DailyMed Label: Biltricide

DailyMed Label: Biltricide

2023

DailyMed Prescription

Biltricide

praziquantel

Bayer HealthCare Pharmaceuticals Inc.

NDC: 50419-747

NDC: 50419-747

NDC: 50419-747

NDC: 50419-747

NDC: 50419-747

NDC: 50419-747

NDC: 50419-747

NDC: 50419-747

NDC: 50419-747

Biltricide (praziquantel) is an anthelmintic, trematodicide provided in tablet form for oral administration. Praziquantel is 2-(cyclohexylcarbonyl)-1,2,3,6,7, 11b-hexahydro-4H-pyrazino [2, 1-a] isoquinolin-4-one with the molecular formula; C 19 H 24 N 2 O 2 . The structural formula is as follows: Praziquantel is a white to nearly white crystalline powder of bitter taste. The compound is stable under normal conditions and melts at 136 to 140°C with decomposition. The active substance is hygroscopic. Praziquantel is easily soluble in chloroform and dimethylsulfoxide, soluble in ethanol and very slightly soluble in water. Biltricide tablets contain 600 mg of praziquantel. Inactive ingredients: corn starch, hypromellose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, povidone, sodium lauryl sulfate, and titanium dioxide . Chemical Structure

Biltricide is indicated in patients aged 1 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/Opisthorchis viverrini (approval of this indication was based on studies in which the two species were not differentiated) Biltricide is 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 : 20 mg/kg bodyweight 3 times a day separated by 4 to 6 hours for 1 day only. ( 2.1 ) • Clonorchiasis and Opisthorchiasis : 2 5 mg/kg 3 times a day separated by 4 to 6 hours for 1 day only. ( 2.1) • Take with water during meals. Do not chew or keep segments in the mouth. ( 2.2 ) • For pediatric patients under 6 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 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. 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. 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. Biltricide 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.

Biltricide tablets contain 600 mg of praziquantel. The tablets are white to orange tinged, film-coated, oblong with three scores (notches), imprinted with “BAYER” on one side and “LG” on the other side. • Tablets: 600 mg (with three scores (notches) on the tablet) ( 3 )

Biltricide is contraindicated in: • Patients who previously have shown hypersensitivity to praziquantel or any of the excipients in Biltricide. • 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 Biltricide. • Patients taking strong Cytochrome P450 3A enzyme (CYP3A) inducers, such as rifampin, [see Warnings and Precautions ( 5.6 ) and Drug Interactions ( 7.1 , 7.2 )] . • Known hypersensitivity to Biltricide or any of its ingredients. ( 4.1 ) • Concomitant administration with strong Cytochrome P450 3A enzyme (CYP 3A) inducers such as rifampin. ( 4 , 5.6 7.1)

• 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 : Biltricide can exacerbate central nervous system pathology due to schistosomiasis. Consider whether to administer to individuals reporting a 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 Biltricide administration. Monitor patients with cardiac arrhythmias during treatment ( 5.4). The use of Biltricide 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. Biltricide can exacerbate central nervous system pathology due to schistosomiasis, paragonimiasis, or Taenia solium cysticercosis. As a general rule, consider whether to administer Biltricide to individuals reporting a 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. Data from two observational cohort studies in patients indicate that treatment with Biltricide 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. Bradycardia, ectopic rhythms, ventricular fibrillation, and AV blocks has been observed with Biltricide administration. Monitor patients with cardiac arrhythmias during treatment. 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 Biltricide to hepatosplenic schistosomiasis patients with moderate or severe liver impairment (Child-Pugh Class B or C). Concomitant administration of strong CYP 3A inducers, such as rifampin, with Biltricide is contraindicated since therapeutically effective levels of praziquantel are unlikely to be achieved. [see Contraindications ( 4 ), Drug Interactions ( 7.1 ), and Clinical Pharmacology ( 12.3 )]. Avoid concomitant administration of Biltricide with moderate CYP 3A inducers, such as efavirenz, due to risk of a clinically significant decrease in praziquantel plasma concentrations which may lead to reduced therapeutic effect of Biltricide [see Drug Interactions ( 7.1 )] . In patients receiving a clinically significant CYP 3A inducer drug who need immediate treatment for schistosomiasis, alternative agents for schistosomiasis should be considered, where possible. If Biltricide is necessary immediately, increase monitoring for reduced anthelmintic efficacy associated with Biltricide [see Drug Interactions ( 7.1 )]. In patients receiving a clinically significant CYP 3A inducer drug whose treatment could be delayed, discontinue the CYP 3A inducer drug at least 2 weeks to 4 weeks before administration of Biltricide and, where possible, consider starting alternative medications that are not CYP 3A inducers. The CYP 3A inducer drug can be restarted one day after completion of Biltricide treatment, if needed [see Drug Interactions ( 7.1 )].

