| 1.1 Substance|
| 1.2 Group|
| 1.3 Synonyms|
| 1.4 Identification numbers|
| 1.4.1 CAS number|
| 1.4.2 Other numbers|
| 1.5 Brand names, Trade names|
| 1.6 Manufacturers, Importers|
| 2.1 Main risks and target organs|
| 2.2 Summary of clinical effects|
| 2.3 Diagnosis|
| 2.4 First aid measures and management principles|
|3. PHYSICO-CHEMICAL PROPERTIES|
| 3.1 Origin of the substance|
| 3.2 Chemical structure|
| 3.3 Physical properties|
| 3.3.1 Properties of the substance|
| 3.3.2 Properties of the locally available formulation|
| 3.4 Other characteristics|
| 3.4.1 Shelf-life of the substance|
| 3.4.2 Shelf-life of the locally available formulation|
| 3.4.3 Storage conditions|
| 3.4.4 Bioavailability|
| 3.4.5 Specific properties and composition|
| 4.1 Indications|
| 4.2 Therapeutic dosage|
| 4.2.1 Adults|
| 4.2.2 Children|
| 4.3 Contraindications|
|5. ROUTES OF ENTRY|
| 5.1 Oral|
| 5.2 Inhalation|
| 5.3 Dermal|
| 5.4 Eye|
| 5.5 Parenteral|
| 5.6 Other|
| 6.1 Absorption by route of exposure|
| 6.2 Distribution by route of exposure|
| 6.3 Biological half-life by route of exposure|
| 6.4 Metabolism|
| 6.5 Elimination by route of exposure|
|7. PHARMACOLOGY AND TOXICOLOGY|
| 7.1 Mode of action|
| 7.1.1 Toxicodynamics|
| 7.1.2 Pharmacodynamics|
| 7.2 Toxicity|
| 7.2.1 Human data|
| 184.108.40.206 Adults|
| 220.127.116.11 Children|
| 7.2.2 Relevant animal data|
| 7.2.3 Relevant in vitro data|
| 7.3 Carcinogenicity|
| 7.4 Teratogenicity|
| 7.5 Mutagenicity|
| 7.6 Interactions|
| 7.7 Main adverse effects|
|8. TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS|
| 8.1 Material sampling plan|
| 8.1.1 Sampling and specimen collection|
| 18.104.22.168 Toxicological analyses|
| 22.214.171.124 Biomedical analyses|
| 126.96.36.199 Arterial blood gas analysis|
| 188.8.131.52 Haematological analyses|
| 184.108.40.206 Other (unspecified) analyses|
| 8.1.2 Storage of laboratory samples and specimens|
| 220.127.116.11 Toxicological analyses|
| 18.104.22.168 Biomedical analyses|
| 22.214.171.124 Arterial blood gas analysis|
| 126.96.36.199 Haematological analyses|
| 188.8.131.52 Other (unspecified) analyses|
| 8.1.3 Transport of laboratory samples and specimens|
| 184.108.40.206 Toxicological analyses|
| 220.127.116.11 Biomedical analyses|
| 18.104.22.168 Arterial blood gas analysis|
| 22.214.171.124 Haematological analyses|
| 126.96.36.199 Other (unspecified) analyses|
| 8.2 Toxicological Analyses and Their Interpretation|
| 8.2.1 Tests on toxic ingredient(s) of material|
| 188.8.131.52 Simple Qualitative Test(s)|
| 184.108.40.206 Advanced Qualitative Confirmation Test(s)|
| 220.127.116.11 Simple Quantitative Method(s)|
| 18.104.22.168 Advanced Quantitative Method(s)|
| 8.2.2 Tests for biological specimens|
| 22.214.171.124 Simple Qualitative Test(s)|
| 126.96.36.199 Advanced Qualitative Confirmation Test(s)|
| 188.8.131.52 Simple Quantitative Method(s)|
| 184.108.40.206 Advanced Quantitative Method(s)|
| 220.127.116.11 Other Dedicated Method(s)|
| 8.2.3 Interpretation of toxicological analyses|
| 8.3 Biomedical investigations and their interpretation|
| 8.3.1 Biochemical analysis|
| 18.104.22.168 Blood, plasma or serum|
| 22.214.171.124 Urine|
| 126.96.36.199 Other fluids|
| 8.3.2 Arterial blood gas analyses|
| 8.3.3 Haematological analyses|
| 8.3.4 Interpretation of biomedical investigations|
| 8.4 Other biomedical (diagnostic) investigations and their interpretation|
| 8.5 Overall Interpretation of all toxicological analyses and toxicological investigations|
| 8.6 References|
|9. CLINICAL EFFECTS|
| 9.1 Acute poisoning|
| 9.1.1 Ingestion|
| 9.1.2 Inhalation|
| 9.1.3 Skin exposure|
| 9.1.4 Eye contact|
| 9.1.5 Parenteral exposure|
| 9.1.6 Other|
| 9.2 Chronic poisoning|
| 9.2.1 Ingestion|
| 9.2.2 Inhalation|
| 9.2.3 Skin exposure|
| 9.2.4 Eye contact|
| 9.2.5 Parenteral exposure|
| 9.2.6 Other|
| 9.3 Course, prognosis, cause of death|
| 9.4 Systematic description of clinical effects|
| 9.4.1 Cardiovascular|
| 9.4.2 Respiratory|
| 9.4.3 Neurological|
| 188.8.131.52 CNS|
| 184.108.40.206 Peripheral nervous system|
| 220.127.116.11 Autonomic nervous system|
| 18.104.22.168 Skeletal and smooth muscle|
| 9.4.4 Gastrointestinal|
| 9.4.5 Hepatic|
| 9.4.6 Urinary|
| 22.214.171.124 Renal|
| 126.96.36.199 Other|
| 9.4.7 Endocrine and reproductive systems|
| 9.4.8 Dermatological|
| 9.4.9 Eye, ear, nose, throat: local effects|
| 9.4.10 Haematological|
| 9.4.11 Immunological|
| 9.4.12 Metabolic|
| 188.8.131.52 Acid-base disturbances|
| 184.108.40.206 Fluid and electrolyte disturbances|
| 220.127.116.11 Others|
| 9.4.13 Allergic reactions|
| 9.4.14 Other clinical effects|
| 9.4.15 Special risks|
| 9.5 Other|
| 9.6 Summary|
| 10.1 General principles|
| 10.2 Relevant laboratory analyses|
| 10.2.1 Sample collection|
| 10.2.2 Biomedical analysis|
| 10.2.3 Toxicological analysis|
| 10.2.4 Other investigations|
| 10.3 Life supportive procedures and symptomatic/specific treatment|
| 10.4 Decontamination|
| 10.5 Elimination|
| 10.6 Antidote treatment|
| 10.6.1 Adults|
| 10.6.2 Children|
| 10.7 Management discussion|
|11. ILLUSTRATIVE CASES|
| 11.1 Case reports from literature|
| 11.2 Internally extracted data on cases|
| 11.3 Internal cases|
|12. Additional information|
| 12.1 Availability of antidotes|
| 12.2 Specific preventive measures|
| 12.3 Other|
|14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE ADDRESS(ES)|
Amino-4-quinoline (quinoline derivative)
1.4 Identification numbers
1.4.1 CAS number
1.4.2 Other numbers
Chloroquine dihydrochloride: 3545-67-3
Chloroquine diphospate: 50-63-5
Chloroquine phosphate: 1446-17-9
Chloroquine sulfate: 132-73-0
VB2450000 Chloroquine diphosphate
VB2625000 Chloroquine phosphate
VB2630000 Chloroquine sulfate
VB9642000 Chloroquine dihydrochloride
1.5 Brand names, Trade names
1.6 Manufacturers, Importers
2.1 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
2.2 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: apnoea.
