Praziquantel

Praziquantel is a an Anthelmintic Agent belonging to pharmacology class of Antiparasitic Agent Class

Praziquantel can be used in the treatment of Helminths

Praziquantel is rapidly absorbed from the GI tract (>80%) and distributed into the CSF and enters breast milk. Plasma protein binding: Approx 80% and get Undergoes rapid and extensive hepatic metabolism via hydroxylation by CYP2B1 and CYP3A4 isoenzymes to inactive metabolites and get excreted Via urine, mainly as metabolites. Plasma elimination half-life: Approx 1-1.5 hr (parent drug); approx 4 hr (metabolites).

The common side effects associated with Praziquantel include Dizziness, headache, malaise, Abdominal distress, nausea

Praziquantel is available in the form of Tablets.

The molecule is available in India, USA, Japan, Germany.

Praziquantel is a pyrazinoisoquinoline anthelmintic agent w/ a broad spectrum of activity against trematodes (flukes) and cestodes (tapeworms). It increases the cell permeability to Ca in schistosomes, causing strong contractions and paralysis of worm musculature leading to detachment of suckers from the blood vessel walls and to dislodgement.

The Tmax of Praziquantel was about 1-4 hours.

Onset of Action: Most patients have response to treatment within 2 hours.

Praziquantel is available in Tablets

Tablet: May be broken in half to achieve a smaller initial dose

Oral: According to the manufacturer, administer tablets with water during meals; however, some experts prefer administration 30 minutes before or 2 hours after a meal when treating tapeworm infections (eg, taeniasis). Tablets should be promptly swallowed to avoid bitter taste that may cause gagging or vomiting. Tablets may be halved or quartered; do not chew. Tablets may be crushed or disintegrated and mixed with semi-solid food or liquid; use within 1 hour of mixing. Tablets are scored and may be split into four 150 mg segments.

Praziquantel can be used in the treatment of Helminths.

Increases the cell permeability to calcium in schistosomes, causing strong contractions and paralysis of worm musculature leading to detachment of suckers from the blood vessel walls and to dislodgment.

Praziquantel is approved for use in the following clinical indications

Helminths: Treatment of infections in patients ≥1 year caused by the following: All species of Schistosoma (eg, Schistosoma mekongi, Schistosoma japonicum, Schistosoma mansoni, Schistosoma haematobium) and the liver flukes Clonorchis sinensis/Opisthorchis viverrini.

Although not approved there have been certain off labelled uses documented for Praziquantel which includes:

Neurocysticercosis, parenchymal; Tapeworms.

Clonorchiasis/opisthorchiasis: Oral: 25 mg/kg/dose 3 times daily for 1 to 2 days .

Neurocysticercosis, parenchymal (>2 viable cysts) (off-label use): Oral: 50 mg/kg/day in 3 divided doses (in combination with albendazole) for 10 to 14 days; may be repeated if persistent viable lesions on 6-month follow-up imaging . Note: Initiate adjunctive corticosteroid therapy prior to initiation of antiparasitic therapy. Antiparasitic therapy should not be initiated in patients with untreated hydrocephalus, calcified lesions, or cysticercal encephalitis; consult an infectious diseases specialist for specific treatment recommendations

Schistosomiasis: Note: Repeat treatment may be needed in 2 to 4 weeks to increase effectiveness.

S. haematobium, Schistosoma intercalatum, or S. mansoni: Oral: 40 mg/kg/day as a single dose or in 2 divided doses for 1 day .

S. japonicum or S. mekongi: Oral: 60 mg/kg/day in 2 or 3 divided doses for 1 day .

Tapeworms (off-label use):

Dwarf tapeworm (Hymenolepis nana): Oral: 25 mg/kg as a single dose .

Fish tapeworm (Diphyllobothrium spp.), beef or pork tapeworm (Taenia spp.): Oral: 5 to 10 mg/kg as a single dose ; 10 mg/kg may have a higher cure rate for taeniasis.

Tablets

600 mg

Tablet

• Dose Adjustment in Pediatric Patient:

Flukes:

Clonorchiasis (Clonorchis sinensis [Chinese liver fluke]); Opisthorchiasis (Opisthorchis viverrini [Southeast Asian liver fluke]): Children and Adolescents: Oral: 25 mg/kg/dose 3 times daily at 4- to 6-hour intervals for 1 to 2 days .

Fasciolopsiasis (Fasciolopsis buski [intestinal fluke]):Limited data available: Children and Adolescents: Oral: 25 mg/kg/dose 3 times daily for 1 day .

Paragonimiasis (Paragonimus spp. [lung fluke]): Limited data available: Children and Adolescents: Oral: 25 mg/kg/dose 3 times daily for 2 to 3 days .

Schistosomiasis (Bilharziasis):

Treatment: Note: Repeat treatment may be needed in 2 to 4 weeks to increase effectiveness.

