Risperidone

May alter cardiac conduction; life-threatening arrhythmias have occurred with therapeutic doses of antipsychotics. Use caution with history of conduction abnormalities. Relative to other neuroleptics, risperidone has a low risk of arrhythmias (APA [Lehman 2004]).

May cause anticholinergic effects (confusion, agitation, constipation, xerostomia, blurred vision, urinary retention); use with caution in patients with decreased gastrointestinal motility, urinary retention, BPH, xerostomia, or visual problems. Relative to other neuroleptics, risperidone has a low potency of cholinergic blockade (Richelson 1999).

May mask toxicity of other drugs or conditions (eg, intestinal obstruction, Reyes syndrome, brain tumor) due to antiemetic effects.

Leukopenia, neutropenia, and agranulocytosis (sometimes fatal) have been reported in clinical trials and postmarketing reports with antipsychotic use; presence of risk factors (eg, pre-existing low WBC or history of drug-induced leuko-/neutropenia) should prompt periodic blood count assessment. Discontinue therapy at first signs of blood dyscrasias or if absolute neutrophil count 3.

An increased incidence of cerebrovascular effects (eg, transient ischemic attack, stroke), including fatalities, has been reported in placebo-controlled trials of risperidone for the unapproved use in elderly patients with dementia-related psychosis.

May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery, driving). May be low to moderately sedating in comparison with other antipsychotics (Richelson 1999); dose-related effects have been observed.

Has been reported with atypical antipsychotics; risk profile may differ between agents. Discrepant results have been reported in clinical trials, regarding lipid changes associated with risperidone (American Diabetes Association, 2004).

Antipsychotic use has been associated with esophageal dysmotility and aspiration; use with caution in patients at risk of pneumonia (eg, Alzheimer disease).

May cause extrapyramidal symptoms (EPS), including pseudoparkinsonism, acute dystonic reactions, akathisia, and tardive dyskinesia (risk of these reactions is generally much lower relative to typical/conventional antipsychotics; frequencies reported are similar to placebo). Risk of dystonia (and possibly other EPS) may be greater with increased doses, use of conventional antipsychotics, males, and younger patients. Factors associated with greater vulnerability to tardive dyskinesia include older in age, female gender combined with postmenopausal status, Parkinson disease, pseudoparkinsonism symptoms, affective disorders (particularly major depressive disorder), concurrent medical diseases such as diabetes, previous brain damage, alcoholism, poor treatment response, and use of high doses of antipsychotics (APA [Lehman 2004]; Soares-Weiser 2007). Consider therapy discontinuation with signs/symptoms of tardive dyskinesia.

May increase the risk for falls due to somnolence, orthostatic hypotension, and motor or sensory instability. Complete fall risk assessments at baseline and periodically during treatment in patients with diseases or on medications that may also increase fall risk.

Atypical antipsychotics have been associated with development of hyperglycemia; in some cases, may be extreme and associated with ketoacidosis, hyperosmolar coma, or death. Use with caution in patients with diabetes or other disorders of glucose regulation; monitor for worsening of glucose control.

Risperidone is associated with greater increases in prolactin levels as compared to other antipsychotic agents; clinical significance of hyperprolactinemia in patients with breast cancer or other prolactin-dependent tumors is unknown. Risk factors for hyperprolactinemia in patients taking risperidone include female gender, younger age at onset of illness, and higher scores on the Positive and Negative Symptom Scale (PANSS). Additionally, higher doses are associated with greater elevations in prolactin concentrations (Bo 2016).

Hypersensitivity reactions including anaphylactic reactions and angioedema have been reported.

Few case reports describe intraoperative floppy iris syndrome (IFIS) in patients receiving risperidone and undergoing cataract surgery (Ford 2011). Prior to cataract surgery, evaluate for prior or current risperidone use. The benefits or risks of interrupting risperidone prior to surgery have not been established; clinicians are advised to proceed with surgery cautiously.