Gastrointestinal symptoms: severe gastrointestinal irritation;
nausea, vomiting, cramps, diarrhoea.
Children are specially sensitive to toxic effects.
Dizziness, nausea, vomiting, diarrhoea, headache, drowsiness,
blurred vision, diplopia, blindness, convulsions, coma,
hypotension, cardiogenic shock, cardiac arrest and impaired
respiration are the characteristic features of chloroquine
Electrocardiography (ECG) may show decrease of T wave,
widening of QRS, ventricular tachycardia and fibrillation.
Hypokalaemia (potassium < 3 mmol/L) is associated with severe
High serum chloroquine levels confirm the diagnosis.
Concentrations higher than 5 mg/L are usually observed in
2.4 First aid measures and management principles
Patients with acute chloroquine overdose should always be
admitted in an intensive care unit.
Monitor vital signs (ECG, blood pressure, respiration) and
measure serum electrolytes, especially, potassium.
- supportive treatment: artificial ventilation, cardiac
- inotropic and vasopressor drugs: adrenaline, isoproterenol,
dopamine, and hypertonic sodium solutions,
- diazepam IV to prevent or reduce cardiotoxicity,
- gastric emptying and activated charcoal.
3. PHYSICO-CHEMICAL PROPERTIES
3.1 Origin of the substance
Chloroquine was originally synthesized in 1934 by Bayer in
Chloroquine is prepared by the condensation of 4-7-
dichloroquinoline with 1-diethylamino-4-aminopentane.
3.2 Chemical structure
7-chloro-4-(4-diethylamino-1-methylbutylamino)quinoline, or N4-
C18H26CIN3 Molecular weight: 319.92
C18H29ClN3.2H3PO4 MW = 515.92
C18H29ClN3.H3PO4 MW = 417.92
C18H26ClN3. H2SO4 MW = 418.00
C18H26ClN3.2HCl MW = 392.84
3.3 Physical properties
3.3.1 Properties of the substance
Chloroquine is a white or slightly yellow, odourless
crystalline powder with a bitter taste. Melting point:
87 to 92°C. Very slightly soluble in water, soluble in
chloroform, ether and dilute acids.
Chloroquine diphosphate is a white, bitter, crystalline
powder that exists in two polymorphic forms, one melting
between 193°C and 195°C, and the other between 210°C and
215°C (mixture of the forms melt between 193°C and 215°C.
Readily soluble in water at acidic pH. Practically insoluble
in alcohol, methanol, ether, chloroform.
Chloroquine sulfate is a white, odourless, bitter,
crystalline powder. Melting point: 205°C to 210°C.
Readily soluble in water and methanol. Hydroxychloride
chloroquine is a colourless liquid, pH between 5.5 and 6.5.
Solutions of chloroquine phosphate and hydroxychloroquine
sulfate have a pH = 4.5.
3.3.2 Properties of the locally available formulation
No data available.
3.4 Other characteristics
3.4.1 Shelf-life of the substance
At least five years.
3.4.2 Shelf-life of the locally available formulation
To be completed.
3.4.3 Storage conditions
Chloroquine diphosphate is stable to heat in solution of
pH 4.0 to 6.5. Chloroquine phosphate and chloroquine
sulfate are sensitive to light.
To be added by the local poisons centre.
3.4.5 Specific properties and composition
No data available.
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.
Amoebiasis - Chloroquine is used for the treatment of
extraintestinal amebiasis (usually in combination with amebicides).
Discoid lupus erythematosus and rheumatoid arthritis (acute and
chronic). Chloroquine may be used for the treatment of these
Other less common indications are: amebic liver abscess,
polymorphus light eruption, prophyria cutanea tarda, solar
urticaria, chronic cutaneous vasculitis.
4.2 Therapeutic dosage
Oral: 600 to 900 mg the lst day, then 300 mg daily
I.M.: 200 to 300 mg/day for three to five days.
Oral: 100 mg/day or one dose of 300 mg weekly for six
Oral: 600 mg/day for three days then 300 mg/day.
Discoid lupus erythematosus and rheumatoid arthritis
Oral: 300 mg/day.
Oral: 10 mg/kg as loading dose, then 5 mg/kg/day
for four days.
IM: is not recommended in children.
Oral: age below 1 year: 25 mg every two days
age over 1 year: 25 to 50 mg per day
or: 5 mg/kg one dose weekly.
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
Chloroquine in doses used for malaria prophylaxis is safe in
pregnancy and breast feeding (Kasilo et al. 1988).
5. ROUTES OF ENTRY
Oral absorption is the most frequent cause of intoxication.
Intoxication after parenteral administration is rare. Abu
Aisha et al. (1979) reported a fatal outcome after 250 mg IV
chloroquine in a 42-year-old man.
6.1 Absorption by route of exposure
Readily and almost completely absorbed from the
Bioavailability is 89% for tablets (Gustafsson et al., 1983).
Half time of absorption is 0.56 h (Adelusi et al., 1982).
Peak plasma concentration is reached 1.5 to 3 hours after
6.2 Distribution by route of exposure
Protein binding: 5O to 65% (Walker et al. 1983).
Apparent volume of distribution is very high: 116 to 285 L/kg
(Gustafsson et al., 1983).
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
Very low concentrations in intestinal wall.
Crosses the placenta.
6.3 Biological half-life by route of exposure
Plasma terminal half-life is mean 278 hours (Gustafsson et al.
1983) or 70 to 120 hours (USP, 1988).
Shorter plasma elimination half-lives have been reported in
children: 75 to 136 hours.
Chloroquine undergoes partly hepatic metabolism.
The main active metabolite is desethylchloroquine. Plasma
half-life of desethylchloroquine is similar to chloroquine
(Walker et al., 1983).
6.5 Elimination by route of exposure
Chloroquine is eliminated very slowly. About 55% is excreted
in urine and 19% in faeces within 77 days following therapy
with 310 mg for 14 days (McChesnay et al. 1967).
Kidney: in urine about 70% is unchanged chloroquine and 23% is
desethylchloroquine (Gustafsson et al., 1983).
Renal clearance is mean 410 ml/min (Gustafsson et al., 1983).
Total body clearance: mean 722 ml/min (Gustafsson et al.,
It is excreted in breast milk (USP, 1988).
7. PHARMACOLOGY AND TOXICOLOGY
7.1 Mode of action
The cardiotoxicity of chloroquine is related to it
quinidine-like (membrane/stabilizing) effects.
