Praziquantel
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Praziquantel is an anthelmintic effective against flatworms. As of 2005, praziquantel is the primary treatment for human schistosomiasis, for which it is usually effective in a single dose. It is also used to treat echinococcosis, cysticercosis, intestinal tapeworms and the liver flukes except for fascioliasis. In veterinary medicine it is widely used against tapeworms, going by the trade name of Droncit.
Praziquantel is not licensed for use in humans in the UK; it is however available as a veterinary antibiotic, and is available for use in humans on a named-patient basis.
Category
Anthelmintic
US Brand Names
BILTRICIDE®
FDA Package Insert
Description | Clinical Pharmacology | Microbiology | Indications and Usage | Contraindications | Warnings and Precautions | Adverse Reactions | Drug Interactions | Overdosage | Clinical Studies | Dosage and Administration | How Supplied | Labels and Packages
Mechanism of Action
Although the mode of action is not exactly known at present, there is experimental evidence that Praziquantel increases the permeability of the membranes of parasite cells (certain schistosomes) for calcium ions. The drug thereby induces contraction of the parasites resulting in paralysis in the contracted state. The dying parasites are dislodged from their site of action in the host organism and may enter systemic circulation or may be destroyed by host immune reaction (phagocytosis). Additional mechanisms - focal disintegrations and disturbances of oviposition (laying of eggs) - are seen in other types of sensitive parasites. Another hypothesis on the mechanism of action of praziquantel has been recently reported. The drug seems to interfere with adenosine uptake, in cultured worms. This effect may have therapeutical relevance given that the schistosome, as the taenia and the echinococcus (other praziquantel sensistive parasites), is unable to synthesize purines de novo.
Historical Perspective
Praziquantel was developed in the laboratories for parasitological research of Bayer AG in Germany (Elberfeld) in the mid 1970s. Since then it has proven indispensable in more and more indications and is recognized as such by the World Health Organization.
Pharmacokinetics
Praziquantel is well (approximately 80%) absorbed from the GI Tract. Due to extensive first pass metabolization only relatively small amounts enter systemic circulation. Praziquantel has a serum halflife of 0.8 to 1.5 hours (metabolites 4 to 5 hours) in adults with normal renal and liver function. In patients with significantly impaired liver function (Child Pugh classes B and C) the serum halflife is increased to 3 to 8 hours. Praziquantel and its metabolites are mainly excreted in the urine, within 24 hours after a single oral dose 70 to 80% are recovered in urine, but less than 0.1% are found as the unchanged drug. Praziquantel is metabolized through the cytochrome P450 pathway 3A4. Agents that induce or inhibit Cyp450 3A4 (ie phenytoin, rifampin, azole antifungals) will have an effect the metabolism of praziquantel.
Side effects
The majority of side-effects develop due to the killing of parasites, release of contents of parasites and consequent host immune reactions. The heavier the parasite burden, the heavier and more frequent the side effects normally are.
- Central Nervous System : Frequent are dizziness, headache and malaise. Drowsiness, somnolence, fatigue and vertigo have also been seen. Almost all patients with cerebral cysticercosis experience CNS side effects related to the cell-death of the parasites (headache, worsening of preexisting neurological problems, seizures, arachnoiditis, and meningism). These side effects may be life-threatening and can be reduced by coadministration of corticoids. It is strongly recommended that all patients with cerebral cysticercosis are hospitalized during treatment.
- GI Tract : Approximately 90% of all patients have abdominal pain or cramps with or without nausea and vomiting. Diarrhea may develop and may be severe with colicky. Sweating, fever, and sometimes bloody stools may emerge together with diarrhea.
- Liver : Asymptomatic and transient increases of liver enzymes (AST and ALT) are noted frequently (up to 27%). No case of symptomatic liver damage has ever been seen so far.
- Other Locations/Body as a Whole : Low Back Pain, myalgia, arthralgia, fever, sweating, various cardiac arrhythmias, and hypotension.