Chloroquine: Difference between revisions

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{{drugbox
{{DrugProjectFormSinglePage
| IUPAC_name = ''N'''-(7-chloroquinolin-4-yl)-''N'',''N''-diethyl-pentane-1,4-diamine  
|authorTag={{AJ}}
| image =
|genericName=Chloroquine phosphate
| CAS_number = 54-05-7  
|aOrAn=a
| ATC_prefix = P01  
|drugClass=[[aminoquinoline]] [[antimalarial]]
| ATC_suffix = BA01  
|indicationType=treatment
| PubChem = 2719  
|indication=for the suppressive treatment and for acute attacks of [[malaria]] due to [[P. vivax]], [[P. malariae]], [[P. ovale]], and susceptible strains of [[P. falciparum]]. The drug is also indicated for the treatment of [[amebiasis|extraintestinal amebiasis]].
| DrugBank = APRD00468
|hasBlackBoxWarning=Yes
| C = 18 |H = 26 |Cl = 1 |N = 3  
|adverseReactions=[[cardiovascular]], [[dermatological]], [[immunological]], [[neurological]] and [[ophthalmological]] (see Adverse Reactions section)
| molecular_weight = 319.872 [[Gram|g]]/[[Mole (unit)|mol]]  
|blackBoxWarningTitle=WARNING
| bioavailability =  
|blackBoxWarningBody=* For Malaria and Extraintestinal Amebiasis
| protein_bound =  
|fdaLIADAdult=* Chloroquine phosphate tablets are indicated for the suppressive treatment and for acute attacks of [[malaria]] due to [[P. vivax]], [[P. malariae]], [[P. ovale]], and susceptible strains of [[P. falciparum]]. The drug is also indicated for the treatment of [[extraintestinal amebiasis]].
| metabolism =  
 
| elimination_half-life = 1-2 months
* Chloroquine phosphate tablets does not prevent relapses in patients with [[P. vivax|vivax]] or [[malaria|malariae malaria]] because it is not effective against exoerythrocytic forms of the parasite, nor will it prevent [[P. vivax|vivax]] or [[malaria|malariae infection]] when administered as a prophylactic. It is highly effective as a suppressive agent in patients with [[P. vivax|vivax]] or [[malaria|malariae malaria]], in terminating acute attacks, and significantly lengthening the interval between treatment and relapse. In patients with [[malaria|falciparum malaria]] it abolishes the acute attack and effects complete cure of the [[infection]], unless due to a resistant strain of [[P. falciparum]].
| pregnancy_category =  
 
| legal_status =
=====Dosing Information=====
| routes_of_administration =  
 
* The dosage of chloroquine phosphate is often expressed or calculated as the base. Each 250 mg tablet of chloroquine phosphate is equivalent to 150 mg base. In [[infants]] and children the dosage is preferably calculated on the body weight.
 
* Malaria:
 
:* Suppression— Adult Dose: 500 mg (= 300 mg base) on exactly the same day of each week.
 
:* If circumstances permit, suppressive therapy should begin two weeks prior to exposure. However, failing this in adults, an initial double (loading) dose of 1 g (= 400 mg base), or in children 10 mg base/kg may be taken in two divided doses, six hours apart. The suppressive therapy should be continued for eight weeks after leaving the [[endemic|endemic area]].
 
* For Treatment of Acute Attack:
 
:* An initial dose of 1 g (= 400 mg base) followed by an additional 500 mg (= 300 mg base) after six to eight hours and a single dose of 500 mg (= 300 mg base) on each of two consecutive days. This represents a total dose of 2.5 g chloroquine phosphate or 1.5 g base in three days.
 
:* The dosage for adults of low body weight and for [[infants]] and children should be determined as follows:
:** First dose: 10 mg base per kg (but not exceeding a single dose of 400 mg base).
:** Second dose: (6 hours after first dose) 5 mg base per kg (but not exceeding a single dose of 300 mg base).
:** Third dose: (24 hours after first dose) 5 mg base per kg.
 
:** Fourth dose: (36 hours after first dose) 5 mg base per kg.
 
* For radical cure of [[malaria|vivax]] and [[malaria|malariae malaria]] concomitant therapy with an [[aminoquinoline|8-aminoquinoline]] compound is necessary.
 
* Extraintestinal Amebiasis:
 
:* Adults:1 g (400 mg base) daily for two days, followed by 500 mg (300 mg base) daily for at least two to three weeks. Treatment is usually combined with an effective [[amebiasis|intestinal amebicide]].
|offLabelAdultGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Chloroquine in adult patients.
|offLabelAdultNoGuideSupport=* [[Hemophagocytic syndrome]]
* [[Porphyria cutanea tarda]]
* [[Sarcoidosis]]
* [[Ulcerative colitis]]
|fdaLIADPed=* [[Malaria]]:
 
=====Dosing Information=====
 
* The dosage of chloroquine phosphate is often expressed or calculated as the base. Each 250 mg tablet of chloroquine phosphate is equivalent to 150 mg base. In [[infants]] and children the dosage is preferably calculated on the body weight.
 
