WARNINGS
Therapeutically effective levels of praziquantel may not be achieved with concomitant administration of strong inducers of cytochrome P450 such as rifampin.
PRECAUTIONS
General:
Approximately 80% of a dose of praziquantel is excreted in the kidneys, almost exclusively (>99%) in the form of metabolites. Excretion might be delayed in patients with impaired renal function, but accumulation of unchanged drug would not be expected. Therefore, dose adjustment for renal impairment is not considered necessary. Nephrotoxic effects of praziquantel or its metabolites are not known.
Caution should be exercised in the administration of the usual recommended dose of praziquantel to hepatosplenic schistosomiasis patients with moderate to severe liver impairment (Child-Pugh class B and C). Reduced metabolism of praziquantel by the liver in these patients may lead to considerably higher and longer lasting plasma concentrations of unmetabolized praziquantel (See CLINICAL PHARMACOLOGY/Special Populations).
Minimal increases in liver enzymes have been reported in some patients.
Patients suffering from cardiac irregularities should be monitored during treatment.
When schistosomiasis or fluke infection is found to be associated with cerebral cysticercosis it is advised to hospitalize the patient for the duration of treatment.
Information for Patients:
Patients should be warned not to drive a car and not to operate machinery on the day of BILTRICIDE® treatment and the following day.
Drug Interactions:
Concomitant administration of drugs that increase the activity of drug metabolizing liver enzymes (Cytochrome P450), e.g. antiepileptic drugs (phenytoin, phenobarbital and carbamazepine), dexamethasone, may reduce plasma levels of praziquantel.
Concomitant administration of rifampin should be avoided (see WARNINGS).
Concomitant administration of drugs that decrease the activity of drug metabolizing liver enzymes (Cytochrome P 450), e.g. cimetidine, ketoconazole, itraconazole, erythromycin may increase plasma levels of praziquantel.
Chloroquine, when taken simultaneously, may lead to lower concentrations of praziquantel in blood. The mechanism of this drug-drug interaction is unclear.
Grapefruit juice was reported to produce a 1.6-fold increase in the Cmax and a 1.9-fold increase in the AUC of praziquantel. However, the effect of this exposure increase on the therapeutic effect and safety of praziquantel has not been systematically evaluated.
Mutagenesis, Carcinogenesis:
Mutagenic effects in Salmonella tests found by one laboratory have not been confirmed in the same tested strain by other laboratories. Long term carcinogenicity studies in rats and golden hamsters did not reveal any carcinogenic effect.
Pregnancy Category B:
Reproduction studies have been performed in rats and rabbits at doses up to 40 times the human dose and have revealed no evidence of impaired fertility or harm to the fetus due to praziquantel. There are, however, no adequate and well-controlled studies in pregnant women. An increase of the abortion rate was found in rats at three times the single human therapeutic dose. While animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
Nursing mothers:
Praziquantel appeared in the milk of nursing women at a concentration of about 1/4 that of maternal serum. Women should not nurse on the day of BILTRICIDE® treatment and during the subsequent 72 hours.
Pediatric use:
Safety in children under 4 years of age has not been established.
Geriatric use:
Clinical studies of praziquantel did not include a sufficient number of subjects ages 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older patients cannot be ruled out.
This drug is known to be substantially excreted by the kidney. Because elderly patients are more likely to have decreased renal function, the risk of toxic reactions to this drug may be greater in these patients.
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