Side effects in humans may include poor coordination, abdominal pain, vomiting, headache, and allergic reactions.[4] While it may be used during pregnancy, it is not recommended for use during breastfeeding.[4] Praziquantel is in the anthelmintic class of medications.[3] It works partly by affecting the function of the worm's sucker.[3]
The majority of side effects develop due to the release of the contents of the parasites as they are killed and the consequent host immune reaction. The heavier the parasite burden, the heavier and more frequent the side effects normally are.[citation needed]
Central nervous system (CNS): Frequently occurring side effects 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 pre-existing neurological problems, seizures, arachnoiditis, and meningism). These side effects may be life-threatening and can be reduced by coadministration of corticosteroids. All patients with cerebral cysticercosis are strongly recommended to be hospitalized during treatment.
Gastrointestinal tract: About 90% of all patients have abdominal pain or cramps with or without nausea and vomiting. Diarrhea may develop and may be severe with colic. Sweating, fever, and sometimes bloody stools may occur 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 been seen so far.
Other locations/body as a whole: Lower back pain, myalgia, arthralgia, fever, sweating, various cardiac arrhythmias, and hypotension
Pregnancy
The WHO states praziquantel is safe during pregnancy (although does not recommend use during the first trimester).[22][23] Animal studies have failed to reveal evidence of fetal harm. Praziquantel is effective in reducing schistosomiasis during pregnancy.[24] Another trial found that treatment with praziquantel did not increase the rates of low birthweight, fetal death, or congenital anomalies.[25]
Drug interactions
The antibiotic rifampicin decreases plasma concentrations of praziquantel.[26]
The drug's mode of action is not exactly known at present, but experimental evidence indicates praziquantel increases the permeability of the membranes of schistosome cells towards calcium ions. The drug thereby induces contraction of the parasites' muscle, 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 including focal disintegrations and disturbances of oviposition (laying of eggs) are seen in other types of sensitive parasites.[citation needed]
Another hypothesis regarding the mechanism of action is that it interferes with adenosine uptake in worms.[31] This effect may have therapeutical relevance given that the schistosome, as the Taenia and the Echinococcus (other praziquantel-sensitive parasites), is unable to synthesize purines, such as adenosine, de novo.[citation needed]
Bayer's Animal Health Division website states, "Praziquantel is active against cestodes (tapeworms). Praziquantel is absorbed, metabolized in the liver, and excreted in the bile. Upon entering the digestive tract from the bile, cestocidal activity is exhibited. Following exposure to praziquantel, the tapeworm loses its ability to resist digestion by the mammalian host. Because of this, whole tapeworms, including the scolices (plural of "scolex"), are very rarely passed after administration of praziquantel. In many instances, only disintegrated and partially digested pieces of tapeworms will be seen in the stool. The majority of tapeworms are digested and are not found in the feces."[32]
Praziquantel is administered as a racemate, but only the (R)-enantiomer is biologically active; the enantiomers may be separated using a resolution of an amine obtained from praziquantel.[33]
Pharmacokinetics
Praziquantel is well absorbed (about 80%) from the gastrointestinal tract. However, due to extensive first-pass metabolism, only a relatively small amount enters systemic circulation. Praziquantel has a serumhalf-life of 0.8 to 1.5 hours in adults with normal renal and liver function. Metabolites have a half-life of 4 to 5 hours. In patients with significantly impaired liver function (Child-Pugh score B and C), the serum half-life is increased to 3 to 8 hours. Praziquantel and its metabolites are mainly excreted renally; within 24 h after a single oral dose, 70 to 80% is found in urine, but less than 0.1% as the unchanged drug. Praziquantel is metabolized through the cytochrome P450 pathway via CYP3A4. Agents that induce or inhibit CYP3A4 such as phenytoin, rifampin, and azole antifungals will affect the metabolism of praziquantel.[citation needed]
Praziquantel has a particularly dramatic effect on patients with schistosomiasis. Studies of those treated have shown that within six months of receiving a dose of praziquantel, up to 90% of the damage done to internal organs due to schistosomiasis infection can be reversed.[14]
History
Praziquantel was developed in the laboratories for parasitological research of Bayer AG and Merck KGaA in Germany (Elberfeld and Darmstadt) in the mid-1970s.[citation needed]
Interceptor Plus chewable tablets (combination with milbemycin) (Elanco) for veterinary use. Note regular Interceptor only has milbemycin and does not contain praziquantel.
Praziquantel is on the World Health Organization's List of Essential Medicines.[5]
Praziquantel is not licensed for use in humans in the UK, but it can be imported when necessary on a named-patient basis.[35] It is available in the UK as a veterinary anthelmintic.
Praziquantel is FDA approved in the US for the treatment of schistosomiasis and liver flukes, although it is effective in other infections.[36]
^ abWorld Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
^Mas-Coma S, Bargues MD, Valero MA (October 2005). "Fascioliasis and other plant-borne trematode zoonoses". International Journal for Parasitology. 35 (11–12): 1255–1278. doi:10.1016/j.ijpara.2005.07.010. PMID16150452.
^Rim HJ, Chu DS, Lee JS, Joo KH, Won CY (December 1978). "[Anthelmintic Effects Of Various Drugs Against Metagonimiasis]". Kisaengch'unghak Chapchi. The Korean Journal of Parasitology. 16 (2): 117–122. doi:10.3347/kjp.1978.16.2.117. PMID12902772.
^Taraschewski H, Mehlhorn H, Bunnag D, Andrews P, Thomas H (November 1986). "Effects of praziquantel on human intestinal flukes (Fasciolopsis buski and Heterophyes heterophyes)". Zentralblatt für Bakteriologie, Mikrobiologie und Hygiene. Series A: Medical Microbiology, Infectious Diseases, Virology, Parasitology. 262 (4): 542–550. doi:10.1016/s0176-6724(86)80148-1. PMID3799097.
^"WHO } Guideline". World Health Organisation: Schistosomiasis. Archived from the original on June 17, 2007. Retrieved 4 March 2020.
^"WHO } Strategy"(PDF). WHO (2022) "WHO Guideline on control and elimination of human schistosomiasis" ISBN 978-92-4-004160-8. Retrieved 2 October 2024.
^Masimirembwa CM, Naik YS, Hasler JA (January 1994). "The effect of chloroquine on the pharmacokinetics and metabolism of praziquantel in rats and in humans". Biopharmaceutics & Drug Disposition. 15 (1): 33–43. doi:10.1002/bdd.2510150103. PMID8161714. S2CID45098166.
^Metwally A, Bennett JL, Botros S, Ebeid F (April 1995). "Effect of cimetidine, bicarbonate and glucose on the bioavailability of different formulations of praziquantel". Arzneimittel-Forschung. 45 (4): 516–518. PMID7779153.
^Angelucci F, Basso A, Bellelli A, Brunori M, Pica Mattoccia L, Valle C (August 2007). "The anti-schistosomal drug praziquantel is an adenosine antagonist". Parasitology. 134 (Pt 9): 1215–1221. doi:10.1017/S0031182007002600. PMID17428352. S2CID22482704.
-praziquantel-from-xtal-3D-bs-17.png)