:* The weekly suppressive dosage is 5 mg calculated as base, per kg of body weight, but should not exceed the adult dose regardless of weight.
|offLabelPedGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Chloroquine in pediatric patients.
|offLabelPedNoGuideSupport=* [[Hemophagocytic syndrome]]
* [[Porphyria cutanea tarda]]
|contraindications=* Use of this drug is contraindicated in the presence of [[retinal]] or [[visual field]] changes either attributable to [[aminoquinoline|4-aminoquinoline]] compounds or to any other etiology, and in patients with known [[hypersensitivity]] to [[aminoquinoline|4-aminoquinoline]] compounds. However, in the treatment of acute attacks of [[malaria]] caused by susceptible strains of [[Plasmodium|plasmodia]], the physician may elect to use this drug after carefully weighing the possible benefits and risks to the patient.
|warnings=* It has been found that certain strains of [[P. falciparum]] have become resistant to [[4- aminoquinoline]] compounds (including [[chloroquine]] and [[hydroxychloroquine]]). [[Chloroquine resistance]] is widespread and, at present, is particularly prominent in various parts of the world including sub-Saharan Africa, Southeast Asia, the Indian subcontinent, and over large portions of South America, including the Amazon basin1.
 
* Before using chloroquine for prophylaxis, it should be ascertained whether chloroquine is appropriate for use in the region to be visited by the traveler. Chloroquine should not be used for treatment of [[Plasmodium falciparum|P.falciparum infections]] acquired in areas of chloroquine resistance or [[malaria]] occurring in patients where chloroquine prophylaxis has failed.
 
* Patients infected with a resistant strain of [[Plasmodium|plasmodia]] as shown by the fact that normally adequate doses have failed to prevent or cure clinical [[malaria]] or [[parasitemia]] should be treated with another form of [[malaria|antimalarial therapy]].
 
* [[Retinopathy]]/[[maculopathy]], as well as [[macular degeneration]] have been reported, and irreversible [[retinal damage]] has been observed in some patients who had received long-term or high-dosage [[aminoquinoline|4-aminoquinoline]] therapy. [[Retinopathy]] has been reported to be dose related. Risk factors for the development of [[retinopathy]] include age, duration of treatment, high daily and/or cumulated doses.
 
* When prolonged therapy with any antimalarial compound is contemplated, initial (base line) and periodic [[ophthalmologic]] examinations (including [[visual acuity]], expert [[slit-lamp]], [[fundoscopy|funduscopic]], and [[visual field|visual field tests]]) should be performed.
 
* If there is any indication (past or present) of abnormality in the [[visual acuity]], [[visual field]], or [[retinal macular]] areas (such as pigmentary changes, loss of [[foveal reflex]]), or any visual symptoms (such as light flashes and streaks) which are not fully explainable by difficulties of accommodation or [[cornea|corneal opacities]], the drug should be discontinued immediately and the patient closely observed for possible progression. [[Retinal]] changes (and visual disturbances) may progress even after cessation of therapy.
 
* Acute [[extrapyramidal]] disorders may occur with chloroquine. These adverse reactions usually resolve after treatment discontinuation and/or symptomatic treatment.
 
* All patients on long-term therapy with this preparation should be questioned and examined periodically, including testing knee and [[ankle reflexes]], to detect any evidence of [[muscular weakness]]. If weakness occurs, discontinue the drug.
 
* A number of fatalities have been reported following the accidental ingestion of chloroquine, sometimes in relatively small doses (0.75 g or 1 g chloroquine phosphate in one 3-year-old child). Patients should be strongly warned to keep this drug out of the reach of children because they are especially sensitive to the [[aminoquinoline|4-aminoquinoline]] compounds.
 
* Use of chloroquine phosphate in patients with psoriasis may precipitate a severe attack of [[psoriasis]]. When used in patients with [[porphyria]] the condition may be exacerbated. The drug should not be used in these conditions unless in the judgment of the physician the benefit to the patient outweighs the potential risks.
 
* Usage in Pregnancy: [[radioactive|Radioactively tagged]] chloroquine administered intravenously to [[pregnant]] [[pigmented]] CBA mice passed rapidly across the [[placenta]] and accumulated selectively in the [[melanin]] structures of the fetal eyes. It was retained in the [[ocular]] tissues for five months after the drug had been eliminated from the rest of the body. There are no adequate and well-controlled studies evaluating the safety and efficacy of chloroquine in [[pregnant]] women. Usage of chloroquine during [[pregnancy]] should be avoided except in the suppression or treatment of malaria when in the judgment of the physician the benefit outweighs the potential risk to the [[fetus]].
 
=====Precautions=====
 
* Hematological Effects/Laboratory Tests
:* [[CBC|Complete blood cell counts]] should be made periodically if patients are given prolonged therapy. If any severe blood disorder appears which is not attributable to the disease under treatment, discontinuance of the drug should be considered.
 
:* The drug should be administered with caution to patients having [[G-6-PD]] ([[glucose-6 phosphate dehydrogenase]]) deficiency.
 
* Auditory Effects
 
:* In patients with preexisting [[auditory]] damage, chloroquine should be administered with caution. In case of any defects in hearing, chloroquine should be immediately discontinued, and the patient closely observed.
 
* Hepatic Effects
 
:* Since this drug is known to concentrate in the [[liver]], it should be used with caution in patients with [[hepatic disease]] or [[alcoholism]] or in conjunction with known [[hepatotoxic]] drugs.
 
* Central Nervous System Effects
 
:* Patients with a history of [[epilepsy]] should be advised about the risk of chloroquine provoking [[seizures]].
|clinicalTrials=====Special Senses:Ocular:=====
 
* [[Maculopathy]] and [[macular degeneration]] have been reported and may be irreversible; irreversible [[retina|retinal damage]] in patients receiving long-term or high-dosage [[aminoquinoline|4-aminoquinoline]] therapy; visual disturbances (blurring of vision and difficulty of focusing or accommodation); [[nyctalopia]]; [[Scotoma|
scotomatous vision]] with [[visual field|field defects]] of paracentral, pericentral ring types, and typically [[Scotoma|temporal scotomas]], e.g., difficulty in reading with words tending to disappear, seeing half an object, misty vision, and fog before the eyes. Reversible [[corneal opacities]] have also been reported.
 
