gastrointestinal symptoms: severe gastrointestinal irritation; nausea, vomiting, cramps, diarrhea. Children are specially sensitive to toxic effects. Dizziness, nausea, vomiting, diarrhea, headache, drowsiness, blurred vision, diplopia, blindness, convulsions, coma, hypotension, cardiogenic shock, cardiac arrest and impaired respiration are the characteristic features of chloroquine poisoning. Electrocardiography (ECG) may show decrease of T wave, widening of QRS, ventricular tachycardia and fibrillation. Hypokalemia is associated with severe poisoning. Contraindications: Hepatic and renal function impairment, blood disorders, gastrointestinal illnesses, glucose-6-phosphate dehydrogenase (G-6-PD) deficiency, severe neurological disorders, retinal or visual field changes. Chloroquine should not be used in association with gold salts or phenylbutazone. Routes of entry: Oral: Oral absorption is the most frequent cause of intoxication. Parenteral: Intoxication after parenteral administration is rare. A fatal outcome reported was after 250 mg IV chloroquine in a 42-year-old man. Absorption by route of exposure: Readily and almost completely absorbed from the gastrointestinal tract. Bioavailability is 89% for tablets. Peak plasma concentration is reached 1.5 to 3 hours after ingestion. Distribution by route of exposure: Protein binding: 5O to 65%. Chloroquine accumulates in high concentrations in kidney, liver, lung and spleen, and is strongly bound in melanin-containing cells (eye and skin). Red cell concentration is five to ten times the plasma concentration. Very low concentrations are found in the intestinal wall. Crosses the placenta. Biological half-life by route of exposure: Plasma terminal half-life is mean 278 hours or 70 to 120 hours. Shorter plasma elimination half-lives have been reported in children: 75 to 136 hours. Metabolism: Chloroquine undergoes metabolism by hepatic mechanisms. The main active metabolite is desethylchloroquine. Plasma half-life of desethylchloroquine is similar to chloroquine. Elimination by route of exposure: Chloroquine is eliminated very slowly. About 55% is excreted in urine and 19% in feces within 77 days following therapy with 310 mg for 14 days. Kidney: in urine about 70% is unchanged chloroquine and 23% is desethylchloroquine. It is excreted in breast milk. Toxicodynamics: The cardiotoxicity of chloroquine is related to it quinidine-like (membrane/stabilizing) effects. Chloroquine has a negative inotropic action, inhibits spontaneous diastolic depolarization, slows conduction, lengthens the effective refractory period and raises the electrical threshold. This results in depression of contractility, impairment of conductivity, decrease of excitability, but with possible abnormal stimulus re-entry mechanism. Hypokalemia: Acute hypokalemia may occur in acute poisoning. It is probably related to intracellular transport of potassium by a direct effect on cellular membrane permeability. Neurological symptoms: Neurological symptoms in acute overdose may be related to a direct toxic effect on CNS or to cerebral ischemia due to circulatory failure or respiratory insufficiency. The mechanism of the anti-inflammatory effect is not known. Toxicity: Human data: Chloroquine has a low margin of safety; the therapeutic, toxic and lethal doses are very close. Fatalities have been reported in children after chloroquine overdoses. Interactions: Chloroquine toxicity may be increased by all drugs with quinidine-like effects. Combination with hepatotoxic or dermatitis-causing medication should be avoided, as well as with heparin (risk of hemorrhage) and penicillamine. Eye: Keratopathy and retinopathy may occur when large doses of chloroquine are used for long periods. Changes occurring in the cornea are usually completely reversible on discontinuing treatment; changes in the retina, pigmentary degeneration of the retina, loss of vision, scotomas, optic nerve atrophy, field defects and blindness are irreversible. Retinopathy is considered to occur when the total cumulative dose ingested exceeds 100 g. Blurring of vision, diplopia may occur with short-term chloroquine therapy and are reversible. ANIMAL/PLANT STUDIES: The following progression of ECG changes was observed in dogs with experimental overdosage: severe tachycardia preceded by loss of voltage and widening of QRS, followed by sinus bradycardia, ventricular tachycardia, ventricular fibrillation and finally asystole.
International Programme on Chemical Safety; Poisons Information Monograph: Chloroquine (PIM 123) (1994) Available from, as of October 24, 2005: https://www.inchem.org/pages/pims.html
The mechanism of plasmodicidal action of chloroquine is not completely certain. Like other quinoline derivatives, it is thought to inhibit heme polymerase activity. This results in accumulation of free heme, which is toxic to the parasites. nside red blood cells, the malarial parasite must degrade hemoglobin to acquire essential amino acids, which the parasite requires to construct its own protein and for energy metabolism. Digestion is carried out in a vacuole of the parasite cell. During this process, the parasite produces the toxic and soluble molecule heme. The heme moiety consists of a porphyrin ring called Fe(II)-protoporphyrin IX (FP). To avoid destruction by this molecule, the parasite biocrystallizes heme to form hemozoin, a non-toxic molecule. Hemozoin collects in the digestive vacuole as insoluble crystals. Chloroquine enters the red blood cell, inhabiting parasite cell, and digestive vacuole by simple diffusion. Chloroquine then becomes protonated (to CQ2+), as the digestive vacuole is known to be acidic (pH 4.7); chloroquine then cannot leave by diffusion. Chloroquine caps hemozoin molecules to prevent further biocrystallization of heme, thus leading to heme buildup. Chloroquine binds to heme (or FP) to form what is known as the FP-Chloroquine complex; this complex is highly toxic to the cell and disrupts membrane function. Action of the toxic FP-Chloroquine and FP results in cell lysis and ultimately parasite cell autodigestion. In essence, the parasite cell drowns in its own metabolic products.

