praziquantel Praziquantel is 2-(cyclohexylcarbonyl)-1,2,3,6,7,11b-hexahydro-4H-pyrazino (2,1a) isoquinolin-4-one. CAS Number: 55268-74-1
Praziquantel is a white crystalline powder of bitter taste. The compound is stable under normal conditions and melts at 136degC-140degC with decomposition. The active substance is hygroscopic. Praziquantel is easily soluble in chloroform and dimethylsulfoxide, soluble in ethanol and very slightly soluble in water. The molecular formula is C19H24N2O2. The structural formula is as follows: Biltricide lacquer coated tablets are available as 600 mg of praziquantel. Besides the active ingredient, Biltricide tablets also contain the following excipients: maize starch, magnesium stearate, microcrystalline cellulose, povidone 25, sodium lauryl sulphate, macrogol 4000, hypromellose, titanium dioxide (CI77891).
Animal studies show that praziquantel induces a rapid contraction of schistosomes by a specific effect on the permeability of the cell membrane. The medicine further causes vacuolisation and disintegration of the schistosome tegument. The effect is more marked on the adult than on young worms.
After oral administration praziquantel is rapidly absorbed (80%). It is, however, subject to first pass effect and extensive metabolism. One hour after administration approximately 6% only of the medicine in serum is in the unmetabolized form. Both the unchanged medicine and the metabolites are excreted primarily 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.
Treatment of schistosoma infections due to various types of blood fluke (eg Schistosoma haematobium, S.japonicum, S.mekongi, S.mansoni).
Known hypersensitivity to praziquantel or any of the excipients. Ocular cysticercosis - parasite destruction within the eye may cause irreparable damage. The concomitant administration of strong inducers of Cytochrome P 450 such as rifampicin must be avoided as therapeutically effective plasma levels may not be achieved.
Since 80% of praziquantel and its metabolites are excreted in the kidneys, excretion might be delayed in patients with impaired renal function. Nephrotoxic effects of praziquantel are not known. In uncompensated liver insufficiency and in patients with hepatosplenic schistosomiasis caution should be taken, since due to reduced drug metabolisation in the liver, considerably higher and longer lasting concentrations of unmetabolised praziquantel can occur in vascular and/or collateral circulation leading to prolonged plasma half-life. If necessary, the patient may be hospitalised for the duration of the treatment. Published in vitro data have shown a potential lack of efficacy of praziquantel against migrating schistosomulae. Data from two observational cohort studies in patients indicate that treatment with praziquantel in the acute phase of infection may not prevent progression into chronic phase. In addition, the use of praziquantel in patients with schistosomiasis may be associated with clinical deterioration (paradoxical reactions, serum sickness Jarisch-Herxheimer like reactions: sudden inflammatory immune response suspected to be caused by the release of schistosomal antigens). These reactions predominantly occur in patients treated during the acute phase of schistosomiasis. They may lead to potentially life-threatening events .e.g. respiratory failure, encephalopathy, and/or cerebral vasculitis. 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 advised to hospitalise the patient for the duration of treatment. As praziquantel can exacerbate central nervous system pathology due to schistosomiasis, paragonimiasis or Taenia solium cysticercosis, as a general rule this medicine should not be administered to individuals reporting a history of epilepsy and/or other signs of potential central nervous system involvement such as subcutaneous nodules suggestive of cysticercosis. Neurocysticercosis is not an approved indication due to insufficient data. In animals, venous thrombosis and the development of granulomas at the site of worm attachment has been observed following treatment with praziquantel. Patients treated with praziquantel (for neurocysticercosis) have had a high incidence of severe headache and seizures. Some patients also developed intracranial hypertension. Because of the potential for undiagnosed neurocysticercosis to be present in patients originating from endemic areas, extra care is necessary in managing such patients. If cerebral cysticercosis is present and treatment is still considered essential, the patient should be hospitalized under specialist care.
Reproduction studies performed so far in rats and rabbits have revealed no evidence of impaired fertility or harm to the fetus due to praziquantel. An increase in abortion rate was seen in rats given single doses of 300 mg/kg. There are no adequate and well controlled studies on the use of praziquantel in pregnant women. Because animal reproduction studies are not always predictive of human response, for safety reasons praziquantel should not be used in pregnancy unless clearly needed.