Chloroquine has a negative inotropic ction, inhibits
spontaneous diastolic depolarization, slows conduction,
lengthens the effective refractory period and raises the
electrical threshold (Jaeger et al., 1987). This
results in depression of contractility, impairment of
conductivity, decrease of excitability, but with
possible abnormal stimulus re-entry mechanism. The
following progression of ECG changes was observed in
dogs with experimental overdosage (Don Michael and
Aiwazzadey, 1970): severe tachycardia preceded by loss
of voltage and widening of QRS, followed by sinus
bradycardia, ventricular tachycardia, ventricular
fibrillation and finally asystole.
Hypokalaemia: Acute hypokalaemia may occur in acute
poisoning (Lofaso et al., 1986; Jaeger et al., 1987).
It is probably related to intracellular transport of
potassium by a direct effect on cellular membrane
Neurological symptoms: Neurological symptoms in acute
overdose may be related to a direct toxic effect on CNS
or to cerebral ischaemia due to circulatory failure or
Chloroquine and its 4 amino-quinoline congeners block
the enzymatic synthesis of DNA and RNA. Chloroquine is
an excellent blood schizonticide but has no effect on
secondary tissue schizonts and on sporozoites. It
inhibits the erythrocytic stage of development of
plasmodia. Thus relapses may occur after cessation of
The mechanism of the anti-inflammatory effect is not
Chloroquine has a quinidine-like (membrane stabilizing)
effect on the cardiovascular system.
7.2.1 Human data
Chloroquine has a low margin of safety; the
therapeutic, toxic and lethal doses are very
In adults fatalities have been reported after
ingestion of 2.25 to 3 g chloroquine (Britton &
Kevau, 1978). Without treatment, a dose of 4 g
is usually lethal.
So 20 mg/Kg is a toxic dose, 30 mg/Kg may be
lethal and 40 mg/Kg is usually lethal without
early intensive therapy (Jaeger et al., 1987).
Vitris and Aubert (1983) distinguished three
types of overdose:
Dose Severity Symptoms Plasma(g)
absorbed of poisoning chloroquine
> 4 severe neurological > 5
2 to 4 moderate neurologic 2.5 to 5
< 2 mild ./. < 2.5
Abu Aisha et al. (1979) reported fatal outcome
after an intravenous administration of 250 mg in
a 42-year-old man.
20 mg/kg (i.e., twice the maximal therapeutic
dose) is a toxic dose.
Fatalities have been reported in children after
chloroquine overdoses; in a three-year-old boy
after 300 mg (Clyde, 1966); in a three-year-old
child after 1 gram, a 14-month-old child after 1
to 2 grams (Markowitz & McGinley, 1964) and in a
three-year-old child after 0.75 to 1 gram (Cann
& Verhulst, 1961).
7.2.2 Relevant animal data
DSO L (mg/kg)
IV Intraperi- Subcutaneous Oral
Mouse 40 250 150 200-400
Rat - 102 - 1050
Rabbit 8 - - 75
Dogs 100 - - -
7.2.3 Relevant in vitro data
No data available.
No teratogenic effects reported in therapeutic doses but in
high doses see 9.4.15 B.
No data available.
Chloroquine toxicity may be increased by all drugs with
Combination with hepatotoxic or dermatitis-causing medication
should be avoided, as well as with heparin (risk of
haemorrhage) and penicillamine (USP, 1988).
May interfere with rabies vaccination (Kasilo, 1988).
7.7 Main adverse effects
Chloroquine is generally well tolerated when given in
antimalarial doses and when side effects occur they are
rapidly reversible on withdrawal of the drug. Higher doses
used for prolonged periods are more likely to produce adverse
effects (Reynolds, 1982).
The following adverse effects have been reported during
- Cardiovascular: ECG changes, flattening and inversion of T
waves, prolongation of QT interval.
- Neurological: toxic psychosis with hallucinations and
agitation, peripheral neuropathy, myopathy, convulsions.
- Gastrointestinal: nausea, vomiting, diarrhoea, abdominal
- Dermatological: pruritus, maculopapular eruption,
exfoliative dermatitis, purpuric skin reactions,
photosensitivity, hyperpigmentation, alopecia, greying of
- 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.
- Ear: tinnitus and deafness are rare.
- Haematological: leucopenia, methaemoglobinaemia.
- Other: pronounced porphyrinuria after chloroquine treatment
in patients with cutaneous porphyria has been reported.
8. TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS
8.1 Material sampling plan
8.1.1 Sampling and specimen collection
18.104.22.168 Toxicological analyses
22.214.171.124 Biomedical analyses
126.96.36.199 Arterial blood gas analysis
188.8.131.52 Haematological analyses
184.108.40.206 Other (unspecified) analyses
8.1.2 Storage of laboratory samples and specimens
220.127.116.11 Toxicological analyses
18.104.22.168 Biomedical analyses
22.214.171.124 Arterial blood gas analysis
126.96.36.199 Haematological analyses
188.8.131.52 Other (unspecified) analyses
8.1.3 Transport of laboratory samples and specimens
184.108.40.206 Toxicological analyses
220.127.116.11 Biomedical analyses
18.104.22.168 Arterial blood gas analysis
22.214.171.124 Haematological analyses
126.96.36.199 Other (unspecified) analyses
8.2 Toxicological Analyses and Their Interpretation
8.2.1 Tests on toxic ingredient(s) of material
188.8.131.52 Simple Qualitative Test(s)
184.108.40.206 Advanced Qualitative Confirmation Test(s)
220.127.116.11 Simple Quantitative Method(s)
18.104.22.168 Advanced Quantitative Method(s)
8.2.2 Tests for biological specimens
22.214.171.124 Simple Qualitative Test(s)
126.96.36.199 Advanced Qualitative Confirmation Test(s)
188.8.131.52 Simple Quantitative Method(s)
184.108.40.206 Advanced Quantitative Method(s)
220.127.116.11 Other Dedicated Method(s)
8.2.3 Interpretation of toxicological analyses
8.3 Biomedical investigations and their interpretation
8.3.1 Biochemical analysis
18.104.22.168 Blood, plasma or serum
22.214.171.124 Other fluids
8.3.2 Arterial blood gas analyses
8.3.3 Haematological analyses
8.3.4 Interpretation of biomedical investigations
8.4 Other biomedical (diagnostic) investigations and their
8.5 Overall Interpretation of all toxicological analyses and
9. CLINICAL EFFECTS
9.1 Acute poisoning
Severity of chloroquine poisoning is related to the
cardiotoxic effects. Symptoms appear rapidly after
ingestion and may include: dizziness, nausea, vomiting,
diarrhoea and headache.
Neurological symptoms: drowsiness, blurred vision,
diplopia, blindness, convulsions and coma.
Respiratory symptoms: polypnoea, apnoea.
Cardiovascular symptoms: hypotension, cardiogenic shock,
cardiac arrest. ECG - decrease of T wave, widening of
QRS, ventricular tachycardia and fibrillation.
Hypokalaemia (K < 3 mmol/L) is associated with severe
9.1.3 Skin exposure
9.1.4 Eye contact
9.1.5 Parenteral exposure
Clinical effects are similar to those observed after
ingestion. See Section 9.1.1.
