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Praziquantel
General information
Praziquantel, initially introduced as a veterinary cesticidal drug, was found to have efficacy against all the human species of schistosomes (including cerebral forms), fasciolopsiasis, cysticercosis, paragonimiasis (lung fluke), Clonorchis sinensis (oriental liver fluke), and Opisthorchis viverrini infections. It is used in a single oral dose of 40 mg/kg, except in infestations with Schistosoma japonicum , Clonorchis , and Paragonimus , for which more prolonged administration is required, doses varying from 40 to 70 mg/kg/day depending on the infecting species. Evaluation of the result of praziquantel treatment has shown a lower laboratory rate of success than reported for clinical response [ ].
Praziquantel is effective in human cysticercosis in doses of 10–100 mg/kg for 3–21 days [ ]. Initially, longer courses of praziquantel were advocated, but even shorter treatment regimens are equally effective: a complete course can be administered in a single day with comparable efficacy as conventional therapy of 15 days. Praziquantel was originally introduced as a racemic mixture; there is evidence that the levorotatory isomer is relatively more effective, but has the same incidence of adverse reactions [ ].
Praziquantel is well absorbed and penetrates cyst walls, but it undergoes first-pass metabolism, especially when given together with glucocorticoids and anticonvulsants.
General adverse effects and adverse reactions
Although adverse reactions to praziquantel are common they tend to be mild and it is rarely necessary to withdraw praziquantel for this reason; even when used in relatively high doses, as in schistosomiasis, praziquantel has, according to the British National Formulary (September 2005), “the most attractive combination of effectiveness, broad-spectrum activity, and low toxicity [of all antihelminthic drugs].” The most common problems relate not so much to direct adverse reactions to the drug as to allergic and inflammatory reactions in the host to the presence of dying parasites. Fever, headache, meningism, and exacerbation of neurological symptoms have all been noted; these symptoms tend to be more severe when the pretreatment parasitic infection is widespread and intense [ ]. The main adverse reactions to praziquantel are abdominal discomfort, diarrhea, nausea and vomiting, dizziness, and somnolence [5, ]. Among children somnolence was seen in 11%. Headaches, rashes, and fever are less common [ ]. Non-specific reactions observed in a minority of patients taking praziquantel include generalized weakness, swelling of the legs, epigastric area, scrotum, or more generally, fatigue.
Drug studies
Observational studies
Echinococcosis
The management and operative complications in 70 patients with hydatid disease aged 10–78 years have been studied retrospectively to assess the impact of albendazole and praziquantel compared with surgery [ ]. In all, 39 patients received albendazole and praziquantel in combination and 19 received albendazole alone; none was treated with praziquantel alone. The combined use of albendazole and praziquantel preoperatively significantly reduced the number of cysts that contained viable protoscolices.
Of 552 patients with hydatid disease who were given albendazole plus praziquantel, eight (14%) reported mild adverse reactions, including diarrhea, vomiting, rises in alanine and aspartate aminotransferase activities, headaches and dysgeusia [8].
Neurocysticercosis
Praziquantel is generally used to treat neurocysticercosis in an oral dose of 50 mg/kg/day (divided into three doses) for 15 days. Sedation can be marked and driving should be avoided. Liver enzymes sometimes increase. Ocular cysticercosis should not be treated with praziquantel, because destruction of the parasite within the eye can cause irreparable lesions.
A one-day intensive course of praziquantel has been used experimentally, but results vary, and when there are multiple brain cysts present the outcome is poor [ ]. When used for this purpose in a dose of 25 mg/kg at 2-hour intervals, adverse reactions included mild headache, dizziness, nausea, and vomiting. All the adverse reactions remitted with analgesics or dexamethasone 0.2 mg/kg/day and continued for 2 days.