12.1.2 Hepatotoxicity

Despite use for more than 50 years, chloroquine has rarely been linked to serum aminotransferase elevations or to clinically apparent acute liver injury. In patients with acute porphyria and porphyria cutanea tarda, chloroquine can trigger an acute attack with fever and serum aminotransferase elevations, sometimes resulting in jaundice. Hydroxychloroquine does not cause this reaction and appears to have partial beneficial effects in porphyria. In clinical trials of chloroquine for COVID-19 prevention and treatment, there were no reports of hepatotoxicity, and rates of serum enzyme elevations during chloroquine treatment were low and similar to those in patients receiving placebo or standard of care.

Likelihood score: D (possible rare cause of clinically apparent liver injury).

12.1.3 Drug Induced Liver Injury

Compound
chloroquine
DILI Annotation
Less-DILI-Concern
Severity Grade
3
Label Section
Adverse reactions
References

M Chen, V Vijay, Q Shi, Z Liu, H Fang, W Tong. FDA-Approved Drug Labeling for the Study of Drug-Induced Liver Injury, Drug Discovery Today, 16(15-16):697-703, 2011. PMID:21624500 DOI:10.1016/j.drudis.2011.05.007

M Chen, A Suzuki, S Thakkar, K Yu, C Hu, W Tong. DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans. Drug Discov Today 2016, 21(4): 648-653. PMID:26948801 DOI:10.1016/j.drudis.2016.02.015

12.1.4 Evidence for Carcinogenicity

No data are available in humans. Inadequate evidence of carcinogenicity in animals. OVERALL EVALUATION: Group 3: The agent is not classifiable as to its carcinogenicity to humans.
IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: https://monographs.iarc.fr/ENG/Classification/index.php, p. S7 60 (1987)

12.1.5 Carcinogen Classification

1 of 2
IARC Carcinogenic Agent
Chloroquine
IARC Carcinogenic Classes
Group 3: Not classifiable as to its carcinogenicity to humans
IARC Monographs

Volume 13: (1977) Some Miscellaneous Pharmaceutical Substances

Volume Sup 7: Overall Evaluations of Carcinogenicity: An Updating of IARC Monographs Volumes 1 to 42, 1987; 440 pages; ISBN 92-832-1411-0 (out of print)

2 of 2
Carcinogen Classification
3, not classifiable as to its carcinogenicity to humans. (L135)

12.1.6 Health Effects

Possible heath effects include an irreversible retinal damage, visual disturbances, nyctalopia; scotomatous vision with field defects of paracentral, pericentral ring types, and typically temporal scotomas, nerve type deafness; tinnitus, reduced hearing in patients with preexisting auditory damage. Other effects include pleomorphic skin eruptions, skeletal muscle myopathy, hypotension, electrocardiographic change as well as neuropsychiatric changes including psychosis, delirium, personality changes and depression (RxList, A308).

12.1.7 Effects During Pregnancy and Lactation

◉ Summary of Use during Lactation

Very small amounts of chloroquine are excreted in breast milk; when given once weekly, the amount of drug is not sufficient to harm the infant nor is the quantity sufficient to protect the child from malaria. United Kingdom malaria treatment guidelines recommend that weekly chloroquine 500 mg be given until breastfeeding is completed and primaquine can be given. Breastfeeding infants should receive the recommended dosages of chloroquine for malaria prophylaxis.In HIV-infected women, elevated viral HIV loads in milk were decreased after treatment with chloroquine to a greater extent than other women who were treated with the combination of sulfadoxine and pyrimethamine. Because no information is available on the daily use of chloroquine during breastfeeding, hydroxychloroquine or another agent may be preferred in this situation, especially while nursing a newborn or preterm infant.