=====Auditory:=====
 
* [[Sensorineural hearing loss|Nerve type deafness]]; [[tinnitus]], reduced hearing in patients with preexisting [[auditory|auditory damage]].
 
=====Musculoskeletal System:=====
 
* [[myopathy|Skeletal muscle myopathy]] or [[neuromyopathy]] leading to progressive weakness and [[myopathy|atrophy of proximal muscle groups]], which may be associated with mild [[sensory]] changes, [[depression]] of [[tendon reflexes]] and abnormal nerve conduction, have been noted.
 
=====Gastrointestinal system:=====
 
* [[Hepatitis]], increased [[liver enzymes]], [[anorexia]], [[nausea]], [[vomiting]], [[diarrhea]], [[abdominal cramps]].
 
=====Skin and appendages:=====
 
* Rare reports of [[erythema multiforme]], [[Stevens-Johnson syndrome]], [[toxic epidermal necrolysis]], [[exfoliative dermatitis]] and similar desquamation-type events. [[dermatitis|Pleomorphic skin eruptions]], [[skin]] and [[mucosal]] pigmentary changes; [[lichen planus|lichen planus-like eruptions]], [[pruritus]], [[urticaria]], [[anaphylactic]]/[[anaphylactoid reaction]] including [[angioedema]]; [[drug rash]] with [[eosinophilia]] and systemic symptoms ([[drug rash|DRESS syndrome]]); [[photosensitivity]] and hair loss and bleaching of [[hair|hair pigment]].
 
=====Hematologic system:=====
 
* Rarely, [[pancytopenia]], [[aplastic anemia]], reversible [[agranulocytosis]], [[thrombocytopenia]] and [[neutropenia]].
 
=====[[Nervous system]]:=====
 
* [[seizures|Convulsive seizures]], mild and transient [[headache]], [[polyneuritis]]. [[Extrapyramidal disorder|Acute extrapyramidal disorders]] (such as [[dystonia]], [[dyskinesia]], [[Extrapyramidal disorder|tongue protrusion]], [[torticollis]]). [[Neuropsychiatric]] changes including [[psychosis]], [[delirium]], [[anxiety]], [[agitation]], [[insomnia]], [[confusion]], [[hallucinations]], [[personality changes]], and [[depression]].
 
=====Cardiac system:=====
 
* Rarely, [[hypotension]], [[electrocardiographic]] change particularly, inversion or depression of the [[T-wave]] with [[QRS prolongation|widening of the QRS]] [[QT prolongation|complex prolonged QT interval]], [[atrioventricular block]], [[heart failure]] and [[cardiomyopathy]].
|postmarketing=There is limited information regarding <i>Postmarketing Experience</i> of Chloroquine phosphate in the drug label.
|drugInteractions=====Antacids and kaolin:=====
 
* Antacids and kaolin can reduce absorption of chloroquine; an interval of at least 4 hours between intake of these agents and chloroquine should be observed.
 
=====Cimetidine:=====
 
* Cimetidine can inhibit the metabolism of chloroquine, increasing its plasma level. Concomitant use of [[cimetidine]] should be avoided.
 
=====Ampicillin:=====
 
* In a study of healthy volunteers, chloroquine significantly reduced the [[bioavailability]] of [[ampicillin]]. An interval of at least two hours between intake of this agent and chloroquine should be observed.
 
=====Cyclosporine:=====
 
* After introduction of chloroquine (oral form), a sudden increase in serum [[cyclosporine]] level has been reported. Therefore, close monitoring of serum [[cyclosporine]] level is recommended and, if necessary, chloroquine should be discontinued.
 
=====Mefloquine:=====
 
* Co-administration of chloroquine and [[mefloquine]] may increase the risk of [[convulsions]].
 
* The [[blood|blood concentrations]] of chloroquine and desethylchloroquine (the major metabolite of chloroquine, which also has [[antimalarial]] properties) were negatively associated with log [[antibody|antibody titers]]. Chloroquine taken in the dose recommended for [[malaria prophylaxis]] can reduce the antibody response to primary [[immunization]] with [[intradermal]] human diploid-cell rabies vaccine.
|FDAPregCat=C
|useInPregnancyFDA=* [[radioactive|Radioactively tagged]] chloroquine administered intravenously to [[pregnant]] pigmented CBA mice passed rapidly across the [[placenta]] and accumulated selectively in the [[melanin]] structures of the [[fetal]] [[eyes]]. It was retained in the [[eye|ocular tissues]] for five months after the drug had been eliminated from the rest of the body. There are no adequate and well-controlled studies evaluating the safety and efficacy of chloroquine in pregnant women. Usage of chloroquine during [[pregnancy]] should be avoided except in the suppression or treatment of malaria when in the judgment of the physician the benefit outweighs the potential risk to the [[fetus]].
|useInPregnancyAUS=* '''Australian Drug Evaluation Committee (ADEC) Pregnancy Category'''
 
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Chloroquine phosphate in women who are pregnant.
|useInLaborDelivery=There is no FDA guidance on use of Chloroquine phosphate during labor and delivery.
|useInNursing=* Because of the potential for serious adverse reactions in nursing infants from chloroquine, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the potential clinical benefit of the drug to the mother.
 
