What are the interactions between Risperidone and other medications?

Risperidone and Uzedy: Drug Interactions and Clinical Considerations

Risperidone has no documented direct pharmacokinetic or pharmacodynamic interactions with Uzedy (risperidone extended-release injectable suspension), as they are formulations of the same active compound; however, when using risperidone in any form, clinicians must carefully manage interactions with CYP2D6 inhibitors, CYP3A/P-gp inducers, and centrally-acting medications. 1

Critical Drug Interactions Requiring Dose Adjustment

CYP2D6 Inhibitors (Require Dose Reduction)

• Fluoxetine and paroxetine significantly increase risperidone exposure (AUC increases 1.4-1.8 fold), necessitating dose re-evaluation with a maximum daily dose not exceeding 8 mg 1
• The active moiety (risperidone + 9-hydroxy-risperidone) increases by 30-80% depending on the inhibitor dose 1

CYP3A/P-gp Inducers (Require Dose Increase)

• Carbamazepine reduces risperidone exposure by approximately 50% (AUC ratio 0.51, Cmax ratio 0.55), requiring upward dose titration up to twice the patient's usual dose 1
• This interaction is clinically significant and can lead to treatment failure if not addressed 1

Interactions NOT Requiring Dose Adjustment

• Ranitidine, cimetidine, erythromycin, and amitriptyline produce minimal changes in risperidone exposure (AUC changes 1.1-1.2 fold) and do not require dose modifications 1
• Lithium, valproate, and digoxin show no clinically relevant pharmacokinetic interactions with risperidone 1

Pharmacodynamic Interactions Requiring Caution

Centrally-Acting Drugs and Alcohol

• Exercise caution when combining risperidone with other CNS-active medications or alcohol due to additive central nervous system effects 1
• This includes benzodiazepines, opioids, and other sedating medications 2

Hypotensive Agents

• Risperidone may enhance hypotensive effects of antihypertensive medications due to its alpha-adrenergic blocking properties 1
• Orthostatic hypotension is a common problem requiring monitoring, particularly in elderly patients 3, 4
• Start with lower doses (0.25-0.5 mg) in older or frail patients 3

Dopaminergic Medications

• Risperidone antagonizes the effects of levodopa and dopamine agonists through its dopamine D2 receptor antagonism 1
• Avoid concurrent use in Parkinson's disease patients or adjust expectations for reduced antiparkinsonian efficacy 1

Clozapine

• Chronic clozapine administration may decrease risperidone clearance, potentially requiring dose adjustment 1

Special Considerations for Combination Therapy

Stimulant Combinations (Pediatric ADHD with ID/IDD)

• Risperidone can be safely combined with stimulants in children with intellectual disability and ADHD, with the combination showing better hyperactivity control than stimulants alone 2
• The combination does not increase adverse events compared to risperidone monotherapy 2
• Weight gain occurs similarly regardless of stimulant co-administration (mean 2.84 kg over 6 weeks) 2
• Common side effects in the combination include less somnolence and vomiting but more rhinitis and increased appetite compared to risperidone alone 2

Mood Stabilizer Combinations

• Risperidone is commonly used as adjunctive therapy with mood stabilizers in schizoaffective disorder and bipolar disorder 5
• Mean effective dose in combination therapy is approximately 4.7 mg/day 5
• No significant pharmacokinetic interactions with lithium or valproate require dose adjustment 1

Monitoring Requirements for Drug Interactions

When Using CYP2D6 Inhibitors

• Monitor for increased extrapyramidal symptoms, as risk increases with higher risperidone exposure 3, 4
• Watch for excessive sedation and orthostatic hypotension 3
• Consider dose reduction if side effects emerge 1

When Using CYP3A Inducers

• Monitor for loss of therapeutic efficacy 1
• Assess clinical response regularly and titrate dose upward as needed 1
• Maximum dose may reach twice the usual therapeutic dose 1

With Hypotensive Medications

• Measure blood pressure in both supine and standing positions to detect orthostatic changes 6
• Risk of falls is significant, particularly in elderly patients 3

Common Pitfalls to Avoid

• Do not assume all SSRIs interact equally: Only fluoxetine and paroxetine (potent CYP2D6 inhibitors) require dose adjustment; sertraline and citalopram have minimal effects 1
• Do not overlook the carbamazepine interaction: This is one of the most clinically significant interactions, reducing risperidone levels by 50% 1
• Do not combine with multiple sedating medications without careful monitoring, as additive CNS depression can impair function and increase fall risk 2, 1
• Do not use standard adult doses in elderly patients taking multiple medications; start at 0.25-0.5 mg and titrate slowly 3
• Do not ignore weight gain as a metabolic interaction concern when combining with other weight-promoting medications like valproate or other atypical antipsychotics 2, 3