No data available.
9.2 Chronic poisoning
The most relevant features of chronic poisoning are
keratopathy, retinopathy and neurological symptoms (see
Section 7.7, main side effects).
9.2.3 Skin exposure
9.2.4 Eye contact
9.2.5 Parenteral exposure
No data available.
No data available.
9.3 Course, prognosis, cause of death
The most important feature of acute chloroquine intoxication
is the rapid onset (within one to three hours) of severe toxic
Drowsiness appears early within 10 to 30 minutes of ingestion.
Severe cardiovascular symptoms appear within one to three
hours of ingestion. Fatal outcome usually occur within two to
three hours. Cardiovascular symptoms may last for 48 hours.
After the 48th hour patients usually recover.
Criteria of severe intoxications are: dose ingested higher
than 3 to 4 g, hypotension, cardiogenic shock, QRS widening,
ventricular arrhythmias, hypokalaemia. Severity of the
intoxication is closely related to the serum potassium
concentration (Lofaso et al., 1987; Jaeger et al., 1987).
Cause of death
The cause of death is circulatory arrest which occurs
predominantly during the first few hours of the intoxication
and is related to cardiac insufficiency or ventricular
9.4 Systematic description of clinical effects
Cardiovascular symptoms are present in 50 to 60% of the
cases (Jaeger et al., 1987).
Cardiac arrest: may occur within one to two hours
following ingestion. It is related to cardiac
insufficiency, ventricular dysrhythmia or asystole.
After the eighth hour, cardiac arrest is mostly related
to ventricular dysrhythmia and especially "torsade de
Shock: Hypotension is frequent and may rapidly progress
to a cardiogenic shock with increased venous pressure.
Haemodynamic studies showed a decrease of cardiac output
and a peripheral vasodilatation (Bavoux et al., 1987).
Ventricular dysrhythmia: Ventricular tachycardia and
fibrillation may occur up to 24 to 28 hours after
Ventricular extrasystoles and torsade de pointes mainly
occur after the eighth hour post-ingestion.
ECG changes: Repolarization abnormalities: flattening
of T wave increase of QT interval, increase of U wave,
depression of ST segment. Conduction abnormalities:
increase of QRS duration (QRS > 0.08 sec).
Atrioventricular block. Ventricular dysrhythmias:
fibrillation, extrasystoles, torsades de pointes.
ECG changes are not uncommon during high dosage
treatments: T wave abnormalities, prolongation of the QT
interval. Cardiomyopathy and heart block have rarely
Hyperpnoea is frequent. Apnoea may occur, especially at
the onset of convulsions or cardiac failure.
No data available.
Drowsiness appears early within 10 to 30 minutes
post-ingestion. Coma is less common and is in
most cases associated with circulatory failure.
A concomitant ingestion of psychotropic drugs
should be suspected in the case of deep coma
without circulatory failure. CNS
hyperexcitability with agitation and convulsions
usually precedes circulatory arrest.
Several cases of acute psychosis ascribed to
chloroquine have been reported. Symptoms
included confusion, agitation, aggressiveness,
personality changes, psychotic symptoms and
depression. Seizures preceded by blurring of
vision have also occurred in a few patients at
126.96.36.199 Peripheral nervous system
Quadriplegia concomitant with severe
hypokalaemia has been reported (Lofaso et al.,
Peripheral neuritis, neuromyopathy and myopathy
have been described as a complication of long-
term chloroquine therapy. The onset is
insidious with a progressive weakness first
affecting the proximal muscle of the lower
extremities. Increased serum levels of SGOT and
SGPT may be present. Reduction in efferent
nerve conduction time and EMG abnormalities of
neuropathy and myopathy can be found.
Involuntary movements with protrusion of tongue
and other extrapyramidal symptoms have been
recorded (Reynolds, 1982).
188.8.131.52 Autonomic nervous system
No data available.
184.108.40.206 Skeletal and smooth muscle
No data available.
Nausea, vomiting, abdominal cramps and diarrhoea.
Haematemesis gastric and duodenal erosions has been
reported after therapeutic doses of chloroquine
phosphate (Bhasin & Chhina, 1989)
Nausea, vomiting and diarrhoea may occur. Stomatitis has
rarely been reported.
Acute: No direct hepatotoxic effect has been reported.
Increase in hepatic enzymes may be observed after
Chronic: Chloroquine administered in high doses may
elevate serum aspartate-aminotransferase (SGOT)
Acute: No direct nephrotoxic effect has been
reported. An acute renal failure related to
cardiogenic shock may occur.
Chronic: No data available.
No data available.
9.4.7 Endocrine and reproductive systems
No data available.
Acute: No data available.
Chronic: Skin lesions have been attributed to the use
of chloroquine. Photosensitivity and photoallergic
dermatitis have been reported, particularly in patients
on long-term therapy with high dosages. Pronounced
porphyrinuria after chloroquine has occurred in patients
with porphyria cutanea tarda.
Pigmentation abnormalities may occur and include: blue
black pigmentation involving the palate, facial,
pretibial and subungual areas, bleaching of the scalp,
9.4.9 Eye, ear, nose, throat: local effects
Acute: Visual disturbances are frequent (10 to 38% of
the cases) and include blurred or impaired colour vision,
diplopia, photophobia and sometimes blindness.
Blindness, however, is always transient and recovers
Chronic: Keratopathy and retinopathy may occur in a
large number of patients when large doses of chloroquine
are used for a long period. Both side effects are dose-
related. The incidence of keratopathy is high (30 to
70% of treated patients) and corneal changes are usually
completely reversible on discontinuing treatment.
Changes in the retina are irreversible and may become
worse even though the drug is discontinued. Symptoms
are: difficulty in reading, scotomata, defective colour
vision, photophobia, blindness. The typical retinal
picture is an intact foveal area surrounded by a
depigmented ring, narrowing of the arteria and optic
disk atrophy. Retinal changes occur very early and may
appear as a first symptom. Electro-oculogram and
electro-retinogram show early depression in chloroquine
Acute: Tinnitus may occur. Deafness is observed
Chronic: Ototoxicity has been mentioned occasionally.
Tinnitus and deafness were described related to high
Throat: No data available.
Acute: No data available.
Chronic: Leucopenia has been reported after long-term
therapy. Haemoglobinuria with acute renal failure has
been reported in patients with glucose-6-phosphate
dehydrogenase deficiency (G6PD).
No data available.
220.127.116.11 Acid-base disturbances
Acute: Metabolic acidosis may occur in severe
poisoning with circulatory failure.
Chronic: No data available.
18.104.22.168 Fluid and electrolyte disturbances
Acute: Hypokalaemia is almost always present
in severe intoxications. The severity of
chloroquine intoxication is closely related to
the serum potassium concentration.
Hypokalaemia appears within three hours of
ingestion (Jaeger et al., 1987). Severe
hypokalaemia of 0.8 to 1.1 mmol/L have been
reported (Lofaso et al., 1987). Hypokalaemia
is probably due to an intracellular transport
of potassium by a direct toxic effect of
chloroquine on cellular membrane permeability.
