Eperon Drug Interactions

Pharmacodynamic-related Interactions: Centrally-acting Drugs and Alcohol: Given the primary CNS effects of Eperon, it should be used with caution in combination with other centrally acting drugs or alcohol.
Levodopa and Dopamine Agonists: Eperon may antagonize the effect of levodopa and other dopamine agonists.
Drugs with Hypotensive Effects: Clinically significant hypotension has been observed postmarketing with concomitant use of risperidone and antihypertensive treatment.
Drugs Known to Prolong the QT interval: Caution is advised when prescribing Eperon with drugs known to prolong the QT interval.
Pharmacokinetic-related Interactions: Food does not affect the absorption of Eperon Risperidone is mainly metabolized through CYP2D6, and to a lesser extent through CYP3A4. Both risperidone and its active metabolite 9- hydroxyrisperidone are substrates of P-glycoprotein (P-gp). Substances that modify CYP2D6 activity, or substances strongly inhibiting or inducing CYP3A4 and/or P-gp activity, may influence the pharmacokinetics of the risperidone active antipsychotic fraction.
Strong CYP2D6 Inhibitors: Co-administration of Eperon with a strong CYP2D6 inhibitor may increase the plasma concentrations of risperidone, but less so of the active antipsychotic fraction. Higher doses of a strong CYP2D6 inhibitor may elevate concentrations of the risperidone active antipsychotic fraction (e.g., paroxetine, see as follows). When concomitant paroxetine or another strong CYP2D6 inhibitor, especially at higher doses, is initiated or discontinued, the physician should re-evaluate the dosing of Eperon.
CYP3A4 and/or P-gp Inhibitors: Coadministration of Eperon with a strong CYP3A4 and/or P-gp inhibitor may substantially elevate plasma concentrations of the risperidone active antipsychotic fraction. When concomitant itraconazole or another strong CYP3A4 and/or P-gp inhibitor is initiated or discontinued, the physician should re-evaluate the dosing of Eperon.
CYP3A4 and/or P-gp Inducers: Co-administration of Eperon with a strong CYP3A4 and/or P-gp inducer may decrease the plasma concentrations of the risperidone active antipsychotic fraction. When concomitant carbamazepine or another strong CYP3A4 and/or P-gp inducer is initiated or discontinued, the physician should re-evaluate the dosing of Eperon.
Highly Protein-bound Drugs: When Eperon is taken together with other highly protein-bound drugs, there is no clinically relevant displacement of either drug from the plasma proteins. When using concomitant medication, the corresponding label should be consulted for information on the route of metabolism and the possible need to adjust dosages.
Pediatric Population: Interaction studies have only been performed in adults. The relevance of the results from these studies in pediatric patients is unknown.
Examples: Examples of drugs that may potentially interact or that were shown not to interact with risperidone are listed as follows: Antibacterials: Erythromycin, a CYP3A4 inhibitor, does not change the pharmacokinetics of risperidone and the active antipsychotic fraction.
Rifampicin, a strong CYP3A4 inducer and a P-gp inducer, decreased the plasma concentrations of the active antipsychotic fraction.
Anticholinesterases: Donepezil and galantamine, both CYP2D6 and CYP3A4 substrates, do not show a clinically relevant effect on the pharmacokinetics of risperidone and the active antipsychotic fraction.
Antiepileptics: Carbamazepine, a strong CYP3A4 inducer and P-gp inducer, has been shown to decrease the plasma levels of the active antipsychotic fraction of risperidone.
Topiramate modestly reduced the bioavailability of risperidone, but not that of the active antipsychotic fraction. Therefore, this interaction is unlikely to be of clinical significance.
Eperon does not show a clinically relevant effect on the phaimacokinetics of valproate or topiramate.
Antifungals: Itraconazole, a strong CYP3A4 inhibitor and a P-gp inhibitor, at a dosage of 200mg/day increased the plasma concentrations of the active antipsychotic fraction by about 70%, at risperidone doses of 2 to 8mg/day.
Ketoconazole, a strong CYP3A4 inhibitor and a P­gp inhibitor, at a dosage of 200mg/day increased the plasma concentrations of risperidone and decreased the plasma concentration of 9-hydroxyrisperidone.
Antipsychotics: Phenothiazines, may increase the plasma concentrations of risperidone but not those of the active antipsychotic fraction.
Aripiprazole, a CYP2D6 and CYP3A4 substrate: There is insufficient clinical evidence to evaluate the effect of risperidone, on the pharmacokinetics of the sum of aripiprazole and its active metabolite, dehydroaripiprazole.
Antivirals: Protease inhibitors: No formal study data are available; however, since ritonavir is a strong CYP3A4 inhibitor and a weak CYP2D6 inhibitor, ritonavir and ritonavir-boosted protease inhibitors potentially raise concentrations of the risperidone active antipsychotic fraction.
Beta-Blockers: Some beta-blockers may increase the plasma concentrations of risperidone but not those of the active antipsychotic fraction.
Calcium Channel Blockers: Verapamil, a moderate inhibitor of CYP3A4 and an inhibitor of P-gp, increases the plasma concentration of risperidone and the active antipsychotic fraction.
Digitalis Glycosides: Risperidone does not show a clinically relevant effect on the pharmacokinetics of digoxin.
Diuretics: Furosemide: See Precautions regarding increased mortality in elderly patients with dementia concomitantly receiving furosemide.
Gastrointestinal Drugs: H2-receptor antagonists: Cimetidine and ranitidine, both weak inhibitors of CYP2D6 and CYP3A4, increased the bioavailability of risperidone, but only marginally that of the active antipsychotic fraction.
Lithium: Risperidone does not show a clinically relevant effect on the pharmacokinetics of lithium.
SSRIs and Tricyclic Antidepressants: Fluoxetine, a strong CYP2D6 inhibitor, increases the plasma concentration of risperidone, but less so of the active antipsychotic fraction. Paroxetine, a strong CYP2D6 inhibitor, increases the plasma concentrations of risperidone, but, at dosages up to 20mg/day, less so of the active antipsychotic fraction. However, higher doses of paroxetine may elevate concentrations of the risperidone active antipsychotic fraction.
Tricyclic antidepressants may increase the plasma concentrations of risperidone but not those of the active antipsychotic fraction. Amytriptyline does not affect the pharmacokinetics of risperidone or the active antipsychotic fraction.
Sertraline, a weak inhibitor of CYP2D6, and fluvoxamine, a weak inhibitor of CYP3A4, at dosages up to 100mg/day are not associated with clinically significant changes in concentrations of the risperidone active antipsychotic fraction. However, doses higher than 100mg/day of sertraline or fluvoxamine may elevate concentrations of the risperidone active antipsychotic fraction.