Posology and method of administration
Non-immune subjects entering a malarious area are advised to begin daily treatment with Paludrine 1 week before, or if this is not possible, then at least 2 days before entering the malarious area.  The daily dose of Paludrine should be continued throughout exposure to risk and for 4 weeks after leaving the area.

A single dose of Avloclor should be taken each week on the same day each week.  Start one week before exposure to risk and continue until 4 weeks after leaving the malarious area.

Each dose should be taken with water after food.

Adults and children over 14 years: Take two Paludrine tablets daily as directed above.  Take two Avloclor tablets once a week as directed above.

Children: Do not give to children under 1 year.  The following single dose of Paludrine should be taken at the same time each day and the following single dose of Avloclor should be taken once a week on the same day each week.





Paludrine
Avloclor



(at the same time each day)
(on the same day each week)

1 to 4 years
Half of a tablet
Half of a tablet

5 to 8 years
One tablet
One tablet

9 to 14 years
One and a half tablets
One and a half tablets


For a young child the dose may be administered crushed and mixed with milk, honey or jam.

Provided the Paludrine tablet fragment gives the minimum amount specified, precise accuracy in children's dosage is not essential since the drug possesses a wide safety margin.

The Avloclor dose given to children should be calculated on their body weight (5 mg chloroquine base/kg/week) and must not exceed the adult dose regardless of weight.

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.

Paludrine and Renal Impairment: Based on a theoretical model derived from a single dose pharmacokinetic study, the following guidance is given for adults with renal impairment.  (See also Sections 4.3 and 4.4).

Creatinine clearance (ml/min/1.73 m2 )
Dosage

60
200 mg once daily (standard dose)

20 to 59
100 mg once daily

10 to 19
50 mg every second day

< 10
50 mg once weekly


The grade of renal impairment and/or the serum creatinine concentration may be approximately equated to creatinine clearance levels as indicated below.


Creatinine clearance (ml/min/1.73 m2 )
Approx* serum creatinine (micromol/1)
Renal Impairment Grade (arbitrarily divided for dosage purposes)

60
-
-

20 to 59
150 to 300
Mild

10 to 19
300 to 700
Moderate

< 10
> 700
Severe


*Serum creatinine concentration is only an approximate guide to renal function unless corrected for age, weight and sex.

Avloclor and Hepatic or Renally Impaired Patients: Caution is necessary when giving Avloclor to patients with renal disease or hepatic disease.


Special warnings and precautions for use
When used as malaria prophylaxis official guidelines and local information on prevalence of resistance to anti-malarial drugs should be taken into consideration.

Paludrine should be used with caution in patients with severe renal impairment.  (See also Section 4.2).  There have been rare reports of haematological changes in such patients.  Caution is necessary when giving Avloclor to patients with renal disease.

Caution is necessary when giving Avloclor to patients with impaired hepatic function, particularly when associated with cirrhosis.

Caution is also necessary in patients with porphyria.  Avloclor may precipitate severe constitutional symptoms and an increase in the amount of porphyrins excreted in the urine.  This reaction is especially apparent in patients with high alcohol intake.

Avloclor should be used with care in patients with a history of epilepsy.  Potential risks and benefits should be carefully evaluated before use in subjects taking anti-convulsant therapy or with a history of epilepsy as, rarely, cases of convulsions have been reported in association with chloroquine.

The use of Avloclor in patients with psoriasis may precipitate a severe attack.

Caution is advised in patients with glucose-6-phosphate dehydrogenase deficiency, as there may be a risk of haemolysis.


Prolonged or high dose Avloclor therapy:

Considerable caution is needed in the use of Avloclor for long-term high dosage therapy and such use should only be considered when no other drug is available.

Irreversible retinal damage and corneal changes may develop during long term therapy and after the drug has been discontinued.  Ophthalmic examination prior to and at 3 ' 6 monthly intervals during use is required if patients are receiving chloroquine

' At continuous high doses for longer than 12 months

' As weekly treatment for longer than 3 years

' When total consumption exceeds 1.6g/kg (cumulative dose 100g).

Full blood counts should be carried out regularly during extended treatment as bone marrow suppression may occur rarely.


Interaction with other medicinal products and other forms of interaction
Antacids (aluminium, calcium and magnesium salts) may reduce the absorption of proguanil and chloroquine, so antacids should be taken well separated from Paludrine and Avloclor (at least two hours before or after).

If the patient is taking cyclosporin then chloroquine may cause an increase in cyclosporin levels.

Pre-exposure intradermal human diploid-cell rabies vaccine should not be administered to patients taking chloroquine as this may suppress antibody response.  When vaccinated against rabies, that vaccine should precede the start of antimalarial dosing, otherwise the effectiveness of the vaccine might be reduced.

Chloroquine significantly reduces levels of praziquantel.  Caution is therefore advised during co-administration.  Prescribers may consider increasing the dose of praziquantel if the patient does not respond to the initial dose.

Amiodarone:
chloroquine and hydroxchloroquine increase the risk of cardiac arrhythmias including ventricular arrhythmias, bradycardias and cardiac conduction defect.  Concurrent use is contra-indicated.

Anticoagulants:
proguanil can potentiate the anticoagulant effect of warfarin and related anticoagulants through a possible interference with their metabolic pathways.  Caution is advised when initiating or withdrawing malaria prophylaxis with Paludrine in patients on continuous treatment with anticoagulants.

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).

Pregnancy and lactation
Pregnancy