quinine
Antimalarial· Brands: Qualaquin, Quinex, QuinbisulIMIVPO
Mechanism of action
Quinine exerts antimalarial activity by concentrating in the food vacuole of the parasite, where it inhibits the polymerization of heme into hemozoin, thus facilitating the accumulation of toxic heme. It also inhibits nucleic acid and protein synthesis and may cause depolarization of the parasite membrane. These actions are schizonticidal against the asexual erythrocytic forms of Plasmodium species.
Pharmacokinetics
The elimination half-life is approximately 11 hours in healthy adults, but it is prolonged to about 16–18 hours in severe falciparum malaria.
Indications & dosing
Uncomplicated chloroquine-resistant falciparum malaria
Weight-based dose: 10 mg/kg (max 600 mg). Give with doxycycline or clindamycin for 7 days.
- adult · PO: 600 mg every 8 hours · Weight-based dose: 10 mg/kg (max 600 mg). Give with doxycycline or clindamycin for 7 days.
Severe malaria
Loading dose 20 mg/kg (max 1.2 g) IV over 4 hours, then maintenance 10 mg/kg (max 600 mg) every 8 hours until oral therapy possible. Total duration 7 days.
- adult · IV: 10 mg/kg every 8 hours · Loading dose 20 mg/kg (max 1.2 g) IV over 4 hours, then maintenance 10 mg/kg (max 600 mg) every 8 hours until oral therapy possible. Total duration 7 days.
Babesiosisoff-label
Off-label. Use with clindamycin, typically for 7-10 days.
- adult · PO: 650 mg every 8 hours · Off-label. Use with clindamycin, typically for 7-10 days.
Contraindications & precautions
- Hypersensitivity to quinine or related alkaloids (e.g. quinidine, mefloquine) · Risk of anaphylaxis.
- Myasthenia gravis · Quinine can exacerbate muscle weakness.
- Optic neuritis or history of visual field defects · Risk of permanent visual damage.
- Severe prior adverse reaction to quinine (e.g. haemolytic anaemia, thrombocytopenia, blackwater fever) · Avoid re-exposure.
- Congenital long QT syndrome or clinically significant QT prolongation · Risk of torsades de pointes.
- Glucose-6-phosphate dehydrogenase (G6PD) deficiency · May precipitate haemolysis; use only if essential and with close monitoring.
- Monitor blood glucose during therapy, especially in pregnant women and patients with malnutrition.
- Use with caution in renal impairment; reduce dose and monitor levels if necessary.
- Use with caution in patients with cardiac disease or those on QT-prolonging drugs; obtain ECG if risk factors.
- Avoid in patients with G6PD deficiency unless the benefits clearly outweigh the risks.
- Caution with drugs that interact, e.g. warfarin, digoxin, and antiepileptics; check for interactions.
- Do not use for leg cramps; quinine is not recommended for this indication due to safety risks.
Adverse effects
- Cinchonism (tinnitus, headache, nausea, visual disturbance)
- Hypoglycaemia (especially in pregnancy)serious
- QT prolongation and ventricular arrhythmias (including torsades de pointes)serious
- Thrombocytopenia, haemolytic anaemia (including blackwater fever)serious
- Hypersensitivity reactions (anaphylaxis, angioedema)serious
- Ocular toxicity (visual field defects, optic neuropathy)serious
- Ototoxicity (permanent hearing loss)serious
- Neurotoxicity (seizures, confusion, coma)serious
Interactions
- digoxinmajorAvoid concurrent use if possible. If co-prescription is necessary, monitor serum digoxin concentrations, renal function, and electrocardiogram closely. Reduce the digoxin dose empirically (e.g., by 25% to 50%) and adjust based on digoxin levels and clinical response. Monitor for signs of digoxin toxicity.
Renal & hepatic adjustment
- eGFR 0–9: Reduce maintenance dose to 50% of the usual dose. Loading dose is unchanged.
- eGFR 10–30: Reduce maintenance dose to 75% of the usual dose. Monitor for toxicity.
- eGFR 31+: No adjustment required.
- Hepatic impairment (mild): No adjustment required.
- Hepatic impairment (moderate): Use with caution. Consider reducing maintenance dose and monitoring clinical response and toxicity.
- Hepatic impairment (severe): Reduce maintenance dose and monitor closely. Avoid if possible.
Monitoring, pregnancy & toxicity
- Blood glucose · Before and during treatment, especially in severe malaria
- ECG (QT interval) · Before and during treatment, especially with high doses or concurrent QT-prolonging drugs
- Cinchonism symptoms (e.g., tinnitus, visual disturbance) · At each clinical review
- Full blood count · Before and during treatment; monitor for thrombocytopenia
- Renal function (creatinine, electrolytes) · Before and during treatment
- Pregnancy: Quinine is an effective treatment for malaria in pregnancy, including severe disease, and is recommended by WHO. The benefits outweigh the risks, but it is not used for prevention. Monitor for hypoglycaemia and cinchonism.
- Toxicity: Cinchonism: tinnitus, headache, nausea, visual disturbances, vertigo · Mild symptoms are reversible on dose reduction. For severe symptoms, stop the drug.
- Toxicity: Hypoglycaemia · Monitor blood glucose; treat with IV dextrose.
- Toxicity: Cardiac toxicity: QT prolongation, ventricular arrhythmias · Monitor ECG; correct electrolyte imbalances; stop drug; consider magnesium sulfate per local protocol.
- Toxicity: Severe toxicity: hypotension, coma, renal failure, blindness · Supportive care; activated charcoal if recent ingestion; consider haemodialysis in severe cases.
Clinical notes
Quinine is the drug of choice for severe falciparum malaria, typically given as an intravenous infusion in a hospital setting, and is also used for chloroquine-resistant malaria. It may be used for nocturnal leg cramps, but this is off-label and the risk of adverse effects generally outweighs benefit. Common adverse effects include cinchonism (tinnitus, headache, nausea), hypoglycemia, and cardiac arrhythmias. Dose adjustment is required in renal impairment and in the elderly. Always check local guidelines and resistance patterns.
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BNF; local formulary