Data Sheet

NIVAQUINE^®

Chloroquine sulphate, 200 mg tablet, 68 mg/5 ml syrup

Presentation

Tablets:

Yellowish buff film-coated tablets containing 200 mg chloroquine sulphate (equivalent to 150 mg chloroquine base) impressed 'Nivaquine 200' on one face, reverse plain.

Syrup:

A bright, golden syrup containing 68 mg chloroquine sulphate (equivalent to 50 mg chloroquine base) in each 5 ml.

Uses

Actions

NIVAQUINE is a 4-aminoquinoline compound which has a high degree of activity against the asexual erythrocytic forms of all species of malarial parasites.
NIVAQUINE also exerts a beneficial effect in certain collagen diseases and protects against the effects of solar radiation. Its mode of action in these conditions has not yet been identified. It is also active against Entamoeba histolytica and Giardia lamblia.

Indications

It is indicated for the suppression and clinical cure of all forms of malaria and, in addition, produces radical cure of falciparum malaria.
It is employed in the treatment of rheumatoid arthritis, juvenile rheumatoid arthritis, discoid and systemic lupus erythematosus and skin conditions aggravated by sunlight.
In the absence of standard recommended therapy NIVAQUINE may be used in hepatic amoebiasis and giardiasis.

Dosage And Administration

Suppression Of Malaria

Adults

2 x 200 mg tablets in a single dose on the same day each week during exposure.

Elderly

No specific dosage recommendations.

Children

5 mg/kg (as chloroquine base) at weekly intervals. This may be conveniently administered as NIVAQUINE syrup according to the following schedule:

It is advisable to start taking NIVAQUINE two weeks before entering an endemic area and to continue for six weeks after leaving.
These dosages are those recommended by the World Health Organisation.

Treatment Of Malaria

Non-immune subjects

Adults

The above dosage is intended as a guide in the treatment of Plasmodium falciparum malaria. However, due to variation in the strain sensitivity, it may sometimes be necessary to increase the duration of treatment by administering two NIVAQUINE tablets (300 mg chloroquine base) daily on days 4 to 7.

Infants and children

NIVAQUINE syrup can be conveniently used in this age group to permit flexibility of dosage.

Partially immune subjects

Adults

A single dose of four NIVAQUINE tablets (600 mg chloroquine base) will provide an effective course of treatment.

Infants and children

Repeated infection with many species and strains of malaria parasite prevalent in highly endemic malarial areas eventually produces a high degree of immune response frequently resulting in modification of the symptoms of clinical attack. This is particularly obvious in adults but less so in adolescents and children. Immunity is uncommon in very young age groups with the exception of infants up to the age of about 6 months who are partly protected by transplacental derived maternal antibodies. It is therefore advisable to treat previously exposed children in the same way as non-immune children.

Rheumatoid Arthritis

Adults

1 x 200 mg tablet daily.

Children

3 mg/kg bodyweight daily.

Systemic Lupus Erythematous

Adults

1 x 200 mg tablet daily until maximum improvement is obtained, followed by a smaller maintenance dose.

Children

3 mg/kg bodyweight daily.

Light Sensitive Skin Eruptions

Adults

1 or 2 x 200 mg tablets daily during the period of maximum light exposure.

Children

3 mg/kg bodyweight daily during the period of maximum light exposure.

Treatment should be discontinued if no improvement has occurred after six months.

Contraindications

The use of chloroquine is contraindicated

• in pregnancy
• in patients with known hypersensitivity to 4-aminoquinoline compounds
• in patients with retinal or visual field changes. In case of acute attack of malaria, physician may elect to use this drug after carefully weighing the possible benefits and risks for the patient

Pregnancy

Category A (prophylaxis)
Category D (treatment)
Chloroquine crosses the placenta barrier and NIVAQUINE is generally contraindicated in pregnancy. However, at recommended doses for prophylaxis and treatment of malaria, chloroquine has been safely used in pregnant women. Therefore, clinician may decide to administer chloroquine during pregnancy if he considers that the benefits outweigh the potential risk. The safety of chloroquine in pregnant women receiving long term therapy with high dosages of chloroquine has not been established.. Ocular or inner ear damage may occur in infants born of mothers who receive high doses of chloroquine throughout pregnancy.

Lactation

Although chloroquine is excreted in breast milk, the amount is insufficient to confer any benefit on the infant. Separate chemoprophylaxis for the infant is required.

Warnings and Precautions For Use

As irreversible retinal damage may occur in patients with prolonged treatment, ophthalmological examination should be performed before starting and regularly during therapy. NIVAQUINE has a temporary effect on visual accommodation and patients should be warned regarding driving or operating machinery.

