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Praziquantel

P02B - Trematodicides ATC P02BA01 Small molecule approved 1982 Oral Natural product

JFDA label: Epiquantel 600mg Tab

Mechanism of Action

Blocker of Voltage-activated calcium channel beta 1 subunit — Voltage-activated calcium channel beta 1 subunit blocker; Blocker of Voltage-activated calcium channel beta 2 subunit — Voltage-activated calcium channel beta 2 subunit blocker

TargetActionGene / class
Voltage-activated calcium channel beta 1 subunit efficacy BLOCKER
Voltage-activated calcium channel beta 2 subunit efficacy BLOCKER

Indications

Approved

  • Helminths

Off-label

  • Cysticercosis
  • Tapeworms

Antimicrobial Spectrum

Expected / intrinsic spectrum (EUCAST breakpoints & labels) — not local resistance. Source: openfda-label.

Helminths

OrganismActivityMIC
Schistosoma hematobium Active
Schistosoma japonicum Active
Schistosoma mansoni Active
Schistosoma mekongi Active

Contraindications

Source: Lexicomp

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

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Nervous system disorders (3)

Not Known Dizziness · headache · malaise

Gastrointestinal disorders (2)

Not Known Abdominal distress · nausea

Skin and subcutaneous tissue disorders (1)

Not Known Urticaria

General disorders and administration site conditions (1)

Not Known Fever

Dosing

Source: Lexicomp

Schistosomiasis: Oral: 20 mg/kg/dose 3 times daily at 4- to 6-hour intervals for 1 day Clonorchiasis/opisthorchiasis: Oral: Manufacturer’s labeling: 25 mg/kg/dose 3 times daily at 4- to 6-hour intervals for 1 day Alternate recommendations (off-label dose): 25 mg/kg/dose 3 times daily for 2 days (Drugs for Parasitic Infections 2013) Cysticercosis (off-label use): Oral: 50 mg/kg/day divided every 8 hours for 14 days (Takayanagui, 2004) Tapeworms (off-label use): Oral: 5-10 mg/kg as a single dose (25 mg/kg for Hymenolepis nana) (Liu, 1996)
(For additional information see "Praziquantel: Pediatric drug information") Children ≥4 years and Adolescents: Refer to adult dosing.
Refer to adult dosing.
No dosage adjustment necessary.
There are no dosage adjustments provided in manufacturer’s labeling. However, total drug exposure in moderate-to-severe impairment is increased.

Warnings & Precautions

Source: Lexicomp

Cardiovascular disease

Use with caution in patients with cardiac abnormalities.

Cerebral cysticercosis

It is recommended to hospitalize patients with cerebral cysticercosis for the duration of treatment.

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.

Schistosomiasis

Praziquantel may not be effective against migrating shistosomulae; observational data indicate that praziquantel treatment in the acute phase of the infection may not prevent progression from asymptomatic to acute shistosomiasis, or from asymptomatic/acute disease to chronic disease. In addition, use in patients with shistosomiasis 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 shistosomal antigens. Such reactions typically occur during the acute disease phase, and may lead to life-threatening events such as respiratory failure, encephalopathy, and/or cerebral vasculitis.

Seizures

Use not recommended in patients with a history of seizures or signs of central nervous system involvement (eg, subcutaneous nodules suggestive of cysticercosis); may exacerbate condition. Concurrent drug therapy issues:

Drug/drug interactions

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Therapeutic levels of praziquantel may not be achieved with concurrent administration of strong inducers of cytochrome P450 (eg, rifampin); concurrent use is contraindicated. Other warnings/precautions:

Patient information

Patients should be instructed to not drive or operate machinery on the day of treatment and the day after treatment.

Pregnancy & Lactation

Pregnancy

FDA category B

Adverse effects have not been observed in animal reproduction studies. Use in pregnant women only if clearly needed.

Lactation

Appears in breast milk at a concentration of ¼ that of maternal serum. Women should be advised to not breast-feed on the day of treatment and for 72 hours after treatment.

Monitoring

Clinical pearlLiver function tests; monitor patients with cardiac irregularities during treatment; monitor for seizures; culture urine or feces for ova prior to instituting therapy

Chemistry & Properties

2D structure
FormulaC19H24N2O2
Molecular weight312.41 g/mol
IUPAC name2-(cyclohexanecarbonyl)-3,6,7,11b-tetrahydro-1H-pyrazino[2,1-a]isoquinolin-4-one
CAS55268-74-1
PubChem CID4891
InChIKeyFSVJFNAIGNNGKK-UHFFFAOYSA-N
logP2.53 (XLogP 2.7)
Polar surface area40.62 Ų
H-bond acceptors / donors2 / 0
Drug-likeness (QED)0.80
Lipinski violations0
SMILESO=C(C1CCCCC1)N1CC(=O)N2CCc3ccccc3C2C1

Biology & Pharmacokinetics

Pharmacokinetics predicted

Bioavailability70.0%
Half-life1.404 h
Volume of distribution0.734 L/kg
Protein binding81.1%
BBB penetrantYes

Enzyme interactions

EnzymeRoleDetail
CYP1A2Inhibitor
CYP1A2Substrate
CYP2B6Inhibitor
CYP2C19Inhibitor
CYP2C19Substrate
CYP2C9Inhibitor
CYP2C9Substrate
CYP2D6Substrate
CYP3A4Substrate

Transporters

BCRP (Inhibitor)BSEP (Inhibitor)BSEP (Inhibitor)MRP1 (Inhibitor)MRP2 (Inhibitor)MRP4 (Inhibitor)OATP1B1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)OATP1B3 (Inhibitor)P-gp (Inhibitor)P-gp (Substrate)

Drug–drug interactions (83, DDInter)

Interacting drugSeverityManagement
Apalutamide major
Carbamazepine major
Enzalutamide major
Fosphenytoin major
Lumacaftor major
Mitotane major
Phenobarbital major
Phenytoin major
Primidone major
Rifabutin major
Rifampicin major
Rifapentine major
St. John's Wort major
Abametapir (topical) moderate
Aminoglutethimide moderate
Amobarbital moderate
Armodafinil moderate
Bexarotene moderate
Bosentan moderate
Brigatinib moderate
Butabarbital moderate
Butalbital moderate
Cenobamate moderate
Chloroquine moderate
Dabrafenib moderate
Darunavir moderate
Deferasirox moderate
Dexamethasone moderate
Doravirine moderate
Duvelisib moderate
Echinacea moderate
Efavirenz moderate
Elagolix moderate
Eslicarbazepine moderate
Etravirine moderate
Fedratinib moderate
Felbamate moderate
Fosnetupitant moderate
Fostamatinib moderate
Glycerol phenylbutyrate moderate

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Registered Products (1)

BrandForm / strengthPackAgentCitizen (JOD)
Epiquantel Tablet 600 mg 4 tab AL-Faiasel Drug Store 3.400