Paragonimiasis
Paragonimiasis is a food-borne parasitic disease common in Southeast Asia, especially in Japan, Korea, The Philippines, Taiwan, and parts of China. In Japan, paragonimiasis is caused by either Paragonimus westermani or Paragonimus miyazakii . Traditionally bithionol was used to treat paragonimiasis, a food-borne zoonosis that is endemic in limited areas of the world. However, owing to the need for long-term administration and moderate to severe adverse reactions, such as nausea and diarrhea, bithionol has been replaced by praziquantel. At a dose of 75 mg/kg/day for only 2–3 days, praziquantel has the advantage of an easier dosing schedule in combination with excellent therapeutic efficacy. Adverse reactions to praziquantel in paragonimiasis, if any, are mild and transient [ ]. In patients with pleural effusion, pleural fluid must be drained before starting chemotherapy; insufficient drainage often causes complications, such as chronic empyema or insufficient inflation of the lungs. Praziquantel is also effective for cutaneous, cerebral, or any form of extrapulmonary paragonimiasis.
The radiological features and treatment of paragonimiasis have been described in 13 patients (10 men, three women, aged 25–77 years) [ ]. All were treated with praziquantel 75 mg/kg/day for 2–3 days. One patient with empyema was also given bithionol. There was mild urticaria in two patients and no serious adverse reactions.
Schistosomiasis
The current chemotherapeutic armory for schistosomiasis has been reviewed [ ]. Since the development of praziquantel in 1970, morbidity and mortality due to schistosomiasis has been significantly reduced. Nevertheless, praziquantel does not prevent reinfection, and repeated treatments are usually necessary in endemic areas. In addition, there are at least two threatening consequences of relying on single-drug therapy. One is the possibility of infection with a praziquantel-resistant strain and the other is an increase in the frequency of acute manifestations of the disease, for which praziquantel is not effective. The most common adverse reactions are usually mild and include headache, dizziness, nausea, diarrhea, abdominal pain, and anorexia.
Two courses of praziquantel (40 mg/kg 4 weeks apart) for Schistosoma haematobium infection have been evaluated in 354 school children aged 5–15 years [ ]. The two doses of praziquantel were highly effective. Of the 354 children, 165 complained of one (33%), two (11%), or even three symptoms (2.5%). These adverse reactions occurred within 1 hour of treatment, were mild, and gradually resolved without specific interventions; abdominal pain (18%), nausea (12%), headache (9.6%), and dizziness (9.6%) were the most common. None of the symptoms appeared to be related to the intensity of the infection. Significantly more girls than boys complained of vomiting, dizziness, and abdominal pain and they were more frequent among older children. There were fewer adverse reactions after the second dose. Only 43 (13%) of the children reported adverse reactions after the second treatment dose, and headache was the most prevalent. The children who reported adverse reactions after the first dose were no more likely to report adverse reactions after the second dose than children who were asymptomatic after the first dose.
The effect of a single oral dose of praziquantel 40 mg/kg against Schistosoma mansoni has been studied in a rural community in Côte d’Ivoire [ ]. Among the 200 individuals treated, 25 reported one or more adverse reactions within 24 hours after treatment. A significantly higher proportion of individuals with high infection intensities (over 400 Schistosoma mansoni eggs/gram of feces) reported diarrhea and dizziness compared with those with light or moderate infections. None of the other adverse reactions, such as itching (n = 5), vomiting (n = 2), headache (n = 2), nausea (n = 2), and urticaria (n = 1) was associated with the severity of the infection, nor with age. Abdominal pain was the only adverse effect associated with (female) sex.
Tapeworm infections
The efficacy and safety of praziquantel in Diphyllobothrium nihonkaiense infections has been studied in 14 Japanese men who took a single dose of praziquantel 5–10 mg/kg [ ]. All were cured and had not expelled proglottides after 1 year of follow-up. There were no adverse reactions.
Tenia infections
In a report from India the efficacy and safety of treatment of niclosamide-resistant Tenia saginata infections with praziquantel 10 mg/kg orally has been confirmed in 185 consecutive patients [ ]. Follow-up stool examinations at 4 and 12 weeks showed a cure rate of 96%. Eleven patients were lost to follow-up, and eight still produced proglottides at the end of 12 weeks. None passed the worm in their stools, since praziquantel destructs the worm, after which the scolex and worm are digested. Thirty patients (16%) reported minimal adverse reactions, such as nausea (n = 4), abdominal discomfort (n = 10), and giddiness (n = 16).
Comparative studies
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