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Click on icon to see table/diagram/imageEffect of Risperidone on Other Drugs: Lithium: Repeated oral doses of RISPERDAL (3 mg twice daily) did not affect the exposure (AUC) or peak plasma concentrations (Cmax) of lithium (n=13). Dose adjustment for lithium is not recommended.
Valproate: Repeated oral doses of RISPERDAL (4 mg once daily) did not affect the pre-dose or average plasma concentrations and exposure (AUC) of valproate (1000 mg/day in three divided doses) compared to placebo (n=21). However, there was a 20% increase in valproate peak plasma concentration (Cmax) after concomitant administration of RISPERDAL. Dose adjustment for valproate is not recommended.
Digoxin: RISPERDAL (0.25 mg twice daily) did not show a clinically relevant effect on the pharmacokinetics of digoxin. Dose adjustment for digoxin is not recommended.
Pharmacodynamic-related Interactions: Centrally-Acting Drugs and Alcohol: Given the primary CNS effects of risperidone, caution should be used when RISPERDAL is taken in combination with other centrally-acting drugs and alcohol.
Drugs with Hypotensive Effects: Because of its potential for inducing hypotension, RISPERDAL may enhance the hypotensive effects of other therapeutic agents with this potential.
Levodopa and Dopamine Agonists: RISPERDAL may antagonize the effects of levodopa and dopamine agonists.
Clozapine: Chronic administration of clozapine with RISPERDAL may decrease the clearance of risperidone.
Risperdal Consta: The interactions of RISPERDAL CONSTA with coadministration of other drugs have not been systematically evaluated. The drug interaction data provided in this section is based on studies with oral RISPERDAL.
Centrally-Acting Drugs and Alcohol: Given the primary CNS effects of risperidone, caution should be used when RISPERDAL CONSTA is administered in combination with other centrally-acting drugs or alcohol.
Drugs with Hypotensive Effects: Because of its potential for inducing hypotension, RISPERDAL CONSTA may enhance the hypotensive effects of other therapeutic agents with this potential.
Levodopa and Dopamine Agonists: RISPERDAL CONSTA may antagonize the effects of levodopa and dopamine agonists.
Amitriptyline: Amitriptyline did not affect the pharmacokinetics of risperidone or of risperidone and 9‑hydroxyrisperidone combined following concomitant administration with oral RISPERDAL.
Cimetidine and Ranitidine: Cimetidine and ranitidine increased the bioavailability of oral risperidone by 64% and 26%, respectively. However, cimetidine did not affect the AUC of risperidone and 9‑hydroxyrisperidone combined, whereas ranitidine increased the AUC of risperidone and 9‑hydroxyrisperidone combined by 20%.
Clozapine: Chronic administration of clozapine with risperidone may decrease the clearance of risperidone.
Lithium: Repeated doses of oral RISPERDAL (3 mg twice daily) did not affect the exposure (AUC) or peak plasma concentrations (Cmax) of lithium (N=13).
Valproate: Repeated doses of oral RISPERDAL (4 mg once daily) did not affect the pre-dose or average plasma concentrations and exposure (AUC) of valproate (1000 mg/day in three divided doses) compared to placebo (N=21). However, there was a 20% increase in valproate peak plasma concentration (Cmax) after concomitant administration of oral RISPERDAL.
Digoxin: Oral RISPERDAL (0.25 mg twice daily) did not show a clinically relevant effect on the pharmacokinetics of digoxin.
Topiramate: Oral RISPERDAL administered at doses from 1-6 mg/day concomitantly with topiramate 400 mg/day resulted in a 23% decrease in risperidone Cmax and a 33% decrease in risperidone AUC0-12 hour at steady state. Minimal reductions in the exposure to risperidone and 9‑hydroxyrisperidone combined, and no change for 9-hydroxyrisperidone were observed. This interaction is unlikely to be of clinical significance. There was no clinically relevant effect of oral RISPERDAL on the pharmacokinetics of topiramate.
Drugs That Inhibit CYP 2D6 and Other CYP Isozymes: Risperidone is metabolized to 9-hydroxyrisperidone by CYP 2D6, an enzyme that is polymorphic in the population and that can be inhibited by a variety of psychotropic and other drugs [see Pharmacology: Pharmacokinetics under Actions]. Drug interactions that reduce the metabolism of risperidone to 9-hydroxyrisperidone would increase the plasma concentrations of risperidone and lower the concentrations of 9-hydroxyrisperidone. Analysis of clinical studies involving a modest number of poor metabolizers (n≅70 patients) does not suggest that poor and extensive metabolizers have different rates of adverse effects. No comparison of effectiveness in the two groups has been made.
