- 1. Name of the medicinal product
- 2. Qualitative and quantitative composition
- 3. Pharmaceutical form
- 4. Clinical particulars
- 4.1 Therapeutic indications
- 4.2 Posology and method of administration
- 4.3 Contraindications
- 4.4 Special warnings and precautions for use
- 4.5 Interaction with other medicinal products and other forms of interaction
- 4.6 Fertility, pregnancy and lactation
- 4.7 Effects on ability to drive and use machines
- 4.8 Undesirable effects
- 4.9 Overdose
- 5. Pharmacological properties
- 5.1 Pharmacodynamic properties
- 5.2 Pharmacokinetic properties
- 5.3 Preclinical safety data
- 6. Pharmaceutical particulars
- 6.1 List of excipients
- 6.2 Incompatibilities
- 6.3 Shelf life
- 6.4 Special precautions for storage
- 6.5 Nature and contents of container
- 6.6 Special precautions for disposal and other handling
- 7. Marketing authorisation holder
- 8. Marketing authorisation number(s)
- 9. Date of first authorisation/renewal of the authorisation
- 10. Date of revision of the text
a) Treatment of malaria
i) P. falciparum and P. malariae infectionsAdults: A single dose of four tablets, followed by two tablets six hours later and then two tablets a day for two days.Children: A single dose of 10mg base/kg, followed by 5mg base/kg six hours later and then 5mg base/kg a day for two days.
|Age (years)||Initial dose||Second dose 6 hours after first||Dose on each of the two subsequent days|
|1 4||1 Tablet||½ Tablet||½Tablet|
|5 8||2 Tablets||1 Tablet||1 Tablet|
|9 -14||3 Tablets||1½ Tablets||1½ Tablets|
ii) P. vivax and P. ovale infectionsAdults: A single dose of four tablets, followed by two tablets six hours later and then two tablets a day for two days. Follow with a course of treatment with primaquine if a radical cure is required.Children: A single dose of 10mg base/kg, followed by 5mg base/kg six hours later and then 5mg base/kg a day for two days. Follow with a course of treatment with primaquine if a radical cure is required.Elderly Patients: There are no special dosage recommendations for the elderly, but it may be advisable to monitor elderly patients so that optimum dosage can be individually determined.Hepatic or Renally Impaired Patients: Caution is necessary when giving Avloclor to patients with renal disease or hepatic disease.
b) Prophylaxis and suppression of malariaAdults: Two tablets taken once a week, on the same day each week. Start one week before exposure to risk and continue until four weeks after leaving the malarious area.Children: A single dose of 5mg chloroquine base/kg per week on the same day each week. Start one week before exposure to risk and continue until four weeks after leaving the malarious area.For practical purposes, children aged over 14 years may be treated as adults. The dose given to infants and children should be calculated on their body weight and must not exceed the adult dose regardless of weight.
|1 - 4 years 5 - 8 years 9 - 14 years||½ tablet 1 tablet 1½ tablets|
c) Amoebic hepatitisAdults: Four tablets daily for two days followed by one tablet twice daily for two or three weeks.Elderly Patients: There are no special dosage recommendations for the elderly, but it may be advisable to monitor elderly patients so that optimum dosage can be individually determined.Hepatic or Renally Impaired Patients: Caution is necessary when giving Avloclor to patients with renal disease or hepatic disease.
d) Lupus erythematosusAdults: One tablet twice daily for one to two weeks followed by a maintenance dosage of one tablet daily.Elderly Patients: There are no special dosage recommendations for the elderly, but it may be advisable to monitor elderly patients so that optimum dosage can be individually determined.Hepatic or Renally Impaired Patients: Caution is necessary when giving Avloclor to patients with renal disease or hepatic disease.
e) Rheumatoid arthritisAdults: The usual dosage is one tablet daily.Elderly Patients: There are no special dosage recommendations for the elderly, but it may be advisable to monitor elderly patients so that optimum dosage can be individually determined.Hepatic or Renally Impaired Patients: Caution is necessary when giving Avloclor to patients with renal disease or hepatic disease.
