Summary of Product Characteristics (SmPC) - Quinine Bisulphate 300 mg tablets
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 the active substance or to any of the excipients listed in section 6.1.
- haemoglobinuria
- tinnitus
- myasthenia gravis, quinine may cause severe respiratory distress and dysphagia in these patients
- optic neuritis.
4.4 Special warnings and precautions for use
The administration of quinine to a patient who has previously been suffering from a chronic and inadequately controlled malarial infection may precipitate an attack of blackwater fever. However, in some cases deficiency of glucose-6-phosphate dehydrogenase may have been involved. Glucose 6-phosphate dehydrogenase (G6PD) deficient patients with malaria or taking quinine to treat leg cramps may be at an increased risk of haemolytic anaemia during quinine therapy.
Quinine should not be withheld from pregnant women who have life threatening malaria (see section 4.6).
Treatment with quinine should be monitored in case signs of resistance develop.
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.
May cause severe respiratory distress and dysphagia in patients with myasthenia gravis.
Renal impairment which may be due to an immune mechanism may occur. Hypoglycaemia may 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.
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.
Cardiac disorders
Quinine has dose-dependent QT-prolonging effects. Caution is recommended in patients with conditions which predispose to QT prolongation and in patients with atrioventricular block.
1.1 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.
Amantadine: Quinine can reduce the renal clearance of amantadine.
Ciclosporin: Quinine can decrease plasma concentrations of ciclosporin.
Cardiac glycosides: Quinine increases plasma concentrations of cardiac glycosides and reduced dosage of concomitant cardiac glycosides such as digoxin to half the maintenance dose may be necessary.
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.
Antiarrhythmics: Concomitant use of amiodarone should be avoided due to the increased risk of ventricular arrhythmias. The plasma concentration of flecainide is increased by quinine. Concomitant use of quinidine may increase the possibility of cinchonism.
Antibacterials: There is an increased risk of ventricular arrhythmias when moxifloxacin is given with quinine. Rifampicin can reduced the serum levels of quinine, therefore reducing its therapeutic effect.
Anticoagulants: Quinine may cause hypoprothrombinaemia and enhance the effects of anticoagulants.
Antihistamines: Concomitant use of terfenadine should be avoided due to the increased risk of ventricular arrhythmias.
Antimalarials: According to the manufacturer of artemether with lumefantrine concomitant use should be avoided. There is an increased risk of convulsions when given with mefloquine. Chloroquine and quinine appear to be antagonistic when given together for P falciparum malaria. There is a decrease in plasma concentrations of primaquine.
Hypoglycaemics: Concurrent use with oral hypoglycaemics may increase the risk of hypoglycaemia .
Suxamethonium: Quinine enhances the neuromuscular effects of suxamethonium. Concomitant use of quinidine may increase the possibility of cinchonism.
Ulcer-healing drugs: Cimetidine inhibits quinine metabolism leading to increase plasma-quinine concentrations.
Caution is advised when administering quinine with drugs which could prolong the QT interval.
Quinine may increase the levels of phenobarbital and of carbamazepine.
Patients should be monitored closely during concomitant use of quinine with these agents.
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 contra-indication 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 bisulphate should not be given to nursing mothers unless the benefits outweigh the risks.
Fertility
No data available
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
Some patients are hypersensitive to quinine bisulphate and they may experience the
symptoms of cinchonism together with asthma and other allergic manifestations
including angioneurotic oedema and haemolytic anaemia.
Cinchonism is more common in overdose, but may occur even after normal doses of
quinine. In its mild form symptoms include tinnitus, impaired hearing, rashes,
headache, nausea and disturbed vision. Its more severe manifestations symptoms may include gastrointestinal symptoms, oculotoxicity, CNS disturbances, cardiotoxicity and death (see section 4.9). Visual disorders may include blurred vision, defective colour perception, visual field constriction and total blindness.