◉ Effects in Breastfed Infants

Several authors have pointed out that malaria prophylaxis in nursing mothers with chloroquine is common in endemic areas. As of the revision date, no reports of adverse reactions in breastfed infants have been published.

◉ Effects on Lactation and Breastmilk

Relevant published information was not found as of the revision date.

12.1.8 Exposure Routes

Inhalation Completely absorbed from gastrointestinal tract

12.1.9 Symptoms

Convulsive seizures. Mild and transient headache.

12.1.10 Acute Effects

12.1.11 Treatment

Treatment is symptomatic and must be prompt with immediate evacuation of the stomach by emesis (at home, before transportation to the hospital) or gastric lavage until the stomach is completely emptied. If finely powdered, activated charcoal is introduced by stomach tube, after lavage, and within 30 minutes after ingestion of the antimalarial, it may inhibit further intestinal absorption of the drug. To be effective, the dose of activated charcoal should be at least five times the estimated dose of chloroquine ingested. Convulsions, if present, should be controlled before attempting gastric lavage. (L1712)
L1712: RxList: The Internet Drug Index (2009). http://www.rxlist.com/

12.1.12 Interactions

Concurrent use of penicillamine /with chloroquine/ may increase penicillamine plasma concentrations, increasing the potential for serious hematologic and/or renal adverse reactions as well as the possibility of severe skin reactions.
Thomson.Micromedex. Drug Information for the Health Care Professional. 25th ed. Volume 1. Plus Updates. Content Reviewed by the United States Pharmacopeial Convention, Inc. Greenwood Village, CO. 2005., p. 838
Concurrent use /of mefloquine and chloroquine may increase the risk of seizures.
Thomson.Micromedex. Drug Information for the Health Care Professional. 25th ed. Volume 1. Plus Updates. Content Reviewed by the United States Pharmacopeial Convention, Inc. Greenwood Village, CO. 2005., p. 838
Concurrent use of other hepatotoxic medications with chloroquine may increase the potential for hepatotoxicity and should be avoided.
Thomson.Micromedex. Drug Information for the Health Care Professional. 25th ed. Volume 1. Plus Updates. Content Reviewed by the United States Pharmacopeial Convention, Inc. Greenwood Village, CO. 2005., p. 838
Concurrent use may cause a sudden increase in cyclosporine plasma concentrations; close monitoring of serum cyclosporine level is recommended following concurrent use of chloroquine; chloroquine should be discontinued if necessary.
Thomson.Micromedex. Drug Information for the Health Care Professional. 25th ed. Volume 1. Plus Updates. Content Reviewed by the United States Pharmacopeial Convention, Inc. Greenwood Village, CO. 2005., p. 838
For more Interactions (Complete) data for CHLOROQUINE (16 total), please visit the HSDB record page.

