Quinine

Caution is advised when administering quinine with drugs which could prolong the QT interval.

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.

There is an increased risk of hypoglycaemia when quinine is taken concurrently with hypoglycaemics.

Quinine may cause hypoprothrombinaemia and enhance the effects of anticoagulants.

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 can reduce the renal clearance of amantadine with risk of amantadine toxicity (including headache, nausea, dizziness).

Concomitant use of amiodarone with quinine should be avoided due to the increased risk of ventricular arrhythmias.

Concomitant use of astemizole and terfenadine with quinine should be avoided due to the increased risk of ventricular arrhythmias.

There may be an increased risk of side effects if quinine is used with other antimalarials, for example, chloroquine, halofantrine and mefloquine (increased risk of convulsions), although this should not prevent their use in severe cases. Quinine may increase the plasma concentration of mefloquine. Chloroquine and quinine appear to be antagonistic when given together for P. falciparum malaria. There is an increased risk of ventricular arrhythmias with halofantrine.

Quinine can decrease serum plasma concentrations of ciclosporin.

Cimetidine inhibits quinine metabolism leading to increased plasma-quinine concentrations.

The plasma concentration of flecainide is increased by quinine. Concomitant use of quinidine may increase the possibility of cinchonism.

There is an increased risk of ventricular arrhythmias when moxifloxacin is given with quinine.

Quinine may increase the levels of phenobarbital and of carbamazepine. Patients should be monitored closely during concomitant use of quinine with these agents.

There is an increased risk of ventricular arrhythmias and concomitant use should be avoided with pimozide or thioridazine.

Rifampicin can reduced the serum levels of quinine, therefore reducing its therapeutic effect.

Quinine enhances the neuromuscular effects of suxamethonium.

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. Quinine should be used with caution in patients with atrial fibrillation, heart block, other cardiac conduction defects, or other serious heart disease. Quinine may cause hypoprothrombinaemia and enhance the effects of anticoagulants.

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.

Large doses of quinine can induce abortion. 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.

Treatment 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 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. Infants at risk for glucose-6-phosphate dehydrogenase deficiency should not be breast-fed until this disease can be ruled out. However, quinine sulfate should not be given to nursing mothers unless the benefits outweigh the risks.

Quinine may cause visual disturbances and vertigo, hence patients should be advised that if affected they should not drive or operate machinery.

Adverse drug reactions are ranked by frequency, the most frequent first, using the following convention: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), not known (cannot be estimated from the available data).

Frequency Not Known:

Blood and lymphatic system disorders: Thrombocytopenia, intravascular coagulation, hypoprothrombinaemia, haemoglobinuria, haemolytic-uremic syndrome, pancytopenia, haemolysis agranulocytosis, thrombocytopenic purpura.

Immune system disorders: Eczematous dermatitis, oedema, erythema, lichen planus, hypersensitivity reactions (asthma, angioneurotic oedema, photosensitivity, hot and flushed skin, fever, pruritis, thrombocytopenic purpura and urticaria).

Metabolism and nutrition disorders: Hypoglycaemia.

Psychiatric disorders: Agitation, confusion.

Nervous system disorders: Headache, vertigo, excitement, loss of consciousness, coma, death.

Eye disorders: Blurred vision, defective colour perception, visual field constriction.

Ear and labyrinth disorders: Tinnitus, impaired hearing.

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, T wave flattening.

Respiratory, thoracic and mediastinal disorders: Bronchospasm, dyspnoea.

Gastrointestinal disorders: Diarrhoea, nausea, vomiting, abdominal pain*.

Skin and subcutaneous tissue disorders: Flushing, rash, urticaria, eczematous dermatitis, oedema, erythema, lichen planus, pruritis, photosensitivity, Stevens-Johnson syndrome.

Musculoskeletal and connective tissue disorders: Muscle weakness, aggravation of Myasthenia gravis

Renal and urinary disorders: Renal insufficiency, acute renal failure (may be due to an immune mechanism or to circulatory failure), oliguria.

Reproductive system and breast disorders: Abortion**

General disorders and administration site conditions: Cinchonism***

* May occur after long term administration of quinine.
** Toxic doses of quinine may induce abortion, but it is unwise to withhold the drug if less toxic antimalarials are not available.
*** 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. Visual disorders (blurred vision, defective colour perception, visual field constriction and total blindness).