Chloroquine should be used with caution in patients with:

• a history of epilepsy, as seizures have been reported.
• impaired liver or renal function
• porphyria (possible occurrence of acute episodes)
• psoriasis (possible exacerbation of the lesions)
• severe gastro-intestinal, neurological and blood disorders and in patients receiving anticoagulant therapy

Bone marrow depression, including aplastic anaemia, occurs rarely. Full blood counts should therefore be carried out regularly during extended treatment. Resistance of Plasmodin Falciparum to chloroquine is well documented. Therefore, epidemiological data should be considered before starting therapy with chloroquine.

Effects On Ability To Drive And Use Machines

Patients should be warned about the potential for transient vision disorders and advised not to drive or operate machinery if these symptoms occur.

Undesirable Effects

NIVAQUINE is usually well tolerated. Undesirable effects are usually very rare, mild and reversible.

Skin reactions

• skin eruptions, pruritus, urticaria, hair loss, bluish-black pigmentation particularly of nails and mucosae and possible reversible cases of exacerbation of psoriasis.
• angioedema

Peripheral and central nervous system

• seizures (these may result from cerebral malaria, such patients should receive an injection of phenobarbitone to prevent seizures in a dose of 3.5 mg/kg in addition to intravenous administration of NIVAQUINE).
• polyneuritis and neuromyopathy

Body as a whole

• headache

Psychiatric disorders

• psychiatric disorders such as anxiety, agitation, insomnia, confusion, hallucinations, delirium.

Vision disorders

• transient blurred vision and reversible corneal opacity
• cases of retinopathy have been reported during long term, high dose therapy. Ophthalmological examination should always be carried out before and regularly (3 - 6 monthly intervals) during treatment. Retinal damage is particularly likely to occur if treatment has been given for longer than one year, or if the total dosage has exceeded 1.6g/kg bodyweight. These precautions also apply to patients receiving chloroquine continuously at weekly intervals as a prophylactic against malarial attack for more than three years.

Cardiovascular system (during long therapy at high doses)

• cardiomyopathy
• possible occurrence of rare heart rhythm disorders

Haematology

• agranulocytosis, pancytopenia and thrombopenia

Hearing disorders

• ototoxicity such as tinnitus, reduced hearing, nerve deafness

Gastrointestinal effects

• Gastrointestinal disturbance such as nausea, vomiting and diarrhoea.

Interactions

No information

Overdosage

Chloroquine is rapidly absorbed and is highly toxic in overdose. Children are particularly susceptible.
The main symptoms of overdosage include circulatory collapse due to a potent cardiotoxic effect, respiratory arrest. Symptoms may progress rapidly after initial headache, drowsiness, visual disturbances, nausea and vomiting. Death may result from circulatory or respiratory failure or cardiac dysrhythmia.
Single acute overdosage with chloroquine may be rapidly lethal, patient must be promptly hospitalised, preferably in an intensive care unit and intensive and supportive treatment, including monitoring, instituted immediately.
Gastric lavage should be carried out urgently, first protecting the airway and instituting artificial ventilation where necessary. There is a risk of cardiac arrest following aspiration of gastric contents in more serious cases. Activated charcoal left in the stomach may reduce the absorption of any remaining chloroquine from the gut.
In addition, and as soon as massive overdosage is suspected or associated with serious toxic symptoms, it has been shown that an early administration of adrenaline (eg 0.2 mg by sloe infusion) and diazepam (eg 0.5 mg/kg over a ten minute infusion) could improve survival.
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 symptomatic cases merit observation for several days.
Circulatory status (with central venous pressure measurement), respiration, plasma electrolytes and blood gases should be monitored, with correction of hypokalaemia and acidosis if indicated. Cardiac arrhythmias should not be treated unless life threatening; drugs with quinidine-like effect should be avoided.

Pharmaceutical Precautions

Store below 25°C. Protect from light.

Medicine Classification

Prescription Medicine.

Package Quantities

Pack of 28 tablets
Bottle of 100 ml syrup.

Further Information

NIVAQUINE tablets also contain glucose.
NIVAQUINE syrup contains saccharin sodium, sugars, sodium L-glutamate, methyl hydroxybenzoate and propyl hydroxybenzoate.

Name & Address

Distributed by:
Rhône-Poulenc Rorer New Zealand Limited
PO Box P.O. Box 34010
Birkenhead
Auckland
Phone: (09)480-3770

Date Of Preparation

21/05/99