* The excretion of chloroquine and the major metabolite, desethylchloroquine, in [[breast milk]] was investigated in eleven [[lactating]] mothers following a single oral dose of chloroquine (400 mg base). The maximum daily dose of the drug that the infant can receive from [[breastfeeding]] was about 0.7% of the maternal start dose of the drug in malaria chemotherapy. Separate [[chemoprophylaxis]] for the [[infant]] is required.
|useInPed=* A number of fatalities have been reported following the accidental ingestion of chloroquine, sometimes in relatively small doses (0.75 g or 1 g chloroquine phosphate in one 3-year-old child). Patients should be strongly warned to keep this drug out of the reach of children because they are especially sensitive to the 4-aminoquinoline compounds.
|useInGeri=* Clinical studies of chloroquine phosphate did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. However, this drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased [[renal function]], care should be taken in dose selection and it may be useful to monitor [[renal function]].
|useInGender=There is no FDA guidance on the use of Chloroquine phosphate with respect to specific gender populations.
|useInRace=There is no FDA guidance on the use of Chloroquine phosphate with respect to specific racial populations.
|useInRenalImpair=There is no FDA guidance on the use of Chloroquine phosphate in patients with renal impairment.
|useInHepaticImpair=* Since this drug is known to concentrate in the [[liver]], it should be used with caution in patients with [[hepatic impairment|hepatic disease]] or [[alcoholism]] or in conjunction with known [[hepatotoxic]] drugs.
|useInReproPotential=There is no FDA guidance on the use of Chloroquine phosphate in women of reproductive potentials and males.
|useInImmunocomp=There is no FDA guidance one the use of Chloroquine phosphate in patients who are immunocompromised.
 
<!--Administration and Monitoring-->
|administration=* Oral
|monitoring=====Cyclosporine=====
 
* After introduction of chloroquine (oral form), a sudden increase in serum [[cyclosporine]] level has been reported. Therefore, close monitoring of serum [[cyclosporine]] level is recommended and, if necessary, chloroquine should be discontinued.
 
=====Geriatric Use=====
 
* Clinical studies of chloroquine phosphate did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. However, this drug is known to be substantially excreted by the [[kidney]], and the risk of [[toxicity|toxic reactions]] to this drug may be greater in patients with [[impaired renal function]]. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection and it may be useful to monitor [[renal function]].
|IVCompat=There is limited information regarding <i>IV Compatibility</i> of Chloroquine phosphatein the drug label.
 
<!--Overdosage-->
|overdose=====Symptoms:=====
 
* Chloroquine is very rapidly and completely absorbed after ingestion. [[Toxic]] doses of chloroquine can be [[fatal]]. As little as 1 g may be fatal in children. [[toxicity|Toxic symptoms]] can occur within minutes. These consist of [[headache]], [[drowsiness]], [[visual disturbances]], [[nausea]] and [[vomiting]], [[cardiovascular collapse]], [[shock]] and [[convulsions]] followed by sudden and early [[respiratory arrest|respiratory]] and [[cardiac arrest]]. [[Hypokalemia]] has been observed with [[arrhythmias]] in cases of [[intoxication]]. The [[electrocardiogram]] may reveal [[atrial arrhythmia|atrial standstill]], [[heart rhythm|nodal rhythm,]] prolonged intraventricular conduction time, and progressive [[bradycardia]] leading to [[ventricular fibrillation]] and/or [[cardiac arrest|arrest]]. Cases of [[Extrapyramidal disorder|extrapyramidal disorders]] have also been reported in the context of chloroquine overdose.
 
=====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]]. If due to [[cerebral]] stimulation, cautious administration of an [[barbiturate|ultra short-acting barbiturate]] may be tried but, if due to [[anoxia]], it should be corrected by [[oxygen]] administration and [[artificial respiration]], [[ECG|monitor ECG]]. In [[shock]] with [[hypotension]], a potent [[vasopressor]] should be administered. Replace [[fluids]] and [[electrolytes]] as needed. Cardiac compressing or [[cardiac pacing|pacing]] may be indicated to sustain the [[circulation]]. Because of the importance of supporting [[respiration]], [[tracheal intubation]] or [[tracheostomy]], followed by [[gastric lavage]], may also be necessary. [[Peritoneal dialysis]] and [[exchange transfusions]] have also been suggested to reduce the level of the drug in the [[blood]].
 
* Intervention options can involve: [[diazepam]] for life-threatening symptoms, [[seizures]] and [[sedation]], [[epinephrine]] for treatment of [[vasodilation]] and [[myocardium|myocardial depression]], [[potassium|potassium replacement]] with close monitoring of [[potassium|serum potassium levels]].
 
* A patient who survives the acute phase and is asymptomatic should be closely observed for at least six hours. [[Fluids]] may be forced, and sufficient [[ammonium chloride]] (8 g daily in divided doses for adults) may be administered for a few days to acidify the urine to help promote urinary excretion in cases of both [[overdosage]] or sensitivity.
|drugBox={{Drugbox2
| Watchedfields = changed
| verifiedrevid = 459442331
| IUPAC_name = (''RS'')-''N'''-(7-chloroquinolin-4-yl)-''N'',''N''-diethyl-pentane-1,4-diamine
| image = Chloroquine.png
 
<!--Clinical data-->
| tradename = Aralen
| Drugs.com = {{drugs.com|monograph|aralen-phosphate}}
| licence_US = Chloroquine
| legal_US = Rx-only
 
<!--Pharmacokinetic data-->
| metabolism = Liver
| elimination_half-life = 1–2 months
 
<!--Identifiers-->
| CASNo_Ref = {{cascite|correct|CAS}}
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 54-05-7
| ATC_prefix = P01
| ATC_suffix = BA01
| PubChem = 2719
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00608
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 2618
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 886U3H6UFF
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D02366
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 3638
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 76
| NIAID_ChemDB = 000733
 