The following adverse reactions are classified by system organ class and ranked
under heading of frequency using the following convention: Not known (frequency cannot be estimated from the available data)
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 |
| 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 |
Reporting suspected adverse reactions
Reporting 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 at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
4.9 Overdose
Symptoms
Quinine overdosage may lead to serious side effects including irreversible visual loss, and can be fatal.
In acute overdosage, symptoms of cinchonism may occur, including convulsions, nausea, vomiting, tinnitus, deafness, headache, vasodilation 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.
Elimination from the body may be assisted by the acidification of the urine with ammonium chloride. Haemodialysis and haemoperfusion should be instituted but this has limited value because quinine is extensively metabolised in the liver and only a small proportion is excreted unchanged in the urine. Signs of haemolytic anaemia may be indicative of a need to treat acute renal failure. Respiratory failure may be combatted by assisted respiration. Cardiac rhythm should be monitored.
Vasodilators such as nicotinic acid and amylnitrite may be given in an attempt to reverse visual impairment. Beneficial effects have been achieved with stellate ganglion block. The average fatal dose in adults has been reported to be with 8 g, with death resulting in a few hours or delayed for 1-2 days.
Large doses can induce abortion.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Quinine alkaloid.
ATC Code: P01B C01.
Quinine is a cinchona alkaloid and a 4-methanolquinoline antimalarial agent which is a rapidly-acting blood schizontocide with activity against Plasmodium falciparum, P vivax, P ovale and P malariae. It is active against the gametocytes of P malariae and P vivax, but not against mature gametocytes of P falciparum. Since it has no activity against exoerythrocytic forms, quinine does not produce a radical cure in vivax or ovale malarias.
Mechanism of action
The precise mechanism of action of quinine is unclear but it may interfere with lysosome function or nucleic acid synthesis in the malaria parasite.
Pharmacodynamic effects
Quinine has effects on the motor end-plate of skeletal muscle and prolongs the refractory period. Like quinidine, quinine is a sodium channel blocker and,
therefore, has local anaesthetic, and both anti- and proarrhythmic activity.
5.2 Pharmacokinetic properties
The pharmacokinetics of quinine are altered significantly by malaria infection, the
major effects being reductions in both its apparent volume of distribution and its
clearance.
Absorption:
Quinine is rapidly and almost completely absorbed from the GI tract and peak
concentrations in the circulation are attained about 1-3 hours after oral administration
of the sulphate.
Distribution:
Plasma protein binding is about 70% in healthy subjects and rises to 90% or more in
patients with malaria.
Quinine is widely distributed throughout the body. Concentrations attained in the CSF of patients with cerebral malaria have been reported to be about 2-7% of those in the plasma.
Metabolism:
Quinine is extensively metabolised in the liver and rapidly excreted mainly in the
urine. Estimates of the proportion of unchanged quinine excreted in the urine vary
from less than 5% to 20%. The pharmacokinetics of quinine are altered significantly
by malaria infection, with reductions in both the apparent volume of distribution and
clearance.
Elimination:
Excretion is increased in acid urine. The elimination half-life is about 11 hours in
healthy subjects but may be prolonged in patients with malaria. Small amounts of
quinine also appear in the bile and saliva.
Quinine crosses the placenta and is excreted in the breast milk.
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:
Hypromellos
e
Ethylcellulos
e Diethyl
phthalate
Titanium
dioxide
6.2 Major Incompatibilities
Not applicable
6.3 Shelf life
48 months
6.4 Special precautions for storage
Blister packs: Do not store above 25°C. Store in the original package.
6.5 Nature and contents of container
Blister pack of 28 tablets.
6.6 Special precautions for disposal
No special precautions
7 MARKETING AUTHORISATION HOLDER
Genesis Pharmaceuticals Limited 1st Floor, 16/17 College Green Dublin, D02 V078
Ireland
8 MARKETING AUTHORISATION NUMBER(S)
PL 62354/0121
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
13/07/2001
10 DATE OF REVISION OF THE TEXT
25/09/2026