Adult: As quinine dihydrochloride: Initially, 20 mg/kg loading dose (Max: 1,400 mg) infused over 4 hours with maintenance infusions started after 8 hours. Maintenance: 10 mg/kg (Max: 700 mg) 8 hourly infused over 4 hours. Alternatively, in intensive care units, initial loading dose of 7 mg/kg may be administered over 30 minutes, followed immediately by the 1st of the maintenance infusions. If parenteral treatment is required for >48 hours, reduce maintenance dose to 5-7 mg/kg. Loading dose should not be given if the patient has received quinine or mefloquine during the previous 12 hours. Child: As quinine dihydrochloride: Infused at a rate not exceeding 5 mg/kg/hour.
Oral Falciparum malaria
Adult: As quinine sulfate/bisulfate (tab): 600 mg 8 hourly for 7 days. As quinine sulfate (cap): 648 mg 8 hourly for 7 days. If resistance is known or suspected on completion of the course, additional follow-on treatment with doxycycline or clindamycin may be given in uncomplicated infections. Child: As quinine sulfate/bisulfate (tab): 10 mg/kg 8 hourly for 7 days.
Oral Nocturnal leg cramps
Adult: As quinine sulfate (tab): 200 mg at bedtime once daily. Max: 300 mg daily. As quinine bisulfate (tab): 300 mg once daily at bedtime.
Special Patient Group
Pharmacogenomics:
G6PD deficiency is an inherited X-linked genetic trait wherein women may be homozygous or heterozygous for a variant, while men may be hemizygous. Both homozygous deficient women and hemizygous deficient men may experience a full expression of G6PD deficiency. The prevalence of different G6PD variants varies geographically and approx 400 million people are estimated to carry genetic variation leading to G6PD deficient activity. G6PD deficiency may be correlated with malaria distribution worldwide, and with high frequency in individuals from Mediterranean basin, Southeast Asia, Africa, Middle East, and India.
It has been reported that patients receiving quinine for the treatment of malaria, including those who are with G6PD deficiency are at an increased risk of developing acute haemolytic anaemia The cause for the acute hemolytic anaemia in quinine-treated patients with malaria and its potential relationship with G6PD deficiency has not been determined. Closely monitor Hb and hematocrit levels during quinine treatment. Quinine should be discontinued if patients develop acute hemolytic anaemia.
Renal Impairment
Falciparum malaria Oral: As quinine sulfate/bisulfate (tab): Dose reduction may be necessary. As quinine sulfate (cap): Initially, 648 mg followed after 12 hours by maintenance doses of 324 mg 12 hourly. Intravenous: Severe: Reduce maintenance dose to 5-7 mg/kg 8 hourly.
Hepatic Impairment
Falciparum malaria Oral: Severe: Not recommended. Intravenous: Severe: Reduce maintenance dose to 5-7 mg/kg 8 hourly.
Administration
Should be taken with food. Take w/ food to minimise GI discomfort.
Reconstitution
Dilute in NaCl 0.9% to a concentration of dihydrochloride 60-100 mg/mL.
Incompatibility
As 6% sterile concentrate for IV infusion: Incompatible with amiodarone, pancuronium bromide, atracurium besylate, suxamethonium chloride, mivacurium chloride, pipecuronium bromide, rapacuronium bromide, alcuronium chloride, cisatracurium besylate, doxacurium chloride, gallamine triethiodide, metocurine iodide, decamethonium bromide, rocuronium bromide, vecuronium chloride, tubocurarine chloride, diuretics particularly furosemide, mannitol, heparin, and IV ketamine.
Contraindications
Hypersensitivity to quinine, quinidine or mefloquine. History of possible hypersensitivity reactions (including blackwater fever), immune thrombocytopenia, thrombotic thrombocytopenic purpura, haemolytic uraemic syndrome; haemolysis or haemoglobinuria, prolonged QT interval, tinnitus, optic neuritis, myasthenia gravis.
Special Precautions
Patient with conditions predisposing to QT-interval prolongation, atrioventricular block, atrial fibrillation or flutter, heart block, other cardiac conduction defects or serious heart disease; G6PD deficiency. Renal and hepatic impairment. Children. Pregnancy and lactation.