The following serious or otherwise important adverse reactions are discussed elsewhere in the labeling:

Moderate CYP 3A Inducers : Avoid concomitant administration of moderate CYP 3A inducers, for example, efavirenz ( 5.6 , 7.1 ) Concomitant administration of Biltricide with Strong and Moderate CYP 3A inducers decrease praziquantel AUC and Cmax [see Clinical Pharmacology ( 12.3 )] which may reduce the efficacy of Biltricide. Concomitant administration of a Strong CYP 3A inducer, such as rifampin, with Biltricide is contraindicated [see Contraindications ( 4)] . Concomitant administration of a Moderate CYP 3A inducer, such as efavirenz, should be avoided unless the benefit outweighs the risks [see Warnings and Precautions ( 5.6 ) and Clinical Pharmacology ( 12.3 ).] 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 Biltricide has not been systematically evaluated [see Dosage and Administration ( 2.2 )].

• Pediatrics : Safety has not been established in pediatric patients younger than 1 year of age. ( 8.4 ) • Hepatic Impairment: Monitor patients for adverse reactions when administering the recommended dose of Biltricide to hepatosplenic schistosomiasis patients with moderate to severe liver impairment (Child-Pugh Class B or C). ( 8.6 )

Biltricide is supplied as 600 mg tablets containing praziquantel. The tablets are white to orange tinged, film-coated, oblong tablets with three scores. The tablet is coded with “BAYER” on one side and “LG” on the reverse side. Biltricide is available in bottles of six 600 mg tablets, NDC 50419-747-01. Store below 86°F (30°C).

Praziquantel is an anthelmintic drug [see Microbiology ( 12.4 )] . After oral administration, 80% of an administered Biltricide dose is absorbed, with maximal serum concentrations of praziquantel achieved 1 to 3 hours after dosing. Following oral administration of Biltricide, the elimination half-life of praziquantel in serum ranges between 0.8 to 1.5 hours. Praziquantel is rapidly metabolized by the cytochrome P450 enzyme system and undergoes a first pass effect after oral administration of Biltricide. Approximately 80% of an oral dose of Biltricide is excreted in the kidneys, almost exclusively (greater than 99%) in the form of praziquantel metabolites. 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 B and C), praziquantel half-life, C max, and AUC increased progressively with the degree of hepatic impairment. In Child-Pugh class B, the increases in mean half-life, C max, and AUC relative to Group 1 were 1.58-fold, 1.76-fold, and 3.55-fold, respectively. The corresponding increases in Child-Pugh class C patients were 2.82-fold, 4.29-fold, and 15-fold for half-life, C max, 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 Biltricide under fasting conditions.   Patient   Group Half-life (hr) T max (hr) C max (µg/mL) AUC (µg/mL* hr)   Normal hepatic   function   (Group 1) 2.99 ± 1.28 1.48 ± 0.74 0.83 ± 0.52 3.02 ± 0.59   Child-Pugh A   (Group 2) 4.66 ± 2.77 1.37 ± 0.61 0.93 ± 0.58 3.87 ± 2.44   Child-Pugh B   (Group 3) 4.74 ± 2.16 a 2.21 ± 0.78 a,b 1.47 ± 0.74 a,b 10.72 ± 5.53 a,b   Child-Pugh C   (Group 4) 8.45 ± 2.62 a,b,c 3.2 ± 1.05 a,b,c 3.57 ± 1.30 a,b,c 45.35 ± 17.50 a,b,c a) p<0.05 compared to Group 1 b) p<0.05 compared to Group 2 c) p<0.05 compared to Group 3 Excretion of praziquantel following oral administration of Biltricide might be delayed in patients with impaired renal function, but accumulation of unchanged drug would not be expected. In a crossover study with a 2-week washout period, 10 healthy subjects ingested a single 40 mg/kg oral dose of Biltricide following pre-treatment with oral rifampin (600 mg daily for 5 days). Plasma praziquantel concentrations were undetectable in 7 out of 10 subjects. When a single 40 mg/kg oral dose of Biltricide was administered to these same healthy subjects two weeks after discontinuation of rifampin, the mean praziquantel AUC and C max were 23% and 35% lower, respectively, than when Biltricide was given alone. In a crossover study, 20 healthy subjects ingested a single 40 mg/kg oral dose of Biltricide following pre-treatment with oral efavirenz (400 mg daily for 13 days). Oral efavirenz reduced the mean praziquantel AUC and C max by 77% (95% confidence interval: 38% to 91%) and 79% (95% confidence interval: 41% to 92%), respectively, when coadministered with Biltricide compared to Biltricide given alone. Praziquantel induces a rapid contraction of schistosomes by a 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 a potential lack of efficacy of praziquantel against migrating schistosomulae [see Warnings and Precautions ( 5.3 )] .

Mutagenicity studies of praziquantel published in the scientific literature are inconclusive. Long term oral carcinogenicity studies in rats and golden hamsters did not reveal any carcinogenic effect at doses up to 250 mg/kg/day (about half of the human daily dose based on body surface area). Praziquantel had no effect on fertility and general reproductive performance of male and female rats when given at oral doses ranging from 30 to 300 mg/kg body weight (up to 0.65 times the human daily dose based on body surface area).

Biltricide 600 mg Tablets Bottle Label 8339661            NDC 50419-747-01 Biltricide® Tablets (praziquantel) 600 mg 6 Tablets Rx Only biltricide label.jpg