Class: Anthelmintics
VA Class: AP200
Chemical Name: 2-(Cyclohexylcarbonyl)-1,2,3,6,7,11b-hexahydro-4H-pyrazino(2,1-a)isoquinolin-4-one
CAS Number: 55268-74-1
Brands: Biltricide
Introduction
Anthelmintic agent; pyrazinoisoquinoline derivative.2 3 4 5
Uses for Praziquantel
Schistosomiasis
Treatment of schistosomiasis (bilharziasis) caused by all Schistosoma species pathogenic to humans.1 14 15 16 17 18 19 20 21 24 25 26 27 28 29 30 32 33 34 35 38 40 41 42 55 56 87 88 89 128 133 134 140
Drug of choice for treatment of infections caused by S. haematobium, S. japonicum, S. mansoni, S. mekongi,3 4 6 9 11 14 15 16 29 32 33 34 38 55 87 88 89 128 133 134 and S. intercalatum.11
Used for treatment of individual patients3 9 12 14 16 17 21 140 and in mass-treatment and control programs.3 6 9 12 15 18 19 20 89
Effective against all stages of Schistosoma infection, including acute phase3 6 9 12 14 15 17 18 19 20 140 and chronic phase (which may be associated with hepatosplenic involvement).9 12 15 16 21 27 30 81
May be effective for treatment of severe schistosomiasis (e.g., neuroschistosomiasis).140 141 Initiate promptly to prevent substantial morbidity and long-term sequelae;140 141 may be initiated in cases of suspected neuroschistosomiasis pending results of confirmative tests.141
Cure rates generally lower in children6 38 and in patients with massive infections.6
Clonorchiasis
Treatment of clonorchiasis caused by Clonorchis sinensis (Chinese liver fluke).1 3 4 9 11 22 25 26 31 43 87 88 90 91 92 93 102 103 104 105 118 119 128 129 134 Drug of choice.87 88 128 134
Opisthorchiasis
Treatment of opisthorchiasis caused by Opisthorchis viverrini (Southeast Asian liver fluke).1 3 4 9 11 25 26 29 44 87 94 95 96 97 102 104 105 118 119 126 128 130 131 132 134 Drug of choice.87 88 128 130 134
Other Trematode (Fluke) Infections
Treatment of trematode (fluke) infections caused by Fasciolopsis buski† (intestinal fluke),11 87 88 107 Heterophyes heterophyes† (intestinal fluke),11 87 Metagonimus yokogawai† (intestinal fluke),9 11 106 Metorchis conjunctus† (North American liver fluke), Nanophyetus salmincola† (formerly Troglotrema salmincola) (intestinal fluke),135 136 and Paragonimus westermani† (lung fluke).3 4 9 11 37 55 88 98 99 100 101 Drug of choice.55 87 88 134
Has been effective in a limited number of patients for treatment of infections caused by P. kellicotti† (American lung fluke),48 P. heterotrema† (lung fluke),111 and P. uterobilateralis† (African lung fluke).71
Has been used in a limited number of patients for treatment of infections caused by Fasciola hepatica† (sheep liver fluke),87 108 but treatment failures have been reported.88 110 134 Drug of choice is triclabendazole (not commercially available in the US); alternatives are bithionol (not commercially available in the US; may be available from the CDC) and nitazoxanide.134 146
Cestode (Tapeworm) Infections
Treatment of cestodiasis (tapeworm infections) caused by Diphyllobothrium latum† (fish tapeworm),2 4 46 47 134 Dipylidium caninum† (dog and cat tapeworm),46 134 Taenia saginata† (beef tapeworm),2 4 46 134 T. solium† (pork tapeworm),4 11 46 87 134 142 143 144 145 and Hymenolepis nana† (dwarf tapeworm).2 3 4 9 11 23 46 87 134
Drug of choice.55 87 134 Effective against the adult, juvenile, and larval stages of susceptible cestodes.4 46
Cysticercosis
Treatment of cysticercosis†, including neurocysticercosis†, caused by the larval form of T. solium (Cysticercus cellulosae).3 9 11 46 52 53 55 72 73 74 88 113 114 115 116 121 123 124 134
