Residon Mechanism of Action

Pharmacology: Pharmacodynamics: Drugs known to prolong the QT interval: As with other antipsychotics, caution is advised when prescribing risperidone with medicinal products known to prolong the QT interval, such as antiarrhythmics (e.g., quinidine, dysopiramide, procainamide, propafenone, amiodarone, sotalol), tricyclic antidepressants (i.e., amitriptyline), tetracyclic antidepressants (i.e., maprotiline), some antihistamines, other antipsychotics, some antimalarials (i.e., quinine and mefloquine), and with medicines causing electrolyte imbalance (hypokalemia, hypomagnesiaemia), bradycardia, or those which inhibit the hepatic metabolism of risperidone. This list is indicative and not exhaustive.
Centrally-Acting Drugs and Alcohol: Risperidone should be used with caution in combination with other centrally-acting substances notably including alcohol, opiates, antihistamines and benzodiazepines due to the increased risk of sedation.
Levodopa and Dopamine Agonists: Risperidone may antagonise the effect of levodopa and other dopamine agonists. If this combination is deemed necessary, particularly in end-stage Parkinson's disease, the lowest effective dose of each treatment should be prescribed.
Drugs with Hypotensive Effect: Clinically significant hypotension has been observed postmarketing with concomitant use of risperidone and antihypertensive treatment.
Paliperidone: Concomitant use of oral Risperidone Tablets with paliperidone is not recommended as paliperidone is the active metabolite of risperidone and the combination of the two may lead to additive active antipsychotic fraction exposure.
Pharmacokinetics: Food does not affect the absorption of Risperidone Tablets. 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.
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 dosage.
Paediatric Population: Interaction studies have only been performed in adults. The relevance of the results from these studies in paediatric patients is unknown. The combined use of psychostimulants (e.g., methylphenidate) with Risperidone in children and adolescents did not alter the pharmacokinetics and efficacy of Risperidone.
Antibacterials: Erythromycin, a moderate CYP3A4 inhibitor and P-gp inhibitor, does not change the pharmacokinetics of risperidone and the active antipsychotic fraction.
Antipsychotic Fraction: Anticholinesterases: Donepezil and galantamine, both CYP2D6 and CYP3A4 substrates, do not show a clinically relevant effect on the pharmacokinetics of risperidone and the active antipsychotic fraction.
Antiepileptics: Carbamazepine, a strong CYP3A4 inducer and a P-gp inducer, has been shown to decrease the plasma concentrations of the active antipsychotic fraction of risperidone. Similar effects may be observed with e.g., phenytoin and phenobarbital which also indue CYP3A4 hepatic enzyme, as well as P-glycoprotein.
Topiramate modestly reduced the bioavailability of risperidone, but not that of the active antipsychotic fraction. Therefore, this interaction is unlikely to be of clinical significance.
Antifungals: 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, 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 may increase the plasma concentrations of risperidone but not those of the active antipsychotic fraction.
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 potentialy 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: H-receptor antagonist: Cimetidine and ranitidine, both weak inhibitors of CYP2D6 and CYP3A4, increased the bioavailability of risperidone, but only marginally that of the active antipsychotic fraction.
SSRIs and Tricyclic antidepressants: Fluoxetine, a strong CYP2D6 inhibitor, increases the plasma concentration of risperidone, but less so of the active antipsychotic fraction.
Paroxetine, a strong CYPD6, increases the plasma concentrations of risperidone, but at dosages up to 20 mg/day, less so of the active antipsychotic fraction. However, higher doses of paroxetine may elevate concentrations of the risperidone active antipsychotic fraction.
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, 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.