Praziquantel Drug Information

Recommended Dosage Schistosomiasis

The recommended dosage for the treatment of schistosomiasis is 20 mg/kg bodyweight administered orally three times a day separated by 4 to 6 hours, for 1 day only. Clonorchiasis and Opisthorchiasis The recommended dosage for the treatment of clonorchiasis and opisthorchiasis is 25 mg/kg bodyweight administered orally three times a day separated by 4 to 6 hours for 1 day only.

Administration Take tablets with water during meals. Do not chew or keep

the tablets (or parts of tablets) in the mouth; the bitter taste may cause gagging or vomiting. To prevent choking in pediatric patients under 6 years of age, the tablets may be crushed or disintegrated and mixed with semi-solid food or liquid. Use crushed or disintegrated tablets within 1 hour of mixing.

Praziquantel 600 mg tablets have three scores which can be split into four segments at the scores. When broken, each of the four segments contains 150 mg of praziquantel so that the dosage can be adjusted to the patient’s bodyweight. Segments are broken off by pressing the score (notch) with thumbnails.

If one-quarter of a tablet is required, this is best achieved by breaking the segment from the outer end.

The following serious or otherwise important adverse reactions are discussed elsewhere in the labeling: Clinical Deterioration Central Nervous System (CNS) Effects Potential Lack of Efficacy During the Acute Phase of Schistosomiasis Cardiac Arrhythmias Hepatic Impairment in Hepatosplenic Schistosomiasis Patients Concomitant Administration with Strong Cytochrome P450 Inducers The following adverse reactions associated with the use of praziquantel were identified in clinical studies, published literature or postmarketing reports. Because some of these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The following adverse reactions were observed in both adults and pediatric patients: General disorders and administration site conditions: malaise, pyrexia Nervous system disorders: headache, dizziness Gastrointestinal disorders: abdominal discomfort, nausea Skin and subcutaneous tissue disorders: urticaria Such adverse reactions may be more frequent and/or serious in patients with a heavy worm burden.

Additional adverse reactions reported from worldwide post marketing experience and from publications with praziquantel and various formulations of praziquantel include: Blood and lymphatic system disorders: eosinophilia Cardiac disorders: arrhythmia (including bradycardia, ectopic rhythms, ventricular fibrillation, AV blocks) Ear and labyrinth disorders: vertigo, tinnitus Eye disorders: visual disturbance Gastrointestinal disorders: abdominal pain, bloody diarrhea, vomiting General disorders and administration site conditions: polyserositis, asthenia, fatigue, gait disturbance Hepatobiliary disorders: hepatitis Immune system disorders: allergic reaction, generalized hypersensitivity, anaphylactic reaction Metabolism and nutrition disorders: anorexia Musculoskeletal and connective tissue disorders: myalgia Nervous system disorders: convulsion, somnolence, intention tremor Respiratory, thoracic and mediastinal disorders: pneumonitis, dyspnea, wheezing Skin and subcutaneous tissue disorders: pruritus, rash, Stevens-Johnson syndrome Pediatric patients 1 to 17 years of age treated with praziquantel tablets and various formulations of praziquantel experienced similar adverse reactions as those observed in adult patients. The adverse reactions reported were malaise, headache, dizziness, abdominal discomfort (with or without nausea), pyrexia and urticaria. To report SUSPECTED ADVERSE REACTIONS, contact Endo at 1-800-828-9393 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

CYP 3A Inducers Strong and Moderate

CYP 3A Inducers Concomitant administration of praziquantel with Strong and Moderate CYP 3A inducers decrease praziquantel AUC and C max which may reduce the efficacy of praziquantel. Concomitant administration of a Strong CYP 3A inducer, such as rifampin, with praziquantel is contraindicated. Concomitant administration of a Moderate CYP 3A inducer, such as efavirenz, should be avoided unless the benefit outweighs the risks

CYP450 Inhibitors

Concomitant administration of drugs that decrease the activity of drug metabolizing liver enzymes (CYP450 inhibitors), for example, cimetidine, ketoconazole, itraconazole, erythromycin, and ritonavir may increase plasma concentrations of praziquantel. In addition, grapefruit juice was also reported to produce a 1.6-fold increase in the C max and a 1.9-fold increase in the AUC of praziquantel. The effect of this exposure increase on the safety of praziquantel has not been systematically evaluated.

Pregnancy Risk Summary Published studies have not identified an association with praziquantel use during pregnancy and major birth defects, miscarriage or adverse maternal or fetal outcomes (see Data). In animal reproduction studies conducted in pregnant rats and rabbits no adverse developmental outcomes were observed with oral administration of praziquantel during organogenesis at approximately 0.65 times (rats) or 1.3 times (rabbits) the highest recommended human daily dose of 75 mg/kg/day, based on body surface area. The estimated background risk of major birth defects and miscarriage for the indicated population are unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Human Data Two randomized controlled clinical trials have been conducted using praziquantel for the treatment of schistosoma infection in pregnant women. In one randomized controlled trial in pregnant women with schistosoma ( S. japonicum) infection, 186 pregnant women were treated with praziquantel compared to 184 women who received placebo.

Treatment with praziquantel during pregnancy had no effect on birthweight, and there were no differences in rates of miscarriage, fetal death and major birth defects between the praziquantel­-treated and control patients. In another randomized controlled trial that included 2,507 pregnant women in Uganda, 18% of women were infected with schistosoma infection. Treatment with praziquantel during pregnancy had no effect on mean birth weight, perinatal mortality or major birth defects.

In other published studies, including a retrospective observational study, case series and case reports, there have been no reports of major birth defects, stillbirths or other adverse pregnancy outcomes associated with the use of praziquantel during pregnancy. Animal Data No evidence of fetal harm was observed in rats and rabbits at praziquantel dose levels of 30 to 300 mg/kg body weight given repeatedly by oral administration during the period of organogenesis. These doses were up to 0.65 times (rats) or 1.3 times (rabbits) the highest recommended human daily dose of 75 mg/kg/day, based on body surface area.

Pediatric Use Safety and dosing recommendations of praziquantel in pediatric patients 1 to 17 years have been established. Safety of praziquantel in pediatric patients younger than 1 year of age has not been established. Post-marketing experience and published literature indicates that pediatric patients 1 to 17 years of age treated with praziquantel experience similar adverse reactions as adults treated with praziquantel .

Praziquantel is contraindicated in: Patients who previously have shown hypersensitivity to praziquantel or any of the excipients in praziquantel tablets. Patients with ocular cysticercosis; since parasite destruction within the eye that occurs because of hypersensitivity reaction to the dead parasite after treatment may cause irreversible lesions, ocular cysticercosis must not be treated with praziquantel. Patients taking strong Cytochrome P450 3A enzyme (CYP 3A) inducers, such as rifampin . Known hypersensitivity to praziquantel or any of its ingredients.

Concomitant administration with strong Cytochrome P450 3A enzyme (CYP 3A) inducers such as rifampin.