Praziquantel and albendazole are drugs of choice, but treatment of neurocysticercosis is controversial.55 134 147 148
Corticosteroids usually used concomitantly to reduce frequency and severity of adverse nervous system effects (CSF reaction syndrome).52 55 65 73 74 76 114 115 116 121 123 134 Anticonvulsant therapy also may be necessary.52 55 65 73 74 76 114 115 116 121 123 134
In some patients with neurocysticercosis†, risk of severe adverse effects may outweigh potential benefits.147 148
Do not use in patients with intraocular cysticercosis† because of risk of irreversible intraocular lesions secondary to killing of the cysts.1 88 85 117 Ocular and spinal cysts generally are not treated with anthelmintic drugs since irreparable damage may occur, even with concomitant corticosteroids.55 134
Hydatid Disease
Unlikely to be effective in the treatment of larval Echinococcus infections (hydatid cysts)†.4 60 61 Treatment of choice is surgical resection of the cysts; if surgery is contraindicated or cysts rupture spontaneously during surgery, mebendazole or albendazole is treatment of choice.83 134
Because praziquantel kills Echinococcus (e.g., protoscoleces), it may be useful for perioperative prophylaxis or when cyst contents are spilled during surgery.122 134
Praziquantel Dosage and Administration
Administration
Oral Administration
Administer orally with meals.1
Tablets may be halved or quartered to allow administration of individualized doses.1 Swallow the tablets, halves, and/or quarters with a sufficient amount of water during meals.1
Do not chew tablets.1 Retention of the tablets or tablet segments in the mouth may cause gagging or vomiting as a result of the drug's bitter taste.1
Dosage
Pediatric Patients
Schistosomiasis
Oral
Children ≥4 years of age: 20 mg/kg 3 times daily for 1 day; space doses 4–6 hours apart.1
Some clinicians recommend 20 mg/kg twice daily for 1 day for schistosomiasis caused by Schistosoma haematobium or S. mansoni.134 Doses of 40 mg/kg given as a single dose or in 2 equally divided doses have been effective in some patients with schistosomiasis caused by any species.3 6 9 12 14 15 16 17 19 20 128 133
Clonorchiasis
Oral
Children ≥4 years of age: 25 mg/kg 3 times daily for 1 day; 1 11 25 26 31 43 44 87 88 90 91 92 94 95 96 102 104 105 128 129 130 134 space doses 4–6 hours apart.1
Alternatively, 40–50 mg/kg given as a single dose has been effective in some patients,31 126 131 132 but may be associated with lower cure rates.31
Opisthorchiasis
Oral
Children ≥4 years of age: 25 mg/kg 3 times daily for 1 day;1 11 25 26 31 43 44 87 88 90 91 92 94 95 96 102 104 105 128 129 130 134 space doses 4–6 hours apart.1
Alternatively, 40–50 mg/kg given as a single dose has been effective in some patients,31 126 131 132 but may be associated with lower cure rates.31
Other Trematode (Fluke) Infections†
Fasciolopsis buski†, Heterophyes heterophyes†, or Metagonimus yokogawai† Infections
Oral
25 mg/kg 3 times daily for 1 day.11 87 88 134
Nanophyetus salmincola† Infections
Oral
20 mg/kg 3 times daily for 1 day.134 135 136
Paragonimus westermani† or P. uterobilateralis† Infections
Oral
25 mg/kg 3 times daily for 2 days.71 134
Fasciola hepatica† Infections
Oral
25 mg/kg 3 times daily for 5–8 days has been used,87 but treatment failures have occurred.88 110 134
Cestode (Tapeworm) Infections
Oral
Diphyllobothrium latum† (Fish Tapeworm), Dipylidium caninum† (Dog and Cat Tapeworm), Taenia saginata† (Beef Tapeworm), or T. solium† (Pork Tapeworm) Infections