<!--Chemical data-->
| C=18 | H=26 | Cl=1 | N=3  
| molecular_weight = 319.872 [[Gram|g]]/[[Mole (unit)|mol]]
| smiles = Clc1cc2nccc(c2cc1)NC(C)CCCN(CC)CC
| InChI = 1/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)
| InChIKey = WHTVZRBIWZFKQO-UHFFFAOYAT
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 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)
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = WHTVZRBIWZFKQO-UHFFFAOYSA-N
}}
}}
|mechAction=====Microbiology=====
* Mechanism of Action: Chloroquine is an antimalarial agent. While the drug can inhibit certain [[enzymes]], its effect is believed to result, at least in part from its interaction with [[DNA]]. However, the mechanism of [[plasmodium|plasmodicidal]] action of chloroquine is not completely certain.
* Activity in vitro and in vivo: Chloroquine is active against the [[erythrocyte|erythrocytic forms]] of [[Plasmodium vivax]], [[Plasmodium malariae]], and susceptible [[strains]] of [[Plasmodium falciparum]] (but not the [[gametocytes]] of [[P. falciparum]]). It is not effective against exoerythrocytic forms of the parasite.


{{SI}}
* In vitro studies with [[trophozoites]] of [[Entamoeba histolytica]] have demonstrated that chloroquine phosphate also possesses [[amebiasis|amebicidal activity]] comparable to that of [[emetine]].


{{EH}}
* Drug Resistance: Resistance of [[Plasmodium falciparum]] to chloroquine is widespread and cases of [[Plasmodium vivax]] have been reported.
==Overview==
|structure=* Chloroquine phosphate, USP is a 4-aminoquinoline compound for oral administration. It is a white crystalline powder; odorless; has a bitter taste, and is discolored slowly on exposure to light. It is freely soluble in water, practically insoluble in alcohol, in chloroform and in ether.
'''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==
* Each tablet, for oral administration, contains 250 mg of chloroquine phosphate, USP (equivalent to 150 mg base).
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.
* Inactive ingredients: colloidal silicon dioxide, corn starch, hypromellose, magnesium stearate, microcrystalline cellulose, polyethylene glycol 400, polyethylene glycol 3350, polysorbate 80, povidone, sodium starch glycolate, talc, and titanium dioxide.


(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)
* Chemically, it is 7-chloro-4-((4-(diethylamino)-1-methylbutyl)amino) quinoline phosphate (1:2) and has the following molecular structure:


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.
[[File:683px-Chloroquine.png|thumb|none|400px|This image is provided by the National Library of Medicine.]]


==Malaria prevention==
<!--Pharmacodynamics-->
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>
|PD=There is limited information regarding <i>Pharmacodynamics</i> of Chloroquine phosphate in the drug label.


== Doses ==
<!--Pharmacokinetics-->
Per the Centers for Disease Control (CDC):
|PK=* Chloroquine is rapidly and almost completely absorbed from the [[gastrointestinal tract]], and only a small proportion of the administered dose is found in the stools. Approximately 55% of the drug in the plasma is bound to nondiffusible plasma constituents. Excretion of chloroquine is quite slow, but is increased by acidification of the urine. Chloroquine is deposited in the tissues in considerable amounts. In animals, from 200 to 700 times the plasma concentration may be found in the [[liver]], [[spleen]], [[kidney]], and [[lung]]; [[leukocytes]] also concentrate the drug. The [[brain]] and [[spinal cord]], in contrast, contain only 10 to 30 times the amount present in [[plasma]].
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.
* Chloroquine undergoes appreciable degradation in the body. The main metabolite is desethylchloroquine, which accounts for one fourth of the total material appearing in the urine; bisdesethylchloroquine, a carboxylic acid derivative, and other metabolic products as yet uncharacterized are found in small amounts. Slightly more than half of the urinary drug products can be accounted for as unchanged chloroquine.
|nonClinToxic=There is limited information regarding <i>Nonclinical Toxicology</i> of Chloroquine phosphate in the drug label.


==Adverse effects==
<!--Clinical Studies-->
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.
|clinicalStudies=There is limited information regarding <i>Clinical Studies</i> of Chloroquine phosphate 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.
<!--How Supplied-->
|howSupplied=Chloroquine phosphate tablets, USP 250 mg are white to off-white, round, film-coated tablets, debossed with “RF” and “27” on one side and break line on the other side.


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&ndash;102 | url=http://pediatrics.aappublications.org/cgi/content/abstract/27/1/95?ijkey=0c507c09d8450f8c8bbadf109d6428e93ad2619f&keytype2=tf_ipsecsha }}</ref>
NDC 63304-460-03 Bottles of 10


==Mechanism of action==
NDC 63304-460-50 Bottles of 50
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.


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.
NDC 63304-460-10 Bottles of 1000


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.  
Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.


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].
Protect from light and moisture.


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.
You may report side effects to FDA at 1-800-FDA-1088.
|storage=* Store at 20 - 25° C (68 - 77° F).
|packLabel=NDC 63304-460-03


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]].
CHLOROQUINE PHOSPHATE TABLETS,USP


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]]. 
250 mg


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).
For Use in Malaria and Extraintestinal Amebiasis Only


==Notes==
Rx only
<div class="references-small" {{#if: {{{colwidth|}}}| style="-moz-column-width:{{{colwidth}}}; column-width:{{{colwidth}}};" | {{#if: {{{1|}}}| style="-moz-column-count:{{{1}}}; column-count:{{{1}}} }}};" |}}>
<references/>
</div>


==References==
10 Tablets
*Plowe CV. Antimalarial drug resistance in Africa: strategies for monitoring and deterrence. Curr Top Microbiol Immunol. 2005;295:55-79.
|fdaPatientInfo=There is limited information regarding <i>Patient Counseling Information</i> of Chloroquine phosphate in the drug label.
*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.


