Praziquantel

PRAZIQUANTEL

Praziquantel is effective in the treatment of schistosome infections of all species and most other trematode and cestode infections, including cysticercosis. The drug’s safety and effectiveness as a single oral dose have also made it useful in mass treatment of sev-eral infections.

Basic Pharmacology

Praziquantel is a synthetic isoquinoline-pyrazine derivative. It is rapidly absorbed, with a bioavailability of about 80% after oral administration. Peak serum concentrations are reached 1–3 hours after a therapeutic dose. Cerebrospinal fluid concentrations of prazi-quantel reach 14–20% of the drug’s plasma concentration. About 80% of the drug is bound to plasma proteins. Most of the drug is rapidly metabolized to inactive mono- and polyhydroxylated prod-ucts after a first pass in the liver. The half-life is 0.8–1.5 hours. Excretion is mainly via the kidneys (60–80%) and bile (15–35%). Plasma concentrations of praziquantel increase when the drug is taken with a high-carbohydrate meal or with cimetidine; bioavail-ability is markedly reduced with some antiepileptics (phenytoin, carbamazepine) or with corticosteroids.

Praziquantel appears to increase the permeability of trematode and cestode cell membranes to calcium, resulting in paralysis, dislodgement, and death. In schistosome infections of experimen-tal animals, praziquantel is effective against adult worms and immature stages, and it has a prophylactic effect against cercarial infection.

Clinical Uses

Praziquantel tablets are taken with liquid after a meal; they should be swallowed without chewing because their bitter taste can induce retching and vomiting.

A. Schistosomiasis

Praziquantel is the drug of choice for all forms of schistosomiasis. The dosage is 20 mg/kg per dose for two (S mansoni and S haema-tobium) or three (S japonicum and S mekongi) doses at intervals of4–6 hours. High cure rates (75–95%) are achieved when patients are evaluated at 3–6 months; there is marked reduction in egg counts in those not cured. The drug is effective in adults and children and is generally well tolerated by patients in the hepatos-plenic stage of advanced disease. There is no standard regimen for acute schistosomiasis (Katayama syndrome), but standard doses as described above, often with corticosteroids to limit inflammation from the acute immune response and dying worms, are recom-mended. Increasing evidence indicates rare S mansoni drug resis-tance, which may be countered with extended courses of therapy (eg, 3–6 days at standard dosing) or treatment with oxamniquine. Effectiveness of praziquantel for chemoprophylaxis has not been established.

B. Clonorchiasis, Opisthorchiasis, and Paragonimiasis

Standard dosing is 25 mg/kg three times daily for 2 days for each of these fluke infections.

C. Taeniasis and Diphyllobothriasis

A single dose of praziquantel, 5–10 mg/kg, results in nearly 100% cure rates for T saginata, T solium, and D latum infections. Because praziquantel does not kill eggs, it is theoretically possible that larvae of T solium released from eggs in the large bowel could penetrate the intestinal wall and give rise to cysticercosis, but this hazard is probably minimal.

D. Neurocysticercosis

Albendazole is now the preferred drug, but when it is not appropri-ate or available, praziquantel has similar efficacy. Indications for praziquantel are similar to those for albendazole. The praziquantel dosage is 100 mg/kg/d in three divided doses for 1 day, then 50 mg/ kg/d to complete a 2- to 4-week course. Clinical responses to ther-apy vary from dramatic improvements of seizures and other neuro-logic findings to no response and even progression of the disease. Praziquantel—but not albendazole—has diminished bioavailabilitywhen taken concurrently with a corticosteroid. Recommendations on use of both antihelminthics and corticosteroids in neurocysticer-cosis vary.

Hymenolepis nana 

Praziquantel is the drug of choice for H nana infections and the first drug to be highly effective. A single dose of 25 mg/kg is taken initially and repeated in 1 week.

F. Hydatid Disease

In hydatid disease, praziquantel kills protoscoleces but does not affect the germinal membrane. Praziquantel is being evaluated as an adjunct with albendazole pre- and postsurgery. In addition to its direct action, praziquantel enhances the plasma concentration of albendazole.

G. Other Parasites

Limited trials at a dosage of 25 mg/kg three times daily for 1–2 days indicate effectiveness of praziquantel against fasciolopsia-sis, metagonimiasis, and other forms of heterophyiasis. Praziquantel was not effective for fascioliasis, however, even at dosages as high as 25 mg/kg three times daily for 3–7 days.

Adverse Reactions, Contraindications, & Cautions

Mild and transient adverse effects are common. They begin within several hours after ingestion of praziquantel and may persist for about 1 day. Most common are headache, dizziness, drowsiness, and lassitude; others include nausea, vomiting, abdominal pain, loose stools, pruritus, urticaria, arthralgia, myalgia, and low-grade fever. Mild and transient elevations of liver enzymes have been reported. Several days after starting praziquantel, low-grade fever, pruritus, and skin rashes (macular and urticarial), sometimes asso-ciated with worsened eosinophilia, may occur, probably due to the release of proteins from dying worms rather than direct drug tox-icity. The intensity and frequency of adverse effects increase with dosage such that they occur in up to 50% of patients who receive 25 mg/kg three times in 1 day.

In neurocysticercosis, neurologic abnormalities may be exac-erbated by inflammatory reactions around dying parasites. Common findings in patients who do not receive corticoster-oids, usually presenting during or shortly after therapy, are head-ache, meningismus, nausea, vomiting, mental changes, and seizures (often accompanied by increased cerebrospinal fluid pleocytosis). More serious findings, including arachnoiditis, hyperthermia, and intracranial hypertension, may also occur. Corticosteroids are commonly used with praziquantel in the treatment of neurocysticercosis to decrease the inflammatory reaction, but this is controversial and complicated by knowledge that corticosteroids decrease the plasma level of praziquantel up to 50%. Praziquantel is contraindicated in ocular cysticercosis, because parasite destruction in the eye may cause irreparable damage. Some workers also caution against use of the drug in spinal neurocysticercosis.The safety of praziquantel in children younger than age 4 years is not established, but no specific problems in young children have been documented. Indeed, the drug appears to be better tolerated in children than in adults. Praziquantel increased abortion rates in rats and therefore should be avoided in pregnancy if possible. Because the drug induces dizziness and drowsiness, patients should not drive during therapy and should be warned regarding activities requiring particular physical coordination or alertness.