PRAZIQUANTEL Drug Interactions: What You Need to Know

INTERACTIONS Moderate CYP 3A Inducers : Avoid concomitant administration of moderate CYP 3A inducers, for example, efavirenz ( 5.6 , 7.1 )

7.1 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 <span class="opacity-50 text-xs">[see Clinical Pharmacology (12.3) ]</span> which may reduce the efficacy of praziquantel. Concomitant administration of a Strong CYP 3A inducer, such as rifampin, with praziquantel is contraindicated <span class="opacity-50 text-xs">[see Contraindications (4) ]</span>. Concomitant administration of a Moderate CYP 3A inducer, such as efavirenz, should be avoided unless the benefit outweighs the risks <span class="opacity-50 text-xs">[see Warnings and Precautions (5.6) and Clinical Pharmacology (12.3) .]</span>

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, 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 <span class="opacity-50 text-xs">[see Dosage and Administration (2.2) ]</span>.

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 [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 3A enzyme (CYP 3A) inducers such as rifampin. ( 4 , 5.6 , 7.1 )

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 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 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 Central Nervous System (CNS)

Effects

Praziquantel can exacerbate central nervous system pathology due to schistosomiasis, paragonimiasis, or Taenia solium cysticercosis. As a general rule, consider whether to administer praziquantel 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.

5.3 Potential Lack 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 Hepatic Impairment in Hepatosplenic Schistosomiasis Patients Reduced hepatic metabolism of praziquantel results in higher and sustained plasma concentrations of unmetabolized praziquantel in patients with liver impairment <span class="opacity-50 text-xs">[see Clinical Pharmacology (12.3) ]</span>. 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 B or C).

5.6 Concomitant Administration with Cytochrome P450 Enzyme Inducers Strong Cytochrome P450 3A Enzyme (CYP 3A)

Inducers

Concomitant administration of strong CYP 3A inducers, such as rifampin, with praziquantel 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) ]. Moderate CYP 3A Inducers Avoid concomitant administration of praziquantel 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 praziquantel. [ 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 praziquantel is necessary immediately, increase monitoring for reduced anthelmintic efficacy associated with praziquantel [ 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 praziquantel 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 praziquantel treatment, if needed [see Drug Interactions (7.1) ]