ADVERSE REACTIONS SECTION.

6 ADVERSE REACTIONS. The following serious or otherwise important adverse reactions are discussed elsewhere in the labeling:Clinical Deterioration [see Warnings and Precautions (5.1)] Central Nervous System (CNS) Effects [see Warnings and Precautions (5.2)] Potential Lack of Efficacy During the Acute Phase of Schistosomiasis [see Warnings and Precautions (5.3)] Cardiac Arrhythmias [see Warnings and Precautions (5.4)] Hepatic Impairment in Hepatosplenic Schistosomiasis Patients [see Warnings and Precautions (5.5)] Concomitant Administration with Strong Cytochrome P450 Inducers [see Warnings and Precautions (5.6)] 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 population of uncertain size, it is not always possible to reliably estimate their frequency or establish causal relationship to drug exposure.The following adverse reactions were observed in both adults and pediatric patients:General disorders and administration site conditions: malaise, pyrexiaNervous system disorders: headache, dizzinessGastrointestinal disorders: abdominal discomfort, nauseaSkin and subcutaneous tissue disorders: urticariaSuch adverse reactions may be more frequent and/or serious in patients with 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: eosinophiliaCardiac disorders: arrhythmia (including bradycardia, ectopic rhythms, ventricular fibrillation, AV blocks)Ear and labyrinth disorders: vertigo, tinnitusEye disorders: visual disturbanceGastrointestinal disorders: abdominal pain, bloody diarrhea, vomitingGeneral disorders and administration site conditions: polyserositis, asthenia, fatigue, gait disturbanceHepatobiliary disorders: hepatitisImmune system disorders: allergic reaction, generalized hypersensitivity, anaphylactic reactionMetabolism and nutrition disorders: anorexiaMusculoskeletal and connective tissue disorders: myalgiaNervous system disorders: convulsion, somnolence, intention tremorRespiratory, thoracic and mediastinal disorders: pneumonitis, dyspnea, wheezingSkin and subcutaneous tissue disorders: pruritus, rash, Stevens-Johnson syndromePediatric patients to 17 years of age treated with praziquantel tablets and various formulations of praziquantel experienced similar adverse reactions as those observed in adult patients.. Clinical Deterioration [see Warnings and Precautions (5.1)] Central Nervous System (CNS) Effects [see Warnings and Precautions (5.2)] Potential Lack of Efficacy During the Acute Phase of Schistosomiasis [see Warnings and Precautions (5.3)] Cardiac Arrhythmias [see Warnings and Precautions (5.4)] Hepatic Impairment in Hepatosplenic Schistosomiasis Patients [see Warnings and Precautions (5.5)] Concomitant Administration with Strong Cytochrome P450 Inducers [see Warnings and Precautions (5.6)] The adverse reactions reported were malaise, headache, dizziness, abdominal discomfort (with or without nausea), pyrexia and urticaria. (6)To report SUSPECTED ADVERSE REACTIONS, contact Par Pharmaceutical at 1-800-828-9393 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

CLINICAL PHARMACOLOGY SECTION.

