There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of {{PAGENAME}} in adult patients.
<!--Non–Guideline-Supported Use (Adult)-->
|offLabelAdultNoGuideSupport======Condition1=====
* Dosing Information
:* Dosage
=====Condition2=====
There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of {{PAGENAME}} in adult patients.
<!--Pediatric Indications and Dosage-->
<!--FDA-Labeled Indications and Dosage (Pediatric)-->
|fdaLIADPed======Condition1=====
* Dosing Information
:* Dosage
=====Condition2=====
There is limited information regarding <i>FDA-Labeled Use</i> of {{PAGENAME}} in pediatric patients.
<!--Off-Label Use and Dosage (Pediatric)-->
<!--Guideline-Supported Use (Pediatric)-->
|offLabelPedGuideSupport======Condition1=====
* Developed by:
* Class of Recommendation:
* Strength of Evidence:
* Dosing Information
:* Dosage
=====Condition2=====
There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of {{PAGENAME}} in pediatric patients.
<!--Non–Guideline-Supported Use (Pediatric)-->
|offLabelPedNoGuideSupport======Condition1=====
* Dosing Information
:* Dosage
=====Condition2=====
There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of {{PAGENAME}} in pediatric patients.
<!--Contraindications-->
|contraindications=* Condition1
<!--Warnings-->
|warnings=* Description
====Precautions====
* Description
<!--Adverse Reactions-->
<!--Clinical Trials Experience-->
|clinicalTrials=There is limited information regarding <i>Clinical Trial Experience</i> of {{PAGENAME}} in the drug label.
=====Body as a Whole=====
=====Cardiovascular=====
=====Digestive=====
=====Endocrine=====
=====Hematologic and Lymphatic=====
=====Metabolic and Nutritional=====
=====Musculoskeletal=====
=====Neurologic=====
=====Respiratory=====
=====Skin and Hypersensitivy Reactions=====
=====Special Senses=====
=====Urogenital=====
=====Miscellaneous=====
<!--Postmarketing Experience-->
|postmarketing=There is limited information regarding <i>Postmarketing Experience</i> of {{PAGENAME}} in the drug label.
=====Body as a Whole=====
=====Cardiovascular=====
=====Digestive=====
=====Endocrine=====
=====Hematologic and Lymphatic=====
=====Metabolic and Nutritional=====
=====Musculoskeletal=====
=====Neurologic=====
=====Respiratory=====
=====Skin and Hypersensitivy Reactions=====
=====Special Senses=====
=====Urogenital=====
=====Miscellaneous=====
<!--Drug Interactions-->
|drugInteractions=* Drug
:* Description
<!--Use in Specific Populations-->
|FDAPregCat=
|useInPregnancyFDA=* '''Pregnancy Category'''
|useInPregnancyAUS=* '''Australian Drug Evaluation Committee (ADEC) Pregnancy Category'''
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of {{PAGENAME}} in women who are pregnant.
|useInLaborDelivery=There is no FDA guidance on use of {{PAGENAME}} during labor and delivery.
|useInNursing=There is no FDA guidance on the use of {{PAGENAME}} with respect to nursing mothers.
|useInPed=There is no FDA guidance on the use of {{PAGENAME}} with respect to pediatric patients.
|useInGeri=There is no FDA guidance on the use of {{PAGENAME}} with respect to geriatric patients.
|useInGender=There is no FDA guidance on the use of {{PAGENAME}} with respect to specific gender populations.
|useInRace=There is no FDA guidance on the use of {{PAGENAME}} with respect to specific racial populations.
|useInRenalImpair=There is no FDA guidance on the use of {{PAGENAME}} in patients with renal impairment.
|useInHepaticImpair=There is no FDA guidance on the use of {{PAGENAME}} in patients with hepatic impairment.
|useInReproPotential=There is no FDA guidance on the use of {{PAGENAME}} in women of reproductive potentials and males.
|useInImmunocomp=There is no FDA guidance one the use of {{PAGENAME}} in patients who are immunocompromised.
<!--Administration and Monitoring-->
|administration=* Oral
* Intravenous
|monitoring=There is limited information regarding <i>Monitoring</i> of {{PAGENAME}} in the drug label.
* Description
<!--IV Compatibility-->
|IVCompat=There is limited information regarding <i>IV Compatibility</i> of {{PAGENAME}} in the drug label.
