Quinine Dihydrochloride

Indications

Quinine Dihydrochloride is used for: Malaria, Nocturnal leg cramps

Adult Dose

Intravenous Malaria Adult: As diHCl: Initially, 20 mg/kg to max 1.4 g over 4 hr w/ maintenance infusion started after 8 hr. Maintenance infusions: 10 mg/kg to max 700 mg over 4 hr 8 hrly. Loading dose should not be given if patient received quinine, quinidine, halofantrine or mefloquine during the previous 12 hr. Hepatic impairment: Mild to moderate (Child-Pugh class A and B): No dosage adjustment needed. Severe: Reduce maintenance dose to 5-7 mg/kg of quinine salt 8 hrly.

Child Dose

Intravenous Malaria Child: <5 mg/kg/hr by slow IV infusion.

Renal Dose

Renal impairment: Severe: Reduce maintenance dose to 5-7 mg/kg of quinine salt 8 hrly.

Administration

Contra Indications

Hypersensitivity to quinine, mefloquine or quinidine. Patients w/ nocturnal leg cramps; prolonged QT interval, tinnitus or optic neuritis, myasthenia gravis, G6PD deficiency, haemolysis and who had suffered from black water fever. Concomitant use w/ ritonavir, mefloquine, rifampicin, class IA and class III antiarrhythmic agents, neuromuscular blocking agents, other drugs known to cause QT prolongation, and Al- and/or Mg-containing antacids.

Precautions

Patients w/ cardiac conduction defects, heart block or AF. Pregnancy and lactation. Monitoring Parameters Monitor for signs of cardiotoxicity. Monitor blood glucose levels, CBC w/ platelet count, LFT, ECG; ophthalmologic exam.

Pregnancy-Lactation

Pregnancy No evidence that quinine causes uterine contractions at doses recommended for malaria treatment May stimulate the pregnant uterus at doses several-times higher than those used to treat malaria There are extensive published data but few well-controlled studies of quinine sulfate in pregnant women Published data on over 1,000 pregnancy exposures to quinine did not show an increase in teratogenic effects over the background rate in the general population; however, the majority of these exposures were not in the first trimester Used during pregnancy only if the potential benefit justifies the potential risk to the fetus Clinical considerations Treatment of malaria in pregnancy is important P falciparum malaria carries a higher risk of morbidity and mortality in pregnant women than in the general population Pregnant women with P falciparum malaria have an increased incidence of fetal loss (including spontaneous abortion and stillbirth), preterm labor and delivery, intrauterine growth retardation, low birth weight, and maternal death Hypoglycemia, due to increased pancreatic secretion of insulin, associated with quinine use, particularly in pregnant women Lactation Low levels of quinine in breast milk; amounts ingested by infant are small and would not be expected to cause any adverse effects Dosage in milk is far below those required to treat an infant for malaria Do not use in mothers with an infant who is glucose-6-phosphate dehydrogenase (G6PD) deficient Relatively small amounts of quinine in tonic water ingested by breastfeeding women have caused hemolysis in G6PD-deficient infants

Interactions

Reduced renal clearance of amantadine. Reduced clearance w/ cimetidine. Increased anticoagulant effect of warfarin and other anticoagulants. Reduced plasma levels of ciclosporin. Increased plasma levels of digoxin. Increased risk of myopathy and rhabdomyolysis w/ atorvastatin. May enhance hypoglycaemic effects of oral antidiabetics. Potentially Fatal: Increased risk of QT prolongation and torsade de pointes w/ mefloquine, class IA antiarrhythmic agents (e.g. quinidine, procainamide, disopyramide) and class III antiarrhythmic agents (e.g. amiodarone, sotalol, dofetilide) and other drugs known to cause QT prolongation (e.g. halofantrine, pimozide, thioridazine). Potentiates neuromuscular blockade w/ neuromascular blocking agents. Decreased plasma levels w/ rifampicin. Increased serum levels w/ ritonavir. May delay or decrease absorption w/ Al- and/or Mg-containing antacids.

Side Effects

Side effects of Quinine Dihydrochloride : <1% Flushing of the skin, Anginal symptoms, Fever, Rash, Pruritus, Hypoglycemia, Epigastric pain, Hemolysis in G6PD deficiency, Thrombocytopenia, Hepatitis, Nightblindness, Diplopia, Optic atrophy, Impaired hearing, Hypersensitivity reaction Frequency Not Defined Severe headache, Nausea, Vomiting, Diarrhea, Blurred vision, Tinnituscinchonism (risk of cinchonism is directly related to dose and duration of therapy) Potentially Fatal: Sinus arrest, AV block, ventricular fibrillation and sudden death especially with IV use.

Mode of Action

Quinine is a cinchona alkaloid and a 4-methanolquinoline. It rapidly acts on blood schizontocide by interfering w/ lysosomal function or nucleic acid synthesis in the Plasmodia spp. It has no activity against exoerythrocytic forms.