Chloroquin

log Kow = 4.63

4.3

4.61

WHITE TO SLIGHTLY YELLOW, CRYSTALLINE POWDER

Colorless crystals

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/

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/

VERY SLIGHTLY SOL IN WATER; SOL IN DIL ACIDS, CHLOROFORM, ETHER

Insoluble in alcohol, benzene, chloroform, ether.

1.75e-02 g/L

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

Pharmaceuticals

Antimalarial medicines > For chemoprevention

87-89.5

87 °C

289 °C

Stable to heat in solutions of pH 4.0 to 6.5 /Chloroquine Diphosphate/

SENSITIVE TO LIGHT. /PHOSPHATE/

SENSITIVE TO LIGHT. /SULFATE/

10.1

pKa = 10.1

Warning

H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]

P264, P270, P301+P317, P330, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 41 reports by companies from 2 notifications to the ECHA C&L Inventory.

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/

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.

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.

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.

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)

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.

Concurrent use /of mefloquine and chloroquine may increase the risk of seizures.

Concurrent use of other hepatotoxic medications with chloroquine may increase the potential for hepatotoxicity and should be avoided.

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.

For more Interactions (Complete) data for CHLOROQUINE (16 total), please visit the HSDB record page.

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).

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.

Although chloroquine has relatively few side effects when taken as prescribed, higher doses of chloroquine have been shown to have severe adverse effects. The most severe adverse effects associated with high doses of chloroquine include retinal toxicity, long and subtle symptoms of reduced visual acuity, diplopia, and bilateral loss of vision. High doses have also been shown to cause severe psychiatric issues, such as paranoia, hallucinations, and suicidal ideations.

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.

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.

Chloroquine toxicity is rare but has been known to occur when unusually high doses of chloroquine are ingested or after chronic IV administration. Accidental ingestion has also occurred in children. When toxicity is present, the most common symptom is retinal toxicity. Treatment of chloroquine toxicity includes mechanical ventilation and administration of diazepam and epinephrine, although these methods have not been a proven method of treatment in all cases.

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.

/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.

/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).

/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.

/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.

For more Human Toxicity Excerpts (Complete) data for CHLOROQUINE (27 total), please visit the HSDB record page.

Chloroquine

Group 3: Not classifiable as to its carcinogenicity to humans

Volume 13: (1977) Some Miscellaneous Pharmaceutical Substances

1987

1987

3, not classifiable as to its carcinogenicity to humans. (L135)

Benchmark Dataset for the Liver Toxicity Knowledge Base (LTKB)

chloroquine

Aralen

Antiprotozoals

3

less-DILI-concern drugs

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/

P - Antiparasitic products, insecticides and repellents

P01BA01

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.

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.

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.

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.

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.

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.

Terminal elimination half-life is 1 to 2 months.

... extremely slow elimination, with a terminal elimination half-life of 200 to 300 hours)

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.

Hepatic (partially), to active de-ethylated metabolites. Principal metabolite is desethylchloroquine

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

886U3H6UFF

CHLOROQUINE

Established Pharmacologic Class [EPC] - Antimalarial

Chloroquine is an Antimalarial.

Agents which are destructive to amebae, especially the parasitic species causing AMEBIASIS in man and animal.

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)

Drugs that are used to treat RHEUMATOID ARTHRITIS.

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.

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.

The volume of distribution of chloroquine is 200-800L/kg.

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.

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.

MEDICATION

Antimalarial, antiamebic, antitheuratic, Lupus erthematus supressant

Mesh Heading: Amebicides, antimalarials, antirheumatic Agents

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

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).

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

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

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

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

H. Andersag et al., US 2233970 (1941 to Winthrop)

Condensation of 4,7-dichloroquinoline with 1-diethylamino-4-aminopentane: German patent 683692 (1939);

Chloroquine phosphate, USP ... is available as tablets containing either 250 or 500 mg of diphosphate. Approximately 60% of diphosphate represents base. /Chloroquine phosphate/

Arechin; Avloclor; Imagon; Malaquin; Resochin; Tresochin. /Chloroquine diphosphate/

Nivaquine. /Chloroquine Sulfate/

Tablets (as the phosphate), 500 mg. Vials (as the dihydrochloride), 50 mg/ml.

Chloroquine Phosphate: Oral tablets 300 mg or 150 mg (of chloroquine).