<!--Overdosage-->
|overdose====Acute Overdose===
{{SI}}
====Signs and Symptoms====
* Description
==Overview==
====Management====
'''Chloroquine''' is a 4-aminoquinoline drug long used in the treatment or prevention of [[malaria]]. As it also mildly suppresses the [[immune system]], it is used in some [[autoimmune disorder]]s, such as [[rheumatoid arthritis]] and [[lupus erythematosus]]. After the [[malaria]] parasite ''[[Plasmodium falciparum]]'' started to develop widespread resistance to chloroquine, new potential utilisations of this cheap and widely available drug have been investigated. For example, chloroquine is in clinical trials as an investigational [[antiretroviral]] in humans with [[AIDS|HIV-1/AIDS]] and as a potential [[antiviral]] agent against [[chikungunya]] fever. Moreover, the radiosensitizing and chemosensitizing properties of chloroquine are beginning to be exploited in anticancer strategies in humans.
==Pharmacology==
* Description
Chloroquine has a very high [[volume of distribution]], as it diffuses into the body's [[adipose tissue]]. Chloroquine and related quinines have been associated with cases of [[retina]]l toxicity, particularly when provided at higher doses for longer time frames. Accumulation of the drug may result in deposits that can lead to blurred vision and [[blindness]]. With long term doses, routine visits to an [[optometrist]] or [[ophthalmologist]] are recommended.
Chloroquine is also a lysosomotropic agent, meaning that it accumulates preferentially in the [[lysosomes]] of cells in the body. The pKa for the quinoline nitrogen of chloroquine is 8.5, meaning that it is ~10% deprotonated at physiological pH as calculated by the [[Henderson-Hasselbalch equation]]. This decreases to ~0.2% at a lysosomal pH of 4.6. Because the deprotonated form is more membrane permeable than the protonated form, this results in a quantitative "trapping" of the compound in lysosomes.
===Chronic Overdose===
(Note that a quantitative treatment of this phenomenon involves the pKas of all nitrogens in the molecule; this treatment, however, suffices to show the principle)
There is limited information regarding <i>Chronic Overdose</i> of {{PAGENAME}} in the drug label.
The lysosomotropic character of chloroquine is believed to account for much of its anti-malarial activity; the drug concentrates in the acidic food vacuole of the parasite and interferes with essential processes.
<!--Pharmacology-->
==Malaria prevention==
<!--Drug box 2-->
Chloroquine can be used for preventing malaria from ''[[Plasmodium]] [[Plasmodium vivax|vivax]]'', ''[[Plasmodium ovale|ovale]]'' and ''[[Plasmodium malariae|malariae]]''. Many areas of the world have widespread strains of chloroquine-resistant ''P. falciparum'', so other [[antimalarials]] like [[mefloquine]] or [[atovaquone]] may be advisable instead. Combining chloroquine with [[proguanil]] may be more effective against chloroquine-resistant [[Plasmodium falciparum]] than treatment with chloroquine alone, but is no longer recommended by the [[Centers for Disease Control and Prevention|CDC]] due to the availability of more effective combinations.<ref> CDC. Health information for international travel 2001--2002. Atlanta, Georgia: U.S. Department of Health and Human Services, Public Health Service, 2001. </ref>
|drugBox=<!--Mechanism of Action-->
|mechAction=*
== Doses ==
<!--Structure-->
Per the Centers for Disease Control (CDC):
|structure=*
Directions for Use
The adult dosage is 500 mg chloroquine phosphate once a week.
- Take the first dose of chloroquine 1 week before arrival in the malaria-risk area.
- Take chloroquine once a week, on the same day of the week, while in the malaria-risk area.
- Take chloroquine once a week for 4 weeks after leaving the malaria-risk area.
Chloroquine should be taken on a full stomach to lessen nausea.
Chloroquine produced by Global Pharm is a white, round tablet with 7010 printed on one side. It is recommended that you do not chew the tablet, because it tastes horrible, and bitter.
: [[File:{{PAGENAME}}01.png|thumb|none|600px|This image is provided by the National Library of Medicine.]]
==Adverse effects==
<!--Pharmacodynamics-->
At the doses used for prevention of malaria, [[adverse drug reaction|side effects]] include gastrointestinal problems such as [[Abdominal pain|stomach ache]], [[itch]], [[headache]] and [[Cycloplegia|blurred vision]]. When doses are extended over a number of months it is important to watch out for a slow onset of "changes in moods" (i.e.[[Clinical depression|depression]], [[anxiety]]). These may be more pronounced with higher doses used for treatment. Chloroquine tablets have an unpleasant metallic taste.
|PD=There is limited information regarding <i>Pharmacodynamics</i> of {{PAGENAME}} in the drug label.
