Biltricide (Praziquantel) is a trematodicide provided in tablet form for the oral treatment of schistosome infections and infections due to liver fluke.

Biltricide (Praziquantel)   (praziquantel) is 2-(cyclohexylcarbonyl)-1,2,3,6,7, 11b-hexahydro-4H-pyrazino [2, 1-a] isoquinolin-4-one with the molecular formula; CHNO. The structural formula is as follows:

Praziquantel is a white to nearly white crystalline powder of bitter taste. The compound is stable under normal conditions and melts at 136-140°C with decomposition. The active substance is hygroscopic. Praziquantel is easily soluble in chloroform and dimethylsulfoxide, soluble in ethanol and very slightly soluble in water.

Biltricide (Praziquantel) tablets contain 600 mg of praziquantel. Inactive ingredients: corn starch, magnesium stearate, microcrystalline cellulose, povidone, sodium lauryl sulfate, polyethylene glycol, titanium dioxide and hypromellose.

Praziquantel induces a rapid contraction of schistosomes by a specific effect on the permeability of the cell membrane. The drug further causes vacuolization and disintegration of the schistosome tegument.

After oral administration Biltricide (Praziquantel) is rapidly absorbed (80%), subjected to a first pass effect, metabolized and eliminated by the kidneys. Maximal serum concentration is achieved 1-3 hours after dosing. The half-life of praziquantel in serum is 0.8-1.5 hours.

Biltricide (Praziquantel) is indicated for the treatment of infections due to: all species of schistosoma (for example, and ), and infections due to the liver flukes, (approval of this indication was based on studies in which the two species were not differentiated).

Biltricide (Praziquantel) is contraindicated in patients who previously have shown hypersensitivity to the drug or any of the excipients. Since parasite destruction within the eye may cause irreversible lesions, ocular cysticercosis must not be treated with this compound.

Concomitant administration with strong Cytochrome P450 (P450) inducers, such as rifampin, is contraindicated since therapeutically effective blood levels of praziquantel may not be achieved (see PRECAUTIONS/Drug Interactions). In patients receiving rifampin who need immediate treatment for schistosomiasis, alternative agents for schistosomiasis should be considered. However, if treatment with praziquantel is necessary, rifampin should be discontinued 4 weeks before administration of praziquantel. Treatment with rifampin can then be restarted one day after completion of praziquantel treatment (see PRECAUTIONS/).

Therapeutically effective levels of Biltricide (Praziquantel) may not be achieved when administered concomitantly with strong P450 inducers, such as rifampin (see ).

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 ).

Minimal increases in liver enzymes have been reported in some patients.

Patients suffering from cardiac irregularities should be monitored during treatment.

As Biltricide (Praziquantel) can exacerbate central nervous system pathology due to schistosomiasis, as a general rule this drug should not be administered to individuals reporting a history of epilepsy and/or other signs of potential central nervous systems involvement such as subcutaneous nodules suggestive of cysticercosis.

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.

Concomitant administration of rifampin, a strong P450 inducer, with praziquantel is contraindicated and must be avoided (see ). In a crossover study with a 2-week washout period, 10 healthy subjects ingested a single 40 mg/kg dose of praziquantel following pre-treatment with oral rifampin (600 mg daily for 5 days). Plasma praziquantel concentrations were undetectable in 7 out of 10 subjects. When a single 40 mg/kg dose of praziquantel was administered to these healthy subjects two weeks after discontinuation of rifampin, the mean praziquantel AUC and C were 23% and 35% lower, respectively, than when praziquantel was given alone. In patients receiving rifampin, for example, as part of a combination regimen for the treatment of tuberculosis, alternative agents for schistosomiasis should be considered. However, if treatment with praziquantel is necessary, treatment with rifampin should be discontinued 4 weeks before administration of praziquantel. Treatment with rifampin can then be restarted one day after completion of praziquantel treatment.

Concomitant administration of other drugs that increase the activity of drug metabolizing liver enzymes (P450 inducers), for example, antiepileptic drugs (phenytoin, phenobarbital and carbamazepine), and dexamethasone, may also reduce plasma levels of praziquantel. Concomitant administration of drugs that decrease the activity of drug metabolizing liver enzymes (P 450 inhibitors), for example, 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 Cand 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.

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.

In general Biltricide (Praziquantel)   is very well tolerated. Side effects are usually mild and transient and do not require treatment. The following side effects were observed generally in order of severity: malaise, headache, dizziness, abdominal discomfort with or without nausea, rise in temperature and, rarely, urticaria. Such symptoms can, however, also result from the infection itself. Such side effects may be more frequent and/or serious in patients with a heavy worm burden.

In rats and mice the acute LD was about 2,500 mg/kg. No data are available in humans. In the event of overdose a fast-acting laxative should be given.

The dosage recommended for the treatment of schistosomiasis is: 20 mg/kg bodyweight three times a day as a one day treatment, at intervals of not less than 4 hours and not more than 6 hours. The recommended dose for clonorchiasis and opisthorchiasis is: 25 mg/kg bodyweight three times a day as a one day treatment, at intervals of not less than 4 hours and not more than 6 hours. The tablets should be washed down unchewed with water during meals. Keeping the tablets or segments thereof in the mouth can reveal a bitter taste which can promote gagging or vomiting.

Biltricide (Praziquantel)   is supplied as a 600 mg white to orange tinged, film-coated, oblong tablet with three scores. The tablet is coded with “BAYER” on one side and “LG” on the reverse side. When broken, each of the four segments contains 150 mg of active ingredient so that the dosage can be easily adjusted to the patient’s bodyweight.

Segments are broken off by pressing the score (notch) with thumbnails. If 1/4 of a tablet is required, this is best achieved by breaking the segment from the outer end.

Biltricide (Praziquantel) is available in bottles of 6 tablets.

Manufactured for:

Bayer HealthCare Pharmaceuticals Inc.Wayne, NJ 07470Manufactured in Germany

04/11   

©2011 Bayer HealthCare Pharmaceuticals Inc.      Printed in USA