==External links==
<!--Precautions with Alcohol-->
* [http://www.leadershipmedica.com/scientifico/sciemag02/scientificaing/5savae/5savaing.htm Chloroquine Anti-HIV action]
|alcohol======Hepatic Effects=====
 
* Since this drug is known to concentrate in the liver, it should be used with caution in patients with hepatic disease or alcoholism or in conjunction with known [[hepatotoxic|hepatotoxic drugs]].
|brandNames=* Aralen Phosphate®
|drugShortage=
}}
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|fileName=Chloroquine drug label01.png
}}
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{{Antimalarials}}
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[[Category:Antimalarial agents]]
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[[Category:Quinolines]]
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[[Category:Drug]]

Latest revision as of 20:00, 11 March 2015

Chloroquine
Black Box Warning
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Adeel Jamil, M.D. [2]

Disclaimer

WikiDoc MAKES NO GUARANTEE OF VALIDITY. WikiDoc is not a professional health care provider, nor is it a suitable replacement for a licensed healthcare provider. WikiDoc is intended to be an educational tool, not a tool for any form of healthcare delivery. The educational content on WikiDoc drug pages is based upon the FDA package insert, National Library of Medicine content and practice guidelines / consensus statements. WikiDoc does not promote the administration of any medication or device that is not consistent with its labeling. Please read our full disclaimer here.

Black Box Warning

WARNING
See full prescribing information for complete Boxed Warning.
* For Malaria and Extraintestinal Amebiasis

Overview

Chloroquine is a aminoquinoline antimalarial that is FDA approved for the treatment of for the suppressive treatment and for acute attacks of malaria due to P. vivax, P. malariae, P. ovale, and susceptible strains of P. falciparum. The drug is also indicated for the treatment of extraintestinal amebiasis.. There is a Black Box Warning for this drug as shown here. Common adverse reactions include cardiovascular, dermatological, immunological, neurological and ophthalmological (see Adverse Reactions section).

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

  • Chloroquine phosphate tablets does not prevent relapses in patients with vivax or malariae malaria because it is not effective against exoerythrocytic forms of the parasite, nor will it prevent vivax or malariae infection when administered as a prophylactic. It is highly effective as a suppressive agent in patients with vivax or malariae malaria, in terminating acute attacks, and significantly lengthening the interval between treatment and relapse. In patients with falciparum malaria it abolishes the acute attack and effects complete cure of the infection, unless due to a resistant strain of P. falciparum.
Dosing Information
  • The dosage of chloroquine phosphate is often expressed or calculated as the base. Each 250 mg tablet of chloroquine phosphate is equivalent to 150 mg base. In infants and children the dosage is preferably calculated on the body weight.
  • Malaria:
  • Suppression— Adult Dose: 500 mg (= 300 mg base) on exactly the same day of each week.
  • If circumstances permit, suppressive therapy should begin two weeks prior to exposure. However, failing this in adults, an initial double (loading) dose of 1 g (= 400 mg base), or in children 10 mg base/kg may be taken in two divided doses, six hours apart. The suppressive therapy should be continued for eight weeks after leaving the endemic area.
  • For Treatment of Acute Attack:
  • An initial dose of 1 g (= 400 mg base) followed by an additional 500 mg (= 300 mg base) after six to eight hours and a single dose of 500 mg (= 300 mg base) on each of two consecutive days. This represents a total dose of 2.5 g chloroquine phosphate or 1.5 g base in three days.
  • The dosage for adults of low body weight and for infants and children should be determined as follows:
    • First dose: 10 mg base per kg (but not exceeding a single dose of 400 mg base).
    • Second dose: (6 hours after first dose) 5 mg base per kg (but not exceeding a single dose of 300 mg base).
    • Third dose: (24 hours after first dose) 5 mg base per kg.
    • Fourth dose: (36 hours after first dose) 5 mg base per kg.
  • Extraintestinal Amebiasis:
  • Adults:1 g (400 mg base) daily for two days, followed by 500 mg (300 mg base) daily for at least two to three weeks. Treatment is usually combined with an effective intestinal amebicide.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Chloroquine in adult patients.

Non–Guideline-Supported Use

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

Dosing Information
  • The dosage of chloroquine phosphate is often expressed or calculated as the base. Each 250 mg tablet of chloroquine phosphate is equivalent to 150 mg base. In infants and children the dosage is preferably calculated on the body weight.
  • The weekly suppressive dosage is 5 mg calculated as base, per kg of body weight, but should not exceed the adult dose regardless of weight.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Chloroquine in pediatric patients.

Non–Guideline-Supported Use

Contraindications

  • Use of this drug is contraindicated in the presence of retinal or visual field changes either attributable to 4-aminoquinoline compounds or to any other etiology, and in patients with known hypersensitivity to 4-aminoquinoline compounds. However, in the treatment of acute attacks of malaria caused by susceptible strains of plasmodia, the physician may elect to use this drug after carefully weighing the possible benefits and risks to the patient.