A serious side effect is also a rare toxicity in the eye (generally with chronic use), and requires regular monitoring even when symptom-free. The daily safe maximum doses for eye toxicity can be computed from one's height and weight using this [http://www.numericalexample.com/content/view/24/33 calculator]. The use of Chloroquine has also been associated with the development of Central Serous Retinopathy.
<!--Pharmacokinetics-->
|PK=There is limited information regarding <i>Pharmacokinetics</i> of {{PAGENAME}} in the drug label.
Chloroquine is very dangerous in overdose. It is rapidly absorbed from the gut and death often occurs within 2½ hours of taking the drug. The [[therapeutic index]] for chloroquine is small and just doubling the normal dose of chloroquine can be fatal.<ref>{{cite journal | author=Cann HM, Verhulst HL | title=Fatal acute chloroquine poisoning in children | year=1961 | journal=Pediatrics | volume=27 | issue=1 | pages=95–102 | url=http://pediatrics.aappublications.org/cgi/content/abstract/27/1/95?ijkey=0c507c09d8450f8c8bbadf109d6428e93ad2619f&keytype2=tf_ipsecsha }}</ref>
<!--Nonclinical Toxicology-->
|nonClinToxic=There is limited information regarding <i>Nonclinical Toxicology</i> of {{PAGENAME}} in the drug label.
==Mechanism of action==
<!--Clinical Studies-->
Inside the [[red blood cell]]s, the malarial [[parasite]] must degrade the [[hemoglobin]] for the acquisition of essential amino acids, which the parasite requires to construct its own protein and for energy metabolism. This is essential for parasitic growth and division inside the red blood cell. It is carried out in the digestive vacuole of the parasite cell.
|clinicalStudies=There is limited information regarding <i>Clinical Studies</i> of {{PAGENAME}} in the drug label.
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 polymerizes heme to form [http://jhmalaria.jhsph.edu/hemozoin/ hemozoin], a non-toxic molecule. Hemozoin collects in the digestive vacuole as insoluble crystals.
<!--How Supplied-->
|howSupplied=*
|storage=
|packLabel=
<!--Patient Counseling Information-->
|fdaPatientInfo=There is limited information regarding <i>Patient Counseling Information</i> of {{PAGENAME}} in the drug label.
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 polymerization of heme, thus leading to heme build up. 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.
<!--Precautions with Alcohol-->
|alcohol=* Alcohol-{{PAGENAME}} interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
The effectiveness of chloroquine against the parasite has declined as resistant strains of the parasite evolved which effectively neutralized the drug via mechanism that drains chloroquine away from the digestive vacuole. CQ-Resistant cells efflux chloroquine at 40 times the rate of CQ-Sensitive cells, this is related to a number of mutations that trace back to transmembrane proteins of the digestive vacuole, including an essential mutation in the PfCRT gene (Plasmodium falciparum Chloroquine Resistance Transporter). This mutated protein may actively pump chloroquine from the cell. Resistant parasites frequently have mutated products or amplified expression of [[ABC transporters]] that pump out the chloroquine, typically PfMDR1 and PfMDR2 (Plasmodium falciparum Multi-Drug Resistance genes). Resistance has also been conferred by reducing the lower transport activity of the intake mechanism, so less chloroquine is imported into the parasite[http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=9006900&dopt=Abstract].
<!--Brand Names-->
|brandNames=* ®<ref>{{Cite web | title = | url = }}</ref>
Research on the mechanism of chloroquine and how the parasite has acquired chloroquine resistance is still ongoing, and this article is not by any means fact. Other theories of chloroquine's mechanism of action suggest DNA intercalation or a combination of the disrupted membrane function of the lysosome.
<!--Look-Alike Drug Names-->
|lookAlike=* A® — B®<ref name="www.ismp.org">{{Cite web | last = | first = | title = http://www.ismp.org | url = http://www.ismp.org | publisher = | date = }}</ref>
Against rheumatoid arthritis, it operates by inhibiting [[lymphocyte]] proliferation, [[phospholipase A]], release of [[enzyme]]s from [[lysosome]]s, release of [[reactive oxygen species]] from [[macrophage]]s, and production of [[IL-1]].
