RiteMED Risperidone Drug Interactions

Centrally-acting drugs and alcohol: Given the primary CNS effects of risperidone, caution should be exercised when risperidone is concomitantly used with other centrally-acting medicines or alcohol.
Drugs with hypotensive effects: Because of its potential for inducing hypotension, risperidone may enhance the hypotensive effects of other therapeutic agents. Clinically significant hypotension has been observed post-marketing with concomitant use of risperidone and antihypertensive treatment.
Drugs known to prolong the QT interval: Caution should be exercised when risperidone is prescribed in combination with other medicine that are thought to prolong the QT interval or medicines known to cause electrolyte imbalance.
Strong CYP2D6 inhibitors (e.g., paroxetine): Concomitant use of risperidone 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. When concomitant paroxetine or another strong CYP2D6 inhibitor, particularly at higher doses, is initiated or discontinued, the physician should re-evaluate the dosing of risperidone.
CYP3A4 and/or P-gp inhibitors (e.g., itraconazole, ketoconazole): Concomitant use of risperidone with a strong CYP3A4 and 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 risperidone.
Ketoconazole increased the plasma concentrations of risperidone and decreased the plasma concentrations of 9-hydroxyrisperidone.
CYP3A4 and/or P-gp inducers (e.g., carbamazepine): Concomitant use of risperidone 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 inhibitor is initiated or discontinued, the physician should re-evaluate the dosing of risperidone.
Highly protein-bound drugs: When risperidone is concomitantly used with highly protein-bound drugs, there is no clinically relevant displacement of either drug from the plasma proteins.
Tricyclic antidepressants (e.g., amitriptyline): May increase the plasma concentrations of risperidone but not those of the active antipsychotic fraction. Amitriptyline does not affect the pharmacokinetics of risperidone or the active antipsychotic fraction.
Selective serotonin reuptake inhibitors (e.g., fluoxetine, fluvoxamine, sertraline): Fluoxetine increases the plasma concentration of risperidone but less so of risperidone and 9-hydroxyrisperidone combined. When concomitant fluoxetine is initiated or discontinued, the physician should re-evaluate the dosing of risperidone. Sertraline at dosages up to 100 mg per day is not associated with clinically significant changes in concentrations of the risperidone active antipsychotic fraction.
However, doses higher 100 mg per day of sertraline or fluvoxamine may elevate concentrations of the risperidone active antipsychotic fraction.
Clozapine: Chronic administration of clozapine with risperidone may decrease the clearance of risperidone.
Levodopa and dopamine agonists: Risperidone may antagonize the effects of levodopa and other dopamine agonists.
Antibacterials (e.g., erythromycin, rifampicin): Erythromycin did not change the pharmacokinetics of risperidone or risperidone and 9-hydroxyrisperidone combined.
Rifampicin decreased the plasma concentrations of the active antipsychotic fraction.
Anticholinesterases (e.g., galantamine, donepezil): Did not show an effect on the pharmacokinetics of risperidone or risperidone and 9-hydroxyrisperidone combined.
Antiepileptics (e.g., 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. Risperidone does not show a clinically relevant effect on the pharmacokinetics of topiramate.
Antipsychotics (e.g., phenothiazines, aripiprazole): Phenothiazines may increase the plasma concentrations of risperidone but not those of the active antipsychotic fraction.
Risperidone did not affect the pharmacokinetics of the sum of aripiprazole and its active metabolite, dehydroaripiprazole.
Antivirals (e.g., ritonavir): 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 (e.g., verapamil): Increase the plasma concentration of risperidone and the active antipsychotic fraction.
Sodium channel blockers (e.g., quinidine): May increase the plasma concentrations of risperidone but not those of the active antipsychotic fraction.
Digitalis glycosides: Risperidone does not show a clinically relevant effect on the pharmacokinetics of digoxin.
Lithium: Repeated oral doses of risperidone did not affect the C_max of lithium. Dose adjustment for lithium is not recommended.
Valproate: Repeated oral doses of risperidone did not affect the pre-dose or average plasma concentrations and exposure of valproate compared to placebo. However, there was a 20% increase in valproate peak plasma concentration after concomitant administration of risperidone. Dose adjustment for valproate is not recommended.
Digoxin: Risperidone did not show a clinically relevant effect on the pharmacokinetics of digoxin. Dose adjustment for digoxin is not recommended.