Malaria: For chloroquine-resistant Plasmodium falciparum malaria give orally, 600 to 650 mg every eight hours for at least three days in most areas of the world (seven days in Southeast Asia) with concurrent or consecutive administration of 250 mg of tetracycline every six hours for seven days; or concurrent administration of 1.5 grams of sulfadoxine and 75 mg of pyrimethamine combination as a single dose; or concurrent or consecutive administration of 900 mg of clindamycin three times daily for three days.
Nocturnal recumbency leg cramps: Orally, 200 to 300 mg at bedtime and an additional dose of 200 to 300 mg may be taken following the evening meal.
Antimyotonic: Orally, 300 to 650 mg two or three times daily.
Warnings and Precautions about Quinine Sulphate
Haemolysis: Quinine should be stopped immediately if haemolysis occurs, and supportive measures instituted. Haemolysis, with the potential for haemolytic anaemia, has been reported when quinine was administered to patients with glucose-6-phosphate dehydrogenase deficiency.
Prothrombin formation: Quinine is capable of causing hypoprothrombinaemia and may enhance the effects of anticoagulants. The simultaneous administration of vitamin K counteracts the prolongation of the prothrombin time.
Atrial fibrillation: Patients with atrial fibrillation should be digitalised before receiving quinine. Quinine may otherwise cause an increase in the ventricular rate.
Hypersensitivity: Hypersensitivity reactions, including cutaneous flushing, pruritus, rash, fever, facial oedema, gastrointestinal distress, dyspnoea, tinnitus and impairment of vision have been reported. Extreme flushing of the skin with intensed generalised pruritus is the most frequent reported hypersensitivity reaction to the drug. Haemoglobinuria and asthma have also been reported rarely. If evidence of hypersensitivity occurs during quinine therapy, the drug should be discontinued.
Carcinogenicity and Mutagenicity: Tests have not shown quinine to be carcinogenic or mutagenic although in in-bred strains of mice studies have shown an increase in the SCEs per cell, positive micronucleus test results and an increase in chromatid breaks in chromosome aberration tests.
Use in pregnancy: Category D. The use of antimalarial drugs in the treatment of malaria is accepted because the small risk to the foetus is outweighed by the benefits to the mother and the foetus. Prophylaxis in high risk situations is also justified. In high doses quinine causes fetal injuries in the form of deafness, development disturbances and malformations of the extremities and cranium in both animals and humans. Its ability to induce uterine contractions also constitutes a risk of abortion.
Use in lactation: Quinine is excreted in breastmilk in small concentrations and caution should be exercised during breastfeeding.
Side Effects and Adverse Reactions
The long term administration of quinine in normal therapeutic doses may give rise to a train of symptoms known as cinchonism, characterised by tinnitus, headache, nausea, and disturbed vision in its mildest form. If the medication is continued or in overdose symptoms also involve the gastrointestinal tract, central nervous system, cardiovascular system and skin. In some individuals small doses of quinine cause toxic manifestations.
The following adverse reactions have been reported with quinine in therapeutic or excessive dosage:
Haematological: Acute haemolysis, thrombocytopenic purpura, agranulocytosis, hypoprothrombinaemia.
Central Nervous System: Visual disturbances including blurred vision with scotomata, photophobia, diplopia, mydriasis, constricted visual fields, night blindness and disturbed colour perception. Visual disturbances are generally reversible following discontinuation of the drug but in severe cases optic atrophy may result. Tinnitus, deafness and vertigo. Headache, fever, apprehension, restlessness, confusion and syncope.
Dermatological/allergic: Cutaneous rashes (urticarial, papular or scarlatinal), pruritis, flushing of the skin, sweating, occasional oedema of the face.
Respiratory: Asthmatic symptoms.
Cardiovascular: Disturbances in cardiac rhythm or conduction, widening of the QRS complex, hypotension, ventricular tachycardia and anginal symptoms have occurred with prolonged quinine therapy in highly sensitive patients.
Musculoskeletal: Quinine decreases neuromuscular transmission by increasing the threshold of excitability at the myoneural junction and depresses the muscle action potential. It may therefore aggravate the symptoms of patients with myasthenia gravis.
Renal: Anuria, uraemia, haemoglobinuria
Quinine can cause thrombocytopenia which may be fatal. There have been reports of haemolytic uraemic syndrome with acute renal failure following a single dose of quinine 300mg. Acute haemolytic anaemia is rare and normally disappears on withdrawal of the drug.
Interactions with Quinine Sulphate
Excessive amount of beverages containing quinine should not be consumed while taking quinine, as this may increase the risk of adverse reactions and toxicity.
Pyrimethamine: Pyrimethamine may displace quinine from plasma protein binding sites resulting in excessive free quinine and perhaps quinine toxicity.
Digoxin/digitoxin: Increased plasma levels of digoxin have been demonstrated in individuals after concomitant quinine administration. It is recommended that plasma levels of digoxin or digitoxin be determined periodically for those individuals taking either of these glycosides and quinine concomitantly.
Antacids: Concurrent use of antacids containing aluminium may delay or decrease the absorption of quinine.
Anticoagulants: Cinchona alkaloids including quinine have the potential to depress the hepatic enzyme system that synthesises vitamin K dependent clotting factors. The resulting hypoprothrombinaemic effect may enhance the action of warfarin and other oral anticoagulants.
Neuromuscular blocking agents: The effects of neuromuscular blocking agents particularly pancuronium, suxamethonium (succinyl choline) and tubocurarine may be potentiated with quinine and result in respiratory difficulties.
Acidifiers and alkalinisers: Ammonium chloride and other drugs that may lower the pH of the urine (urinary acidifiers) considerably increase the renal excretion of quinine. Conversely urinary alkalinisers e.g. acetazolamide and sodium bicarbonate may increase quinine blood levels with potential for toxicity.
Mefloquine: Because adverse cardiac effects may be additive mefloquine should not be used concomitantly with quinine. Concomitant use of mefloquine and quinine may result in ECG abnormalities or cardiac arrest and may increase the risk of seizures.
Cimetidine: Cimetidine has been reported to reduce the clearance and prolong the elimination half-life of quinine following concomitant administration of the drugs in healthy patients. The clinical significance of this interaction is not known.
Skeletal muscle relaxants: In view if the known effect of quinine in patients with myasthenia gravis it may potentiate the effect of both depolarising and nondepolarising muscle relaxants.
Other: There is an increased risk of inducing ventricular arrhythmias if quinine is given together with halofantrine or other arrhythmogenic drugs such as amiodarone, the antihistamines astemizole and terfenadine, cisapride and the antipsychotic pimozide.
There are reports of quinine reducing renal clearance of amantadine, decreasing plasma concentrations of cyclosporin, inhibiting the metabolism of flecainide and reducing plasma concentrations of primaquine.
Elimination of quinine has been reported to increase in patients also receiving rifampcin.
Quinine and chloroquine may be antagonistic when used for falciparum malaria.
A study of healthy subjects has suggested that blood concentrations of quinine are lower in heavy smokers than in non-smokers potentially impairing efficacy.
Laboratory Tests: Quinine may produce an elevated value for urinary 17-ketogenic steroids when the Zimmerman method is used.