12.1.13 Antidote and Emergency Treatment

Treatment of overdosage of 4-aminoquinoline derivatives must be prompt, since acute toxicity with the drugs can progress rapidly, possibly leading to cardiovascular collapse and respiratory and cardiac arrest. ECG should be monitored. Because of the importance of supporting respiration, early endotracheal intubation and mechanical ventilation may be necessary. Early gastric lavage may provide some benefit in reducing absorption of the drugs, but generally should be preceded by measures to correct severe cardiovascular disturbances, if present, and by respiratory support that includes endotracheal intubation with cuff inflated and in place to prevent aspiration (since seizures may occur). IV diazepam may control seizures and other manifestations of cerebral stimulation and, possibly, may prevent or minimize other toxic effects (eg, cardiotoxicity, including ECG abnormalities and conduction disturbances) of 4-aminoquinoline derivatives. However, additional study and experience are necessary to further establish the effects of diazepam on noncerebral manifestations of toxicity with these drugs. If seizures are caused by anoxia, anoxia should be corrected with oxygen and respiratory support. Equipment and facilities for cardioversion and for insertion of a transvenous pacemaker should be readily available. Administration of IV fluids and placement of the patient in Trendelenburg's position may be useful in managing hypotension, but more aggressive therapy, including administration of vasopressors (eg, epinephrine, isoproterenol, dopamine), may be necessary, particularly if shock appears to be impending. Administration of activated charcoal by stomach tube, after lavage and within 30 min after ingestion of 4-aminoquinoline derivatives, may inhibit further intestinal absorption of the drugs; the dose of activated charcoal should be at least 5 times the estimated dose of chloroquine... ingested. Peritoneal dialysis, hemodialysis, and hemoperfusion do not appear to be useful in the management of overdosage with 4-aminoquinoline derivatives. Patients who survive the acute phase of overdosage and are asymptomatic should be closely observed for at least 48-96 hr after ingestion
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 859
A retrospective study was carried out, over a twelve year period, of all cases of acute chloroquine poisoning where more than 2 g of chloroquine had been taken. It included 386 patients; of these, 60 who had taken drugs other than chloroquine, and 17 who had ingested less than 1 g of the drug, were excluded. The remaining 309 patients were allocated to two groups: a control group, consisting of the patients admitted between January 1973 and April 1980 (n = 146), and a diazepam group, made up of those admitted from May 1980 to December 1989 (n = 163). The patients in the latter group had had the same symptomatic treatment as those in the control group, and had been routinely given a 0.5 mg/kg bolus of diazepam on admission followed by 0.1 mg/kg/day for every 100 mg of chloroquine supposed to have been ingested. Both groups were divided into three subgroups, those patients with cardiorespiratory arrest, and those with, and those without, symptoms on admission. No statistically significant difference was found between either the control and diazepam groups or between subgroups, concerning the distribution of age, sex, amount of chloroquine supposed to have been ingested, delay in hospital admission and death rate. However, there was a higher death rate in the asymptomatic subgroup not treated with diazepam than in the diazepam group. Therefore, the routine use of diazepam for the treatment of acute chloroquine poisoning does not seem to be justified in symptomatic cases and in those with inaugural cardiac arrest.
Demaziere J et al; Ann Fr Anesth Reanim 11 (2): 164-7 (1992)
The effects of diazepam and the incidence of hypoxemia on the course of acute chloroquine poisoning were studied prospectively in 21 patients. Patients excluded were those who had ingested more than one drug or who had major symptoms on admission (systolic blood pressure less than 80 mmHg; QRS greater than 0.12 s; cardiac dysrhythmias, respiratory disturbances). Arterial blood gases were measured on admission (T0) and 15 min after 0.5 mg/kg of diazepam had been given (T1). Gastric lavage was carried out as soon as the results of the blood gases had been obtained, and after treatment of hypoxemia (PaO2 < 90 mmHg). An infusion of diazepam (1 mg/kg/day) was then given. Arterial blood gases were measured after 1 (T2), 6 (T3), 12 (T4) and 24 hr (T5). Hypoxemia was present on admission in four patients who had a PaO2 = 75 + or - 10 mmHg (Pa(sys) = 130 + or - 19 mmHg; blood chloroquine concn = 8.2 + or - 5.2 umol/L; kaliemia /serum potassium/ = 3.1 + or - 0.3 mmol/L; PaCO2 = 35 + or - 1 mmHg). In two patients, hypoxemia decreased after the initial dose of diazepam (T1); however, oxygen was still required by the other two at that time. Oxygen was no longer needed by any patient at T2, as all the blood gas values had returned to normal.
Kempf J, Saissy JM; Ann Fr Anesth Reanim 11 (2): 160-3 (1992)
Emergency and supportive measures: Maintain an open airway and assist ventilation if necessary. Treat seizures, coma, hypotension, and methemoglobinemia if they occur. Treat massive hemolysis with blood transfusions if needed, and prevent hemoglobin deposition in the kidney tubules by alkaline diuresis ... continuously monitor the ECG for at least 6 to 8 hr.
Olson, K.R. (Ed.); Poisoning & Drug Overdose. 4th ed. Lange Medical Books/McGraw-Hill. New York, N.Y. 2004., p. 166
For more Antidote and Emergency Treatment (Complete) data for CHLOROQUINE (8 total), please visit the HSDB record page.

