Dihydroartemisinin Piperaquine

Dihydroartemisinin with piperaquine is an oral fixed-dose artemisinin combination for uncomplicated falciparum malaria, also used for chemoprevention in pregnancy and in seasonal and mass campaigns. Piperaquine has a very long half life, so it prevents new infection for about 4 to 6 weeks after treatment. It prolongs the QT interval and must be taken away from food.

Class. Antimalarial; artemisinin combination therapy.

Mechanism. Dihydroartemisinin damages parasite proteins through free radical formation after activation by haem iron. Piperaquine is a bisquinoline that probably inhibits haem detoxification in the parasite food vacuole.

Pharmacokinetics. Absorption of piperaquine rises with fat, so dosing is fasting. Half life of dihydroartemisinin about 1 hour and of piperaquine about 3 weeks. Metabolised by CYP3A4; piperaquine accumulates with repeated courses.

Uncomplicated falciparum malaria. Once daily for 3 days, with a target dose of 4 mg/kg dihydroartemisinin and 18 mg/kg piperaquine. Weight bands (dihydroartemisinin/piperaquine): - 5 kg to under 8 kg: 20/160 mg; 8 to under 11 kg: 30/240 mg. - 11 to under 17 kg: 40/320 mg; 17 to under 25 kg: 60/480 mg. - 25 to under 36 kg: 80/640 mg; 36 to under 60 kg: 120/960 mg. - 60 to under 80 kg: 160/1280 mg; 80 kg or more: 200/1600 mg.

Chemoprevention in pregnancy and in seasonal campaigns. Specialist and programme use, dosing by weight over 3 days at set intervals.

Loading dose, maintenance dose and titration. Not applicable. Maximum: one 3-day course; repeat courses within 2 months raise QT risk.

Main alternatives. Artemether with lumefantrine.

Contraindications. Hypersensitivity; congenital QT prolongation, family history of sudden death, uncorrected hypokalaemia or hypomagnesaemia; co-prescription with drugs that prolong the QT interval; severe malaria.

Serious adverse effects. QT prolongation, torsades de pointes (rare), hypersensitivity and severe skin reactions (rare).

Common adverse effects. Headache, nausea, abdominal pain, diarrhoea, cough and fever.

Interactions. QT-prolonging drugs (macrolides, fluoroquinolones, antipsychotics, ondansetron) add risk; CYP3A4 inhibitors raise piperaquine; efavirenz lowers piperaquine; avoid food within 3 hours before or after each dose.

Common prescribing errors. Giving with a fatty meal, repeating courses within 2 months, and prescribing with QT-prolonging drugs.

Special groups. - Pregnancy: used from the second trimester, and in the first when other options are unavailable. - Breastfeeding: compatible. - Children: weight-banded from 5 kg. - Older adults: usual dose; check QT drugs. - Kidney impairment: no adjustment. - Liver impairment: caution in severe disease.

Regional points. It is an alternative ACT in several East African countries and is being used in chemoprevention in pregnancy and in school-age children in some programmes; programme use depends on local policy.

Formulations. Tablets 40/320 mg and 20/160 mg; dispersible tablets for infants.

Administration. Once daily for 3 days with water, fasting: no food for 3 hours before or after each dose.

Baseline. Malaria diagnosis, weight, pregnancy status, drug history for QT drugs, potassium and magnesium if risk factors, ECG if possible.

Monitoring. Symptoms and parasite clearance at day 3 and day 28; ECG in those with risk factors.

Stopping thresholds. Stop for QTc over 500 ms or symptomatic arrhythmia, or severe skin reaction.

Referral and escalation. Admission for severe malaria and for palpitations, syncope or QT prolongation.