12 CLINICAL PHARMACOLOGY. 12.1 Mechanism of Action. Praziquantel is an anthelmintic drug [see Microbiology (12.4)]. 12.3 Pharmacokinetics. AbsorptionAfter oral administration, 80% of an administered praziquantel dose is absorbed, with maximal serum concentrations of praziquantel achieved to hours after dosing.EliminationFollowing oral administration of praziquantel, the elimination half-life of praziquantel in serum ranges between 0.8 to 1.5 hours.MetabolismPraziquantel is rapidly metabolized by the cytochrome P450 enzyme system and undergoes first pass effect after oral administration of praziquantel.ExcretionApproximately 80% of an oral dose of praziquantel is excreted in the kidneys, almost exclusively (greater than 99%) in the form of praziquantel metabolites.Specific PopulationsPatients with Hepatic Impairment The pharmacokinetics of praziquantel were studied in 40 patients with Schistosoma mansoni infections with varying degrees of hepatic impairment (See Table 1). In patients with schistosomiasis, the pharmacokinetic parameters did not differ significantly between those with normal hepatic function (Group 1) and those with mild (Child-Pugh class A) hepatic impairment. However, in patients with moderate-to-severe hepatic impairment (Child-Pugh class and C), praziquantel half-life, Cmax, and AUC increased progressively with the degree of hepatic impairment. In Child-Pugh class B, the increases in mean half-life, Cmax, and AUC relative to Group were 1.58-fold, 1.76-fold, and 3.55-fold, respectively. The corresponding increases in Child-Pugh class patients were 2.82-fold, 4.29-fold, and 15-fold for half-life, Cmax, and AUC.Table 1: Pharmacokinetic parameters of praziquantel in four groups of patients with varying degrees of liver function following administration of 40 mg/kg of praziquantel tablets under fasting conditions.Patient GroupHalf-life (hr)Tmax (hr)Cmax(mcg/mL)AUC(mcg/mL hr)Normal hepatic function (Group 1)2.99 +- 1.281.48 +- 0.740.83 +- 0.523.02 +- 0.59Child-Pugh (Group 2)4.66 +- 2.771.37 +- 0.610.93 +- 0.583.87 +- 2.44Child-Pugh (Group 3)4.74 +- 2.16a 2.21 +- 0.78a,b 1.47 +- 0.74a,b 10.72 +- 5.53a,b Child-Pugh (Group 4)8.45 +- 2.62a,b,c 3.2 +- 1.05a,b,c 3.57 +- 1.30a,b,c 45.35 +- 17.50a,b,c a) p<0.05 compared to Group 1b) p<0.05 compared to Group 2c) p<0.05 compared to Group 3Patients with Renal ImpairmentExcretion of praziquantel following oral administration of praziquantel might be delayed in patients with impaired renal function, but accumulation of unchanged drug would not be expected.Drug Interaction StudiesRifampin (CYP450 Inducer)In crossover study with 2-week washout period, 10 healthy subjects ingested single 40 mg/kg oral dose of praziquantel following pre-treatment with oral rifampin (600 mg daily for days). Plasma praziquantel concentrations were undetectable in out of 10 subjects. When single 40 mg/kg oral dose of praziquantel was administered to these same healthy subjects two weeks after discontinuation of rifampin, the mean praziquantel AUC and Cmax were 23% and 35% lower, respectively, than when praziquantel was given alone.. 12.4 Microbiology. Praziquantel induces rapid contraction of schistosomes by specific effect on the permeability of the cell membrane. The drug further causes vacuolization and disintegration of the schistosome tegument. However, the mechanism of action is unknown. Praziquantel is active against schistosoma (for example, Schistosoma mekongi, Schistosoma japonicum, Schistosoma mansoni and Schistosoma hematobium), and infections due to the liver flukes, Clonorchis sinensis/Opisthorchis viverrini [see Indications and Usage (1)]. Published in vitro data have shown potential lack of efficacy of praziquantel against migrating schistosomulae [see Warnings and Precautions (5.3)].

CONTRAINDICATIONS SECTION.

4 CONTRAINDICATIONS. 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 (CYP450) inducers, such as rifampin, [see Warnings and Precautions (5.6) and Drug Interactions 7.1, 7.2)].. 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 (CYP450) inducers, such as rifampin, [see Warnings and Precautions (5.6) and Drug Interactions 7.1, 7.2)].. Known hypersensitivity to praziquantel or any of its ingredients. (4.1)Concomitant administration with strong Cytochrome P450 (CYP450) inducers such as rifampin. (4., 5.4, 7.1). Known hypersensitivity to praziquantel or any of its ingredients. (4.1). Concomitant administration with strong Cytochrome P450 (CYP450) inducers such as rifampin. (4., 5.4, 7.1).

DOSAGE & ADMINISTRATION SECTION.