12.1.14 Human Toxicity Excerpts

/HUMAN EXPOSURE STUDIES/ This prospective study contains clinical and experimental parts. In the clinical study, 125 patients given im chloroquine for malaria were followed for 2 months in order to detect local injection site complications. Adequate local antiseptic conditions were ensured before giving the injection. Twenty three patients (18.4%) had minimal local reaction in the form of redness, induration and/or a lump. No pyogenic abscess was noted in contrast to a previous report.
elZaki K et al; J Trop Med Hyg 94 (3): 206-9 (1991)
/HUMAN EXPOSURE STUDIES/ Cardiotoxicity may be seen with serum levels of 1 mg/L (1000 ng/mL); serum levels reported in fetal cases have ranged from 1 to 210 mg/L (average, 60 mg/L).
Olson, K.R. (Ed.); Poisoning & Drug Overdose. 4th ed. Lange Medical Books/McGraw-Hill. New York, N.Y. 2004., p. 166
/SIGNS AND SYMPTOMS/ The toxicities of antimalarial drugs vary because of the differences in the chemical structures of these compounds. Quinine, the oldest antimalarial, has been used for 300 yr. Of the 200 to 300 compounds synthesized since the first synthetic antimalarial, primaquine in 1926, 15 to 20 are currently used for malaria treatment, most of which are quinoline derivatives. Quinoline derivatives, particularly quinine and chloroquine, are highly toxic in overdose. The toxic effects are related to their quinidine-like actions on the heart and include circulatory arrest, cardiogenic shock, conduction disturbances and ventricular arrhythmias. Additional clinical features are obnubilation, coma, convulsions, respiratory depression. Blindness is a frequent complication in quinine overdose. Hypokalaemia is consistently present, although apparently self-correcting, in severe chloroquine poisoning and is a good index of severity. Recent toxicokinetic studies of quinine and chloroquine showed good correlations between dose ingested, serum concn and clinical features, and confirmed the inefficacy of hemodialysis, hemoperfusion and peritoneal dialysis for enhancing drug removal. The other quinoline derivatives appear to be less toxic. Amodiaquine may induce side effects such as gastrointestinal symptoms, agranulocytosis and hepatitis. The main feature of primaquine overdose is methemoglobinemia. No cases of mefloquine and piperaquine overdose have been reported. Overdose with quinacrine, an acridine derivative, may result in nausea, vomiting, confusion, convulsion and acute psychosis. The dehydrofolate reductase inhibitors used in malaria treatment are sulfadoxine, dapsone, proguanil (chloroguanide), trimethoprim and pyrimethamine. Most of these drugs are given in combination. Proguanil is one of the safest antimalarials. Convulsion, coma and blindness have been reported in pyrimethamine overdose. Sulfadoxine can induce Lyell and Stevens-Johnson syndromes. The main feature of dapsone poisoning is severe methemoglobinemia which is related to dapsone and to its metabolites. Recent toxicokinetic studies confirmed the efficacy of oral activated charcoal, hemodialysis and hemoperfusion in enhancing removal of dapsone and its metabolites. No overdose has been reported with artemesinine, a new antimalarial tested in the People's Republic of China. The general management of antimalarial overdose include gastric lavage and symptomatic treatment.
Jaeger A et al; Med Toxicol Adverse Drug Exp 2 (4): 242-73 (1987)
/SIGNS AND SYMPTOMS/ In the treatment of collagen vascular diseases ... retinopathy has become recognized as a significant potential problem. ... The earliest ophthalmoscopic sign of ... retinopathy is loss of the foveal reflex. This is followed by pigmentary changes in the macula, typically progressing to a pigmented ring surrounding the fovea ("bull's eye lesion") and sometimes accompanied by pigment flecks in the midperiphery. ... The most common complaint is difficulty in reading, which with further questioning can be usually related to paracentral scotomas. Light flashes and streaks and other entopic phenomena may also be present.
Haddad, L.M., Clinical Management of Poisoning and Drug Overdose. 2nd ed. Philadelphia, PA: W.B. Saunders Co., 1990., p. 381
For more Human Toxicity Excerpts (Complete) data for CHLOROQUINE (27 total), please visit the HSDB record page.

