Quinine

Quinine is a cinchona alkaloid given orally or intravenously for malaria when artemisinin drugs are unavailable, for treatment failure, and for first-trimester malaria in some settings. It has a narrow therapeutic window. Hypoglycaemia, cinchonism, QT prolongation and rare haemolysis (blackwater fever) are the main hazards.

Class. Antimalarial; cinchona alkaloid.

Mechanism. Probably inhibits haem polymerisation within the parasite food vacuole, causing toxic haem to build up. It acts on the blood stages of all Plasmodium species.

Pharmacokinetics. Oral bioavailability over 80%. Half life 10 to 12 hours in healthy people and longer in severe malaria. Metabolised by CYP3A4 and excreted in urine. It is highly protein bound.

Uncomplicated malaria (adults and children). Quinine sulfate 10 mg/kg (salt) orally every 8 hours for 7 days, with doxycycline 100 mg twice daily for 7 days (adults) or clindamycin 10 mg/kg twice daily for 7 days (children, pregnancy, under 8 years).

Severe malaria when artesunate is unavailable. Quinine dihydrochloride 20 mg/kg (salt) by intravenous infusion over 4 hours as a loading dose (omit if quinine or mefloquine was given in the last 24 hours), then 10 mg/kg every 8 hours over 2 to 4 hours until oral treatment is possible. Maximum loading dose: 1.4 g.

Dose adjustment. In kidney impairment or when treatment lasts over 48 hours, reduce the maintenance dose to 5 to 7 mg/kg every 8 hours.

Main alternative. Artesunate or an artemisinin combination.

Contraindications. Hypersensitivity; optic neuritis; haemoglobinuria (blackwater fever); G6PD deficiency (caution); congenital QT prolongation; myasthenia gravis.

Serious adverse effects. Hypoglycaemia (especially in pregnancy and children), QT prolongation and arrhythmia, severe cinchonism (hearing loss, visual disturbance), thrombocytopenia and haemolysis, and hypotension with rapid infusion.

Common adverse effects. Tinnitus, headache, nausea, dizziness, blurred vision and bitter taste.

Interactions. - Mefloquine, halofantrine and other QT-prolonging drugs: avoid. - Rifampicin lowers levels; ritonavir raises them. - Digoxin levels rise. - Antacids containing aluminium reduce absorption.

Common prescribing errors. Giving a loading dose after recent quinine or mefloquine, infusing too quickly, not checking glucose, and omitting the second drug in the oral course.

Special groups. - Pregnancy: used with clindamycin in the first trimester when artemisinin combinations are unavailable; monitor glucose. - Breastfeeding: compatible. - Children: weight-based dosing. - Older adults: usual dose with cardiac checks. - Kidney impairment: reduce the dose after 48 hours. - Liver impairment: caution.

Regional points. Quinine remains available in many East African facilities as a fallback for severe malaria when artesunate is out of stock and for first-trimester malaria; hypoglycaemia is a common cause of death during treatment.

Formulations. Tablets 200 mg and 300 mg (sulfate); injection 300 mg/mL (dihydrochloride).

Administration. Oral: after food to reduce nausea. Intravenous: dilute in 5% glucose (10 mL/kg) and infuse over 4 hours (loading), never by bolus.

Baseline. Glucose, ECG if possible, potassium, haemoglobin, renal function, pregnancy test.

Monitoring. Glucose every 4 to 6 hours during infusion; ECG in those with cardiac risk; hearing and vision symptoms; blood pressure.

Stopping thresholds. Stop for QTc over 500 ms, severe hypoglycaemia, optic neuritis or haemoglobinuria.

Referral and escalation. Admission for severe malaria; urgent review for arrhythmia, severe hypoglycaemia or blackwater fever.