pms-Risperidone

pms-Risperidone Drug Interactions

risperidone

Manufacturer:

Pharmascience

Distributor:

T-BOMA
Full Prescribing Info
Drug Interactions
Overview: Centrally-acting Drugs and Alcohol: Given the primary central nervous system effects of risperidone, caution should be used when it is taken in combination with other centrally acting drugs and alcohol.
Levodopa and Dopamine Agonists: Risperidone may antagonize the effects of levodopa and dopamine agonists.
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 medications.
Drugs Known to Prolong the QT interval: Caution is advised when prescribing pms-RISPERIDONE with drugs known to prolong the QT interval.
Drug-Drug Interactions: 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: Coadministration of risperidone with a strong CYP2D6 inhibitor may increase the plasma concentrations of risperidone, but less so of the active antipsychotic fraction (risperidone and 9-hydroxyrisperidone combined). Higher doses of a strong CYP2D6 inhibitor may elevate concentrations of the risperidone active antipsychotic fraction (e.g., paroxetine, see The Effect of Other Drugs on the Metabolism of Risperidone: SSRIs and Tricyclic Antidepressants: Paroxetine 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 pms-RISPERIDONE.
CYP3A4 and/or P-gp Inhibitors: Coadministration of risperidone 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 pms-RISPERIDONE.
CYP3A4 and/or P-gp Inducers: Coadministration 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 inducer is initiated or discontinued, the physician should re-evaluate the dosing of pms-RISPERIDONE.
Highly Protein-bound Drugs: When risperidone is taken together with 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.
Concomitant Use with Furosemide: See Use in Elderly: Use in Geriatric Patients with Dementia: Concomitant Use with Furosemide under Precautions regarding increased mortality in elderly patients with dementia concomitantly receiving furosemide.
The Effect of Other Drugs on the Metabolism of Risperidone: SSRIs and Tricyclic Antidepressants: Fluoxetine: Fluoxetine, a strong CYP 2D6 inhibitor, increases the plasma concentration of risperidone but less so of risperidone and 9-hydroxyrisperidone combined. Pharmacokinetic interaction with fluoxetine was examined in a study which measured steady-state plasma levels of risperidone and its metabolites before and following 3 weeks of co-treatment with fluoxetine (n = 10). The addition of fluoxetine resulted in about a 2- to 3-fold increase in peak and AUC levels of risperidone and about a 50% increase in peak and AUC levels for risperidone and 9-hydroxyrisperidone combined. When concomitant fluoxetine is initiated or discontinued, the physician should re-evaluate the dosing of pms-RISPERIDONE.
Paroxetine: Paroxetine, a strong CYP 2D6 inhibitor, increases the plasma concentration of risperidone but, at dosages up to 20 mg/day, less so of risperidone and 9-hydroxyrisperidone combined. However, higher doses of paroxetine may elevate concentrations of the risperidone active antipsychotic fraction. Pharmacokinetic interaction with paroxetine was examined in a study which measured steady-state plasma levels of risperidone and its metabolites before and following 4 weeks of co-treatment with paroxetine (n = 10). After 4 weeks of paroxetine treatment, the sum of the concentrations of risperidone and 9-hydroxyrisperidone increased significantly by 45% over baseline. When concomitant paroxetine is initiated or discontinued, the physician should re-evaluate the dosing of pms-RISPERIDONE.
Tricyclic antidepressants: Tricyclic antidepressants 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.
Sertraline: Sertraline, a weak inhibitor of CYP2D6, and fluvoxamine, a weak inhibitor of CYP3A4, at dosages up to 100 mg/day are not associated with clinically significant changes in concentrations of the risperidone active antipsychotic fraction. However, doses higher than 100 mg/day of sertraline or fluvoxamine may elevate concentrations of the risperidone active antipsychotic fraction.
Antibacterials: Erythromycin: Erythromycin, a moderate CYP 3A4 inhibitor, did not change the pharmacokinetics of risperidone or risperidone and 9-hydroxyrisperidone combined. Risperidone was administered as a single dose of 1 mg with multiple doses of erythromycin (500 mg q.i.d.) in healthy volunteers (n = 18).
Rifampicin: Rifampicin, a strong CYP3A4 inducer and a P-gp inducer, decreased the plasma concentrations of the active antipsychotic fraction.
Anticholinesterases: Galantamine and Donepezil: Galantamine (n = 15) and donepezil (n = 24), both CYP2D6 and CYP3A4 substrates, did not show an effect on the pharmacokinetics of risperidone or risperidone and 9-hydroxyrisperidone combined. Galantamine 12 mg o.d. was coadministered with risperidone 0.5 mg o.d. in healthy elderly volunteers. Donepezil 5 mg o.d. was coadministered with risperidone 0.5 mg b.i.d. in healthy male volunteers.
Antiepileptics: Carbamazepine and Other CYP 3A4 Enzyme Inducers: Carbamazepine, a strong CYP3A4 inducer and a P-gp inducer, has been shown to decrease substantially the plasma levels of risperidone and its active metabolite, 9-hydroxyrisperidone (n = 11).