12.1.15 Non-Human Toxicity Excerpts

/LABORATORY ANIMALS: Acute Exposure/ The effect of a 2 hr iv chloroquine infusion (0.015, 0.030 and 1.25 ug/min) on renal fluid and electrolyte handling was investigated in the saline infused, Inactin anaesthetized rat. Blood pressure and glomerular filtration rate were not affected by chloroquine administration, remaining around 128 mmHg and 2.4 mL/min, respectively throughout the 5 hr post-equilibration period. Chloroquine produced an increase in Na+ and Cl- excretion without affecting the urine flow. By 1 hr after the start of treatment (0.03 ug chloroquine/min) the Na+ excretion rate had increased to 14.5 + or - 2.1 umol/min (n = 6), and was significantly (P < 0.01) greater than in control animals (8.6 + or - 1.0 umol/min) at the corresponding time. Parallel but lesser increases in Cl- excretion rates were also observed. The plasma aldosterone and corticosterone levels following either 10, 30 or 120 min infusion of chloroquine at 0.03 ug/min did not differ statistically from each other or from control values. It is concluded that acute chloroquine administration induces an increase in Na+ excretion. The mechanism of this natriuresis cannot be established from the present study, but is likely to involve altered tubular handling of Na+.
Musabayane CT et al; J Trop Med Hyg 96 (5): 305-10 (1993)
/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Groups of 10 male and 10 female 21-day-old Osborne-Mendel rats were given 0 (control), 100, 200, 400, 800 or 1000 mg/kg of diet chloroquine for up to 2 years. Inhibition of growth was severe at the 800 and 1000 mg/kg levels but temporary at 400 mg/kg. The toxicity of chloroquine became progressively more severe with increasing dosage, and 100% mortality was observed at the two highest dose levels at 35 and 25 weeks, respectively. No tumours were reported in 86 treated rats or in 15 control rats examined microscopically
IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: https://monographs.iarc.fr/ENG/Classification/index.php, p. V13 51 (1976)
/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ In two year ... study in rats fed diets containing from 100-1000 mg ... /kg of diet/ ... myocardial and voluntary muscle damage, centrilobular necrosis of liver and testicular atrophy were ... observed.
IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: https://monographs.iarc.fr/ENG/Classification/index.php, p. V13 51 (1976)
/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Feeding Egyptian toads (Bufo regularis) with chloroquine and primaquine separately induced tumor formation in 14% and 19% of the animals, respectively. When chloroquine and primaquine were given in combination, the tumor incidence increased to 23.5%. Chloroquine feeding resulted in tumors located in the liver (lymphosarcomas) and primaquine in tumors in the kidney (histiocytic sarcomas). Toads fed chloroquine plus primaquine developed tumors in the liver, kidney, lung, and urinary bladder, and all the tumors were diagnosed as histiocytic sarcomas. It is speculated that one or more metabolites of chloroquine and primaquine (eg, quinone) may be responsible for tumor induction in the toads.
el-Mofty MM et al; Nutr Cancer 18 (2): 191-8 (1992)
For more Non-Human Toxicity Excerpts (Complete) data for CHLOROQUINE (11 total), please visit the HSDB record page.

12.1.16 Human Toxicity Values

... Reports of suicides have indicated that the margin of safety in adults is also small. Without prompt effective therapy, acute ingestion of 5 g or more of chloroquine in adults has usually been fatal, although death has occurred with smaller doses. Fatalities have been reported following the accidental ingestion of relatively small doses of chloroquine (e.g., 750 mg or 1 g of chloroquine phosphate in a 3-year-old child).
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 859

12.1.17 Non-Human Toxicity Values

LD50 Rat oral 330 mg/kg
Verschueren, K. Handbook of Environmental Data on Organic Chemicals. Volumes 1-2. 4th ed. John Wiley & Sons. New York, NY. 2001, p. 551
LD50 Mouse oral 311 mg/kg
Verschueren, K. Handbook of Environmental Data on Organic Chemicals. Volumes 1-2. 4th ed. John Wiley & Sons. New York, NY. 2001, p. 551

12.1.18 Protein Binding

Chloroquine is 46-74% bound to plasma proteins. (-)-chloroquine binds more strongly to alpha-1-acid glycoprotein and (+)-chloroquine binds more strongly to serum albumin.

12.2 Ecological Information

12.2.1 Environmental Water Concentrations

While data specific to chloroquine were not available(SRC, 2005), the literature suggests that some pharmaceutically active compounds originating from human and veterinary therapy are not eliminated completely in municipal sewage treatment plants and are therefore discharged into receiving waters(1). Wastewater treatment processes often were not designed to remove them from the effluent(2). Another concern is that selected organic waste compounds may be degrading to new and more persistent compounds that may be released instead of or in addition to the parent compound(2). Studies have indicated that several polar pharmaceutically active compounds can leach through subsoils(1).
(1) Heberer T; Tox Lett 131: 5-17 (2002)
(2) Koplin DW et al; Environ Sci Toxicol 36: 1202-211 (2002)

12.2.2 Milk Concentrations

EXPERIMENTAL: Small amounts of chloroquine and its major metabolite, desethylchloroquine, are distributed into milk. Following oral administration of a single 300 or 600 mg dose of chloroquine, peak concentration of the drug in milk range from 1.7-7.5 ug/mL and generally are greater than concurrent plasma concentrations.
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 860