Oral
5–10 mg/kg as a single dose.134
Hymenolepis nana† (Dwarf Tapeworm) Infections
Oral
25 mg/kg as a single dose.55 87 134 Eradication may be difficult; retreatment necessary if infection persists.55
Cysticercosis†
Oral
50–100 mg/kg given in 3 divided doses daily for 30 days.134
Adults
Schistosomiasis
Oral
20 mg/kg 3 times daily for 1 day; space doses 4–6 hours apart.1
Some clinicians recommend 20 mg/kg twice daily for 1 day for treatment of schistosomiasis caused by Schistosoma haematobium or S. mansoni.134 Doses of 40 mg/kg given as a single dose or in 2 equally divided doses have been effective in some patients with schistosomiasis caused by any species.3 6 9 12 14 15 16 17 19 20 128 133
Clonorchiasis
Oral
25 mg/kg 3 times daily for 1 day;1 11 25 26 31 43 44 87 88 90 91 92 94 95 96 102 104 105 128 129 130 134 space doses 4–6 hours apart.1
Alternatively, 40–50 mg/kg given as a single dose has been effective in some patients,31 126 131 132 but may be associated with lower cure rates.31
Opisthorchiasis
Oral
25 mg/kg 3 times daily for 1 day;1 11 25 26 31 43 44 87 88 90 91 92 94 95 96 102 104 105 128 129 130 134 space doses 4–6 hours apart.1
Alternatively, 40–50 mg/kg given as a single dose has been effective in some patients,31 126 131 132 but may be associated with lower cure rates.31
Other Trematode (Fluke) Infections†
Fasciolopsis buski †, Heterophyes heterophyes†, or Metagonimus yokogawai† Infections
Oral
25 mg/kg 3 times daily for 1 day. 11 87 88 134
Nanophyetus salmincola† Infections
Oral
20 mg/kg 3 times daily for 1 day.134 135 136
Paragonimus westermani† or P. uterobilateralis† Infections
Oral
25 mg/kg 3 times daily for 2 days.71 134
Fasciola hepatica† Infections
Oral
25 mg/kg 3 times daily for 5–8 days has been used, but treatment failures have occurred.88 110 134 .87
Cestode (Tapeworm) Infections
Diphyllobothrium latum† (Fish Tapeworm), Dipylidium caninum† (Dog and Cat Tapeworm), Taenia saginata† (Beef Tapeworm), or T. solium† (Pork Tapeworm) Infections
Oral
5–10 mg/kg as a single dose.134
Hymenolepis nana† (Dwarf Tapeworm) Infections
Oral
25 mg/kg as a single dose; re-treat if infection persists.55 87 134
Cysticercosis†
Oral
50–100 mg/kg given in 3 divided doses daily for 30 days.134
Neurocysticercosis†
Oral
50 mg/kg given in 3 equally divided doses daily for 14–21 days.52 53 72 74 88 113 115 116 121 Concomitant corticosteroids (e.g., dexamethasone 6–24 mg daily, prednisone 30–60 mg daily) often administered to reduce adverse nervous system effects.52 65 73 74 76 121
Consider repeating therapy in patients who show only partial resolution of cysts 3 months after a course or whose condition deteriorates.53 121 123
Special Populations
Hepatic Impairment
Use caution if usual dosage is used in patients with hepatosplenic schistosomiasis if they have moderate to severe liver impairment (Child-Pugh class B and C).1 (See Hepatic Impairment under Cautions.)
Renal Impairment
Dosage adjustments not necessary in patients with renal impairment.1 (See Pharmacokinetics.)
Geriatric Patients
No specific dosage recommendations at this time.1 (See Geriatric Use under Cautions.)
Cautions for Praziquantel
Contraindications
Hypersensitivity to the drug.1
Intraocular cysticercosis.1 88
Warnings/Precautions
Warnings
Interactions
Therapeutically effective praziquantel concentrations may not be achieved in patients receiving concomitant therapy with drugs that are strong inducers of CYP450 (e.g., rifampin).1 (See Specific Drugs and Food under Interactions.)