Topiramate: Healthy Volunteers: A drug-drug interaction study between risperidone and topiramate was conducted in 12 healthy volunteers (6 males, 6 females), ages 28-40 years, with single-dose administration of risperidone (2 mg) and multiple doses of topiramate (titrated up to 200 mg/day). In the presence of topiramate, systemic exposure of risperidone and 9-hydroxyrisperidone-combined was reduced such that mean AUC0-∞ was 11% lower and mean Cmax was statistically significantly (18%) lower. In the presence of topiramate, systemic exposure of risperidone was statistically significantly reduced such that mean Cmax and AUC0-∞ were 29% and 23% lower, respectively. The pharmacokinetics of 9-hydroxyrisperidone were unaffected. The effects of a single dose (2 mg/day) of risperidone on the pharmacokinetics of multiple doses of topiramate have not been studied.
Patients with Bipolar Disorder: A drug-drug interaction study conducted in 52 patients with various types of bipolar disorder (24 males, 28 females), ages 19-56 years, evaluated the steady-state pharmacokinetics of risperidone and topiramate when administered concomitantly. Eligible subjects were stabilized on a risperidone dose of 1-6 mg/day for 2 to 3 weeks. Topiramate was then titrated up to escalating doses of 100, 250 and 400 mg/day along with risperidone for up to 6 weeks. Risperidone was then tapered and discontinued over 4 weeks while maintaining topiramate (up to 400 mg/day). There was a statistically significant reduction in risperidone systemic exposure (16% and 33% for AUC12 and 13% and 34% for Cmax at the 250 and 400 mg/day doses, respectively). Minimal alterations were observed in the pharmacokinetics of risperidone and 9-hydroxyrisperidone combined and of 9-hydroxyrisperidone. Topiramate systemic exposure was slightly reduced (12.5% for mean Cmax and 11% for mean AUC12) in the presence of risperidone, which achieved statistical significance. There were no clinically significant changes in the systemic exposure of risperidone and 9-hydroxyrisperidone combined or of topiramate. The effects of higher doses of topiramate (> 400 mg/day) are unknown. Therefore, if combination therapy is chosen, patients receiving both risperidone and topiramate should be closely monitored.
Antifungals: Itraconazole: Itraconazole, a strong CYP3A4 inhibitor and a P-gp inhibitor, at a dosage of 200 mg/day increased the plasma concentrations of the active antipsychotic fraction by about 70%, at risperidone doses of 2 to 8 mg/day.
Ketoconazole: Ketoconazole, a strong CYP3A4 inhibitor and a P-gp inhibitor, at a dosage of 200 mg/day increased the plasma concentrations of risperidone and decreased the plasma concentrations of 9-hydroxyrisperidone.
Antipsychotics: Phenothiazines: Phenothiazines may increase the plasma concentrations of risperidone but not those of the active antipsychotic fraction.
Clozapine: Chronic administration of clozapine with risperidone may decrease the clearance of risperidone.
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.
Gastrointestinal Drugs: H2-receptor antagonists (Cimetidine and Ranitidine): Risperidone was administered as a single dose of 1 mg with multiple doses of either cimetidine (400 mg b.i.d.) or ranitidine (150 mg b.i.d.), both weak inhibitors of CYP2D6 and CYP3A4, in healthy young adult volunteers (n = 12). The effect of the drug interaction of cimetidine and ranitidine on risperidone and 9-hydroxyrisperidone combined was minimal.
Effects of Risperidone on the Metabolism of Other Drugs: Aripiprazole: A CYP2D6 and CYP3A4 substrate; Risperidone tablets did not affect the pharmacokinetics of the sum of aripiprazole and its active metabolite, dehydroaripiprazole.
Lithium: Risperidone (3 mg b.i.d.) did not show an effect on the pharmacokinetics of lithium (400, 450 or 560 mg b.i.d.) (n = 13).
Valproate: Risperidone (4 mg o.d.) did not show an effect on the pharmacokinetics of valproate (1,000 mg/day) (n=9). However, more subjects reported adverse events with the risperidone-valproate therapy compared to the placebo-valproate group in the clinical trial.
Digoxin: The effect of risperidone (0.5 mg/day administered b.i.d.) on the steady state plasma concentrations of digoxin (0.125 mg/day) was examined in a double-blind, two-way, crossover trial in healthy elderly volunteers (median age 68 years, range 61 to 75 years, n = 19). Risperidone did not affect the steady state pharmacokinetics of digoxin, and concurrent administration of the two drugs was well tolerated.
In vitro studies, in which risperidone was given in the presence of various, highly protein-bound agents, indicated that clinically relevant changes in protein binding would not occur either for risperidone or for any of the drugs tested.
Psychostimulants: The combined use of psychostimulants (e.g. methylphenidate) with risperidone can lead to the emergence of extrapyramidal symptoms upon change of either or both treatments (see Neurologic: Extrapyramidal symptoms and psychostimulants under Precautions).
Drug-Food Interactions: pms-RISPERIDONE oral solution is compatible with the following beverages: water, coffee, orange juice and low-fat milk. However, it is not compatible with cola or tea. Also see Directions for Use of pms-RISPERIDONE Oral Solution under Cautions for Usage.
Food does not affect the absorption of risperidone.
Drug-Herb Interactions: Interactions with herbal products have not been established.
Drug-Laboratory Interactions: Interactions with laboratory tests have not been established.
Drug-Lifestyle Interactions: Centrally-acting Drugs and Alcohol: Given the primary central nervous system effects of risperidone, caution should be used when it is taken in combination with other centrally acting drugs and alcohol.
Exclusive offer for doctors
Register for a MIMS account and receive free medical publications worth $768 a year.
Sign up for free
Already a member? Sign in