12.2.3 Probable Routes of Human Exposure

CORNEAL DEPOSITS HAVE ... BEEN DESCRIBED AS INDUSTRIAL COMPLICATION IN WORKERS MFR CHLOROQUINE ... . APPARENTLY DEPOSITS ARE SAME AS THOSE PRODUCED BY ORAL ADMIN. ... INDUSTRIALLY MATERIAL MAY HAVE REACHED CORNEA DIRECTLY IN FORM OF DUST, BUT THIS HAS NOT BEEN ESTABLISHED.
Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 216

13 Associated Disorders and Diseases

14 Literature

14.1 Consolidated References

14.2 NLM Curated PubMed Citations

14.3 Springer Nature References

14.4 Thieme References

14.5 Wiley References

14.6 Nature Journal References

14.7 Chemical Co-Occurrences in Literature

14.8 Chemical-Gene Co-Occurrences in Literature

14.9 Chemical-Disease Co-Occurrences in Literature

15 Patents

15.1 Depositor-Supplied Patent Identifiers

15.2 WIPO PATENTSCOPE

15.3 Chemical Co-Occurrences in Patents

15.4 Chemical-Disease Co-Occurrences in Patents

15.5 Chemical-Gene Co-Occurrences in Patents

16 Interactions and Pathways

16.1 Chemical-Target Interactions

16.2 Drug-Drug Interactions

16.3 Drug-Food Interactions

Take with food. Food reduces irritation and increases bioavailability.

16.4 Pathways

17 Biological Test Results

17.1 BioAssay Results

18 Taxonomy

The LOTUS Initiative for Open Natural Products Research: frozen dataset union wikidata (with metadata) | DOI:10.5281/zenodo.5794106

