Praziquantel Dexamethasone

Praziquantel is readily absorbed (80% in 24 hours) after oral administration, with serum concentrations being maximal in 1 to 3 hours the drug has a half-life of 0.8 to 1.5 hours. Its bioavailability is reduced by pheny-toin or carbamazepine and increased by cimetidine. Dexamethasone decreases plasma praziquantel levels by 50%. Praziquantel is excreted by the kidneys. 

Praziquantel Interactions of this drug are reported with carbamazepine, phenytoin, dexamethasone, and chloroquine.182... 

Increased risk of albendazole toxicity with praziquantel and dexamethasone... 

A one-day intensive course of praziquantel has been used experimentally, but results vary, and when there are multiple brain cysts present the outcome is poor (4). When used for this purpose in a dose of 25 mg/kg at 2-hour intervals, adverse effects included mild headache, dizziness, nausea, and vomiting. AH the adverse effects remitted with analgesics or dexamethasone 0.2 mg/kg/day and continued for 2 days. 

A 66-year-old man with neurocysticercosis treated with glucocorticoids and praziquantel developed headache and confusion. He did not have a ventricular shunt inserted. A contrast-enhanced CT scan showed multiple focal enhancing lesions with mild edema. An MRI scan of the head was reported as being most consistent with neurocysticercosis. He was given dexamethasone 2 mg bd and praziquantel 50 mg/kg/day. A few days later his headache worsened, with nausea and drowsiness. After 2 weeks he became stuporose and had to be ventilated. A CT scan showed multiple areas of deep subcortical focal edema near the areas of previously enhancing cysts, a striatocapsular stroke, and obstructive hydrocephalus. Two weeks after the last dose of praziquantel and despite a ventriculostomy tube he died. 

Inducers of hepatic CYPs such as carbamazepine and phenobarbital reduce the bioavaUabihty of praziquantel. Dexamethasone reduces the bioavailability of praziquantel, but the mechanism is not understood. Under certain conditions, praziquantel may increase the bioavailability of albendazole. 

The patient was treated with praziquantel and large doses of dexamethasone. Motor function and sensation improved with treatment, and within a month she was ambulating with assistance in a rehabilitation center. 

A patient with neuroeysticercosis taking phenytoin and phenobarbital for a seizure disorder had no response to praziquantel (four courses in doses of up to 50 mg/kg daily). Praziquantel 50 m g daily and dexamethasone 12 mg daily were started and, after one week, cimetidine 400 mg four times daily was added. The patient s serum praziquantel levels more than doubled with the addition of cimetidine (maximum serum levels raised from 350 to 826 nanograms/mL) and the AUC rose about fourfold, and became similar to that found in control subjects taking praziquantel alone. The patient showed marginal improvement, and continued to slowly improve over the following 4 months. ... 

Not established, but the probable reason is that these anticonvulsants and dexamethasone , (p.236) have enzyme-inducing effects and can therefore increase the metabolism of praziquantel. Cimetidine , (p.236) (an enzyme inhibitor) appears to oppose tiiis effect. However, the fact that praziquantel was still effective in one study suggests that metabolites of praziquantel might be active. ... 

The continuous use of dexamethasone can halve serum praziquantel levels. Two case reports suggest that this may reduce its efficacy in systemic worm infections, whereas another study suggests that efficacy is not affected. 

Eight patients with parenchymal brain cysticercosis taking praziquantel 50 mg/kg (in three divided doses, taken every 8 hours) had a 50% reduction in steady-state serum levels, from 3.13 to 1.55 micrograms/mL, when given dexamethasone 8 mg every 8 hours. Another patient with recurrent neurocysticercosis, who did not respond to praziquantel 50 mg/kg daily, was successfully treated with high-dose praziquantel 100 mg/kg... 

Uncertain. Dexamethasone is an inducer of the cytochrome P450 isoenzyme CYP3A4, and might therefore be expected to reduce levels of praziquantel. Cimetidine , (above) may reverse this effect. 

Information seems to be limited but the pharmacokinetic interaction would appear to be established. Just how much it affects the outcome of treatment for systemic worm infections such as cysticercosis is unknown because the optimum praziquantel levels are still uncertain, and it is possible that the metabolites of praziquantel might be active. The authors of one report suggest that dexamethasone should not be given continuously with praziquantel but only used transiently to resolve inflammatory reactions to praziquantel treatment. Alternatively, limited information suggests the addition of cimetidine may allow dexamethasone to be used. Intravenous methylprednisolone has also been used for acute corticosteroid therapy with praziquantel, and oral prednisone has been used longterm to prevent further tissue damage associated with inflammation but the effect of these corticosteroids on the plasma levels of praziquantel do not appear to have been studied. 

The interaction with dexamethasone is of no importance when praziquantel is used for intestinal worm infections (where its action is a local effect on the worms in the gut). 

Na-Bangchang K, Vanijanonta S, Karbwai J. Plasma concentratic is of praziquantel durir the therapy of neurocysticerosis with praziquantel, in the resence of antiepileptics and dexamethasone. Southeast Asian J Trap Med PtAlic Health (1 5) 26,120- 3. 

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