<!--Drug Shortage Status-->
|drugShortage=
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|fileName={{PAGENAME}}11.png
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<!--Pill Image-->
As an antiviral agent, it impedes the completion of the [[viral life cycle]] by inhibiting some processes occurring within intracellular [[organelles]] and requiring a low [[pH]]. As for [[HIV-1]], chloroquine inhibits the [[glycosylation]] of the [[viral envelope]] [[glycoprotein]] [[gp120]], which occurs within the [[Golgi apparatus]].
The mechanisms behind the effects of chloroquine on [[cancer]] are currently being investigated. The best know effects (investigated in clinical and pre-clinical studies) include radiosensitising effects through [[lysosome]] permeabilisation, and chemosensitising effects through inhibition of drug efflux pumps (ATP-binding cassette transporters)or other mechanisms (reviewed in the second-to-last reference below).
*Plowe CV. Antimalarial drug resistance in Africa: strategies for monitoring and deterrence. Curr Top Microbiol Immunol. 2005;295:55-79.
*Uhlemann AC, Krishna S. Antimalarial multi-drug resistance in Asia: mechanisms and assessment. Curr Top Microbiol Immunol. 2005;295:39-53.
*[http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=9006900&dopt=Abstract Identification of a chloroquine importer in Plasmodium falciparum. Differences in import kinetics are genetically linked with the chloroquine-resistant phenotype.] J Biol Chem. 1997 Jan 31;272(5):2652-8.
*Yam JC, Kwok AK. Ocular toxicity of hydroxychloroquine. Hong Kong Med J. 2006 Aug;12(4):294-304.
*Savarino A, Boelaert JR, Cassone A, Majori G, Cauda R. Effects of chloroquine on viral infections: an old drug against today's diseases? Lancet Infect Dis. 2003 Nov;3(11):722-7.
*Savarino A, Lucia MB, Giordano F, Cauda R. Risks and benefits of chloroquine use in anticancer strategies. Lancet Oncol. 2006 Oct;7(10):792-3.
*Sotelo J, Briceno E, Lopez-Gonzalez MA. Adding chloroquine to conventional treatment for glioblastoma multiforme: a randomized, double-blind, placebo-controlled trial. Ann Intern Med. 2006 Mar 7;144(5):337-43. Summary for patients in: Ann Intern Med. 2006 Mar 7;144(5):I31.
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Black Box Warning
ConditionName:
See full prescribing information for complete Boxed Warning.
ConditionName:
Content
Overview
Chloroquine is a that is FDA approved for the of . There is a Black Box Warning for this drug as shown here. Common adverse reactions include .
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
Condition1
Dosing Information
Dosage
Condition2
Dosing Information
Dosage
Condition3
Dosing Information
Dosage
Condition4
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Dosage
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
Condition1
Developed by:
Class of Recommendation:
Strength of Evidence:
Dosing Information
Dosage
Condition2
There is limited information regarding Off-Label Guideline-Supported Use of Chloroquine in adult patients.
Non–Guideline-Supported Use
Condition1
Dosing Information
Dosage
Condition2
There is limited information regarding Off-Label Non–Guideline-Supported Use of Chloroquine in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
Condition1
Dosing Information
Dosage
Condition2
There is limited information regarding FDA-Labeled Use of Chloroquine in pediatric patients.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
Condition1
Developed by:
Class of Recommendation:
Strength of Evidence:
Dosing Information
Dosage
Condition2
There is limited information regarding Off-Label Guideline-Supported Use of Chloroquine in pediatric patients.
Non–Guideline-Supported Use
Condition1
Dosing Information
Dosage
Condition2
There is limited information regarding Off-Label Non–Guideline-Supported Use of Chloroquine in pediatric patients.
Contraindications
Condition1
Warnings
ConditionName:
See full prescribing information for complete Boxed Warning.
ConditionName:
Content
Description
Precautions
Description
Adverse Reactions
Clinical Trials Experience
There is limited information regarding Clinical Trial Experience of Chloroquine in the drug label.
Body as a Whole
Cardiovascular
Digestive
Endocrine
Hematologic and Lymphatic
Metabolic and Nutritional
Musculoskeletal
Neurologic
Respiratory
Skin and Hypersensitivy Reactions
Special Senses
Urogenital
Miscellaneous
Postmarketing Experience
There is limited information regarding Postmarketing Experience of Chloroquine in the drug label.