19 Classification

19.1 MeSH Tree

19.2 NCI Thesaurus Tree

19.3 ChEBI Ontology

19.4 KEGG: ATC

19.5 KEGG : Antimicrobials

19.6 WHO ATC Classification System

19.7 FDA Pharm Classes

19.8 ChemIDplus

19.9 IUPHAR / BPS Guide to PHARMACOLOGY Target Classification

19.10 ChEMBL Target Tree

19.11 UN GHS Classification

19.12 NORMAN Suspect List Exchange Classification

19.13 CCSBase Classification

19.14 EPA DSSTox Classification

19.15 International Agency for Research on Cancer (IARC) Classification

19.16 LOTUS Tree

19.17 EPA Substance Registry Services Tree

19.18 MolGenie Organic Chemistry Ontology

20 Information Sources

  1. Australian Industrial Chemicals Introduction Scheme (AICIS)
    1,4-Pentanediamine, N4-(7-chloro-4-quinolinyl)-N1,N1-diethyl-
    https://services.industrialchemicals.gov.au/search-assessments/
  2. CAS Common Chemistry
    LICENSE
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    https://creativecommons.org/licenses/by-nc/4.0/
  3. ChemIDplus
    ChemIDplus Chemical Information Classification
    https://pubchem.ncbi.nlm.nih.gov/source/ChemIDplus
  4. DrugBank
    LICENSE
    Creative Common's Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/legalcode)
    https://www.drugbank.ca/legal/terms_of_use
  5. DTP/NCI
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    https://www.cancer.gov/policies/copyright-reuse
  6. EPA DSSTox
    CompTox Chemicals Dashboard Chemical Lists
    https://comptox.epa.gov/dashboard/chemical-lists/
  7. European Chemicals Agency (ECHA)
    LICENSE
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    https://echa.europa.eu/web/guest/legal-notice
  8. FDA Global Substance Registration System (GSRS)
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    https://www.fda.gov/about-fda/about-website/website-policies#linking
  9. Hazardous Substances Data Bank (HSDB)
  10. Human Metabolome Database (HMDB)
    LICENSE
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    http://www.hmdb.ca/citing
  11. BindingDB
    LICENSE
    All data curated by BindingDB staff are provided under the Creative Commons Attribution 3.0 License (https://creativecommons.org/licenses/by/3.0/us/).
    https://www.bindingdb.org/rwd/bind/info.jsp
  12. Comparative Toxicogenomics Database (CTD)
    LICENSE
    It is to be used only for research and educational purposes. Any reproduction or use for commercial purpose is prohibited without the prior express written permission of NC State University.
    http://ctdbase.org/about/legal.jsp
  13. Drug Gene Interaction database (DGIdb)
    LICENSE
    The data used in DGIdb is all open access and where possible made available as raw data dumps in the downloads section.
    http://www.dgidb.org/downloads
  14. IUPHAR/BPS Guide to PHARMACOLOGY
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    https://www.guidetopharmacology.org/about.jsp#license
    Guide to Pharmacology Target Classification
    https://www.guidetopharmacology.org/targets.jsp
  15. Therapeutic Target Database (TTD)
  16. Toxin and Toxin Target Database (T3DB)
    LICENSE
    T3DB is offered to the public as a freely available resource. Use and re-distribution of the data, in whole or in part, for commercial purposes requires explicit permission of the authors and explicit acknowledgment of the source material (T3DB) and the original publication.
    http://www.t3db.ca/downloads
  17. CCSbase
    CCSbase Classification
    https://ccsbase.net/
  18. ChEBI
  19. FDA Pharm Classes
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  20. LiverTox
  21. LOTUS - the natural products occurrence database
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    https://lotus.nprod.net/
  22. NCI Thesaurus (NCIt)
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    https://www.cancer.gov/policies/copyright-reuse
  23. Open Targets
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    https://platform-docs.opentargets.org/licence
  24. ChEMBL
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    http://www.ebi.ac.uk/Information/termsofuse.html
  25. ClinicalTrials.gov
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    https://clinicaltrials.gov/ct2/about-site/terms-conditions#Use
  26. Drug Induced Liver Injury Rank (DILIrank) Dataset
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  27. IUPAC Digitized pKa Dataset
    quinoline, 7-chloro-4-(4-diethylamino-1-methyl)butylamino-
    https://github.com/IUPAC/Dissociation-Constants
  28. Drugs and Lactation Database (LactMed)
  29. Drugs@FDA
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  30. NORMAN Suspect List Exchange
    LICENSE
    Data: CC-BY 4.0; Code (hosted by ECI, LCSB): Artistic-2.0
    https://creativecommons.org/licenses/by/4.0/
    CHLOROQUINE
    NORMAN Suspect List Exchange Classification
    https://www.norman-network.com/nds/SLE/
  31. WHO Model Lists of Essential Medicines
    LICENSE
    Permission from WHO is not required for the use of WHO materials issued under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Intergovernmental Organization (CC BY-NC-SA 3.0 IGO) license.
    https://www.who.int/about/policies/publishing/copyright
  32. EU Clinical Trials Register
  33. MassBank of North America (MoNA)
    LICENSE
    The content of the MoNA database is licensed under CC BY 4.0.
    https://mona.fiehnlab.ucdavis.edu/documentation/license
  34. NIST Mass Spectrometry Data Center
    LICENSE
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    https://www.nist.gov/srd/public-law
  35. SpectraBase
  36. International Agency for Research on Cancer (IARC)
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    https://publications.iarc.fr/Terms-Of-Use
    IARC Classification
    https://www.iarc.fr/
  37. Japan Chemical Substance Dictionary (Nikkaji)
  38. KEGG
    LICENSE
    Academic users may freely use the KEGG website. Non-academic use of KEGG generally requires a commercial license
    https://www.kegg.jp/kegg/legal.html
    Anatomical Therapeutic Chemical (ATC) classification
    http://www.genome.jp/kegg-bin/get_htext?br08303.keg
  39. KNApSAcK Species-Metabolite Database
  40. Natural Product Activity and Species Source (NPASS)
  41. MassBank Europe
  42. Metabolomics Workbench
  43. Nature Chemical Biology
  44. NLM RxNorm Terminology
    LICENSE
    The RxNorm Terminology is created by the National Library of Medicine (NLM) and is in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from NLM. Credit to the U.S. National Library of Medicine as the source is appreciated but not required. The full RxNorm dataset requires a free license.
    https://www.nlm.nih.gov/research/umls/rxnorm/docs/termsofservice.html
  45. PharmGKB
    LICENSE
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    https://www.pharmgkb.org/page/policies
  46. Pharos
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    https://pharos.nih.gov/about
  47. Springer Nature
  48. Thieme Chemistry
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    https://creativecommons.org/licenses/by-nc-nd/4.0/
  49. WHO Anatomical Therapeutic Chemical (ATC) Classification
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    https://www.whocc.no/copyright_disclaimer/
  50. Wikidata
  51. Wikipedia
  52. Wiley
  53. Medical Subject Headings (MeSH)
    LICENSE
    Works produced by the U.S. government are not subject to copyright protection in the United States. Any such works found on National Library of Medicine (NLM) Web sites may be freely used or reproduced without permission in the U.S.
    https://www.nlm.nih.gov/copyright.html
  54. PubChem
  55. GHS Classification (UNECE)
  56. EPA Substance Registry Services
  57. MolGenie
    MolGenie Organic Chemistry Ontology
    https://github.com/MolGenie/ontology/
  58. PATENTSCOPE (WIPO)
  59. NCBI
CONTENTS