2 DOSAGE AND ADMINISTRATION. Schistosomiasis: 20 mg/kg body weight times day separated by to hours for day only. (2.1)Clonorchiasis and Opisthorchiasis: 25 mg/kg times day separated by to hours for day only. (2.1)Take with water during meals. Do not chew or keep segments in the mouth. (2.2)For pediatric patients under years of age, the tablets may be crushed or disintegrated and mixed with semi-solid food or liquid. (2.2)For additional administration instructions see the full prescribing information.. Schistosomiasis: 20 mg/kg body weight times day separated by to hours for day only. (2.1). Clonorchiasis and Opisthorchiasis: 25 mg/kg times day separated by to hours for day only. (2.1). Take with water during meals. Do not chew or keep segments in the mouth. (2.2). For pediatric patients under years of age, the tablets may be crushed or disintegrated and mixed with semi-solid food or liquid. (2.2). For additional administration instructions see the full prescribing information.. 2.1 Recommended Dosage. Schistosomiasis The recommended dosage for the treatment of schistosomiasis is 20 mg/kg body weight administered orally three times day separated by to hours, for day only.Clonorchiasis and OpisthorchiasisThe recommended dosage for the treatment of clonorchiasis and opisthorchiasis is 25 mg/kg body weight administered orally three times day separated by to hours for day only.. 2.2 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 years of age, the tablets may be crushed or disintegrated and mixed with semi-solid food or liquid. Use crushed or disintegrated tablets within 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 patients body weight. Segments are broken off by pressing the score (notch) with thumbnails. If one-quarter of tablet is required, this is best achieved by breaking the segment from the outer end.

DRUG INTERACTIONS SECTION.

7 DRUG INTERACTIONS. Other CYP 450 Inducers: Concomitant administration of other CYP450 inducers, for example, antiepileptic drugs and dexamethasone, may also reduce plasma levels concentrations of praziquantel. (7.1)CYP450 Inhibitors: Concomitant administration of CYP450 inhibitors, for example, cimetidine, ketoconazole, itraconazole, erythromycin. (7.2). Other CYP 450 Inducers: Concomitant administration of other CYP450 inducers, for example, antiepileptic drugs and dexamethasone, may also reduce plasma levels concentrations of praziquantel. (7.1). CYP450 Inhibitors: Concomitant administration of CYP450 inhibitors, for example, cimetidine, ketoconazole, itraconazole, erythromycin. (7.2). 7.1 CYP450 Inducers. RifampinConcomitant administration of rifampin, strong CYP450 inducer, with praziquantel is contraindicated. In patients receiving rifampin, for example, as part of combination regimen for the treatment of tuberculosis, alternative drugs for schistosomiasis should be considered. If treatment with praziquantel is necessary, treatment with rifampin should be discontinued weeks before administration of praziquantel. Treatment with rifampin can then be restarted one day after completion of praziquantel treatment. [See Contraindications (4), Warnings and Precautions (5.6) and Clinical Pharmacology (12.3).] Other CYP 450 InducersConcomitant administration of other drugs that are CYP450 inducers, for example, antiepileptic drugs (phenytoin, phenobarbital and carbamazepine), and dexamethasone, may also reduce plasma concentrations of praziquantel. [See Warnings and Precautions (5.6).] 7.2 CYP450 Inhibitors. Concomitant administration of drugs that decrease the activity of drug metabolizing liver enzymes (CYP450 inhibitors), for example, cimetidine, ketoconazole, itraconazole, erythromycin may increase plasma concentrations of praziquantel. In addition, grapefruit juice was also reported to produce 1.6-fold increase in the Cmax and 1.9-fold increase in the AUC of praziquantel. The effect of this exposure increase on the therapeutic effect and safety of praziquantel has not been systematically evaluated [see Dosage and Administration (2.2)].

INDICATIONS & USAGE SECTION.

1 INDICATIONS AND USAGE. Praziquantel tablets are indicated in patients aged year and older for the treatment of the following infections:Schistosomiasis due to all species of schistosoma (for example, Schistosoma mekongi, Schistosoma japonicum, Schistosoma mansoni and Schistosoma hematobium), andClonorchiasis and Opisthorchiasis due to the liver flukes, Clonorchis sinensis/Opisthorchis viverrini (approval of this indication was based on studies in which the two species were not differentiated). Schistosomiasis due to all species of schistosoma (for example, Schistosoma mekongi, Schistosoma japonicum, Schistosoma mansoni and Schistosoma hematobium), and. Clonorchiasis and Opisthorchiasis due to the liver flukes, Clonorchis sinensis/Opisthorchis viverrini (approval of this indication was based on studies in which the two species were not differentiated). Praziquantel tablets are an anthelmintic indicated in patients aged one year and older for the treatment of the following infections:Schistosomiasis due to all species of schistosoma (for example, Schistosoma mekongi, Schistosoma japonicum, Schistosoma mansoni and Schistosoma hematobium), and,Clonorchiasis and Opisthorchiasis due to the liver flukes, Clonorchis sinensis and Opisthorchis viverrini Schistosomiasis due to all species of schistosoma (for example, Schistosoma mekongi, Schistosoma japonicum, Schistosoma mansoni and Schistosoma hematobium), and,. Clonorchiasis and Opisthorchiasis due to the liver flukes, Clonorchis sinensis and Opisthorchis viverrini.

