Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2022 Publisher: Strides Pharma UK Ltd, Unit 4 Metro Centre, Tolpits Lane, Watford, Hertfordshire, WD18 9SS
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, and disturbed vision (see sections 4.8 and 4.9).
Hypersensitivity to quinine may also occur with symptoms of cinchonism together with urticaria, flushing, pruritus, rash, fever, angioedema, dyspnoea and asthma.
Serious hypersensitivity reactions including Stevens-Johnson syndrome have been reported with quinine.
Quinine should be used with caution in patients with atrial fibrillation, conduction defects and heart block or other serious heart disease. It may cause hypoprothrombinaemia.
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.
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 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 should be monitored in all patients 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 sulfate 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.
Reduce the dosage (or increase intervals between doses) in renal or hepatic disease.
Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine, as it contains lactose.
This medicine contains less than 1 mmol sodium (23 mg) per tablet, i.e. is essentially 'sodium-free'
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 such as 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.
The plasma concentration of mefloquine may be increased.
Amantadine: Quinine can reduce the renal clearance of amantadine.
If quinine is administered the maintenance dose of digoxin should be halved.
Ciclosporin: Quinine can decrease serum 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. Quinine has been reported to increase serum digoxin concentrations and quinine has reduced total body clearance of digoxin.
There is an increased risk of ventricular arrhythmias when quinine is given in combination with other drugs that prolong the QT interval, including amiodarone, moxifloxacin, pimozide, thioridazine, terfenadine and halofantrine and therefore concomitant use with these products should be avoided.
Caution is advised when administering quinine with drugs which could prolong the QT interval.
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 reduce the serum levels of quinine, therefore reducing its therapeutic effect.
Anticoagulants: Quinine may cause hypoprothrombinaemia and enhance the effects of anticoagulants. In one report, reductions in warfarin dosage were necessary after ingestion of large amount of tonic water containing quinine.
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.
There is an increased risk of inducing ventricular arrhythmias if quinine is given with halofantrine. There may be increased risk of convulsions when quinine is given with mefloquine.
Chloroquine and quinine appear to be antagonistic when given together for P falciparum malaria.
Concomitant use of artemether and lumefantrine should be avoided.
Antipsychotics: There is an increased risk of ventricular arrhythmias and concomitant use should be avoided with pimozide or thioridazine.
Hypoglycaemics: Concurrent use with oral hypoglycaemics may increase the risk of hypoglycaemia.
Suxamethonium: Quinine enhances the neuromuscular effects of suxamethonium.
Ulcer-healing drugs: Cimetidine inhibits quinine metabolism leading to increased plasma-quinine concentrations.
Anti-epileptics: Quinine may increase the levels of phenobarbital and of carbamazepine. Patients should be monitored closely during concomitant use of quinine with these agents.
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 sulfate should not be used during pregnancy unless the benefits outweigh the risks.
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.
Quinine sulfate should not be used during pregnancy to treat cramps.
Quinine sulfate is excreted in breast milk, but no problems in humans have been reported. However, quinine sulfate should not be given to nursing mothers unless the benefits outweigh the risks.
The effects of quinine on fertility are unknown.
Quinine may cause visual disturbances and vertigo, hence patients should be advised that if affected they should not drive or operate machinery.
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. In 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.
| MedDRA system organ class | Adverse Reaction |
|---|---|
| Blood and lymphatic system disorders | Thrombocytopenia, intravascular coagulation, hypoprothrombinaemia, haemoglobinuria, oliguria, haemolytic uraemic syndrome, pancytopenia, haemolysis, agranulocytosis, thrombocytopenic purpura. |
| Immune system disorders | Reports have been received of eczematous dermatitis, oedema, erythema and lichen planus. Hypersensitivity reactions such as angioneurotic oedema, photosensitivity, hot and flushed skin, pruritus, thrombocytopenic purpura and urticaria have also been reported. |
| Metabolism and nutritional disorders | Hypoglycaemia may occur after oral administration although it is more common after parenteral administration. |
| Psychiatric disorders | Agitation and confusion. |
| Nervous system disorders | Reports of headache, vertigo, excitement, loss of consciousness, coma and death have been received. |
| Eye disorders | Blurred vision, defective colour perception, visual field constriction, total blindness. |
| Ear and labyrinth disorders | Tinnitus, hearing impaired. |
| Cardiac disorders | Atrioventricular conduction disturbances, a fall in blood pressure coupled with a feeble pulse, prolongation of the QT interval, widening of the QRS complex and T wave flattening has been noted with therapeutic doses. |
| Respiratory, thoracic and mediastinal disorders | Bronchospasm, dyspnoea, asthma may occur. |
| Gastrointestinal Disorders | Nausea, vomiting, diarrhoea, abdominal pain, fever may occur after long term administration of quinine. |
| Skin and subcutaneous tissue disorders | Flushing, rash, urticaria, eczematous dermatitis, oedema, erythema, lichen planus, pruritus, photosensitivity, Stevens-Johnson syndrome. |
| Musculoskeletal and connective tissue disorders | Muscle weakness may occur, aggravation of myasthenia gravis. |
| Renal and urinary disorders | Renal insufficiency and acute renal failure may be due to an immune mechanism or circulatory failure. |
| Reproductive system and breast disorders | Toxic doses of quinine may induce abortion, but it is unwise to withhold the drug if less toxic antimalarials are not available. |
| General disorders and administration site conditions | Fever |
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; website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
Not applicable.
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