Chronic: No data available.
No data available.
9.4.13 Allergic reactions
9.4.14 Other clinical effects
No data available.
9.4.15 Special risks
Chronic: 4-aminoquinolines have been shown to
accumulate selectively in melanin structures of fetal
eyes. They may be retained in ocular tissues for up to
five months after elimination from the rest of the body
Chloroquine in doses used for malaria prophylaxis
appears to be safe for use during pregnancy (Anon.,
1987). However, chloroquine can cross the placental
barrier and bilateral cochleo-vestibular disturbances
have been reported in children of mothers treated with
high doses of chloroquine during pregnancy.
Chloroquine is not contraindicated in pregnancy but
high doses or long-term treatment should be avoided.
Insignificant amounts of chloroquine are found in
breast milk (Clyde & Shut, 1976).
G-6-P-D deficiency: chloroquine may induce haemolysis
The use of chloroquine in porphyrias is controversial
10.1 General principles
Patients with chloroquine overdose should always be admitted
to an intensive care unit. Treatment depends on the dose
ingested and on the severity of poisoning. It includes
gastric lavage. IV diazepam to prevent or reduce
cardiotoxicity, and supportive treatment with artificial
ventilation, inotropic and vasopressor drugs. Vital signs
(ECG, blood pressure, respirations) and serum potassium
concentrations should be monitored.
10.2 Relevant laboratory analyses
10.2.1 Sample collection
Blood samples for chloroquine should be drawn into
plastic tube with heparin. Chloroquine may be
analyzed in whole blood or plasma. Chloroquine
concentrations in whole blood are five to ten times
higher than those in plasma.
Collect samples of urine and gastric aspirate.
because chloroquine may also be analyzed in them.
10.2.2 Biomedical analysis
A biochemical profile with glucose, BUN, creatinine,
electrolytes and blood gases should be obtained on
admission. In severe cases, monitor every four to
six hours serum potassium level during the 24 to 48
10.2.3 Toxicological analysis
Chloroquine analysis is not usually available. A
serum chloroquine concentration less than 2 mg/L,
four to six hours post-ingestion, indicates a mild
The blood fraction used for measuring chloroquine
concentration is important since different
concentrations have been noted when plasma
erythrocytes and whole blood were analyzed.
Chloroquine concentrations are higher in erythrocytes
than in plasma.
Chloroquine may be analyzed by UV spectrometry,
fluorometry and high pressure liquid chromatography
(HPLC). HPLC is the preferred method since
chloroquine and also desethylchloroquine can be
It is crucial to state whether analyses are done on
whole blood, serum or properly separated plasma
(Gustafsson et al., 1983).
In a study of patients under chloroquine therapy
occurrence of side effects was related to chloroquine
serum concentrations (Frisk Holmberg et al., 1979).
No side effects occurred in patients with
concentrations less than 0.39 mg/L whereas 80% of the
patients with levels higher than 0.8 mg/L had side
Vitris and Aubert (1983) distinguished three grades
of severity in chloroquine overdose. Chloroquine
serum concentrations were less than 2.5 mg/L in mild
concentrations, between 2.5 and 5 mg/L in moderate
and higher than 5 mg/L in severe intoxications.
In severe poisoning accompanied by shock or cardiac
arrest, serum concentrations are usually higher than
5 mg/L (Jaeger et al., 1987).
Post-mortem serum blood concentrations reported range
from 1.7 to 132.5 mg/L.
A toxicokinetic study performed in seven cases of
chloroquine poisoning showed a mean plasma half-life
of 24.5 hours, an absorption half-time of two hours.
A mean of 7% chloroquine was removed by gastric
lavage and mean 9.2% was excreted in urine over 49
hours (Jaeger et al., 1987).
10.2.4 Other investigations
10.3 Life supportive procedures and symptomatic/specific
- Observation and monitoring
Monitor systematically vital signs, ECG and blood
pressure. Frequent (at least every five minutes during the
acute phase) blood pressure monitoring is essential for the
detection of circulatory arrest without asystole.
Insert a central venous catheter for monitoring and
- Circulatory arrest
Perform external cardiac massage. Support ventilation
using appropriate mechanical device. Administer oxygen (for
many hours if necessary). Administer adrenaline: 1 to 4 mg
IV in an adult, 0.25 to 0.5 mg by intratracheal route in a
child. Administer sodium bicarbonate for correction of
- Respiratory depression
Should be treated by artificial ventilation.
Artificial ventilation is also indicated when patients
present cardiotoxic symptoms or even when the patient is
asymptomatic and the dose ingested is higher than 3 to 4 g.
- Hypotension, cardiogenic shock
Vasopressor drugs are indicated for the treatment of
cardiogenic shock. Adrenaline appears to be the drug of
choice but isoproterenol or dopamine may be given.
Adrenaline: Administer adrenaline in continuous
infusion. Begin at a dose of 0.25 µg/kg/minute and progress
to 0.1 µg/kg/minute in increments as needed. Five mg
adrenaline diluted in 250 ml of dextrose 5% produces a
concentration of 20 µg/ml.
Isoproterenol: Administer isoproterenol in continuous
infusion. Begin at a dose of 0.3 µg/kg/minute and progress
in 0.2 µg/kg/minute in increments as needed. Four mg
isoproterenol diluted in 250 ml of dextrose 5% produces a
concentration of 16 µg/ml.
Dopamine: Administer dopamine in continuous infusion.
Begin at a dose of 10 µg/kg/minute and progress in 5
µg/kg/minute inincrements as needed. 600 mg dopamine
diluted in 250 ml of dextrose 5% produces a concentration of
- Conduction disturbances
Isoproterenol: Administer adrenaline or isoproterenol
at the same regimens as described above if bradyarrhythmia,
cardiac arrest or AV block occur (even in grade I).
Sodium hypertonic solutions: Sodium hypertonic
solutions may be effective in conduction disturbances due to
quinidine-like membrane stabilizing effects.
(i) molar sodium lactate: 100 to 250 ml over 15 to 45
(ii) molar sodium bicarbonate: administer 100 to 250 ml
of molar sodium bicarbonate solution (8.4 g per cent) over
15 to 45 minutes.
Remark: Add 2 g KCl per 250 ml of these solutions in
order to avoid hypokalaemia. Repeated monitoring of
electrolytes is necessary because hypernatraemia and
hypokalaemia may appear.
- Ventricular dysrhythmias
All antiarrhythmic drugs and especially those with
quinidine-like effects are contraindicated. Electric
countershock is indicated for ventricular tachycardia and
fibrillation and eventually torsades de pointes.
Acceleration of cardiac rhythm by isoproterenol (up to 120
minutes) may be useful for preventing further dysrhythmia
due to re- entry mechanisms.
Initial hypokalaemia may be protective because potassium
and quinidine- like drugs have a synergistic cardiotoxic
effect (Bellet & Wasserman, 1987). Initial hypokalaemia
should be corrected cautiously because intensive potassium
administration may lead to a sudden hyperkalaemia (Lofaso et
al., 1987; Jaeger et al. 1987). Persistent hypokalaemia
beyond eight hours after the ingestion may favour
ventricular dysrhythmia and should be corrected.
