DRUG INTERACTIONS
- Carbamazepine and other enzyme inducers decrease plasma concentrations of risperidone. Increase the RISPERDAL® dose up to double the patient's usual dose. Titrate slowly. (7.1)
- Fluoxetine, paroxetine, and other CYP 2D6 enzyme inhibitors increase plasma concentrations of risperidone. Reduce the initial dose. Do not exceed a final dose of 8 mg per day of RISPERDAL®. (7.1)
The dose of RISPERDAL® should be adjusted when used in combination with CYP2D6 enzyme inhibitors (e.g., fluoxetine, and paroxetine) and enzyme inducers (e.g., carbamazepine) [see Table 18 and Dosage and Administration ]. Dose adjustment is not recommended for RISPERDAL® when co-administered with ranitidine, cimetidine, amitriptyline, or erythromycin [see Table 18 ].
Table 18 Summary of Effect of Coadministered Drugs on Exposure to Active Moiety (Risperidone + 9-Hydroxy-Risperidone) in Healthy Subjects or Patients with Schizophrenia
Coadministered Drug |
Dosing Schedule |
Effect on Active Moiety (Risperidone + 9-Hydroxy-Risperidone (Ratio *) |
Risperidone Dose Recommendation |
Coadministered Drug |
Risperidone |
AUC |
Cmax |
Enzyme (CYP2D6) Inhibitors |
|
|
|
|
|
Fluoxetine |
20 mg/day |
2 or 3 mg twice daily |
1.4 |
1.5 |
Re-evaluate dosing. Do not exceed 8 mg/day |
Paroxetine |
10 mg/day |
4 mg/day |
1.3 |
- |
Re-evaluate dosing. Do not exceed 8 mg/day |
| 20 mg/day |
4 mg/day |
1.6 |
- |
| 40 mg/day |
4 mg/day |
1.8 |
- |
Enzyme (CYP3A/ PgP inducers) Inducers |
|
|
|
|
|
Carbamazepine |
573 ± 168 mg/day |
3 mg twice daily |
0.51 |
0.55 |
Titrate dose upwards. Do not exceed twice the patient's usual dose |
Enzyme (CYP3A) Inhibitors |
|
|
|
|
|
Ranitidine |
150 mg twice daily |
1 mg single dose |
1.2 |
1.4 |
Dose adjustment not needed |
Cimetidine |
400 mg twice daily |
1 mg single dose |
1.1 |
1.3 |
Dose adjustment not needed |
Erythromycin |
500 mg four times daily |
1 mg single dose |
1.1 |
0.94 |
Dose adjustment not needed |
|
|
|
|
|
|
Other Drugs |
|
|
|
|
|
Amitriptyline |
50 mg twice daily |
3 mg twice daily |
1.2 |
1.1 |
Dose adjustment not needed |
Effect 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.
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.
|