Warnings

WARNING
See full prescribing information for complete Boxed Warning.
* For Malaria and Extraintestinal Amebiasis
  • It has been found that certain strains of P. falciparum have become resistant to 4- aminoquinoline compounds (including chloroquine and hydroxychloroquine). Chloroquine resistance is widespread and, at present, is particularly prominent in various parts of the world including sub-Saharan Africa, Southeast Asia, the Indian subcontinent, and over large portions of South America, including the Amazon basin1.
  • Before using chloroquine for prophylaxis, it should be ascertained whether chloroquine is appropriate for use in the region to be visited by the traveler. Chloroquine should not be used for treatment of P.falciparum infections acquired in areas of chloroquine resistance or malaria occurring in patients where chloroquine prophylaxis has failed.
  • If there is any indication (past or present) of abnormality in the visual acuity, visual field, or retinal macular areas (such as pigmentary changes, loss of foveal reflex), or any visual symptoms (such as light flashes and streaks) which are not fully explainable by difficulties of accommodation or corneal opacities, the drug should be discontinued immediately and the patient closely observed for possible progression. Retinal changes (and visual disturbances) may progress even after cessation of therapy.
  • Acute extrapyramidal disorders may occur with chloroquine. These adverse reactions usually resolve after treatment discontinuation and/or symptomatic treatment.
  • All patients on long-term therapy with this preparation should be questioned and examined periodically, including testing knee and ankle reflexes, to detect any evidence of muscular weakness. If weakness occurs, discontinue the drug.
  • A number of fatalities have been reported following the accidental ingestion of chloroquine, sometimes in relatively small doses (0.75 g or 1 g chloroquine phosphate in one 3-year-old child). Patients should be strongly warned to keep this drug out of the reach of children because they are especially sensitive to the 4-aminoquinoline compounds.
  • Use of chloroquine phosphate in patients with psoriasis may precipitate a severe attack of psoriasis. When used in patients with porphyria the condition may be exacerbated. The drug should not be used in these conditions unless in the judgment of the physician the benefit to the patient outweighs the potential risks.
  • Usage in Pregnancy: Radioactively tagged chloroquine administered intravenously to pregnant pigmented CBA mice passed rapidly across the placenta and accumulated selectively in the melanin structures of the fetal eyes. It was retained in the ocular tissues for five months after the drug had been eliminated from the rest of the body. There are no adequate and well-controlled studies evaluating the safety and efficacy of chloroquine in pregnant women. Usage of chloroquine during pregnancy should be avoided except in the suppression or treatment of malaria when in the judgment of the physician the benefit outweighs the potential risk to the fetus.
Precautions
  • Hematological Effects/Laboratory Tests
  • Complete blood cell counts should be made periodically if patients are given prolonged therapy. If any severe blood disorder appears which is not attributable to the disease under treatment, discontinuance of the drug should be considered.
  • Auditory Effects
  • In patients with preexisting auditory damage, chloroquine should be administered with caution. In case of any defects in hearing, chloroquine should be immediately discontinued, and the patient closely observed.
  • Hepatic Effects
  • Central Nervous System Effects
  • Patients with a history of epilepsy should be advised about the risk of chloroquine provoking seizures.

Adverse Reactions

Clinical Trials Experience

Special Senses:Ocular:=

Auditory:
Musculoskeletal System:
Gastrointestinal system:
Skin and appendages:
Hematologic system:
Nervous system:
Cardiac system:

Postmarketing Experience

There is limited information regarding Postmarketing Experience of Chloroquine phosphate in the drug label.

Drug Interactions

Antacids and kaolin:=

  • Antacids and kaolin can reduce absorption of chloroquine; an interval of at least 4 hours between intake of these agents and chloroquine should be observed.
Cimetidine:
  • Cimetidine can inhibit the metabolism of chloroquine, increasing its plasma level. Concomitant use of cimetidine should be avoided.
Ampicillin:
  • In a study of healthy volunteers, chloroquine significantly reduced the bioavailability of ampicillin. An interval of at least two hours between intake of this agent and chloroquine should be observed.
Cyclosporine:
  • After introduction of chloroquine (oral form), a sudden increase in serum cyclosporine level has been reported. Therefore, close monitoring of serum cyclosporine level is recommended and, if necessary, chloroquine should be discontinued.
Mefloquine:

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): C

  • Radioactively tagged chloroquine administered intravenously to pregnant pigmented CBA mice passed rapidly across the placenta and accumulated selectively in the melanin structures of the fetal eyes. It was retained in the ocular tissues for five months after the drug had been eliminated from the rest of the body. There are no adequate and well-controlled studies evaluating the safety and efficacy of chloroquine in pregnant women. Usage of chloroquine during pregnancy should be avoided except in the suppression or treatment of malaria when in the judgment of the physician the benefit outweighs the potential risk to the fetus.


Pregnancy Category (AUS):

  • Australian Drug Evaluation Committee (ADEC) Pregnancy Category

There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Chloroquine phosphate in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Chloroquine phosphate during labor and delivery.

Nursing Mothers

  • Because of the potential for serious adverse reactions in nursing infants from chloroquine, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the potential clinical benefit of the drug to the mother.
  • The excretion of chloroquine and the major metabolite, desethylchloroquine, in breast milk was investigated in eleven lactating mothers following a single oral dose of chloroquine (400 mg base). The maximum daily dose of the drug that the infant can receive from breastfeeding was about 0.7% of the maternal start dose of the drug in malaria chemotherapy. Separate chemoprophylaxis for the infant is required.

Pediatric Use

  • A number of fatalities have been reported following the accidental ingestion of chloroquine, sometimes in relatively small doses (0.75 g or 1 g chloroquine phosphate in one 3-year-old child). Patients should be strongly warned to keep this drug out of the reach of children because they are especially sensitive to the 4-aminoquinoline compounds.

Geriatic Use

  • Clinical studies of chloroquine phosphate did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. However, this drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection and it may be useful to monitor renal function.

Gender

There is no FDA guidance on the use of Chloroquine phosphate with respect to specific gender populations.

Race

There is no FDA guidance on the use of Chloroquine phosphate with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Chloroquine phosphate in patients with renal impairment.

Hepatic Impairment

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Chloroquine phosphate in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Chloroquine phosphate in patients who are immunocompromised.