Administer potassium continuously with frequent control
of plasma potassium levels (every four hours). Add 5 g KCl
to 500 ml of dextrose 5% and do not exceed infusion of more
than 1 g to 1.5 g KCl per hour.
- Gastric lavage
Early gastric lavage is indicated but should be
preceded by symptomatic treatment and intubation with
artificial ventilation in order to avoid sudden cardiac
arrest and lung aspiration. The efficacy of gastric lavage
varies greatly but up to 22% of the dose ingested may be
removed (Jaeger et al., 1987).
If convulsions or cardiovascular disturbances occur,
they should be controlled before attempting gastric lavage.
Because coma, cardiac and respiratory arrests may occur
one to two hours post-ingestion, emesis is contraindicated
unless done immediately after ingestion.
- Oral activated charcoal
Chloroquine is well absorbed by charcoal although its
efficacy has not yet been established. However, oral
activated charcoal is recommended at the end of gastric
lavage and repeated every four hours for 24 hours.
The usefulness of cathartics has not been established.
Cathartics should be used with caution in this situation
because shock and hypokalaemia are frequent.
- Forced diuresis
The low elimination of chloroquine in urine does not
justify forced diuresis (Jaeger et al. 1987). Urine
chloroquine elimination is more dependent on the
haemodynamic status than on infusion of osmotic solutions or
acidification of urine.
Peritoneal dialysis and haemodialysis are of little
value in removing chloroquine from the body. Experimental
studies in dogs showed that haemodialysis removed less than
5% of the administered dose (Van Stone, 1976). In human
poisonings, haemodialysis (Jaeger et al. 1987) and
peritoneal dialysis (Lareng et al. 1980; McCann et al. 1975)
proved to be ineffective.
Haemoperfusion is not recommended.
The following clearances have been reported: clearance
with resin haemoperfusion = 135 ml/min (Heath et al. 1982),
clearance with charcoal haemoperfusion = 45 to 60 ml/minute
(Maier & Benkert, 1984). However, chloroquine has a large
volume of distribution. The amount removed by
haemoperfusion is not significant; only 5% in a case treated
by Heath et al. (1982).
10.6 Antidote treatment
Experimental and clinical studies show that diazepam
may exert a protective effect against chloroquine
cardiotoxicity (Bondurand et al. 1980; Bouvier et al.
1986; Charbonneau et al. 1986; Hoang et al. 1981;
Riou et al. 1986; Riou et al. 1987). Thus, diazepam
should be systematically administered in chloroquine
intoxication when the dose ingested is higher than 2
g (in adults) (Jaeger et al. 1987; Wattel et al.
a) Loading dose
A loading dose of 1 mg/kg is recommended. If
cardiotoxic abnormalities do not improve, higher
doses may be administered.
Diazepam administration should always be associated
with intubation and mechanical ventilation in order
to avoid respiratory depression and with inotropic
vasopressor drugs when cardiotoxic symptoms are
A loading dose of 0.5 mg/kg is recommended if
intubation facilities are not available.
b) Continuous infusion
Further administration of diazepam depends on the
clinical features and on the amount ingested. If
cardiotoxic symptoms are present or if the dose
ingested is higher than 3 g in adult or 30 mg/kg in
child, a continuous infusion of diazepam may be given
at a dose of 5 to 10 mg/hour in adults or 0.25 to 0.4
mg/kg/hour in children over a period of 24/48 hours.
Recurrence of cardiotoxic signs may need additional
direct IV injection of diazepam.
Given that chloroquine cardiotoxicity is rarely
observed later than 48 hours after ingestion,
diazepam administration after the 48th hour appears
not to be justified.
See Section 10.6.1.
10.7 Management discussion
- Outside of intensive care unit (ICU):
(i) Monitor vital signs
a) No treatment: if dose ingested is less than 2 g in
adult(or less than 20 mg/kg in child) and if these patients
do not present cardiotoxic symptoms.
b) Diazepam 0.5 mg/kg: if dose ingested is higher than 2 g
in adult (or higher than 20 mg/kg in child) or if
cardiotoxic symptoms are present with a lower dose ingested.
c) Adrenaline or isoproterenol (see section 10.3) if
cardiotoxic symptoms are present.
(iii) Transfer the patient as soon as possible to an ICU
- Inside the ICU:
(i) Monitor vital signs and biochemical parameters
a) Dose ingested < 2 g in adults (< 20 mg/kg in child)
and no cardiotoxic symptoms: perform gastric lavage.
b) Dose ingested > 2 g in adult (> 20 mg/kg in child)
or patients with cardiotoxic symptoms
- diazepam in a loading dose of 1 mg/kg and then
continuous infusion (see Section 10.6)
- intubation and artificial ventilation
- gastric lavage
- adrenaline or isoproterenol (see Section 10.3)
11. ILLUSTRATIVE CASES
11.1 Case reports from literature
Jaeger et al. (1987) in a review analyzed the frequency of
clinical features observed in 5 series of chloroquine
intoxications (170 cases in total) reported in literature
(Frija, 1975; Britton et al. 1978; Vitris & Aubert, 1983;
Jaeger et al. 1987). Frequency of different signs was:
drowsiness 30 to 45%; coma 9 to 23%; convulsion 4 to 11%;
visual symptoms 12-38%; apnoea 5to 19%; cardiovascular
symptoms 50 to 61%; shock 23%; cardiac arrest 3 to 23%;
widening of QRS 3 to 35%; ventricular tachycardia 11.5%;
ventricular fibrillation 4%; hypokalaemia 23%. Fatalities
occurred in 3 to 19% of the cases.
Lofoso et al. (1981) reported two cases of chloroquine
poisoning with severe hypokalaemia.
Case 1: A 28-year-old man developed cardiac arrest after
ingestion of 10 g chloroquine. Cardiac arrest was
reversible with symptomatic treatment; external cardiac
massage, artificial ventilation, sodium bicarbonate and
adrenaline 21 mg. On admission, patient was comatose, blood
pressure was 80/30 mmHg. ECG showed QRS duration of 0.12
sec. Serum potassium concentration was 1.4 mmol/l, fell to
1.1 mmol/l and was accompanied by a quadriplegia. Potassium
administration (41 g KCl over 33 hours) led to a sudden
hyperkalaemia (8.5 mmol/l) with cardiac arrest on the 38th
hour post-ingestion. The patient died on the third day from
Case 2: A 26-year-old man developed cardiac arrest after
ingestion of 10 g chloroquine. Cardiac arrest was
reversible with symptomatic treatment. But was followed by
shock, widening of QRS and anoxic coma. Serum potassium
concentration was 1.1 mmol/l on admission. Serum potassium
was 2.2 mmol/l on the 12th hour (after 230 mmol potassium
IV) and 4.2 mmol/l on the 26th hour (after a total dose of
365 mmol potassium IV). The patient died on the 8th day
post-ingestion from infections complications. Severe
chloroquine intoxication may induce hypokalaemia, probably
by an intracellular transport of potassium. Intensive
administration of potassium may lead to a subsequent severe
Riou et al. (1988) reported a comparative study of two
groups of patients with severe chloroquine poisoning. The
second group of patients was treated early by diazepam (2
mg/kg over 30 min), intubation with artificial ventilation,
and adrenaline (0.25 µg/kg/min with 0.25 µg/kg/min
increments as needed). Mortality in the group without this
treatment was 91% (11 patients, dose ingested 7.5 ± 0.5 g),
whereas the mortality in the group with this early treatment
was only 9% (11 patients, dose ingested 8.5 ± 0.2 g). Early
treatment with diazepam, artificial ventilation and
adrenaline improved the prognosis of severe chloroquine
A 39-year-old patient was found to be unconscious after
having taken 2.5 g of chloroquine. Treatment consisted
mainly of gastric lavage and diazepam. Experimental and
clinical evidence is presented to show that diazepam in
varying doses significantly decreases the mortality rate
A 29-year-old patient ingested 6 g of chloroquine in a
suicide attempt. After initial ventricular fibrillation, she
rapidly developed a pulmonary oedema with cardiogenic shock.
