Information for the Patient
Biltricide
Pharmacology
Mechanism of Action: 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. The effect is more marked on adult worms compared to young worms. An increased calcium influx may play an important role.
Secondary effects are inhibition of glucose uptake, lowering of glycogen levels and stimulation of lactate release. The action of praziquantel is limited very specifically to trematodes and cestodes; nematodes (including filariae) are not affected.
Clinical Pharmacology: After oral administration, praziquantel is rapidly absorbed (approximately 80%), subjected to a first pass effect, metabolized and eliminated by the kidneys. Maximal serum concentration is achieved 1 to 3 hours after dosing. The half-life of praziquantel in serum is 0.8 to 1.5 hours.
Indications
For the treatment of infections due to the following species of schistosoma: (S. haematobium, S. japonicum, S. mansoni, and S. mekongi), and infections due to the liver flukes C. sinensis/O. viverrini. (Approval of this indication was based on studies in which the two species were not differentiated.)
Precautions
Many categories of drugs are known to inhibit or induce the drug metabolizing family of P450 enzymes located in the liver and intestine. Coadministration of such drugs may impact upon their metabolisms. In some cases serum concentration or bioavailability may be increased and in others decreased. Care must therefore be exercised when coadministering such drugs. Praziquantel is believed to be metabolized via the P450 enzyme system. The following lists some of the drug interactions which have been reported so far with praziquantel. Other causes such as effects upon absorption among others may also exist.
Concomitant administration of praziquantel with strong inducers of cytochrome P450 such as rifampin must be avoided because therapeutically effective levels of praziquantel may not be achieved.
Coadministration with praziquantel of anticonvulsants like phenytoin, fosphenytoin, carbamazepine and phenobarbital or with chloroquine or dexamethasone have been reported to lower praziquantel bioavailability and serum levels. Similar trends have been reported with glucose and bicarbonate.
Cimetidine, miconazole and ketoconazole have been shown to inhibit P450 enzyme mediated metabolism. When coadministered with praziquantel, increased bioavailability and serum levels of praziquantel have been reported. Praziquantel on the other hand has been shown to reduce albendazole bioavailability and serum levels.
Praziquantel appears in the milk of nursing women at a concentration of 20 to 25% that of maternal serum. Breast-feeding should be suspended for the day(s) of treatment and the following 72 hours. The physician should evaluate if the potential benefit clearly outweighs the potential risk (taking into consideration the quality of available alternative artificial nutrition).
Nephrotoxic effects of praziquantel have not been observed. Since 80% of praziquantel and its derivatives are excreted in the kidneys, excretion may be delayed in patients with impaired renal function.
Caution should be taken in patients with uncompensated liver insufficiency or with hepatosplenic schistosomiasis. Because of reduced drug metabolization in the liver, considerably higher and longer lasting concentrations of unmetabolized praziquantel can occur in the vascular system and/or collateral circulation, leading to prolonged plasma half-life. If necessary, the patient may be hospitalized for the duration of treatment. Mild increases in liver enzymes have also been reported in some patients.
Patients suffering from cardiac irregularities should be monitored during treatment.
When schistosomiasis or fluke infection is found in patients living in or coming from areas with endemic human cysticercosis, it is advisable to hospitalize the patient for the duration of treatment.
As praziquantel can exacerbate central nervous system pathology due to schistosomiasis, paragonimiasis, or T. solium cysticercosis, 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.
An increase in the abortion rate was found in rats at 3 times the single human therapeutic dose. Although animal reproduction studies have not brought to light any evidence that the mother or the unborn child might be harmed, these studies are not always predictive of human response. Praziquantel should not be used in pregnancy unless the potential benefit of treating women of reproductive age and pregnant women far outweighs the risk to their health and to the health of their babies (see Warnings).
Supplied
Each white, film-coated, oblong tablet, with 3 scores on both sides and engraved BAYER on one side and LG on the other, contains: praziquantel 600 mg. Nonmedicinal ingredients: cornstarch, magnesium stearate, microcrystalline cellulose, polyvidone 25, sodium lauryl sulfate, polyethylene glycol 4000, methylhydroxypropylcellulose and titanium dioxide. When broken, each of the four segments contains 150 mg of the active ingredient so that the dosage can be easily adjusted to the patient's body weight. Segments are broken off by pressing the score (notch) with thumbnails. If one quarter of a tablet is required, this is best achieved by breaking the segment from the outer end. Bottles of 6. Store at room temperature below 30°C. Protect from light and excessive humidity.
Contraindications
In patients who have previously shown hypersensitivity to the drug or to any of the excipients. Since parasite destruction within the eye may cause irreversible lesions, ocular cysticercosis should not be treated with praziquantel.
The concomitant administration of praziquantel with strong inducers of cytochrome P450 such as rifampin must be avoided as therapeutically effective plasma levels of praziquantel may not be achieved.
Warnings
Safety in children under 4 years of age has not been established.
No adequate and well-controlled studies have been conducted with praziquantel in pregnant women (see Precautions).
Adverse Effects
Adverse reactions vary according to dose and duration of praziquantel medication. Furthermore, they are dependent on the parasite species, extent of parasitization, duration of infection and localization of the parasites in the body.
Adverse reactions are based on publications and on spontaneous reports sorted by CIOMS III categories of frequency and MedDRA System Organ Classes (in internationally agreed order). Frequencies of adverse reactions are mainly based on data from medical literature.
The following adverse reactions have been observed after praziquantel administration. It is often not clear whether the complaints reported by patients or the undesired effects recorded by the physician are caused by praziquantel itself (direct relation), or may be considered to be an endogenous reaction to the death of the parasites (indirect relation) or are symptomatic observations of the infestation (no relation). It may be difficult to differentiate between the possible variations.
Table 1: BiltricideAdverse Drug Reactions Very Common
≥10% | Common
≥1 to <10% | Uncommon
≥0.1 to <1% | Rare
≥0.01 to <0.1% | Very Rare
<0.01% |
| Immune System Disorders |
| | | | | Allergic reaction
Polyserositis
Eosinophilia |
| Nervous System Disorders |
Headache
Dizziness | Vertigo
Somnolence (including drowsiness) | | | Seizures |
| Cardiac Disorders |
| | | | | Unspecific arrhythmias |
| Gastrointestinal Disorders |
Gastrointestinal and abdominal pains
Nausea
Vomiting | Anorexia
Diarrhea (very rarely bloody diarrhea) | | | |
| Skin and Subcutaneous Tissue Disorders |
| | Urticaria | | | Puritus |
| Musculoskeletal, Connective Tissue and Bone |
| | Myalgia | | | |
| General Disorders and Administration Site Conditions |
| | Feeling unwell
Fever | | | |
Mild increases in liver enzymes have been reported in some patients.
Overdose
No data are available regarding overdosage in humans.
In the event of an overdose, a fast-acting laxative is recommended. In rats and mice the acute oral LD50 was approximately 2500 mg/kg and in dogs the oral LD50 was less than 200 mg/kg.
Dosage
Safety and efficacy in children under 4 years of age have not been established (see Warnings).
Administration: The tablets should be swallowed whole with a little liquid, preferably during or after meals. Keeping the tablets (or segments thereof) in the mouth may reveal a bitter taste which can cause gagging or vomiting.
The interval between administration should be at least 4 hours and not more than 6 hours. When broken, each of the 4 segments contains 150 mg of active ingredient so that the dosage can be easily adjusted to the patient's body weight.
