Quinine Bisulphate 300mg Tablets
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Quinine Bisulphate 300mg Tablets
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains Quinine Bisulphate 300 mg For a full list of excipients, see section 6.1
3 PHARMACEUTICAL FORM
Film-coated tablet
White tablets. Engraved MP38 on one side.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
1. Chloroquine-resistant malaria.
2. Treatment and prevention of nocturnal leg cramps in adults and the elderly, when cramps cause regular disruption of sleep (see section 4.2 and Section 4.4).
4.2 Posology and method of administration
Route of administration: oral
1. For the treatment of chloroquine-resistant malaria:
Adults including the elderly:
600 mg of quinine salt 8-hourly for 7 days.
Children:
10 mg of quinine salt per kg bodyweight 8-hourly for 7 days.
2. For the treatment and prevention of nocturnal leg cramps: Adults (including elderly):
The recommended dose is 300mg at bedtime.
A reduction in frequency of leg cramps may take up to 4 weeks to become apparent. Patients should be monitored closely during the early stages of treatment for adverse effects. After an initial trial of 4 weeks, treatment should be stopped if there is no benefit. Treatment should be interrupted at approximately three monthly intervals to reassess the benefit of treatment.
Children:
Not recommended
4.3 Contraindications
Quinine is contra-indicated in patients with:
• hypersensitivity to quinine or to any of the excipient in the tablet
• haemoglobinuria during malaria
• tinnitus
• myasthenia gravis or
• optic neuritis.
4.4 Special warnings and precautions for use
Before use for nocturnal leg cramps, the risks, which include significant adverse effects and interactions (see sections 4.5 and 4.8), should be carefully considered relative to the potential benefits. These risks are likely to be of particular concern in the elderly. Quinine should only be considered when cramps are very painful or frequent, when other treatable causes of cramp have been ruled out, and when non-pharmacological measures have not worked. Quinine sulphate should not be used for this indication during pregnancy (see Section 4.6).
Quinine may cause unpredictable serious and life-threatening thrombocytopenia, which is thought to be an idiosyncratic hypersensitivity reaction. Quinine should not be prescribed or administered to patients who have previously experienced any adverse reaction to quinine, including that in tonic water or other beverages. Patients should be instructed to stop treatment and consult a physician if signs of thrombocytopenia such as unexplained bruising or bleeding occur.
Quinine should be used with caution in patients with atrial fibrillation or other serious heart disease. It may cause hypoprothrombinaemia.
Patients with glucose 6-phosphate dehydrogenase (G6PD) deficiency may develop acute haemolytic anaemia.
May cause severe respiratory distress and dysphagia in patients with myasthenia gravis.
Administration of quinine may give rise to cinchonism, which is generally more severe in overdose, but may also occur in normal therapeutic doses. Patients should be warned not to exceed the prescribed dose, because of the
possibility of serious, irreversible side effects in overdose. Treatment for night cramps should be stopped if symptoms of cinchonism emerge. Such symptoms include tinnitus, impaired hearing, headache, nausea, vomiting, abdominal pain, diarrhoea, vertigo, confusion, hot and flushed skin, blindness and disturbed vision (see section 4.8 and 4.9).
Hypersensitivity to quinine may also occur with symptoms of cinchonism together with urticaria, flushing, pruritis, rash, fever, angioedema, dyspnoea and asthma.
4.5 Interaction with other medicinal products and other forms of interaction
Effect of other drugs on quinine
Quinine is metabolised via hepatic oxidative cytochrome P450 pathways, predominantly by CYP3A4. There is the potential for increased quinine toxicity with concurrent use of potent CYP3A4 inhibitors, which include azole antifungal drugs and HIV protease inhibitors.
Sub-optimal quinine serum levels may result from concomitant use of CYP3A4 inducers, which include rifampicin, barbiturates, carbamazepine and phenytoin.
Care should be taken when quinine is used in combination with other CYP3A4 substrates, especially those causing prolongation of the QT interval.
Effect of quinine on other drugs
The plasma concentration of flecainide, digoxin and mefloquine may be increased.
Quinine can decrease plasma concentrations of ciclosporin.
Other drug interactions
There is an increased risk of ventricular arrhythmias with other drugs which prolong the QT interval, including amiodarone, moxifloxacin, pimozide, thioridazine and halofantrine.
Concurrent use with oral hypoglycaemics may increase the risk of hypoglycaemia .
Quinine may cause hypoprothrombinaemia and enhance the effects of anticoagulants.
Quinine enhances the neuromuscular effects of suxamethonium.
Concomitant use of quinidine may increase the possibility of cinchonism.
Chloroquine and quinine appear to be antagonistic when given together for P falciparum malaria.
4.6 Fertility, Pregnancy and lactation
Pregnancy
Quinine may cause congenital abnormalities of the CNS and extremities. Following administration of large doses during pregnancy, phototoxicity and deafness have been reported in neonates. Quinine Bisulphate should not be used during pregnancy unless the benefits outweigh the risks.
Treatment of chloroquine-resistant strains of falciparium malaria.
Pregnancy in a patient with malaria is not generally regarded as a contraindication to the use of quinine. As malaria infection is potentially serious during pregnancy and poses a threat to the mother and foetus, there appears to be little justification in withholding treatment in the absence of a suitable alternative.
