Droncit 5.68%

Droncit 5.68% (praziquantel) is indicated for the treatment of infections due to: all species of schistosoma (for example, Schistosoma mekongi, Schistosoma japonicum, Schistosoma mansoni and Schistosoma hematobium), and infections due to the liver flukes, Clonorchis sinensis/Opisthorchis viverrini (approval of this indication was based on studies in which the two species were not differentiated).

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.

Droncit 5.68% (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: DRUG INTERACTIONS).

WARNINGS

Therapeutically effective levels of Droncit 5.68% (praziquantel) may not be achieved when administered concomitantly with strong P450 inducers, such as rifampin (see CONTRAINDICATIONS).

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.

As Droncit 5.68% (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.

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 although it is not known whether a pharmacological effect is likely to occur in children. Women should not nurse on the day of Droncit 5.68% (praziquantel) 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.

Adverse Events

In general Droncit 5.68% (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.

Post Marketing Adverse Event Reports

Additional adverse events reported from worldwide post marketing experience and from publications with praziquantel include: abdominal pain, allergic reaction (generalized hypersensitivity) including polyserositis, anorexia, arrhythmia (including bradycardia, ectopic rhythms, ventricular fibrillation, AV blocks), asthenia, bloody diarrhea, convulsion, eosinophilia, myalgia, pruritis, somnolence, vertigo and vomiting.

In rats and mice the acute LD50 was about 2,500 mg/kg. No data are available in humans. In the event of overdose a fast-acting laxative should be given.