Praziquantel has been reported to be excreted in the milk of nursing women. Women should not nurse on the day of Biltricide treatment and during the subsequent 72 hours.
Safety in children has not been established.
Patients should be warned not to be drive or operate machinery on the day of treatment (and during the subsequent 24 hours), as their ability to do so may be temporarily impaired by the use of praziquantel.
Concomitant administration of medicines increasing the activity of drug metabolising liver enzymes (cytochrome P450), e.g. antiepileptic medicines, dexamethasone may reduce plasma levels of praziquantel. Concomitant administration of strong inducers of Cytochrome P450 such as rifampicin must be avoided. Concomitant administration of medicines decreasing the activity of drug metabolising liver enzymes (cytochrome P450) e.g. cimetidine, may increase plasma levels of praziquantel. Chloroquine, when taken simultaneously, can lead to lower concentrations of praziquantel in blood.
Side effects vary according to dose and duration of praziquantel medication; furthermore they are dependent on the parasite species, extent of parasitisation, duration of infection and localisation of the parasites in the body. Side effects occur earlier and are more frequent and pronounced in patients with severe parasitic infestation. Mild increases in liver enzymes have been reported in some patients. 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.
| Very Common | Common | Uncommon | Rare | Very Rare | |
| Immune System Disorders | Allergic reaction Polyserositis Eosinophilia | ||||
| Nervous System Disorders | Headache Dizziness | Vertigo Somnolence (including drowsiness) | Seizures | ||
| Cardiac Disorders | Unspecified arrhythmias | ||||
| Gastrointestinal Disorders | Gastrointestinal and abdominal pains Nausea Vomiting | Anorexia Diarrhoea (very rarely bloody diarrhoea) | |||
| Skin and Subcutaneous Tissue Disorders | Urticaria | Rash | Pruritus | ||
| Musculoskeletal, Connective Tissue and Bone Disorders | Myalgia | ||||
| General Disorders and Administrative Site Conditions | Fatigue | Feeling unwell (asthenia, malaise) Fever |
It is often not clear whether the complaints reported by patients or the undesirable effects reported by the physician are caused by praziquantel itself (I, direct relation), or may be considered to be an endogenous reaction to the death of the parasites produced by praziquantel (II, indirect relation), or are symptomatic observations of the infestation (III, no relation). It may be difficult to differentiate between the possible variations I, II and III.
The doctor must prescribe individual doses for individual cases, according to the diagnosis.
Schistosoma haematobium 20 mg/kg body weight Schistosoma mansoni three times a day Schistosoma japonicum at four hourly intervals Schistosoma mekongi for one day. The tablet has 3 score marks, each fragment contains 150 mg active substance, thus allowing a precise dose to be given, corresponding to the patient's body weight. If 1/4 of a tablet is required, it is convenient to begin by breaking the tablet at one of the outer grooves. The simplest way to break the tablet is to place the thumbnail in the groove.
| BODY WEIGHT IN KG | |||||||||
| 20-25 | 26-33 | 34-41 | 42-48 | 49-56 | 57-63 | 64-70 | 71-78 | 79-86 | |
| No. of tablets corresponding to 1 x 20 mg/kg | 3/4 | 1 | 11/4 | 11/2 | 13/4 | 2 | 21/4 | 21/2 | 23/4 |
Biltricide should be swallowed whole with a little liquid, preferably after meals.
see PRECAUTIONS
see PRECAUTIONS
see PRECAUTIONS
Information on overdosage in humans is not available. Treatment should be supportive and provide symptomatic care. Activated charcoal may reduce absorption of the medicine if given within one to two hours after ingestion. In patients who are not fully conscious or have impaired gag reflex, consideration should be given to administering activated charcoal via a nasogastric tube, once the airway is protected. In cases of overdose, it is advisable to contact the National Poisons Centre (0800 764 766) for recommendations on the management and treatment of overdose.
Biltricide is sold in bottles of 8 tablets. Biltricide tablets contain 600 mg praziquantel. The tablets are white to pale yellow lacquer- coated oblong shaped tablets with three scores with Bayer on one side and "LG" on the reverse. Store below 25 degrees Celsius.
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Prescription Only Medicine
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