Prophylaxis of nocturnal leg-cramps.
Quinine Bisulphate should not be used during pregnancy to treat cramps. Lactation
Quinine Bisulphate is excreted in breast milk, but no problems in humans have been reported. However, quinine sulphate should not be given to nursing mothers unless the benefits outweigh the risks.
4.7 Effects on ability to drive and use machines
Quinine may cause visual disturbances and vertigo, hence patients should be advised that if affected they should not drive or operate machinery.
4.8 Undesirable effects
|
MedDRA system organ class |
Adverse Reaction |
|
Blood and lymphatic system disorders |
Thrombocytopenia, intravascular coagulation, hypoprothrombinaemia, haemoglobinuria, oliguria, haemolytic-uremic syndrome, pancytopenia, haemolysis, agranulocytosis, thrombocytopenic purpura |
|
Immune system disorders |
Generalised hypersensitivity reactions including angioneurotic oedema and fever |
|
Metabolism and nutrition disorders |
Hypoglycaemia |
|
Psychiatric disorders |
Agitation, confusion |
|
Nervous system disorders |
Headache, vertigo |
|
Eye disorders |
Blurred vision, defective colour perception, visual field constriction |
|
Ear and labyrinth disorders |
Tinnitus, impaired hearing |
|
Cardiac disorders |
Atrioventricular conduction disturbances, hypotension, prolongation of the QT interval, widening of the QRS complex and T wave flattening |
4.9 Overdose
Symptoms
Quinine overdosage may lead to serious side effects including irreversible visual loss, and can be fatal.
Symptoms include vomiting, tinnitus, deafness, headache, and visual disturbance.
Features of a significant overdose include convulsions, impairment of consciousness, respiratory depression, QT prolongation, ventricular arrhythmia, cardiogenic shock and renal failure. High doses of quinine are tetrogenic and may cause miscarriage. Hypokalaemia and hypoglycaemia may also occur.
Treatment
Children (< 5 years) who have ingested any amount should be referred to hospital.
Older children and adults should be referred to hospital if more than 30 mg/kg of quinine base has been taken.
Consider activated charcoal (50 g for adults; 1 g/kg for children) if the patient presents within 1 hour of ingestion of more than 30 mg/kg quinine base or any amount in a child under 5 years. Multiple dose activated charcoal will enhance quinine elimination.
Observe patients for at least 12 hours after ingestion. Monitor cardiac conduction and rhythm, serum electrolytes, blood glucose and visual acuity.
Other treatment is symptomatic to maintain blood pressure, respiration, renal function and to treat arrhythmia, convulsions, hypoglycaemia and acidosis.
Note: each 300mg tablet is equivalent to 178mg quinine base.
5 PHARMACOLOGICAL PROPERTIES
5.1
|
Respiratory, thoracic and mediastinal disorders |
Bronchospasm |
|
Gastrointestinal disorders |
Nausea, vomiting, diarrhoea, abdominal pain |
|
Skin and subcutaneous tissue disorders |
Flushing, rash, urticaria, eczematous dermatitis, oedema, erythema, lichen planus, pruritis, photosensitivity |
|
Musculoskeletal and connective tissue disorders |
Muscle weakness, aggravation of myasthenia gravis |
|
Renal and urinary disorders |
Renal insufficiency, acute renal failure |
Pharmacodynamic properties
Quinine is a highly active blood schizonticide and suppresses the asexual cycle of development of malaria parasites in the erythrocytes. It is considered to act by interfering with DNA.
5.2 Pharmacokinetic properties
Quinine is almost completely absorbed from the gastro-intestinal tract. Peak concentrations in the circulation is attained about 1-3 hours after ingestion and about 70% is bound to proteins in the plasma. Quinine is readily diffused across the placenta. It is degraded in the body, mainly in the liver, and only a small proportion is excreted in the urine unchanged.
The plasma half-life is 11 hours.
5.3 Preclinical safety data
No relevant information additional to that contained elsewhere in the SPC.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Core:
Cellulose, microcrystalline Silica, colloidal anhydrous Guar galactomannan Magnesium stearate
Coating:
Hypromellose Ethylcellulose Diethyl phthalate Titanium dioxide Beeswax
6.2 Incompatibilities
Not applicable
6.3 Shelf life
48 months
6.4 Special precautions for storage
Do not store above 25°C. Keep the container tightly closed.
6.5 Nature and contents of container
High-density polystyrene containers with polythene lids and/or polypropylene containers with polythene lids and polyurethane or polythene inserts.
Containers of 16, 21, 28, 30, 50, 56, 60, 84, 90, 100, 112, 120, 140, 150, 168, 180, 500, 1000, 5000, 10000 and 50000 tablets.
6.6 Special precautions for disposal
Not Applicable
7 MARKETING AUTHORISATION HOLDER
Genethics Europe Limited 41-43 Klimentos Towers,
Klimentos, Nicosia Cyprus, 1061
8 MARKETING AUTHORISATION NUMBER(S)
PL 42976/0025
DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
13/07/2001
10
DATE OF REVISION OF THE TEXT
01/04/2016