INFORMATION FOR PATIENTS SECTION.

17 PATIENT COUNSELING INFORMATION. Advise patients to take praziquantel during meals as directed [see Dosage and Administration (2.2)]. Advise patients not to chew tablets and to take them with water [see Dosage and Administration (2.2)] Advise patients that tablets may be crushed or disintegrated and mixed with semi-solid food or liquid or disintegrated to prevent choking in children under years of age. Crushed or disintegrated tablets should be used within hour of mixing [see Dosage and Administration (2.2)]. Advise patients not to take praziquantel tablets if they are allergic to praziquantel or any of its components [see Contraindications (4)]. Advise patients not to take praziquantel if they are taking rifampin [see Contraindications (4) and Warnings and Precautions (5.6, 7.1, 7.2)]. Advise patients that the use of praziquantel can be associated with clinical deterioration during the acute phase of schistosomiasis [see Warnings and Precautions (5.1)]. Advise patients that praziquantel should not be used if they have epilepsy or other CNS effects [see Warnings and Precautions (5.2)]. Advise patients to report any cardiac irregularities to their healthcare provider [see Warnings and Precautions (5.4)]. Advise patients not to drive car and not to operate machinery on the day of praziquantel treatment and the following day.Dist. by:Par Pharmaceutical Chestnut Ridge, NY 10977 U.S.A.Mfg. by:Par Formulations Private Limited,9/215, Pudupakkam, Kelambakkam 603 103.Made in IndiaMfg. Lic. No.: TN00002121OS231-01-74-02Revised: 05/2019. Advise patients to take praziquantel during meals as directed [see Dosage and Administration (2.2)]. Advise patients not to chew tablets and to take them with water [see Dosage and Administration (2.2)] Advise patients that tablets may be crushed or disintegrated and mixed with semi-solid food or liquid or disintegrated to prevent choking in children under years of age. Crushed or disintegrated tablets should be used within hour of mixing [see Dosage and Administration (2.2)]. Advise patients not to take praziquantel tablets if they are allergic to praziquantel or any of its components [see Contraindications (4)]. Advise patients not to take praziquantel if they are taking rifampin [see Contraindications (4) and Warnings and Precautions (5.6, 7.1, 7.2)]. Advise patients that the use of praziquantel can be associated with clinical deterioration during the acute phase of schistosomiasis [see Warnings and Precautions (5.1)]. Advise patients that praziquantel should not be used if they have epilepsy or other CNS effects [see Warnings and Precautions (5.2)]. Advise patients to report any cardiac irregularities to their healthcare provider [see Warnings and Precautions (5.4)]. Advise patients not to drive car and not to operate machinery on the day of praziquantel treatment and the following day.

PHARMACOKINETICS SECTION.