Use may be associated with neuroleptic malignant syndrome (NMS); monitor for mental status changes, fever, muscle rigidity, and/or autonomic instability.

May cause orthostatic hypotension; use with caution in patients at risk of this effect (eg, concurrent medication use which may predispose to hypotension/bradycardia or presence of hypovolemia) or in those who would not tolerate transient hypotensive episodes. Use caution with history of cerebrovascular or cardiovascular disease (MI, heart failure, or ischemic disease).

Rare cases of priapism have been reported.

The possibility of a suicide attempt is inherent in psychotic illness or bipolar disorder; use with caution in high-risk patients during initiation of therapy. Prescriptions should be written for the smallest quantity consistent with good patient care.

Impaired core body temperature regulation may occur; caution with strenuous exercise, heat exposure, dehydration, and concomitant medication possessing anticholinergic effects (Kwok 2005, Martinez 2002).

Significant weight gain has been observed with antipsychotic therapy; incidence varies with product. Monitor waist circumference and BMI. Disease-related concerns:

Use with caution in patients with severe cardiac disease, hemodynamic instability, prior myocardial infarction or ischemic heart disease.

Elderly patients with dementia-related psychosis treated with antipsychotics are at an increased risk of death compared to placebo. Most deaths appeared to be either cardiovascular (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature. Use with caution in patients with Lewy body dementia or Parkinson disease dementia due to greater risk of adverse effects, increased sensitivity to extrapyramidal effects, and association with irreversible cognitive decompensation or death. (APA [Reus 2016]). Risperidone is not approved for the treatment of dementia-releated psychosis. Careful assessment of risk factors for stroke or existing cardiovascular morbidities is required prior to initiation.

Use with caution in patients with hepatic disease or impairment; dosage reduction is recommended.

Use with caution in patients with Parkinson disease; antipsychotics may aggravate the motor disturbances of Parkinson disease (APA [Lehman 2004]; APA [Reus 2016]).

Use with caution in patients with renal disease; dosage reduction is recommended.

Use with caution in patients at risk of seizures, including those with a history of seizures, head trauma, brain damage, alcoholism, or concurrent therapy with medications which may lower seizure threshold. Concurrent drug therapy issues:

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Dosage form specific issues:

Some dosage forms may contain sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol derivative with caution in neonates. See manufacturer’s labeling.

Inform patients with phenylketonuria that dispersible tablets contain phenylalanine.

Vehicle used (polylactide-co-glycolide microspheres) has rarely been associated with retinal artery occlusion in patients with abnormal arteriovenous anastomosis (eg, patent foramen ovale). Not for IV use; administer only as an intramuscular injection. Other warnings/precautions:

When discontinuing antipsychotic therapy, the American Psychiatric Association (APA), Canadian Psychiatric Association (CPA), and World Federation of Societies of Biological Psychiatry (WFSBP) guidelines recommend gradually tapering antipsychotics to avoid physical withdrawal symptoms, including anorexia, anxiety, diaphoresis, diarrhea, dizziness, dyskinesia, headache, myalgia, nausea, paresthesia, restlessness, tremulousness, and vomiting (APA [Lehman 2004]; CPA [Addington 2005]; Lambert 2007; WFSBP [Hasan 2012]). The risk of withdrawal symptoms is highest following abrupt discontinuation of highly anti-cholinergic or dopaminergic antipsychotics (Cerovecki 2013). Additional factors such as duration of antipsychotic exposure, the indication for use, medication half-life, and risk for relapse should be considered. In schizophrenia, there is no reliable indicator to differentiate the minority who will not from the majority who will relapse with drug discontinuation. However, studies in which the medication of well-stabilized patients were discontinued indicate that 75% of patients relapse within 6 to 24 months. Indefinite maintenance antipsychotic medication is generally recommended, and especially for patients who have had multiple prior episodes or 2 episodes within 5 years (APA [Lehman 2004]).