Sensitivity Reactions
Urticaria,1 14 15 16 42 93 100 128 maculopapular rash,102 103 111 128 pruritus,14 15 16 42 93 102 and a generalized hypersensitivity reaction, including polyserositis, have been reported.1
Mild eosinophilia has occurred in patients with schistosomiasis treated with praziquantel.19 40 Consider that eosinophilia can be associated with schistosomiasis38 50 and may be a consequence of a host-mediated immunologic response to antigen release during drug-induced killing of the worms.65 77 78 Similarly, urticaria may result from an immunologic response to antigen release from the worms.100
General Precautions
Precautions Related to Treatment of Neurocysticercosis
CSF reaction syndrome (headache, exacerbation of neurologic signs and symptoms such as seizures, increased CSF protein concentrations and anticysticercal IgG levels, arachnoiditis, meningism, hyperthermia, and intracranial hypertension)52 53 72 73 74 76 114 115 116 121 123 137 occurs in almost all53 74 121 patients during treatment for neurocysticercosis and may rarely be life-threatening.73 114 115 116 Use appropriate corticosteroid therapy to reduce the frequency and severity of adverse nervous system effects.72 73 74 76 114 115 116 121 123
Manufacturer recommends that patients with schistosomiasis who have cerebral cysticercosis be hospitalized during treatment.1
GI Effects
Abdominal pain or discomfort (with or without nausea) occurs frequently.1 3 4 14 15 16 17 38 40 41 42 89 90 91 93 94 96 98 100 102 104 107 108 112 126 130 Vomiting,1 14 15 16 19 38 41 42 93 100 103 107 112 epigastric pain,90 91 93 94 107 126 anorexia,1 14 90 91 92 93 94 98 126 urge to defecate,89 and diarrhea14 16 41 91 93 94 104 107 112 126 130 have been reported.
GI reactions, principally colicky, crampy abdominal pain, occasionally may be severe and occur suddenly within 1 hour after administration of the drug; may be accompanied by fever, sweating, and bloody stools.89
Hepatic Effects
Mild to moderate, transient increases in serum AST and/or ALT concentrations1 occur in about 3–27% of patients;16 104 no evidence of serious adverse hepatic effects, even in patients with schistosomal infection associated with severe hepatosplenic involvement.1 16 81 112
Patients with Cardiac Irregularities
Monitor patients with cardiac irregularities during praziquantel treatment.1
Specific Populations
Pregnancy
Category B.1
Lactation
Distributed into milk; temporarily discontinue nursing on the day of therapy and for 72 hours after administration of the last dose.1
Pediatric Use
Safety in children <4 years of age not established.1
Geriatric Use
Insufficient experience in those ≥65 years of age to determine whether they respond differently than younger adults.1 No evidence of substantial differences in safety and efficacy relative to younger adults, but increased sensitivity cannot be ruled out.1
Substantially eliminated by kidneys; decreased renal function associated with advanced age may increase risk of toxicity.1
Hepatic Impairment
Use caution in hepatosplenic patients with schistosomiasis who have moderate to severe liver impairment (Child-Pugh class B and C);1 hepatic metabolism may be decreased, resulting in considerably higher and more prolonged plasma concentrations of unchanged drug.1
Common Adverse Effects
Dizziness,1 3 15 16 19 41 42 89 90 91 92 93 94 98 102 103 104 107 111 112 126 128 headache,1 4 14 16 19 41 42 89 90 91 92 93 94 96 98 100 102 103 104 107 111 112 121 126 128 130 malaise,1 4 104 121 126 abdominal discomfort (with or without nausea).1 3 4 14 15 16 17 38 40 41 42 89 90 91 93 94 96 98 100 102 104 107 108 112 126 130
Interactions for Praziquantel
Metabolized by CYP isoenzymes (e.g., CYP3A).d
Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes
Inhibitors of CYP isoenzymes: May increase plasma concentrations of praziquantel.1