12.3 Pharmacokinetics. AbsorptionAfter oral administration, 80% of an administered praziquantel dose is absorbed, with maximal serum concentrations of praziquantel achieved to hours after dosing.EliminationFollowing oral administration of praziquantel, the elimination half-life of praziquantel in serum ranges between 0.8 to 1.5 hours.MetabolismPraziquantel is rapidly metabolized by the cytochrome P450 enzyme system and undergoes first pass effect after oral administration of praziquantel.ExcretionApproximately 80% of an oral dose of praziquantel is excreted in the kidneys, almost exclusively (greater than 99%) in the form of praziquantel metabolites.Specific PopulationsPatients with Hepatic Impairment The pharmacokinetics of praziquantel were studied in 40 patients with Schistosoma mansoni infections with varying degrees of hepatic impairment (See Table 1). In patients with schistosomiasis, the pharmacokinetic parameters did not differ significantly between those with normal hepatic function (Group 1) and those with mild (Child-Pugh class A) hepatic impairment. However, in patients with moderate-to-severe hepatic impairment (Child-Pugh class and C), praziquantel half-life, Cmax, and AUC increased progressively with the degree of hepatic impairment. In Child-Pugh class B, the increases in mean half-life, Cmax, and AUC relative to Group were 1.58-fold, 1.76-fold, and 3.55-fold, respectively. The corresponding increases in Child-Pugh class patients were 2.82-fold, 4.29-fold, and 15-fold for half-life, Cmax, and AUC.Table 1: Pharmacokinetic parameters of praziquantel in four groups of patients with varying degrees of liver function following administration of 40 mg/kg of praziquantel tablets under fasting conditions.Patient GroupHalf-life (hr)Tmax (hr)Cmax(mcg/mL)AUC(mcg/mL hr)Normal hepatic function (Group 1)2.99 +- 1.281.48 +- 0.740.83 +- 0.523.02 +- 0.59Child-Pugh (Group 2)4.66 +- 2.771.37 +- 0.610.93 +- 0.583.87 +- 2.44Child-Pugh (Group 3)4.74 +- 2.16a 2.21 +- 0.78a,b 1.47 +- 0.74a,b 10.72 +- 5.53a,b Child-Pugh (Group 4)8.45 +- 2.62a,b,c 3.2 +- 1.05a,b,c 3.57 +- 1.30a,b,c 45.35 +- 17.50a,b,c a) p<0.05 compared to Group 1b) p<0.05 compared to Group 2c) p<0.05 compared to Group 3Patients with Renal ImpairmentExcretion of praziquantel following oral administration of praziquantel might be delayed in patients with impaired renal function, but accumulation of unchanged drug would not be expected.Drug Interaction StudiesRifampin (CYP450 Inducer)In crossover study with 2-week washout period, 10 healthy subjects ingested single 40 mg/kg oral dose of praziquantel following pre-treatment with oral rifampin (600 mg daily for days). Plasma praziquantel concentrations were undetectable in out of 10 subjects. When single 40 mg/kg oral dose of praziquantel was administered to these same healthy subjects two weeks after discontinuation of rifampin, the mean praziquantel AUC and Cmax were 23% and 35% lower, respectively, than when praziquantel was given alone.

PREGNANCY SECTION.

8.1 Pregnancy. Risk SummaryPublished 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 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 to 4% and 15 to 20%, respectively.DataHuman DataTwo 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 birth weight, 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 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 DataNo 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.

USE IN SPECIFIC POPULATIONS SECTION.

8 USE IN SPECIFIC POPULATIONS. Pediatrics: Safety has not been established in pediatric patients younger than year of age. (8.4)Hepatic Impairment: Monitor patients for adverse reactions when administering the recommended dose of praziquantel to hepatosplenic schistosomiasis patients with moderate to severe liver impairment (Child-Pugh Class or C). (8.6). Pediatrics: Safety has not been established in pediatric patients younger than year of age. (8.4). Hepatic Impairment: Monitor patients for adverse reactions when administering the recommended dose of praziquantel to hepatosplenic schistosomiasis patients with moderate to severe liver impairment (Child-Pugh Class or C). (8.6). 8.1 Pregnancy. Risk SummaryPublished 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 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 to 4% and 15 to 20%, respectively.DataHuman DataTwo 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 birth weight, 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 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 DataNo 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.. 8.2 Lactation. Risk Summary Limited data from published literature reports the presence of praziquantel in human milk at low concentrations. There is no information on the effects of praziquantel in the breastfed infant or effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mothers clinical need for praziquantel and any potential adverse effects on the breastfed infant from praziquantel or from the underlying maternal condition. 8.4 Pediatric Use. Safety and dosing recommendations of praziquantel in pediatric patients to 17 years have been established. Safety of praziquantel in pediatric patients younger than year of age has not been established. Post-marketing experience and published literature indicates that pediatric patients to 17 years of age treated with praziquantel experience similar adverse reactions as adults treated with praziquantel [see Adverse Reactions (6)]. 8.5 Geriatric Use. Clinical studies of praziquantel did not include 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 [see Clinical Pharmacology (12.3)]. 8.6 Hepatic Impairment. Following oral administration of praziquantel to patients with liver impairment, reduced hepatic metabolism of praziquantel results in higher and sustained plasma concentrations of unmetabolized praziquantel [see Clinical Pharmacology (12.3)]. Monitor patients for adverse reactions when administering the recommended dose of praziquantel to hepatosplenic schistosomiasis patients with moderate or severe liver impairment (Child-Pugh Class or C). 8.7 Renal Impairment. No dosage adjustment of praziquantel is necessary in patients with renal impairment. Nephrotoxic effects of praziquantel or its metabolites are not known [see Clinical Pharmacology (12.3)].