In vitro studies showed that drugs metabolized by other CYP isozymes, including 1A1, 1A2, 2C9, 2C19, and 3A4, are only weak inhibitors of risperidone metabolism.
Fluoxetine and Paroxetine: Fluoxetine (20 mg once daily) and paroxetine (20 mg once daily), CYP 2D6 inhibitors, have been shown to increase the plasma concentration of risperidone 2.5-2.8 fold and 3-9 fold respectively. Fluoxetine did not affect the plasma concentration of 9-hydroxyrisperidone. Paroxetine lowered the concentration of 9-hydroxyrisperidone by about 10%. When either concomitant fluoxetine or paroxetine is initiated or discontinued, the physician should re‑evaluate the dose of RISPERDAL CONSTA. When initiation of fluoxetine or paroxetine is considered, patients may be placed on a lower dose of RISPERDAL CONSTA between 2 to 4 weeks before the planned start of fluoxetine or paroxetine therapy to adjust for the expected increase in plasma concentrations of risperidone. When fluoxetine or paroxetine is initiated in patients receiving the recommended dose of 25 mg RISPERDAL CONSTA, it is recommended to continue treatment with the 25-mg dose unless clinical judgment necessitates lowering the RISPERDAL CONSTA dose to 12.5 mg or necessitates interruption of RISPERDAL CONSTA treatment. When RISPERDAL CONSTA is initiated in patients already receiving fluoxetine or paroxetine, a starting dose of 12.5 mg can be considered. The efficacy of the 12.5 mg dose has not been investigated in clinical trials [see also Dosage & Administration]. The effects of discontinuation of concomitant fluoxetine or paroxetine therapy on the pharmacokinetics of risperidone and 9-hydroxyrisperidone have not been studied.
Erythromycin: There were no significant interactions between oral RISPERDAL and erythromycin.
Carbamazepine and Other CYP 3A4 Enzyme Inducers: Carbamazepine co-administration with oral RISPERDAL decreased the steady-state plasma concentrations of risperidone and 9-hydroxyrisperidone by about 50%. Plasma concentrations of carbamazepine did not appear to be affected. Co-administration of other known CYP 3A4 enzyme inducers (e.g., phenytoin, rifampin, and phenobarbital) with risperidone may cause similar decreases in the combined plasma concentrations of risperidone and 9‑hydroxyrisperidone, which could lead to decreased efficacy of RISPERDAL CONSTA treatment. At the initiation of therapy with carbamazepine or other known hepatic enzyme inducers, patients should be closely monitored during the first 4-8 weeks, since the dose of RISPERDAL CONSTA may need to be adjusted. A dose increase, or additional oral RISPERDAL, may need to be considered. On discontinuation of carbamazepine or other CYP 3A4 hepatic enzyme inducers, the dosage of RISPERDAL CONSTA should be re-evaluated and, if necessary, decreased. Patients may be placed on a lower dose of RISPERDAL CONSTA between 2 to 4 weeks before the planned discontinuation of carbamazepine or other CYP 3A4 enzyme inducers to adjust for the expected increase in plasma concentrations of risperidone plus 9-hydroxyrisperidone. For patients treated with the recommended dose of 25 mg RISPERDAL CONSTA and discontinuing from carbamazepine or other CYP 3A4 enzyme inducers, it is recommended to continue treatment with the 25-mg dose unless clinical judgment necessitates lowering the RISPERDAL CONSTA dose to 12.5 mg or necessitates interruption of RISPERDAL CONSTA treatment. The efficacy of the 12.5 mg dose has not been investigated in clinical trials [see also Dosage & Administration].
Drugs Metabolized by CYP 2D6: In vitro studies indicate that risperidone is a relatively weak inhibitor of CYP 2D6. Therefore, RISPERDAL CONSTA is not expected to substantially inhibit the clearance of drugs that are metabolized by this enzymatic pathway. In drug interaction studies, oral RISPERDAL did not significantly affect the pharmacokinetics of donepezil and galantamine, which are metabolized by CYP 2D6.
