Quinoline Antimalarials

Quinoline antimalarials (chloroquine, quinine, mefloquine, amodiaquine, piperaquine, and the related amino alcohol lumefantrine) accumulate in the parasite digestive vacuole and block haem polymerisation, so toxic haem builds up and kills the parasite. They act on blood stages only. Chloroquine resistance is now widespread in falciparum malaria, but it still works for other species in many areas.

Pharmacokinetics. Chloroquine and mefloquine have very long half-lives (weeks) and large volumes of distribution. Quinine has a half-life of 8 to 12 hours. Piperaquine has a half-life of 3 to 4 weeks.

• Chloroquine: 25 mg base/kg over 3 days (10 mg/kg, 10 mg/kg, 5 mg/kg) for vivax, ovale, malariae and knowlesi malaria in susceptible areas. Not used for falciparum malaria in Africa.
• Quinine: 10 mg salt/kg every 8 hours for 7 days with doxycycline 100 mg twice daily or clindamycin 5 to 10 mg/kg three times daily, when a combination is unavailable. Intravenous loading 20 mg/kg when artesunate is unavailable.
• Mefloquine: prophylaxis 250 mg weekly, starting 2 to 3 weeks before travel and continuing for 4 weeks after.
• Amodiaquine: 10 mg/kg daily for 3 days within a combination; not used alone for prophylaxis because of liver and marrow toxicity.
• Piperaquine and lumefantrine: partner drugs given only within fixed combinations.

Role. In East Africa, falciparum malaria is treated with artemisinin-based combinations and not with quinolines alone. Chloroquine remains the drug for Plasmodium malariae and knowlesi, and for vivax in areas without resistance, always with primaquine for radical cure.

Quinine. Used for severe malaria when artesunate is unavailable, and for treatment in the first trimester with clindamycin. Infuse slowly and check glucose.

Prophylaxis. Mefloquine for travellers to chloroquine-resistant areas; not for those with seizures or psychiatric history.

Dose adjustment.

• Kidney: reduce quinine by one third to one half after 48 hours in severe impairment.
• Liver: avoid mefloquine and amodiaquine in severe disease.
• Pregnancy: chloroquine and quinine are safe; mefloquine is acceptable in later pregnancy for prophylaxis.
• Children: weight-based dosing.

Contraindications. Quinine with QT prolongation, optic neuritis and haemoglobinuria. Mefloquine with psychiatric disorder or seizures. Chloroquine with retinal disease for prolonged use.

Serious adverse effects. Quinine: cinchonism, hypoglycaemia, QT prolongation, thrombocytopenia, haemolysis. Chloroquine: pruritus (more common in people of African ancestry), QT prolongation, and fatal cardiotoxicity in overdose (narrow therapeutic index; 5 g in adults can be fatal). Mefloquine: dizziness, vivid dreams, depression, psychosis. Amodiaquine: agranulocytosis, hepatitis.

Monitoring. Glucose during quinine therapy; ECG when combining QT-prolonging drugs; full blood count and liver enzymes with prolonged amodiaquine.

Interactions. Quinine raises digoxin levels; mefloquine with quinine or quinidine increases seizure and arrhythmia risk; antacids reduce chloroquine absorption.

Special groups.

• Breastfeeding: chloroquine, quinine and mefloquine are compatible.
• Older adults: QT review.

Referral and escalation. Refer overdose (cardiac monitoring, hypokalaemia, intravenous support), severe malaria, and treatment failure.