WARNINGS AND PRECAUTIONS SECTION.

5 WARNINGS AND PRECAUTIONS. Clinical Deterioration: Potentially life threatening clinical deterioration can occur in patients treated during the acute phase of schistosomiasis. (5.1)Central Nervous System (CNS) Effects: Praziquantel can exacerbate central nervous system pathology due to schistosomiasis. Consider whether to administer to individuals reporting history of epilepsy and/or other signs of potential central nervous systems involvement such as subcutaneous nodules suggestive of cysticercosis. (5.2)Potential Lack of Efficacy for Acute Schistosomiasis: This has been reported in observational studies (5.3).Cardiac Arrhythmias: Bradycardia, ectopic rhythms, ventricular fibrillation, and AV blocks has been observed with praziquantel administration. Monitor patients with cardiac arrhythmias during treatment (5.4).. Clinical Deterioration: Potentially life threatening clinical deterioration can occur in patients treated during the acute phase of schistosomiasis. (5.1). Central Nervous System (CNS) Effects: Praziquantel can exacerbate central nervous system pathology due to schistosomiasis. Consider whether to administer to individuals reporting history of epilepsy and/or other signs of potential central nervous systems involvement such as subcutaneous nodules suggestive of cysticercosis. (5.2). Potential Lack of Efficacy for Acute Schistosomiasis: This has been reported in observational studies (5.3).. Cardiac Arrhythmias: Bradycardia, ectopic rhythms, ventricular fibrillation, and AV blocks has been observed with praziquantel administration. Monitor patients with cardiac arrhythmias during treatment (5.4).. 5.1 Clinical Deterioration. The use of praziquantel in patients with schistosomiasis may be associated with clinical deterioration (for example, paradoxical reactions, serum sickness Jarisch-Herxheimer like reactions: sudden inflammatory immune response suspected to be caused by the release of schistosomal antigens). These reactions predominantly occur in patients treated during the acute phase of schistosomiasis. They may lead to potentially life-threatening events, for example, respiratory failure, encephalopathy, papilledema, and/or cerebral vasculitis. 5.2 CentralNervous System (CNS) Effects. Praziquantel can exacerbate central nervous system pathology due to schistosomiasis, paragonimiasis, or Taenia solium cysticercosis. As general rule, consider whether to administer praziquantel to individuals reporting history of epilepsy and/or other signs of potential central nervous systems involvement such as subcutaneous nodules suggestive of cysticercosis unless the potential benefit justifies the potential risk. Hospitalize the patient for duration of treatment when schistosomiasis or fluke infection is found to be associated with cerebral cysticercosis. 5.3 PotentialLack of Efficacy During the Acute Phase of Schistosomiasis. Data from two observational cohort studies in patients indicate that treatment with praziquantel in the acute phase of infection may not prevent progression from asymptomatic infection to acute schistosomiasis, or from asymptomatic infection/acute schistosomiasis into chronic phase. 5.4 Cardiac Arrhythmias. Bradycardia, ectopic rhythms, ventricular fibrillation, and AV blocks has been observed with praziquantel administration. Monitor patients with cardiac arrhythmias during treatment. 5.5 HepaticImpairment in Hepatosplenic Schistosomiasis Patients. Reduced hepatic metabolism of praziquantel results in higher and sustained plasma concentrations of unmetabolized praziquantel in patients with liver impairment [see Clinical Pharmacology (12.3)]. Monitor patients for adverse reactions when administering the recommended dose of praziquantel to hepatosplenic schistosomiasis patients with moderate or severe liver impairment (Child-Pugh Class or C). 5.6 ConcomitantAdministration with Strong Cytochrome P450 Inducers. Concomitant administration of strong CYP450 inducers, such as rifampin with praziquantel is contraindicated since therapeutically effective levels of praziquantel may not be achieved. [see Contraindications (4) and Drug Interactions (7.1)]. In patients receiving rifampin who need immediate treatment for schistosomiasis, alternative agents for schistosomiasis should be considered. However, if treatment with praziquantel is necessary, discontinue rifampin weeks before administration of praziquantel. Treatment with rifampin can then be restarted one day after completion of praziquantel treatment [see Drug Interactions (7.1, 7.2)].