She was successfully treated with diazepam, epinephrine,
dobutamine and mechanical ventilation. Plasma chloroquine
levels showed and initial peak of 36 µg/ ml. The patient
discharged fully recovered after 19 days (Bauer et al,
11.2 Internally extracted data on cases
Jaeger et al. (1987) studied the relationship between
symptoms, dose absorbed and plasma potassium concentration.
The severity of the intoxication was closely related to the
serum potassium concentration.
Severity Dose absorbed Kalaemia
Mild poisoning (7 cases) 1.3 ± 0.35 4.06 ±
Moderate poisoning (5 cases) 4.4 ± 3.14 3.38 ± 0.3
Severe poisoning (6 cases) 9.75 ± 7.15 0.95 ±
11.3 Internal cases
To be added by the centre using the monograph.
12. Additional information
12.1 Availability of antidotes
Use of diazepam is under research.
12.2 Specific preventive measures
No data available.
No data available.
Abu-Aisha H, Abu-Sabaa HMA, Nur T (1979). Cardiac arrest after
intravenous chloroquine injection. Journal of Tropical Medicine
Hygiene, 82: 36-37.
Adelusi SA, Dawodu AH, Salako LA (1982) Kinetics of the uptake
and elimination of chloroquine in children with malaria. British
Journal of Pharmacology, 14: 483-487.
Barriot P, Riou B (1988) Intoxications sévères par la
chloroquine. Amélioration du pronostic par un traitement
associant diazépam, adrenaline et ventilation mécanique précoce.
Réanimation, Soins Intensifs, Médecine d'Urgence, 4: 55.
Baud FJ (1988). Intoxication aiguë par la chloroquine. Aspects
pronostiques et thérapeutiques. Réanimation, Soins Intensifs,
Médecine d'Urgence, 4: 56-58.
Bauer P, Maire B, Weber M et al (1991) Full recovery after a
chloroquine suicide attempt. Clinical Toxicology. 29: 23 - 30.
Bavous E, N'Saye F, Lofaso F, Muszinski J, Baud FJ (1987) Etude
hémodynamique des intoxications aiguës graves à la chloroquine.
In XXVe Journées du Groupement Français des Centres Anti-Poisons,
Bhasin DK & Chhina RS. (1989) Chloroquine phosphate induced
haemetemesis. Human Toxicology, 8: 387 - 388.
Bismuth Ch (1988) Intoxication aiguë à la chloroquine.
Incidence, physiopathologie, clinique. Réanimation, Soins
Intensifs, Médecine d'Urgence, 4: 49-51.
Bondurand A, N'Dri K, Coffi S, Saracino E (1980a).
L'intoxication à la chloroquine au CHU Abidjan. Afrique Médical,
Bondurand A, Tricoche R, Offoumou, N'Dri D, Coffi K (1980b).
Intoxications aiguës à la chloroquine. Encylopédia Médico-
Chirurgicale: Instantanés Médicaux, 4: 21-23.
Bouvier AM, Bertrand D, Timsit JF, Ricome JL (1986).
Intoxications massives et prolongées par la Nivaquine. Effets du
diazépam. Réanimation, Soins Intensifs, Médecine d'Urgence, 2:
Britton, WJ, Kevau JH (1978). Intentional chloroquine
overdosage. Medical Journal of Australia, 21: 407-410.
Cann HM, Verhulst HL (1961). Fatal acute chloroquine poisoning
in children. Pediatrics, 27: 95-102.
Catchpool JF (1976). Antiprotozoal drugs. In Meyers et al.
(Eds). Review of medical pharmacology. 5th Ed. pp. 605 633,
Lange Medical Publications, Canada.
Charbonneau P, Lacotte J, Lemarchand C, Commeau Ph, Pellerin R,
Bazin C (1986). Effet antiarythimique du diazépam lors des
intoxications à la Chloroquine. Réanimation, Soins Intensifs,
Médecine d'Urgence, 2: 265.
Charbonneau P (1988). Effet antiarythmique du diazépam lors des
intoxications à la chloroquine. Apport de l'exploration
isotopique. Réanimation, Soins Intensifs, Médecine d'Ugence, 4:
Clyde D & Shut C (1976). Transfer of pyrimethamine in human
milk. J Trop Med Hyg, 39: 277-284.
Coffi SD, Bondurand A (1988) L'intoxication à la chloroquine.
L'expérience du CHU de Cocody. Réanimation, Soins Intensifs,
Médecine d'Urgence, 4: 53-56.
Crouzette J, Vicaut E, Palombo S, Girre C, Fournier PE (1983).
Experimental assessment of the protective activity of diazepam on
the acute toxicity of Chloroquine. Journal of Toxicology,
Clinical Toxicology, 20: 271-279.
Crouzette J (1988). Intoxication aiguë à la chloroquine:
démonstration expérimentale d'un effet antagoniste du diazépam.
Réanimation, Soins Intensifs, Médecine d'Urgence, 4: 59-60.
Don Michael TA, Aiwazzadey S (1970). Effects of acute
chloroquine poisoning. American Heart Journal, 79: 831-842.
Frija GA (1975). Intoxication aiguë à la chloroquine. A propos
de 38 cas. Médecine Tropicale, 35: 23-30.
Frisk Holmberg M, Bergovist Y, Domeij-Nyberg B, Hellstrom L,
Jansson F (1979). Chloroquine serum concentration and side
effects: evidence for dose-dependent kinetics. Clinical
Pharmacology and Therapeutics, 25: 345-350.
Frisk Holmberg M, Bergovist Y, Englund U (1983). Chloroquine
intoxication. British Journal of Clinical Pharmacology, 15: 502-
Frisk Holmberg M, Bergovist Y, Termond E, Domeij-Nyberg B (1984).
The single dose kinetics of chloroquine and its major metabolite
desethy-chloroquine in healthy subject. European Journal of
Clinical Pharmacology, 26: 521-530.
Galliot M, Escande C, Chevalier P (1988). Dosage de la
chloroquine et du diazépam dans les liquides biologiques.
Réanimation, Soins Intensifs, Médecine d'Urgence, 4: 55-56.