Schistosoma japonicum, Schistosoma mekongi: Children and Adolescents: Oral: 20 mg/kg/dose 3 times daily for 1 day

Schistosoma mansoni, Schistosoma haematobium, Schistosoma intercalatum: Children and Adolescents: Oral: 20 mg/kg/dose twice daily for 1 day

Control programs for endemic areas: Limited data available: Infants, Children, and Adolescents: Oral: 40 mg/kg as a single dose ; a single dose of 40 mg/kg has been successfully used to treat urogenital S. haematobium in children 1 to 10 years of age and S. mansoni in population that included infants (age range: 5 months to 7 years) ; however, pharmacokinetic data suggests a lower cure rate in infants and preschool children; one possible explanation is that higher doses may be necessary in younger patients due to pharmacokinetic/dynamic differences; in preschool children, a single dose of 60 mg/kg was successfully used in children 3 to 8 years of age in a hyperendemic area to treat S. mansoni

Tapeworms: Limited data available:

Diphyllobothrium latum (fish), Taenia saginata (beef), Taenia solium (pork); intestinal (adult) stage: Children and Adolescents: Oral: 5 to 10 mg/kg as a single dose .

Dipylidium caninum (dog); intestinal (adult) stage: Infants ≥6 months, Children, and Adolescents: Oral: 5 to 10 mg/kg as a single dose .

Hymenolepis nana (dwarf tapeworm): Children and Adolescents: Oral: 25 mg/kg as a single dose.

Neurocysticercosis (Taenia solium [pork tapeworm]); tissue (larvae) stage: Children and Adolescents: Oral: 50 mg/kg/day for 15 days ; Note: May be used in conjunction with antiseizure medication and/or corticosteroids.

Praziquantel may be contraindicated in the following conditions:

Hypersensitivity to praziquantel or any component of the formulation; ocular cysticercosis; concomitant administration with strong cytochrome P450 (CYP450) inducers, such as rifampin.

Significant drug interactions exist, requiring dose/frequency adjustment or avoidance.

The treating physician must closely monitor the patient and keep pharmacovigilance as follows

Disease-related concerns:

• Cardiac arrhythmias: Monitor patients with cardiac arrhythmias during treatment; bradycardia, ectopic rhythms, ventricular fibrillation, and AV blocks have been observed with praziquantel administration.

• Central nervous system effects: Praziquantel may exacerbate central nervous system pathology due to schistosomiasis, paragonimiasis, or Taenia solium cysticercosis. Assess whether the potential benefit justifies the potential risk in patients with a history of seizures and/or other signs of potential central nervous system involvement such as subcutaneous nodules suggestive of cysticercosis.

• Hepatic impairment: Use with caution in patients with moderate to severe hepatic impairment; reduced liver drug metabolism may result in higher and longer lasting plasma concentrations of unmetabolized praziquantel.

• Neurocysticercosis: Appropriate use: Antiparasitic therapy may worsen symptoms of neurocysticercosis by inducing an inflammatory response; adjunctive corticosteroid therapy should be started before initiation of antiparasitic therapy. Antiparasitic therapy should not be initiated in patients with untreated hydrocephalus, calcified lesions, or cysticercal encephalitis. Perform funduscopic exam prior to initiation of antiparasitic therapy to exclude intraocular cysticerci; antiparasitic therapy may lead to blindness in some cases with unsuspected intraocular parasites.

• Schistosomiasis: Praziquantel may not be effective against migrating schistosomulae; observational data indicate that praziquantel treatment in the acute phase of the infection may not prevent progression from asymptomatic to acute schistosomiasis, or from asymptomatic/acute disease to chronic disease. In addition, use in patients with schistosomiasis may be associated with clinical deterioration such as paradoxical reactions or serum sickness Jarisch-Herxheimer-like reactions, which is a sudden inflammatory immune response likely caused by the release of schistosomal antigens. Such reactions typically occur during the acute disease phase, and may lead to life-threatening events such as respiratory failure, encephalopathy, papilledema, and/or cerebral vasculitis.

There is no sufficient scientific evidence traceable regarding use and safety of Praziquantel in concurrent use with alcohol.

Praziquantel is present in breast milk.

In one study, breast milk concentrations were <1% of the maternal dose following maternal use of praziquantel 50 mg/kg as a single oral dose or three 20 mg/kg doses.

Pregnancy Category (FDA): B Pregnancy Category B

Reproduction studies have been performed in rats and rabbits at doses up to forty times the human dose and have revealed no evidence of impaired fertility or harm to the fetus due to praziquantel. There are, however, no adequate and well-controlled studies in pregnant women. An increase of the abortion rate was found in rats at 3 times the single human therapeutic dose. While animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Increased bioavailability with a high-fat meal.

The adverse reactions related to Praziquantel can be categorized as

Common Adverse effects: Dizziness, Headache, Malaise, Abdominal distress, Nausea.

