Risperidoneinteractions

The interactions of UZEDY with co-administration of other drugs have not been studied. The drug interaction data provided in this section is based on studies with oral risperidone. Strong CYP2D6 inhibitors (e.g., fluoxetine, paroxetine): Increase risperidone plasma concentration. Strong CYP3A4 inducers (e.g., carbamazepine): Decrease plasma concentrations of risperidone.

7.1 Drugs Having

Clinically Important Interactions with UZEDY Table 13 includes clinically significant drug interactions with UZEDY.

Table 13: Clinically Important Drug Interactions with UZEDY Strong CYP2D6 Inhibitors Clinical Impact: Concomitant use of UZEDY with strong CYP2D6 inhibitors may increase the plasma exposure of risperidone and lower the plasma exposure of a major active metabolite, 9-hydroxyrisperidone.

Intervention: When initiation of strong CYP2D6 inhibitors is considered, patients may be placed on the lowest dose (50 mg once monthly or 100 mg once every 2 months) of UZEDY prior to the planned start of strong CYP2D6 inhibitors to adjust for the expected increase in plasma concentrations of risperidone. When strong CYP2D6 inhibitors are initiated in patients receiving UZEDY 50 mg once monthly or 100 mg once every 2 months, it is recommended to continue treatment with the same dose unless clinical judgment necessitates interruption of UZEDY treatment. The effects of discontinuation of strong CYP2D6 inhibitors on the pharmacokinetics of risperidone and 9-hydroxyrisperidone have not been studied. Strong CYP3A4 Inducers Clinical Impact: Concomitant use of UZEDY and a strong CYP3A4 inducer may cause decreases in the combined plasma concentrations of risperidone and 9-hydroxyrisperidone which could lead to decreased efficacy of UZEDY.

Intervention: Changes in efficacy and safety should be carefully monitored with any dose adjustment of UZEDY. At the initiation of therapy with a strong CYP3A4 inducer, patients should be closely monitored during the first 4 to 8 weeks. In patients receiving UZEDY at a specific dose, consider increasing the dose to the next highest dose. In patients receiving UZEDY 125 mg once monthly or 250 mg once every 2 months, additional oral risperidone therapy may need to be considered. On discontinuation of a strong CYP3A4 inducer, the dosage of UZEDY or any additional oral risperidone therapy should be reevaluated and, if necessary, decreased to adjust for the expected increase in plasma concentration of risperidone and 9-hydroxyrisperidone. For patients treated with UZEDY 50 mg once monthly or UZEDY 100 mg once every 2 months discontinuing from a strong CYP3A4 inducer, it is recommended to continue treatment with the same dose unless clinical judgment necessitates interruption of UZEDY treatment. Centrally-Acting Drugs and Alcohol Clinical Impact: Due to additive pharmacologic effects, the concomitant use of centrally-acting drugs, including alcohol, may increase nervous system disorders.

Intervention: Caution should be used when UZEDY is administered in combination with other centrally-acting drugs or alcohol.

Hypotensive Agents Clinical Impact: Because of its potential for inducing hypotension, UZEDY may enhance the hypotensive effects of other therapeutic agents with this potential.

Intervention: Caution should be used when UZEDY is administered with other therapeutic effects of other therapeutic agents with this potential.

Dopamine Agonists Clinical Impact: Agents with central antidopaminergic activity such as UZEDY may antagonize the pharmacologic effects of dopamine agonists.

Intervention: Caution should be used when UZEDY is administered in combination with levodopa and dopamine agonists.

Methylphenidate Clinical Impact: Concomitant use with methylphenidate, when there is change in dosage of either medication, may increase the risk of extrapyramidal symptoms (EPS).

Intervention: Monitor for symptoms of EPS with concomitant use of UZEDY and methylphenidate.

7.2 Drugs Having

No Clinically Important Interactions with UZEDY Based on pharmacokinetic studies with oral risperidone, no dosage adjustment of UZEDY is required when administered concomitantly with amitriptyline, cimetidine, ranitidine, clozapine, topiramate, and moderate CYP3A4 inhibitors (erythromycin). Additionally, no dosage adjustment is necessary for lithium, valproate, topiramate, digoxin, and CYP2D6 substrates (donepezil and galantamine) when co-administered with UZEDY.