|Other antimalarials:||increased risk of convulsion with mefloquine.|
|Cardiac glycosides:||hydroxychloroquine and possibly chloroquine increase plasma concentration of digoxin.|
|Parasympathomimetics:||chloroquine and hydroxychloroquine have potential to increase symptoms of myasthenia gravis and thus diminish effect of neostigmine and pyridostigmine.|
|Ulcer healing drugs:||cimetidine inhibits metabolism of chloroquine (increased plasma concentration).|
|System Organ Class||Undesirable Effect and Frequency|
|Blood and lymphatic system disorders||Not known Bone marrow failure Aplastic anaemia Agranulocytosis Thrombocytopenia Neutropenia Pancytopenia|
|Immune system disorders||Not known Hypersensitivity and anaphylactic reactions, including urticaria, angioedema and vasculitis.|
|Metabolism and nutrition disorders||Not known Hypoglycaemia (see section 4.4).|
|Psychiatric Disorders||Rare Hallucinations Not known Psychotic disorder including anxiety, personality change Insomnia Confusion Depression|
|Nervous system disorders||Not known Convulsion (see section 4.4) Visual field defects Headache Neuromyopathy Acute extrapyramidal disorders (such as dystonia, dyskinesia, tongue protrusion, torticollis) (see section 4.4)|
|Eye disorders||Not known Retinal degeneration Macular defects of colour vision Pigmentation Optic atrophy scotomas Blindness Corneal opacity and pigmented deposits Vision blurred Accommodation disorder Diplopia|
|Ear and labyrinth disorders||Not known Tinnitus Hypoacusis Deafness neurosensory|
|Cardiac disorders||Not known Cardiomyopathy (see section 4.4)|
|Vascular Disorders||Not known Hypotension|
|Respiratory, thoracic and mediastinal||Not known Diffuse parenchymal lung disease|
|Gastrointestinal disorders:||Not known Gastrointestinal disorder Nausea Vomiting Diarrhoea Abdominal pain|
|Hepatobiliary disorders||Rare Changes in liver function, including hepatitis and abnormal liver function tests|
|Skin and subcutaneous tissue disorders||Not known Macular, urticarial and purpuric skin eruptions Alopecia Erythema multiforme Drug reaction with eosinophilia and systemic symptoms syndrome (DRESS) Stevens-Johnson syndrome (SJS) Toxic epidermal necrolysis (TEN) Precipitation of psoriasis Pruritus Photosensitivity reaction Lichenoid keratosis Pigmentation disorder * Exfoliative dermatitis Acute generlised exanthematous pustulosis (AGEP)|
|Musculoskeletal and connective tissue disorders||Not known Myopathy|
|Investigations||Not known Electrocardiogram change**|
Reporting of suspected adverse reactionsReporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme, Website: www.mhra.gov.uk/yellowcard.
FeaturesChloroquine is highly toxic in overdose and children are particularly susceptible. The chief symptoms of overdosage include circulatory collapse due to a potent cardiotoxic effect, respiratory arrest and coma. Symptoms may progress rapidly and include: - General features include nausea and vomiting. Hypokalaemia is common in severe poisoning and metabolic acidosis may also develop. Rarely hepatotoxicity, nephritis, gastric haemorrhage, haematological abnormalities and psychiatric features may occur.- Neurological features include headache, dizziness, drowsiness, blurred vision, diplopia and, rarely, blindness, may precede restlessness, increased excitability and convulsions. Coma is less common.- Cardiac features often appear at an early stage. Cardiac arrest may be a presenting feature. Hypotension is very common and may progress to cardiogenic shock and pulmonary oedema. Intraventricular conduction defects with a wide QRS, and prolongation of the QT interval are more common than A-V (atrioventricular) conduction defects. Ventricular tachycardia and fibrillation tend to occur early while torsade de pointes develops after about 8 hours.
ManagementAcute overdose with chloroquine can be rapidly lethal and intensive supportive treatment should be started immediately. Death may result from circulatory or respiratory failure or cardiac arrhythmia but is usually due to cardiac arrest related to the direct effects on the myocardium. If there is no demonstrable cardiac output due to arrhythmias, asystole or electromechanical dissociation, external chest compression should be persisted with for as long as necessary, or until adrenaline and diazepam can be given (see below).Firstly, maintain a clear airway and ensure adequate ventilation. The benefit of gastric decontamination is uncertain, but activated charcoal can be considered for adults and children aged over 5 years, within 1 hour of ingestion of more than 10 mg/kg of chloroquine base as a single dose or for any amount in a child aged 5 years and under, as it may reduce absorption of any remaining chloroquine from the gut. Activated charcoal should also be considered within 1 hour of ingestion of a weekly dose taken on 2 or more consecutive days. Alternatively, gastric lavage may be considered in adults within 1 hour of a potentially life threatening overdose. There is a risk of cardiac arrest following aspiration of gastric contents in more serious cases.Monitor circulatory status (with central venous pressure measurement), cardiac rhythm, respiration, conscious level and urinary output. Check urea & electrolytes, liver function and full blood count in symptomatic patients. Consider arterial blood gas analysis in patients who have a reduced level of consciousness or have reduced oxygen saturation on pulse oximetry.It is not clear if correction of hypokalaemia is essential but it may have a protective effect and should not be corrected in the early stages of poisoning. The degree of hypokalaemia may be correlated with the severity of chloroquine intoxication. If it persists beyond 8 hours, cautious correction should be undertaken with frequent biochemical monitoring of progress. Rebound hyperkalaemia is a risk during recovery. In case of persistent metabolic acidosis consider intravenous sodium bicarbonate. Rapid correction is particularly important if there is prolongation of the QRS interval. DC (direct current) shock is indicated for ventricular tachycardia and ventricular fibrillation. Cardiac arrhythmias should be treated with caution. The use of anti-arrhythmic drugs (such as those with quinidine-like effects) is best avoided since they may depress the myocardium further and exacerbate hypotension. Early administration of the following has been shown to improve survival in cases of serious poisoning:1. Adrenaline infusion until adequate systolic blood pressure (more than 100mg/Hg) is restored; adrenaline reduces the effects of chloroquine on the heart through its inotropic and vasoconstrictor effects.2. Diazepam infusion; diazepam may decrease the cardiotoxicity of chloroquine.Acidification of the urine, haemodialysis, peritoneal dialysis or exchange transfusion have not been shown to be of value in treating chloroquine poisoning. Chloroquine is excreted very slowly, therefore cases of overdosage require observation for several days.
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