Quinine injection Introduction Quinine acts primarily as a schizontocide ie it suppresses the asexual cycle of development of malaria parasites in the erythrocytes. It has little effect on sporozoites or pre-erythrocytic forms of malarial parasites. It does not, therefore, prevent the relapse of Plasmodium vivax infections. Quinine is also gametocidal for P. vivax and P. malariae but not for P. falciparum, and therefore does not prevent transmission of this infection by the mosquito. Plasma concentrations of quinine between 8 and 15mg/litre are effective clinically and are generally non-toxic; such values are usually achieved with the standard therapeutic dose. Approximately 70% of quinine is bound to proteins in the plasma in healthy subjects, rising to about 90% in patients with malaria. The concentration in cerebrospinal fluid is about 2-5% of that in the plasma. Quinine is extensively metabolized, especially in the liver, and excreted in the urine. Estimates of the proportion of unchanged quinine excreted in the urine vary from less than 5% to 20%. The metabolites are excreted in the urine; renal excretion of quinine is twice as rapid when the urine is acidic as when it is alkaline. The elimination half-life in healthy subjects is about eleven hours, but may be prolonged in patients with malaria. The pharmacokinetics of quinine may be altered significantly by malaria infection, with reductions in both clearance and the apparent volume of distribution. Quinine crosses the placenta and is excreted in breast milk. Indications: For the treatment of acute attacks of malaria, including attacks due to chloroquine-resistant or multi-drug-resistant strains of Plasmodium falciparum. Quinine is used parenterally for cerebral, severe or complicated malaria, or when vomiting prevents retention of an orally administered drug. Quinine dihydrochloride is the salt usually employed for the preparation of injections. Dosage and directions for use: In severe or complicated malaria, when the patient is unable to take oral medication, a slow intravenous infusion of quinine is used. In severely ill adults, a loading dose of 20 mg quinine dihydrochloride per kg may be administered by slow, constant rate intravenous infusion diluted in either isotonic fluid or 5% glucose solution (5-10 mL per kg bodyweight depending on the patient's overall fluid balance) over four hours provided that the patient has not received quinine, quinidine or mefloquin during the previous twelve to twenty-four hours, and reliable hospital facilities are available, including cardiac monitoring. The maintenance dose is 10 mg of quinine dihydrochloride per kg in 250 to 500 mL of diluent, preferably 5% glucose solution, by intravenous infusion over four hours, repeated at eight to twelve hourly intervals. For children, a dose of 25 to 30 mg per kg body-mass daily in three divided doses has been recommended. Oral therapy should be substituted as soon as possible and a total of at least seven days therapy should be completed. If, after forty-eight hours of parenteral treatment, the patient is still unable to take oral treatment, or if there is evidence of significant hepatic impairment, the maintenance dose should be reduced by half. The recommended drug dosage adjustment for patients with impaired renal function (ie. a GFR less than 10), is a third of the normal dose. However, the loading dose of quinine should not be reduced in patients with renal and hepatic impairment. If intravenous infusion is not possible, quinine dihydrochloride may be given by intramuscular injection of 10 mg per kg, although this may cause pain and local tissue necrosis. Monitoring of blood levels and side-effects is recommended during quinine therapy. NB: Quinine should never be given by rapid intravenous "push" or bolus injections as this may cause severe or even fatal cardiovascular toxicity. Pregnancy: Quinine should not be withheld from pregnant women with life-threatening malaria if other less hazardous agents are unavailable or inappropriate. Pregnant women seem to be particularly prone to quinine-induced hyperinsulinaemia and hypoglycaemia. Excessive doses may induce abortion, and congenital malformation of the optic and auditory nerves have been reported after failure to induce abortion with quinine. When administered intravenously to pregnant patients, the infusion rate should not exceed 10 mg/kg every eight hours. Contra-indications: Quinine is contra-indicated in patients with a history of hypersensitivity to quinine especially if it takes the form of cutaneous, angioedematous, visual or auditory symptoms. It is also contra-indicated in the presence of haemolysis, and in patients with tinnitus or optic neuritis. Warnings: Quinine must be used with caution in patients with atrial fibrillation or other serious heart disease. Quinine may aggravate symptoms of myasthenia gravis and should be used with care if at all in such patients. Quinine may cause hypoprothrombinaemia and enhance the effects of anticoagulants. Quinine must be stopped immediately if evidence of haemolysis appears. Antimalarial agents and especially quinine, when given for prolonged periods, have been implicated in precipitating black water fever. However, in some cases deficiency of glucose-6-phosphate dehydrogenase may have been involved. Glucose-6-phosphate dehydrogenase- deficient patients with malaria may be at increased risk of haemolysis during quinine therapy. For use in pregnancy, refer 'Dosage and Directions for Use'. 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