Praziquantel

Praziquantel is an oral pyrazinoisoquinoline anthelmintic and the drug of choice for all species of schistosomiasis, for liver fluke infection, and for most tapeworm infections. A single dose cures most schistosomiasis, and annual school-based mass treatment is the backbone of control. It does not kill immature worms, so cure can be incomplete in new infection. Dizziness and abdominal pain are common and short-lived.

Class. Anthelmintic; pyrazinoisoquinoline.

Mechanism. Increases calcium permeability of the worm tegument, causing sustained muscle contraction (spastic paralysis) and vacuolation of the tegument, which exposes the worm to host immune attack.

Pharmacokinetics. About 80% absorbed, with extensive first-pass metabolism by CYP3A4 and CYP1A2. Absorption is increased by food. Half life of the parent 0.8 to 1.5 hours and of metabolites 4 to 5 hours. Excreted mainly in urine as metabolites.

Schistosoma mansoni, S. haematobium, S. intercalatum (adults and children 4 years and over). 40 mg/kg orally as a single dose.

Schistosoma japonicum and S. mekongi. 60 mg/kg in 2 to 3 divided doses in one day.

Repeat dose. A second dose of 40 mg/kg 2 to 4 weeks later is given for persistent egg excretion or when infection is heavy.

Liver flukes (Clonorchis, Opisthorchis). 25 mg/kg three times daily for 2 days.

Intestinal tapeworm (Taenia, Diphyllobothrium). 5 to 10 mg/kg as a single dose.

Hymenolepis nana. 25 mg/kg as a single dose, repeated after 10 days.

Mass drug administration. 40 mg/kg single dose, dosed by height or weight bands, once yearly in school-age children in endemic areas.

Loading dose, maintenance dose and titration. Not applicable. Maximum: 75 mg/kg in a day for liver flukes.

Main alternative. None for schistosomiasis; oxamniquine is not generally available.

Contraindications. Hypersensitivity; ocular cysticercosis; concurrent strong CYP3A4 inducers (rifampicin, carbamazepine, phenytoin) which render it ineffective.

Serious adverse effects. Seizures and neuroinflammation when given for undiagnosed neurocysticercosis, hypersensitivity reactions, and rare arrhythmia.

Common adverse effects. Dizziness, drowsiness, headache, abdominal pain, nausea, diarrhoea and urticaria.

Interactions. - Rifampicin, carbamazepine, phenytoin, phenobarbital and dexamethasone lower levels. - Cimetidine and ketoconazole raise levels. - Chloroquine lowers praziquantel levels.

Common prescribing errors. Dosing by age and not by weight or height, giving to patients on rifampicin, and leaving a 4-week repeat dose out in heavy infection.

Special groups. - Pregnancy: acceptable after the first trimester, and used in endemic areas when benefit is clear. - Breastfeeding: compatible; delay breastfeeding for 6 hours after the dose if possible. - Children: used from 4 years as tablets; a dispersible paediatric formulation exists for younger children where licensed. - Older adults: usual dose. - Kidney impairment: no adjustment. - Liver impairment: reduced dose in decompensated disease; caution.

Regional points. Intestinal schistosomiasis (S. mansoni) is common around Lake Victoria, Lake Albert and Lake Malawi, and urogenital schistosomiasis (S. haematobium) occurs along the coast of Kenya and Tanzania; annual school-based mass treatment is the routine programme, and tablets are dosed with a height pole.

Formulations. Scored tablets 600 mg; dispersible paediatric tablets (where available).

Administration. After a meal, swallowed whole with water, as bitter taste causes vomiting if chewed; divided doses at 4 to 6 hour intervals when 60 mg/kg or more is split.

Baseline. Species by urine filtration or stool Kato-Katz test where available, weight or height, pregnancy status, drug history for inducers.

Monitoring. Egg excretion at 3 to 4 weeks after treatment in selected patients; symptoms for 24 hours after the dose.

Stopping thresholds. Not applicable for a single dose; treat hypersensitivity.

Referral and escalation. Specialist review for neurological symptoms, suspected neurocysticercosis, hepatosplenic disease and haematuria that persists.