Inducers of CYP isoenzymes: May reduce plasma concentrations of praziquantel.1
Specific Drugs and Food
Drug | Interaction | Comments |
|---|---|---|
Anticonvulsants (carbamazepine, phenobarbital, phenytoin) | Decreased praziquantel concentrations1 | |
Antifungals, azoles | Itraconazole or ketoconazole: Increased praziquantel concentrations1 | |
Chloroquine | Decreased praziquantel concentrations1 | |
Cimetidine | Increased praziquantel concentrations1 c | |
Dexamethasone | Decreased praziquantel concentrations1 | |
Erythromycin | Increased praziquantel concentrations1 | |
Grapefruit juice | Increased praziquantel concentrations1 | Clinical importance unclear1 |
Rifampin | Decreased praziquantel concentrations and AUC1 d | Avoid concomitant use1 d |
Praziquantel Pharmacokinetics
Absorption
Bioavailability
About 80% of oral dose is rapidly absorbed from GI tract.1 9 36 Peak serum concentrations attained 1–3 hours after a dose.1
Extensive first-pass metabolism; only a small portion reaches systemic circulation as unchanged drug.4 9 10 36
Distribution
Extent
Distribution into human body tissues and fluids not fully characterized.65 80
In rats, concentrations of free (unbound) praziquantel in CSF were similar to those in serum.4 49 Drug concentration in CSF is 14–20% of the concurrent total (free plus protein-bound) plasma concentration.4
Distributed into milk in concentrations about 25% of maternal serum concentrations.1 36 112
Elimination
Metabolism
Rapidly and extensively metabolized, principally in the liver via hydroxylation to monohydroxylated and polyhydroxylated metabolites.4 36 Unknown if metabolites possess anthelmintic activity.65 80
Elimination Route
Approximately 70–80% of an oral dose excreted in urine within 24 hours, principally as metabolites;1 4 36 less than 0.1% of an oral dose excreted in urine unchanged.36
Half-life
Adults with normal renal and hepatic function: 0.8–1.5 hours.1 2 4 36 Half-life of metabolites is about 4–5 hours.4 36
Special Populations
Hepatic impairment: Pharmacokinetics in patients with Schistosoma mansoni infection and normal hepatic function or mild hepatic impairment (Child-Pugh class A) are similar, but half-life, peak serum concentrations, and AUC are increased in those with moderate to severe hepatic dysfunction (Child-Pugh class B and C).1 Half-life is about 3 hours in those with normal renal function, 4.7 hours in those with mild or moderate hepatic impairment (Child-Pugh class A or B), and 8.5 hours in those with severe hepatic impairment (Child-Pugh class C).1
Renal impairment: Excretion may be delayed; accumulation of unchanged drug not expected.1
Stability
Storage
Oral
Tablets
<30°C1 in tight containers.80
Actions and SpectrumActions
Synthetic, pyrazinoisoquinoline derivative anthelmintic agent2 3 4 5 structurally unrelated to other currently available anthelmintic agents.5
Active against all developmental stages of schistosomes.5 Causes dead or dying worms to be dislodged from their usual sites of residence in the mesenteric or pelvic (e.g., vesical plexus) veins to the liver where they are retained and subsequently elicit host tissue reactions (e.g., phagocytosis).4 5 6 7 8
Dislodgment of schistosomes to the liver is rapid, occurring within 1 hour after administration of a single oral dose.4 5 7 Dislodgment of worms results principally from contraction and paralysis of their musculature and subsequent immobilization of their suckers.2 4 5 6 7 8 112 128
Generally does not kill susceptible adult cestodes (tapeworms) in vivo, but causes worms to be dislodged from their usual sites of residence in the intestine by impairing function of the worms’ suckers.2 Effect is concentration dependent in vitro.2 Also causes irreversible focal vacuolization and subsequent disintegration at specific sites of the cestodal integument.2 62
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