Less Common Adverse effects: Abdominal pain, Anorexia, Atrioventricular block, Bloody diarrhea, Bradycardia, Cardiac arrhythmia, Drowsiness, Ectopic beats, Eosinophilia, Fatigue, Hypersensitivity, Hypersensitivity reaction, Increased liver enzymes (minimal), Myalgia.

Rare Adverse effects: Paradoxical reaction (in schistosomiasis), Polyserositis, Pruritus, Seizure, Serum sickness (in schistosomiasis; Jarisch-Herxheimer-like reaction), Skin rash, Ventricular fibrillation, Vertigo, Vomiting, Weakness.

The clinically relevant drug interactions of Praziquantel is briefly summarized here

Chloroquine: May decrease the serum concentration of Praziquantel. Risk C: Monitor therapy

Cimetidine: May increase the serum concentration of Praziquantel. Risk C: Monitor therapy

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

CYP3A4 Inducers (Moderate): May decrease the serum concentration of Praziquantel. Management: Consider alternatives to this combination when possible. If combined, monitor for reduced praziquantel efficacy if combined with moderate CYP3A4 inducers. Risk D: Consider therapy modification

CYP3A4 Inducers (Strong): May decrease the serum concentration of Praziquantel. Risk X: Avoid combination

CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Praziquantel. Risk C: Monitor therapy

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Praziquantel. Risk C: Monitor therapy

Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Grapefruit Juice: May increase the serum concentration of Praziquantel. Risk C: Monitor therapy

Rifampin: May decrease the serum concentration of Praziquantel. Risk X: Avoid combination.

The common side of Praziquantel include the following

Dizziness, Headache, Malaise, Abdominal Distress, Nausea.

Pregnancy Category (FDA): B Pregnancy Category B

Reproduction studies have been performed in rats and rabbits at doses up to 40 times the human dose and have revealed no evidence of impaired fertility or harm to the fetus due to praziquantel. There are, however, no adequate and well-controlled studies in pregnant women. An increase of the abortion rate was found in rats at three times the single human therapeutic dose. While animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

• Labor and Delivery

There is no FDA guidance on use of Praziquantel during labor and delivery.

• Nursing Mothers

Praziquantel appeared in the milk of nursing women at a concentration of about 1/4 that of maternal serum although it is not known, whether a pharmacological effect is likely to occur in children. Women should not nurse on the day of BILTRICIDE treatment and during the subsequent 72 hours.

• Pediatric Use

Safety in children under 4 years of age has not been established.

• Geriatic Use

Clinical studies of praziquantel did not include a sufficient number of subjects ages 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older patients cannot be ruled out.

This drug is known to be substantially excreted by the kidney. Because elderly patients are more likely to have decreased renal function, the risk of toxic reactions to this drug may be greater in these patients.

• Gender

There is no FDA guidance on the use of Praziquantel with respect to specific gender populations.

• Race

There is no FDA guidance on the use of Praziquantel with respect to specific racial populations.

• Renal Impairment

There is no FDA guidance on the use of Praziquantel in patients with renal impairment.

• Hepatic Impairment

There is no FDA guidance on the use of Praziquantel in patients with hepatic impairment.

• Females of Reproductive Potential and Males

There is no FDA guidance on the use of Praziquantel in women of reproductive potentials and males.

• Immunocompromised Patients

There is no FDA guidance one the use of Praziquantel in patients who are immunocompromised.

The acute toxicity of praziquantel is relatively low, as demonstrated by oral LD₅₀ values ranging between 200 - 2976 mg/kg in various species.

Pharmacodynamics:

Praziquantel is an anthelmintic used in most schistosome and many cestode infestations. Praziquantel effects the permeability of the cell membrane resulting in the contraction of schistosomes. The drug further causes vacuolization and disintegration of the schistosome tegument. The effect is more marked on adult worms compared to young worms. An increased calcium influx may play an important role. Secondary effects are inhibition of glucose uptake, lowering of glycogen levels and stimulation of lactate release. The action of praziquantel is limited very specifically to trematodes and cestodes; nematodes (including filariae) are not affected.

Pharmacokinetics:

Absorption: Rapidly absorbed from the GI tract (>80%). Time to peak plasma concentration: 1-4 hr.

Distribution: Distributed into the CSF and enters breast milk. Plasma protein binding: Approx 80%.

Metabolism: Undergoes rapid and extensive hepatic metabolism via hydroxylation by CYP2B1 and CYP3A4 isoenzymes to inactive metabolites.

Excretion: Via urine, mainly as metabolites. Plasma elimination half-life: Approx 1-1.5 hr (parent drug); approx 4 hr (metabolites).

1. https://www.uptodate.com/contents/Praziquantel -drug-information?search=Praziquantel &source=panel_search_result&selectedTitle=1~148&usage_type=panel&kp_tab=drug_general&display_rank=1#F154338
2. https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/022352s017lbl.pdf
3. https://www.medicaid.nv.gov/Downloads/provider/Praziquantel _2015-1215.pdf
4. https://www.mims.com/india/drug/info/Praziquantel ?type=full&mtype=generic#mechanism-of-action