Chloroquine

319.87

319.87

200-191-2

187208

DTXSID2040446

WHITE TO SLIGHTLY YELLOW, CRYSTALLINE POWDER|Colorless crystals

P - Antiparasitic products, insecticides and repellents

2933499090

28.2

4.6

Solid

1.1±0.1 g/cm3

87-92 °C

212-214 °C @ Press: 0.2 Torr

232.3±27.3 °C

1.592

1.75e-02 g/L

5.0X10-9 mm Hg at 25 deg C (est)

LD50 oral in rat: 330mg/kg

ODORLESS

Bitter taste

10.1None

Henry's Law constant = 1.1X10-12 atm cu-m/mole at 25 °C (est)

10.1|pKa = 10.1

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

USUALLY IS IN A PARTLY HYDRATED FORM|COLORLESS LIQUID; PH BETWEEN 5.5 & 6.5 /CHLOROQUINE HYDROCHLORIDE INJECTION/|WHITE POWDER /CHLOROQUINE DIPHOSPHATE/|Upon decomosition emits NOx|Hydroxyl radical reaction rate constant = 1.5X10-10 cu cm/molec-sec at 25 °C (est)

Stability Stable, but light sensitive. Incompatible with strong oxidizing agents.

P264, P270, P301+P312, P330, P501

H302

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.

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.

|Warning|H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]|P264, P270, P301+P312, P330, and P501|Aggregated GHS information provided by 39 companies from 1 notifications to the ECHA C&L Inventory.

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.

Patients experiencing an overdose may present with headache, drowsiness, visual disturbances, nausea, vomiting, cardiovascular collapse, shock, convulsions, respiratory arrest, cardiac arrest, and hypokalemia. Overdose should be managed with symptomatic and supportive treatment which may include prompt emesis, gastric lavage, and activated charcoal.|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.

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.

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.

... Reports of suicides have indicated that the margin of safety in adults is also small. Without prompt effective therapy, acute ingestion of 5 g or more of chloroquine in adults has usually been fatal, although death has occurred with smaller doses. Fatalities have been reported following the accidental ingestion of relatively small doses of chloroquine (e.g., 750 mg or 1 g of chloroquine phosphate in a 3-year-old child).

LD50 Rat oral 330 mg/kg|LD50 Mouse oral 311 mg/kg

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

While data specific to chloroquine were not available(SRC, 2005), the literature suggests that some pharmaceutically active compounds originating from human and veterinary therapy are not eliminated completely in municipal sewage treatment plants and are therefore discharged into receiving waters(1). Wastewater treatment processes often were not designed to remove them from the effluent(2). Another concern is that selected organic waste compounds may be degrading to new and more persistent compounds that may be released instead of or in addition to the parent compound(2). Studies have indicated that several polar pharmaceutically active compounds can leach through subsoils(1).

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.

CORNEAL DEPOSITS HAVE ... BEEN DESCRIBED AS INDUSTRIAL COMPLICATION IN WORKERS MFR CHLOROQUINE ... . APPARENTLY DEPOSITS ARE SAME AS THOSE PRODUCED BY ORAL ADMIN. ... INDUSTRIALLY MATERIAL MAY HAVE REACHED CORNEA DIRECTLY IN FORM OF DUST, BUT THIS HAS NOT BEEN ESTABLISHED.

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

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

Antimalarial Agents

Mesh Heading: Amebicides, antimalarials, antirheumatic Agents|Antimalarial; antiamebic; antirheumatic. Lupus erythematosus suppressant.|Chloroquine is indicated in the suppressive treatment and the treatment of acute attacks of malaria caused by plasmodium vivax, Plasmodium malariae, Plasmodium ovale, chlrorquine-susceptible strains of P. falciparum. /Included in the US product label/|Chloroquine is indicated for the treatment of amebic liver abscess, usually in combination with and effective intestinal amebicide. However, it is not considered a primary drug. /Included in the US product label/|For more Therapeutic Uses (Complete) data for CHLOROQUINE (13 total), please visit the HSDB record page.

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

... The lethal dose of chloroquine for an adult is estimated at 30 to 50 mg/kg.|Chloroquine doses of more than 5 g given parenterally usually are fatal.|... Fatal dose ... of chloroquine phosphate (2 to 3 g, adult) ... /Chloroquine phosphate/

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

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.

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

Chloroquine oral solution has a bioavailability of 52-102% and oral tablets have a bioavailability of 67-114%. Intravenous chloroquine reaches a C_max of 650-1300µg/L and oral chloroquine reaches a C_max of 65-128µg/L with a T_max 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.|Chloroquine is widely distributed into body tissues. The drug has an apparent volume of distribution of 116-285 L/kg in healthy adults. Animal studies indicate that concn of chloroquine in liver, spleen, kidney, and lung are at least 200-700 times higher than those in plasma, and concentration of the drug in brain and spinal cord are at least 10-30 times higher than those in plasma. Chloroquine binds to melanin containing cells in the eyes and skin; skin concn of the drug are considerably higher than plasma concentration. Animal studies indicate that the drug is concentrated in the iris and choroid and, to a lesser extent, in the cornea, retina, and sclera and is found in these tissues in higher concentration than in other tissues.|Chloroquine is also concentrated in erythrocytes and binds to platelets and granulocytes. Serum concentrations of chloroquine are higher than those in plasma, presumably because the drug is released from platelets during coagulation, and plasma concentrations are 10 to 15% lower than whole blood concentration of the drug.|For more Absorption, Distribution and Excretion (Complete) data for CHLOROQUINE (16 total), please visit the HSDB record page.

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

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 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.

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

/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.

Aralen

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).

Usually dispensed as the phosphate.

GENERAL SAMPLE, FLUOROMETRY (EXCITATION= 350, EMISSION= 405).|Analyte: chloroquine; matrix: chemical identification; procedure: infrared absorption spectrophotometry with comparison to standards|Analyte: chloroquine; matrix: chemical identification; procedure: ultraviolet absorption spectrophotometry with comparison to standards|Analyte: chloroquine; matrix: chemical purity; procedure: dissolution in glacial acetic acid; addition of crystal violet indicator; titration with perchloric acid|For more Analytic Laboratory Methods (Complete) data for CHLOROQUINE (20 total), please visit the HSDB record page.

Determination of chloroquine in blood, plasma, red cells, or urine specimen using spectrophotometer with UV absorption spectrum at 0.0 to 0.1 absorbance range. Recovery is about 90 + or - 2%.|A high-performance liquid chromatography method with fluorescence detection is described for the simultaneous measurement of quinine, chloroquine and mono- and bidesethylchloroquine in human plasma, erythrocytes and urine ... The limit of detection was ca 5 ng/mL of chloroquine and ca 23 ng/mL for quinine ...|Two new methods for the simultaneous detn of chloroquine and its two main metabolites (monodesethylchloroquine and bisdesethylchloroquine) in biol samples, RIA and ELISA, are described ... Sensitivity limits are, respectively, 0.70 nM (3 pg of chloroquine sulfate measured in 10 uLof plasma sample) for RIA, and 10 nM (22 pg of chloroquine sulfate measured in 5 uL of plasma sample) for ELISA. The interassay coefficients of variation are, respectively, <10 and <16% for RIA and ELISA in the range 14 to 410 nM (6 to 180 ng/mL) ...|Analyte: chloroquine; matrix: blood (whole, plasma); procedure: high-performance liquid chromatography with ultraviolet detection at 229 nm; limit of detection: <120 ng/mL|For more Clinical Laboratory Methods (Complete) data for CHLOROQUINE (17 total), please visit the HSDB record page.

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