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 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:

• •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 Biltricide 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 Biltricide 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 Biltricide 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. (6)

To report SUSPECTED ADVERSE REACTIONS, contact Bayer HealthCare Pharmaceuticals Inc. at 1-888-842-2937 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.