Adverse Reactions
Significant: Cinchonism, haemolytic anaemia, blackwater fever, hypoglycaemia. Blood and lymphatic system disorders: Agranulocytosis, pancytopenia, intravascular coagulation. Cardiac disorders: Atrioventricular conduction disturbances, T wave flattening. Ear and labyrinth disorders: Tinnitus, impaired hearing. Eye disorders: Blurred vision, defective colour perception, visual field constriction. Gastrointestinal disorders: Diarrhoea, nausea, vomiting, abdominal pain. General disorders and admin site conditions: Oedema. Musculoskeletal and connective tissue disorders: Muscle weakness. Nervous system disorders: Headache, excitement, loss of consciousness. Psychiatric disorders: Agitation, confusion. Renal and urinary disorders: Renal insufficiency, renal failure, oliguria. Respiratory, thoracic and mediastinal disorders: Bronchospasm, dyspnoea. Skin and subcutaneous tissue disorders: Photosensitivity, erythema, pruritus, urticaria. Potentially Fatal: Severe hypersensitivity reactions, thrombocytopenia, immune thrombocytopenia, haemolytic uremic syndrome (HUS), thrombotic thrombocytopenic purpura (TTP), QT-interval prolongation, torsade de pointes, ventricular fibrillation.
This drug may cause visual disturbances and vertigo, if affected, do not drive or operate machinery.
Monitoring Parameters
Monitor CBC with platelet count, LFTs, blood glucose, and ECG. Perform ophthalmologic exam.
Overdosage
Symptoms: Vomiting, tinnitus, deafness, headache, vasodilation, visual disturbance, convulsions, impairment of consciousness, respiratory depression, QT prolongation, ventricular arrhythmia, cardiogenic shock, renal failure, hypokalaemia, hypoglycaemia, and miscarriage. Management: Symptomatic and supportive treatment. Administer multiple-dose activated charcoal (50 g for adults or 1 g/kg for children) in patients presenting within 1 hour of ingestion of doses >30 mg/kg quinine base or any amount in children <5 years. Maintain blood pressure, respiration, and renal function, and treat arrhythmia, hypoglycaemia, acidosis, and convulsions.
Drug Interactions
Increased risk of inducing ventricular arrhythmia with halofantrine or other drugs known to prolong QT interval (e.g. amiodarone, astemizole, terfenadine, cisapride, moxifloxacin, pimozide, thioridazine). Increased risk of convulsion with mefloquine. May potentiate the effects of anticoagulants, neuromascular blocking agents and oral hypoglycaemic. Reduced renal clearance of amantadine. Decreased plasma concentrations with carbamazepine, phenobarbital, phenytoin, rifampicin. Increased plasma concentration with ritonavir. May delay or decrease absorption with Al- and/or Mg-containing antacids. Reduced plasma levels of ciclosporin. Increased plasma levels of digoxin. Increased risk of myopathy and rhabdomyolysis with atorvastatin.
Lab Interference
May cause positive results with Coomb’s test; false-positive result with urine detection of opioids; false elevation of urinary 17-ketogenic steroids (using Zimmerman method) and catecholamines. May interfere with qualitative and quantitative urine dipstick protein assays.
Action
Description: Quinine, a cinchona alkaloid and a 4-methanolquinoline antimalarial drug, is a rapidly acting schizontocide with activity against Plasmodium falciparum, P vivax, P ovale, and P malariae. It is active against the gametocytes of P malariae and P vivax, except against the mature gametocytes of P falciparum. Quinine depresses oxygen uptake and carbohydrate metabolism, and intercalates into the parasite’s DNA, thereby disrupting its replication and transcription. Pharmacokinetics: Absorption: Rapidly and almost completely absorbed from the gastrointestinal tract. Time to peak plasma concentration: Approx 1-3 hours. Distribution: Widely distributed throughout the body. Poorly penetrates CSF (approx 2-7% of plasma concentration). Crosses placenta and enters breast milk. Volume of distribution: 2.5-7.1 L/kg. Plasma protein binding: Approx 70% (healthy patients); ≥90% (malaria patients). Metabolism: Extensively metabolised in the liver via oxidative CYP450 pathways primarily by CYP3A4 isoenzyme to form 3-hydroxyquinine and other metabolites. Excretion: Via urine (approx 20% as unchanged drug); increases in acidic urine. Elimination half-life: Approx 11 hours (healthy patients).
Chemical Structure
Quinine Source: National Center for Biotechnology Information. PubChem Database. Quinine, CID=3034034, https://pubchem.ncbi.nlm.nih.gov/compound/Chinin (accessed on Mar. 25, 2020)
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