Administration and Monitoring

Administration

  • Oral

Monitoring

Cyclosporine=

  • After introduction of chloroquine (oral form), a sudden increase in serum cyclosporine level has been reported. Therefore, close monitoring of serum cyclosporine level is recommended and, if necessary, chloroquine should be discontinued.
Geriatric Use
  • Clinical studies of chloroquine phosphate did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. However, this drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection and it may be useful to monitor renal function.

IV Compatibility

There is limited information regarding IV Compatibility of Chloroquine phosphatein the drug label.

Overdosage

Symptoms:=

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.
  • A patient who survives the acute phase and is asymptomatic should be closely observed for at least six hours. Fluids may be forced, and sufficient ammonium chloride (8 g daily in divided doses for adults) may be administered for a few days to acidify the urine to help promote urinary excretion in cases of both overdosage or sensitivity.

Pharmacology

Template:Px
Chloroquine
Systematic (IUPAC) name
(RS)-N'-(7-chloroquinolin-4-yl)-N,N-diethyl-pentane-1,4-diamine
Identifiers
CAS number 54-05-7
ATC code P01BA01
PubChem 2719
DrugBank DB00608
Chemical data
Formula Template:OrganicBox atomTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBox 
Mol. mass 319.872 g/mol
SMILES eMolecules & PubChem
Pharmacokinetic data
Bioavailability ?
Metabolism Liver
Half life 1–2 months
Excretion ?
Therapeutic considerations
Licence data

US

Pregnancy cat.

?

Legal status

[[Prescription drug|Template:Unicode-only]](US)

Routes ?

Mechanism of Action

Microbiology=

  • Mechanism of Action: Chloroquine is an antimalarial agent. While the drug can inhibit certain enzymes, its effect is believed to result, at least in part from its interaction with DNA. However, the mechanism of plasmodicidal action of chloroquine is not completely certain.

Structure

  • Chloroquine phosphate, USP is a 4-aminoquinoline compound for oral administration. It is a white crystalline powder; odorless; has a bitter taste, and is discolored slowly on exposure to light. It is freely soluble in water, practically insoluble in alcohol, in chloroform and in ether.
  • Each tablet, for oral administration, contains 250 mg of chloroquine phosphate, USP (equivalent to 150 mg base).
  • Inactive ingredients: colloidal silicon dioxide, corn starch, hypromellose, magnesium stearate, microcrystalline cellulose, polyethylene glycol 400, polyethylene glycol 3350, polysorbate 80, povidone, sodium starch glycolate, talc, and titanium dioxide.
  • Chemically, it is 7-chloro-4-((4-(diethylamino)-1-methylbutyl)amino) quinoline phosphate (1:2) and has the following molecular structure:
This image is provided by the National Library of Medicine.

Pharmacodynamics

There is limited information regarding Pharmacodynamics of Chloroquine phosphate in the drug label.

Pharmacokinetics

  • Chloroquine is rapidly and almost completely absorbed from the gastrointestinal tract, and only a small proportion of the administered dose is found in the stools. Approximately 55% of the drug in the plasma is bound to nondiffusible plasma constituents. Excretion of chloroquine is quite slow, but is increased by acidification of the urine. Chloroquine is deposited in the tissues in considerable amounts. In animals, from 200 to 700 times the plasma concentration may be found in the liver, spleen, kidney, and lung; leukocytes also concentrate the drug. The brain and spinal cord, in contrast, contain only 10 to 30 times the amount present in plasma.
  • Chloroquine undergoes appreciable degradation in the body. The main metabolite is desethylchloroquine, which accounts for one fourth of the total material appearing in the urine; bisdesethylchloroquine, a carboxylic acid derivative, and other metabolic products as yet uncharacterized are found in small amounts. Slightly more than half of the urinary drug products can be accounted for as unchanged chloroquine.

Nonclinical Toxicology

There is limited information regarding Nonclinical Toxicology of Chloroquine phosphate in the drug label.

Clinical Studies

There is limited information regarding Clinical Studies of Chloroquine phosphate in the drug label.

How Supplied

Chloroquine phosphate tablets, USP 250 mg are white to off-white, round, film-coated tablets, debossed with “RF” and “27” on one side and break line on the other side.

NDC 63304-460-03 Bottles of 10

NDC 63304-460-50 Bottles of 50

NDC 63304-460-10 Bottles of 1000

Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.

Protect from light and moisture.

You may report side effects to FDA at 1-800-FDA-1088.

Storage

  • Store at 20 - 25° C (68 - 77° F).

Images

Drug Images

{{#ask: Page Name::Chloroquine |?Pill Name |?Drug Name |?Pill Ingred |?Pill Imprint |?Pill Dosage |?Pill Color |?Pill Shape |?Pill Size (mm) |?Pill Scoring |?NDC |?Drug Author |format=template |template=DrugPageImages |mainlabel=- |sort=Pill Name }}

Package and Label Display Panel

NDC 63304-460-03

CHLOROQUINE PHOSPHATE TABLETS,USP

250 mg

For Use in Malaria and Extraintestinal Amebiasis Only

Rx only

10 Tablets {{#ask: Label Page::Chloroquine |?Label Name |format=template |template=DrugLabelImages |mainlabel=- |sort=Label Page }}

Patient Counseling Information

There is limited information regarding Patient Counseling Information of Chloroquine phosphate in the drug label.

Precautions with Alcohol

Hepatic Effects
  • Since this drug is known to concentrate in the liver, it should be used with caution in patients with hepatic disease or alcoholism or in conjunction with known hepatotoxic drugs.

Brand Names

  • Aralen Phosphate®

Look-Alike Drug Names

There is limited information regarding Chloroquine Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

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