Gnassounou JP, Advenier C (1988) Les effets antagonistes du
diazépam et du RO5-4864 dans l'intoxication aiguë par la
chloroquine chez le rat et chez le cobaye sont-ils de nature
centrale ou périphérique? Réanimation, Soins Intensifs, Médecine
d'Urgence, 4: 61-62.
Gustafsson LL, Bergqvist Y, Ericsson O (1983). Pitfalls in the
measurements of chloroquine concentrations. Lancet, 1: 1227.
Gustafsson LI, Walker O, Alvan G, Beermann B, Estevez F, Gleisner
L, Lindstrom, Sjoqvist F (1983). Disposition of chloroquine in
man after single intravenous and oral doses. British Journal of
Clinical Pharmacology, 15: 471-479.
Heath A, Ahlmen J, Mellstrand T, Wickstrom I (1982). Resin
haemoperfusion in chloroquine poisoning. Journal of Toxicology,
Clinical Toxicology, 19: 1067-1071.
Hess ME, Schmidt CF (1959). Cardiovascular effects of
chloroquine with special reference to its antifibrillatory
action. Circulation Research, 7: 86-92.
Hoang PTD, Pourriat JL, Larmignat P, Lapandry C, Gabry AL, Cupa M
(1982) Intoxications aiguës à la chloroquine. Traitement par le
diazépam. Annales Françaises d'Anesthésie et Réanimation, 1: 321-
Index Nominum (1984) Répertoire des substances médicamenteuses.
Société Suisse de Pharmacie, Genève.
Jaeger A, Sauder PH, Kopferschmitt J, Flesch F (1987)
Hypokaliémie au cours des intoxications par la chloroquine. La
Presse Médicale, 16: 1658-1659.
Jaeger A, Sauder Ph, Kopferschmitt J, Flesch F (1987) Clinical
features and management of poisoning due to antimalarial drugs.
Medical Toxicology, 2: 242-273.
Jaeger A (1988) Intoxication par la chloroquine: aspects toxico-
cinétiques et conséquences thérapeutiques. Réanimation, Soins
Intensifs, Médecine d'Urgence, 4: 52-53.
Kasilo O (1988) Pharmacy, Drug and Toxicology Information Source
Bulletin, Issue 14: 1-8.
Kasilo O, Romero M, Bonati M, Tognoni G (1988) Information on
drug use in pregnancy from a Regional Drug Information Centre's
point of view. Eur J Clin Pharmacol, 35.
Koudogbo B, Asseko, MC, Nguemby Mbina C, Laguerret-Atadou V
(1986) Mode d'action antidotique du diazépam dans le traitement
des intoxications à la chloroquine. Journal de Toxicologie
Clinique et Expérimentale, 6: 307-312.
Lareng L, Fabre M, Jean D, Borzai V (1980) Intoxication par al
Nivaquie. Cahiers d'Anesthésiologie, 28: 112-231.
Lechat Ph (1988) Intoxication aiguë à la chloroquine et atteinte
cardiovasculaire. Réanimation, Soins Intensifs, Médecine
d'Urgence, 4: 51-53.
Lewis RJ, Tatken RL (1979) Registry of toxic effects of chemical
substances. US Department of Health and Human Services,
Lofaso F, Baud FJ, Halna de Fretay X, Staikowsky F, Sidhhom N,
Bismuth C (1986b) Hypokaliémies au cours d'intoxications
massives par la Chloroquine. Trois cas. Réanimation, Soins
Intensifs, Médecine d'Urgence, 2: 236.
Maier RD, Benkert B (1984) Toxikologische Aspekete mehrtägigen
Verlauf einer todlichen Choroquin-intoxikation. Zeitchrift für
rechsmedizin, 92: 37-43.
Markowitz HA, McGinley JM (1964) Chloroquine poisoning in a
child. JAMA, 1: 22-25.
McCann WP, Permisohn R, Palmisano PA (1975) Fatal chloroquine
poisoning in a child: experience with peritoneal dialysis.
Pediatrics, 55: 536-537.
McChesney EW, Fasco MJ, Banks WF (1967) The metabolism of
chloroquine in man during and after repeated oral dosage.
Journal of Pharmacology and Experimental Therapeutics, 158: 323-
Nir I (1984) Antiprotozoal drugs. In Dukes (Eds) Side Effects
of Drugs Annual, 8, pp 273-281. Elsevier Science Publishers BV.
Rajah A (1990) The use of diazepam in chloroquine poisoning.
Anaesthesia, 45: 955-957.
Reynolds JEF (1982) Martindale The Extra Pharmacopoeia. 28th
edition. London, The Pharmaceutical Press
Riou B, Barriot P, Rimailho A, Baud FJ (1988) Treatment of
severe chloroquine poisoning. New England Journal of Medicine,
Riou B (1988) Effects du diazépam dans l'intoxication
expérimentale par la chloroquine. Etudes in vivo et in vitro.
Réanimation, Soins Intensifs, Médecine d'Urgence, 4: 60-61.
Rollo IM (1980) Drugs used in the chemotherapy of malaria. In
Goodman and Gilman (Eds). The pharmacological basis of
therapeutics pp. 1044, 6th ed., Macmillan Company, New York.
Tester Dalderup CBM (1984) Antiprotozoal drugs. In Dukes (Eds)
Meyler's side effects of drugs, 10th ed., pp. 525-537. Elsevier
Van Stone JC (1976) Haemodialysis and chloroquine poisoning.
Journal of Laboratory and Clinical Medicine, 88: 87-90.
Vitris M, Aubert M (1983) Intoxications à la Chloroquine: notre
expérience à propos de 80 cas. Dakar Médical, 28: 593-6022.
Walder O, Dawodu AH, Adeyokunnu AA, Salako LA, Alvan G (1983)
Plasma chloroquine and desethylchloroquine concentrations in
children during and after chloroquine treatment for malaria.
British Journal of Clinical Pharmacology, 16: 701-705.
Wattel F, Bleichner G, Cavallat JKF, Diquet B, Grolleau-Raoux R,
Marieu P (1988) Traitement de l'intoxication aiguë à la
chloroquine. Réanimation, Soins Intensifs, Médicine d'Urgence,
Weniger H (1979) Review of side effects and toxicity of
chloroquine. Bulletin of the World Health Organization, 79: 906.
Windholz M, Budavari S, Blumetti RF, Otterbein ES (1983) The
Merck Index: an encyclopedia of chemicals, drugs, and biologicals,
10th ed. Rahway, New Jersey, Merck & Co., Inc.
White NJ (1985) Clinical pharmacokinetics of antimalarial
drugs. Clinical Pharmacokinetics, 10: 1987-215.
14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE ADDRESS(ES)
Author: A. Jaeger, F. Flesch
Hospices Civils de Strasbourg
Service de Réanimation Médicale et Centre Anti-poisons
67091 Strasbourg Cédex
Telephone:33-88 16 11 44
Telefax: 33-88 16 13 30
Reviewer: R. Fernando
National Poison Information Centre
Faculty of Medicine
Peer Review: Hamilton, Canada, May 1989
London, United Kingdom, March 1990
Review: IPCS, May 1994